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332 results on '"The Churchill hospital"'

1. HIFU Ablation of Soft Tissue Sarcoma (SarcAblate)

Author: Surgical Intervention Trials Unit, Oxford, UK, NIHR Direct Delivery Team, Oxford Radiology Research Unit, Churchill Hospital, Oxford, UK, and Paul Lyon, Primary Investigator
Published: 2024

2. Evaluating Atorvastatin With Omega-3 Fatty Acids in Cardiovascular Risk Reduction in Patients With Type 2 Diabetes (AFORRD)

Author: Churchill Hospital
Published: 2021

3. Open-Label, Non Randomized Phase 2 Study With Safety Run-In

Author: University College London Hospitals, Churchill Hospital, Royal Marsden NHS Foundation Trust, University of Haifa, Weill Medical College of Cornell University, Institut Curie, University Clinical Center, Sarajevo, Clinical Center Kragujevac, Clinical Center Nis, Nis, Institute for Oncology and Radiology Serbia, Belgrade, and University Clinical Centre of Republic of Srpska
Published: 2019

4. PQR309 and Eribulin in Metastatic HER2 Negative and Triple-negative Breast Cancer (PIQHASSO)

Author: Hospital Universitario Ramon y Cajal, Hospital Universitari Vall d'Hebron Research Institute, Institut Català d'Oncologia, Churchill Hospital, Barts Cancer Institute, and Fundación Instituto Valenciano de Oncología
Published: 2019

5. Study of Oral PQR309 in Patients With Advanced Solid Tumors

Author: Roswell Park Cancer Institute, M.D. Anderson Cancer Center, Mayo Clinic, Hospital Clinic of Barcelona, University College London Hospitals, Churchill Hospital, Case Western Reserve University, and University Hospital, Zürich
Published: 2019

6. Elective Cancer Surgery in COVID-19-Free Surgical Pathways during the SARS-CoV-2 Pandemic: An International, Multicenter, Comparative Cohort Study

Author: Writing Group (denotes joint first author) James, C Glasbey (UK), Dmitri Nepogodiev (UK), Joana FF Simoes (Portugal), Omar Omar (UK), Elizabeth Li (UK), Mary, L Venn (UK), Mohammad Abou Chaar (Jordan), Vita Capizzi (Italy), Daoud Chaudhry (UK), Anant Desai (UK), Jonathan, G Edwards (UK), Jonathan, P Evans (UK), Marco Fiore (Italy), Jose Flavio Videria (Portugal), Samuel, J Ford (UK), Ian Ganyli (USA), Ewen, A Griffiths (UK), Rohan, R Gujjuri (UK), Angelos, G Kolias (UK), Haytham MA Kaafarani (USA), Ana Minaya-Bravo (Spain), Siobhan, C McKay (UK), Helen, M Mohan (Ireland), Keith Roberts (UK), Carlos San Miguel-M&#233, ndez (Spain), Peter Pockney (Australia), Richard Shaw (UK), Neil, J Smart (UK), Grant, D Stewart (UK), Sudha Sundar (UK), Raghavan Vidya (UK), Aneel, A Bhangu (UK, Statistical analysis Glasbey JC, Overall guarantor)., Omar, O (Lead statistician), Bhangu, A CovidSurg Operations Committee Kwabena Siaw-Acheampong, Ruth, A Benson, Edward, Bywater, Daoud, Chaudhry, Brett, E Dawson, Jonathan, P Evans, James, C Glasbey, Rohan, R Gujjuri, Emily, Heritage, Conor, S Jones, Sivesh, K Kamarajah, Chetan, Khatri, Rachel, A Khaw, James, M Keatley, Andrew, Knight, Samuel, Lawday, Elizabeth, Li, Harvinder, S Mann, Ella, J Marson, Kenneth, A McLean, Siobhan, C Mckay, Emily, C Mills, Dmitri, Nepogodiev, Gianluca, Pellino, Maria, Picciochi, Elliott, H Taylor, Abhinav, Tiwari, Joana FF Simoes, Isobel, M Trout, Mary, L Venn, Richard JW Wilkin, International Cancer Leads (denotes specialty Principal Investigators) James C Glasbey (Chair), Aneel Bhangu., Colorectal: Neil, J Smart, Ana, Minaya-Bravo, Susan, Moug, Dale, Vimalchandran, Abigail, Vallance, Peter, Pockney, Oesophagogastric: Ewen, A Griffiths, Richard PT Evans, Philip, Townend, Hepatopancreatobilary: Keith Roberts, Siobhan, McKay, John, Isaac, Sohei, Satoi, Thoracic: John Edwards, Aman, S Coonar, Adrian, Marchbank, Edward, J Caruana, Georgia, R Layton, Akshay, Patel, Alessandro, Brunelli, Sarcoma: Samuel Ford, Anant, Desai, Alessandro, Gronchi, Marco, Fiore, Max, Almond, Fabio, Tirotta, Sinziana, Dumitra, Neurosurgery: Angelos Kolias, Stephen, J Price, Daniel, M Fountain, Michael, D Jenkinson, Peter, Hutchinson, Hani, J Marcus, Rory, J Piper, Laura, Lippa, Franco, Servadei, Ignatius, Esene, Christian, Freyschlag, Iuri, Neville, Gail, Rosseau, Karl, Schaller, Andreas, K Demetriades, Faith, Robertson, Alex, Alamri, Head and neck: Richard Shaw, Andrew, G Schache, Stuart, C Winter, Michael, Ho, Paul, Nankivell, Juan Rey Biel, Martin, Batstone, Ian, Ganly, Breast: Raghavan Vidya, Alex, Wilkins, Jagdeep, K Singh, Dinesh, Thekinkattil, Gynaecology: Sudha Sundar, Christina, Fotopoulou, Elaine, Leung, Tabassum, Khan, Luis, Chiva, Jalid, Sehouli, Anna, Fagotti, Paul, Cohen, Murat, Gutelkin, Rahel, Ghebre, Thomas, Konney, Rene, Pareja, Rob, Bristow, Sean, Dowdy, Shylasree TS Rajkumar, Joe, Ng, Keiiji, Fujiwara, Urology: Grant, D Stewart, Benjamin, Lamb, Krishna, Narahari, Alan, McNeill, Alexandra, Colquhoun, John, McGrath, Steve, Bromage, Ravi, Barod, Veeru, Kasivisvanathan, Dissemination Committee Joana FF Simoes (Chair), Tobias Klatte., Tom EF Abbott, Michel, Adamina, Adesoji, O Ademuyiwa, Arnav, Agarwal, Ehab, Alameer, Derek, Alderson, Felix, Alakaloko, Markus, Albertsmeiers, Osaid, Alser, Muhammad, Alshaar, Sattar, Alshryda, Alexis, P Arnaud, Knut Magne Augestad, Faris, Ayasra, Jos&#233, Azevedo, Brittany, K Bankhead-Kendall, Emma, Barlow, Ruth, Blanco-Colino, Amanpreet, Brar, Kerry, A Breen, Chris, Bretherton, Igor Lima Buarque, Joshua, Burke, Mohammad, Chaar, Sohini, Chakrabortee, Peter, Christensen, Daniel, Cox, Moises, Cukier, Miguel, F Cunha, Giana, H Davidson, Salomone Di Saverio, Thomas, M Drake, John, G Edwards, Muhammed, Elhadi, Sameh, Emile, Shebani, Farik, J Edward Fitzgerald, Samuel, Ford, Tatiana, Garmanova, Gaetano, Gallo, Dhruv, Ghosh, Gustavo Mendon&#231, a Ata&#237, de Gomes, Gustavo, Grecinos, Ewen, A Griffiths, Madalegna, Gr&#252, ndl, Constantine, Halkias, Ewen, M Harrison, Intisar, Hisham, Peter, J Hutchinson, Shelley, Hwang, Arda, Isik, Pascal, Jonker, Haytham MA Kaafarani, Angelos, Kolias, Schelto, Kruijff, Ismail, Lawani, Hans, Lederhuber, Sezai, Leventoglu, Andrey, Litvin, Andrew, Loehrer, Markus, W L&#246, ffler, Maria Aguilera Lorena, Maria Marta Madolo, Piotr, Major, Janet, Martin, Hassan, N Mashbari, Dennis, Mazingi, Symeon, Metallidis, Helen, M Mohan, Rachel, Moore, David, Moszkowicz, Joshua, S Ng-Kamstra, Mayaba, Maimbo, Milagros, Niquen, Faustin, Ntirenganya, Maricarmen, Olivos, Kacimi, Oussama, Oumaima, Outani, Marie Dione Parreno-Sacdalanm, Francesco, Pata, Carlos Jose Perez Rivera, Thomas, D Pinkney, Willemijn van der Plas, Ahmad, Qureshi, Dejan, Radenkovic, Antonio Ramos- De la Medina, Keith, Roberts, April, C Roslani, Martin, Ruteg&#229, Ir&#232, ne, Santos, Raza, Sayyed, Andrew, Schache, Andreas, A Schnitzbauer, Seyi-Olajide, Justina O., Neil, Sharma, Richard, Shaw, Sebastian, Shu, Kjetil, Soreide, Antonino, Spinelli, Grant, D Stewart, Malin, Sund, Sudha, Sundar, Stephen, Tabiri, Georgios, Tsoulfas, Gabrielle, H van Ramshorst, Raghavan, Vidya, Dale, Vimalachandran, Oliver, J Warren, Duane, Wedderburn, Naomi, Wright, EuroSurg, European Society of Coloproctology (ESCP), Global Initiative for Children&#8217, s Surgery (GICS), GlobalSurg, GlobalPaedSurg, ItSURG, PTSurg, SpainSurg, Italian Society of Colorectal Surgery (SICCR), Association of Surgeons in Training (ASiT), Irish Surgical Research Collaborative (ISRC), Transatlantic Australasian Retroperitoneal Sarcoma Working Group (TARPSWG), Collaborators (denotes Site Principal Investigators) Argentina: Allemand C, Italian Society of Surgical Oncology (SICO)., Boccalatte, L, Figari, M, Lamm, M, Larra&#241, aga, J, Marchitelli, C, Noll, F, Odetto, D, Perrotta, M, Saadi, J, Zamora, L (Hospital Italiano De Buenos Aires), Alurralde, C, Caram, El, Eskinazi, D, Mendoza, Jp, Usandivaras M (Sanatorio, 9 De Julio Sa), Badra, R, Esteban, A, Garc&#237, a, Js, a, Pm, Gerchunoff, Ji, Lucchini, Sm, NIgra, Ma, Armenia: Hovhannisyan T, Vargas L (Sanatorio Allende)., Australia: Gould T, Stepanyan A (Nairi Medical Center)., Gourlay, R, Griffiths, B (Calvary Mater Newcastle), Gananadha S, McLaren M (Canberra Hospital), Cecire, J, Joshi, N, Salindera, S, Sutherland, A (Coffs Harbour Health Campus), Ahn, Jh, Charlton, G, Chen, S, Gauri, N, Hayhurst, R, Jang, S, Jia, F, Mulligan, C, Yang, W, Ye, G, Zhang, H (Concord Repatriation General Hospital), Ballal, M, Gibson, D, Hayne, D, Moss, J, Richards, T, Viswambaram, P, Vo UG (Fiona Stanley Hospital), Bennetts, J, Bright, T, Brooke-Smith, M, Fong, R, Gricks, B, Lam, Yh, Ong, Bs, Szpytma, M, Watson, D (Flinders Medical Centre), Bagraith, K, Caird, S, Chan, E, Dawson, C, Ho, D, Jeyarajan, E, Jordan, S, Lim, A, Nolan, Gj, Oar, A, Parker, D, Puhalla, H, Quennell, A, Rutherford, L, Townend, P, Von Papen, M, Wullschleger, M (Gold Coast University Hospital), Blatt, A, Cope, D, Egoroff, N, Fenton, M, Gani, J, Lott, N, Pockney, P, Shugg, N (John Hunter Hospital), Elliott M, Phung D (Lifehouse), Phan D, Townend D (Lismore Base Hospital), Bong C, Gundara J (Logan Hospital), Frankel, A (Princess Alexandra Hospital), Bowman S, Guerra GR (Queen Elizabeth Ii Jubilee Hospital), Bolt, J, Buddingh, K, Dudi-Venkata, Nn, Jog, S, Kroon, Hm, Sammour, T, Smith, R, Stranz, C (Royal Adelaide Hospital), Batstone, M, Lah, K, McGahan, W, Mitchell, D, Morton, A, Pearce, A, Roberts, M, Sheahan, G, Swinson, B (Royal Brisbane And Women&#8217, s Hospital), Alam, N, Banting, S, Chong, L, Choong, P, Clatworthy, S, Foley, D, Fox, A, Hii, Mw, Knowles, B, Mack, J, Read, M, Rowcroft, A, Ward, S, Austria: Lanner M (Kardinal Schwarzenberg Klinikum), Wright G (St Vincent&#8217, s Hospital)., K&#246, nigsrainer, I (Landeskrankenhaus Feldkirch), Bauer, M, Freyschlag, C, Kafka, M, Messner, F, 214, fner, D, Tsibulak, I (Medical University Of Innsbruck), Emmanuel, K, Grechenig, M, Gruber, R, Harald, M, hlberger, L, Presl, J, Azerbaijan: Namazov &#304, Wimmer A (Paracelsus Medical University Salzburg)., Barbados: Barker D, Samadov E (Leyla Medical Centerl)., Boyce, R, Corbin, S, Doyle, A, Eastmond, A, Gill, R, Haynes, A, Millar, S, O&#8217, Shea, M, Padmore, G, Paquette, N, Phillips, E, John S, St., Belgium: Flamey N, Walkes K (Queen Elizabeth Hospital)., Pattyn, P (Az Delta), Oosterlinck, W, Van den Eynde, J, Brazil: Gatti A, Van den Eynde R (Uz Leuven)., Nardi, C, Oliva, R (Hospital Geral De Pirajussara), De Cicco, R (Instituto De C&#226, ncer Dr Arnaldo Vieira De Carvalho), Cecconello, I, Gregorio, P, Pontual Lima, L, Ribeiro Junior, U, Takeda, F, Canada: Kidane B, Terra RM (Instituto Do C&#226, ncer De Estado De S&#227, o Paulo). Bulgaria: Sokolov M (University Hospital Alexandrovska)., Srinathan, S (Health Sciences Centre), Boutros, M, Caminsky, N, Ghitulescu, G, Jamjoum, G, Moon, J, Pelletier, J, Vanounou, T, Wong, S (Jewish General Hospital), Dumitra, S, Kouyoumdjian, A (Mcgill University Health Center), Johnston B, Russell C (Saint John Regional Hospital), Demyttenaere, S, Mary&#8217, s Hospital), Garfinkle R (St., Abou-Khalil, J, Nessim, C, Colombia: Almeciga A, Stevenson J (The Ottawa Hospital). Chile: Heredia F (Cl&#237, nica Universitaria De Concepci&#243, n)., Fletcher, A, Merchan A (Centro De Investigaciones Oncol&#243, gicas Cl&#237, nica San Diego, - Ciosad), Puentes LO (Hospital San Jos&#233, Croatia: Ba&#269, i&#263, G, Mendoza Quevedo J (Subred Sur Occidente De Kennedy (Hospital De Kennedy))., Karlovi&#263, D, Kr&#353, ul, D, Zeli&#263, M (University Hospital Center Rijeka), Luksic I, Mamic M (University Hospital Dubrava), Bakmaz, B, 262, oza, I, Dijan, E, Katusic, Z, Mihanovic, J, Cyprus: Frantzeskou K, Rakvin I (Zadar General Hospital)., Gouvas, N, Kokkinos, G, Papatheodorou, P, Pozotou, I, Stavrinidou, O, Czechia: Martinek L, Yiallourou A (Nicosia General Hospital)., Skrovina, M, Szubota, I (Hospital &amp, amp, Oncological Centre Novy Jicin), 381, ateck&#253, J (Slezsk&#225, Nemocnice V Opav&#283, P. o. ), Javurkova, V, Denmark: Avlund T, Klat J (University Hospital Ostrava)., Christensen, P, Harbjerg, Jl, Iversen, Lh, Kjaer, Dw, Kristensen, H&#248, Mekhael, M (Aarhus University Hospital), Ebbeh&#248, j, Al, Krarup, P, Schlesinger, N, Egypt: Abdelsamed A, Smith H (Bispebjerg Hospital)., Azzam, Ay, Salem, H, Seleim, A (Al Azhar University Hospitals), Abdelmajeed, A, Abdou, M, Abosamak, Ne, AL Sayed, M, Ashoush, F, Atta, R, Elazzazy, E, Elhoseiny, M, Elnemr, M, Elqasabi, Ms, Elsayed Hewalla ME, Elsherbini, I, Essam, E, Eweda, M, Ghallab, I, Hassan, E, Ibrahim, M, Metwalli, M, Mourad, M, Qatora, Ms, Ragab, M, Sabry, A, Saifeldin, H, Saleh Mesbah Mohamed Elkaffas, M, Samih, A, Samir Abdelaal, A, Shehata, S, Shenit, K (Alexandria Main University Hospital), Attia, D, Kamal, N, Osman, N (Alexandria Medical Research Institute), Abbas, Am, Abd Elazeem HAS, Abdelkarem, Mm, Alaa, S, Ali, Ak, Ayman, A, Azizeldine, Mg, Elkhayat, H, elghazaly S, M., Monib, Fa, Nageh, Ma, Saad, Mm, Salah, M, Shahine, M, Yousof, Ea, Youssef, A (Assiut University Hospital), Eldaly, A (El-Menshawy Hospital), ElFiky, M, Nabil, A (Kasr Alainy Faculty Of Medicine, Cairo, University), Amira, G, Sallam, I, Sherief, M, Sherif, A (Misr Cancer Center), Abdelrahman, A, Aboulkassem, H, Ghaly, G, Hamdy, R, Morsi, A, Sherif, G (National Cancer Institute), Abdeldayem, H, Abdelkader Salama, I, Balabel, M, Fayed, Y, Sherif AE (National Liver Institute, Finland: Kauppila J, Menoufia University). Ethiopia: Bekele D (Maddawalabu University Goba Referral Hospital)., Sarjanoja, E (L&#228, nsi-Pohja Central Hospital), Helminen, O, Huhta, H, France: Beyrne C, Kauppila JH (Oulu University Hospital)., Jouffret, L, Lugans, L, Marie-Macron, L (Centre Hospitalier Avignon), Chouillard E, De Simone B (Centre Hospitalier Intercommunal Poissy Saint Germain En Laye), Bettoni, J, Dakp&#233, S, Devauchelle, B, Lavagen, N, Testelin, S (Chu Amiens), Boucher, S, Breheret, R, Gueutier, A, Kahn, A, K&#252, n-Darbois, J (Chu Angers), Barrabe, A, Lakkis, Z, Louvrier, A, Manfredelli, S, Mathieu, P (Chu Besan&#231, on), Chebaro, A, Drubay, V, El amrani, M, Eveno, C, Lecolle, K, Legault, G, Martin, L, Piessen, G, Pruvot, Fr, Truant, S, Zerbib, P (Chu Lille), Ballouhey, Q, Barrat, B, Laloze, J, Salle, H, Taibi, A, Usseglio, J (Chu Limoges), Bergeat D, Merdrignac A (Chu Rennes - General Surgery), Le Roy, B, Perotto, Lo, Scalabre, A (Chu Saint Etienne), Aim&#233, A, Ezanno, A, Malgras, B (Hia Begin), Bouche P, Tzedakis S (H&#244, pital Cochin - Aphp), Cotte, E, Glehen, O, Lifante, J (Hopital Lyon Sud), D&#8217, Urso, A, Felli, E, Mutter, D, Pessaux, P, Seeliger, B (Hus, Pole H&#233, pato-Digestif, / Ihu- Strasbourg), Bardet, J, Berry, R, Boddaert, G, Bonnet, S, Brian, E, Denet, C, Fuks, D, Gossot, D, Grigoroiu, M, Laforest, A, Levy-Zauberman, Y, Louis-Sylvestre, C, Moumen, A, Pourcher, G, Seguin-givelet, A, Tribillon, E (Institut Mutualiste Montsouris), Duchalais, E, Espitalier, F, Ferron, C, Germany: Bork U, Malard O (Nantes University Hospital)., Distler, M, Fritzmann, J, Kirchberg, J, Praetorius, C, Riediger, C, Weitz, J, Welsch, T, Wimberger, P (Carl-Gustav-Carus University, Dresden), Tu, Beyer, K, Kamphues, C, Lauscher, J, Loch, Fn, Schineis, C (Charit&#233, University Medicine, Campus Benjamin Franklin), Albertsmeier, M, Angele, M, Kappenberger, A, Niess, H, Schiergens, T, Werner, J (Department of General, Visceral and Transplantation Surgery, Ludwig- Maximilians-Universitat Munich), Becker R, Jonescheit J (Heilig-Geist Hospital Bensheim), Pergolini I, Reim D (Klinikum Rechts Der Isar Tum School Of Medicine), Boeker, C, Hakami, I, Mall, J (Krh Nordstadt-Siloah Hospitals), Liokatis P, Smolka W (LMU Klinikum Campus Innenstadt), Nowak K, Reinhard T (Romed Klinikum Rosenheim), H&#246, lzle, F, Modabber, A, Winnand, P (University Hospital Aachen), Knitschke, M (University Hospital Giessen And Marburg), Kauffmann P, Wolfer S (University Hospital Goettingen / Universit&#228, tsmedizin Goettingen), Kleeff, J, Lorenz, K, Michalski, C, Ronellenfitsch, U, Schneider, R (University Hospital Halle (Saale)), Bertolani, E, nigsrainer, A, L&#246, ffler, Mw, Quante, M, Steidle, C, 220, berr&#252, ck, L, Yurttas, C (University Hospital Tuebingen), Betz, Cs, Bewarder, J, B&#246, ttcher, A, Burg, S, Busch, C, Gosau, M, Heuer, A, Izbicki, J, Klatte, To, Koenig, D, Moeckelmann, N, Nitschke, C, Priemel, M, Smeets, R, Speth, U, Thole, S, Uzunoglu, Fg, Vollkommer, T, Zeller, N (University Medical Center Hamburg- Eppendorf), Battista, Mj, Gillen, K, Hasenburg, A, Krajnak, S, Linz, V, Schwab, R (University Of Mainz, Greece: Angelou K, Department Of Gynaecology And Obstetrics)., Haidopoulos, D, Rodolakis, A (Alexandra General Hospital), Antonakis, P, Bramis, K, Chardalias, L, Contis, I, Dafnios, N, Dellaportas, D, Fragulidis, G, Gklavas, A, Konstadoulakis, M, Memos, N, Papaconstantinou, I, Polydorou, A, Theodosopoulos, T, Vezakis, A (Aretaieion Hospital), Antonopoulou, Mi, Manatakis, Dk, Tasis, N (Athens Naval And Veterans Hospital), Arkadopoulos, N, Danias, N, Economopoulou, P, Kokoropoulos, P, Larentzakis, A, Michalopoulos, N, Selmani, J, Sidiropoulos, T, Tsaousis, V, Vassiliu, P (Attikon University General Hospital), Bouchagier, K, Klimopoulos, S, Paspaliari, D, Stylianidis, G (Evaggelismos General Hospital), Baxevanidou, K, Bouliaris, K, Chatzikomnitsa, P, Efthimiou, M, Giaglaras, A, Kalfountzos, C, Koukoulis, G, Ntziovara, Am, Petropoulos, K, Soulikia, K, Tsiamalou, I, Zervas, K, Zourntou, S (General Hospital Of Larissa &#8220, Koutlimpaneio And Triantafylleio&#8221, Baloyiannis, I, Diamantis, A, Gkrinia, E, Hajiioannou, J, Korais, C, Koukoura, O, Perivoliotis, K, Saratziotis, A, Skoulakis, C, Symeonidis, D, Tepetes, K, Tzovaras, G, Zacharoulis, D (General University Hospital Of Larissa), Alexoudi, V, Antoniades, K, Astreidis, I, Christidis, P, Deligiannidis, D, Grivas, T, Ioannidis, O, Kalaitsidou, I, Loutzidou, L, Mantevas, A, Michailidou, D, Paraskevopoulos, K, Politis, S, Stavroglou, A, Tatsis, D, Tilaveridis, I, Vahtsevanos, K, Venetis, G (George Papanikolaou General Hospital Of Thessaloniki), Karaitianos I, Tsirlis T (Henry Dunant Hospital Center), Charalabopoulos, A, Liakakos, T, Mpaili, E, Schizas, D, Spartalis, E, Syllaios, A, Zografos, C (Laiko University Hospital), Anthoulakis, C, Christou, C, Papadopoulos, V, Tooulias, A, Tsolakidis, D, Tsoulfas, G, Zouzoulas, D (Papageorgiou General Hospital), Athanasakis, E, Chrysos, E, Tsiaousis, J, Xenaki, S, Hong Kong: Futaba K, Xynos E (University Hospital Of Heraklion Crete And Interclinic Hospital Of Crete)., Ho, Mf, Hon, Sf, Mak, Twc, Ng SSM (Prince Of Wales Hospital), Hungary: Banky B, Foo CC (Queen Mary Hospital)., Ireland: Aremu M, Suszt&#225, k N (Szent Borb&#225, la K&#243, rh&#225, z)., Canas-Martinez, A, Cullivan, O, Murphy, C, Owens, P, Pickett, L (Connolly Hospital Blanchardstown), Akmenkalne, L, Byrne, J, Corrigan, M, Cullinane, C, Daly, A, Fleming, C, Jordan, P, Killeen, S, Lynch, N, McCarthy, A, Mustafa, H, Brien, S, Leary, P, Syed, Was, Vernon, L (Cork University Hospital), Callanan, D, Huang, L, Ionescu, A, Sheahan, P (South Infirmary Victoria University Hospital), Balasubramanian, I, Boland, M, Conlon, K, Evoy, D, Fearon, N, Gallagher, T, Geraghty, J, Heneghan, H, Kennedy, N, Maguire, D, McCartan, D, McDermott, Ew, Prichard, Rs, Winter, D (St Vincent&#8217, s University Hospital), Alazawi, D, Barry, C, Boyle, T, Butt, W, Connolly, Em, Donlon, N, Donohue, C, Fahey, Ba, Farrell, R, Fitzgerald, C, Kinsella, J, Larkin, Jo, Lennon, P, Maguire, Pj, Mccormick, P, Mehigan, Bj, Mohan, H, Nugent, T, Sullivan, H, Ravi, N, Reynolds, Jv, Rogers, A, Shokuhi, P, Smith, J, Smith, La, James&#8217, s Hospital), Timon C (St., Bashir, Y, Bass, G, Connelly, T, Earley, H, Elliott, Ja, Gillis, A, Kavanagh, D, Neary, P, riordan, J, Reynolds, Is, Rice, D, Ridgway, P, Umair, M, Whelan, M (Tallaght Hospital), Carroll, P, Collins, C, Corless, K, Finnegan, L, Fowler, A, Hogan, A, Kerin, M, Lowery, A, McAnena, P, McKevitt, K, Nizami, K, Ryan, &#201, Samy, A (University Hospital Galway), Coffey, Jc, Cunningham, R, Devine, M, Nally, D, Peirce, C, Tormey, S (University Hospital Limerick), Hardy, N, Malley, S, Italy: Macina S (Asst Mantua), Ryan M (University Hospital Waterford/University College Cork)., Mariani, Nm, Opocher, E, Pisani Ceretti A (Asst Santi Paolo, E Carlo), Ferrari, F, Odicino, F, Sartori, E (Asst Spedali Civili, Ospedale Di Brescia), Cotsoglou C, Granieri S (Asst Vimercate), Bianco, F, Camillo&#8217, Colledan, M, Tornese, S, Zambelli MF (Asst-Papa Giovanni Xxiii- Bergamo), Bissolotti, G, Fusetti, S, Lemma, F (Azienda Ospedaliera Di Padova), Marino, M, Mirabella, A, Vaccarella, G (Azienda Ospedaliera Ospedali Riuniti Villa Sofia-Cervello, Palermo), Agostini, C, Alemanno, G, Bartolini, I, Bergamini, C, Bruscino, A, Checcucci, C, De Vincenti, R, Di Bella, A, Fambrini, M, Fortuna, L, Maltinti, G, Muiesan, P, Petraglia, F, Prosperi, P, Ringressi, Mn, Risaliti, M, Sorbi, F, Taddei, A, Tucci, R (Azienda Ospedaliera Universitaria Careggi), Bassi, C, Campagnaro, T, Casetti, L, De Pastena, M, Esposito, A, Fontana, M, Guglielmi, A, Landoni, L, Malleo, G, Marchegiani, G, Nobile, S, Paiella, S, Pedrazzani, C, Rattizzato, S, Ruzzenente, A, Salvia, R, Turri, G, Tuveri, M (Azienda Ospedaliera Universitaria Integrata Di Verona), Bellora, P, Aloisio, G, Ferrari, M, Francone, E, Gentilli, S, Nikaj, H (Azienda Ospedaliero Universitaria Maggiore Della Carit&#224, Bianchini, M, Chiarugi, M, Coccolini, F, Di Franco, G, Furbetta, N, Gianardi, D, Guadagni, S, Morelli, L, Palmeri, M, Tartaglia, D (Azienda Ospedaliero Universitaria Pisana), Anania, G, Carcoforo, P, Chiozza, M, De Troia, A, Koleva Radica, M, Portinari, M, Sibilla, Mg, Urbani, A (Azienda Ospedaliero Universitaria Sant&#8217, anna), Fabbri, N, Feo, Cv, Gennari, S, Parini, S, Righini E (Azienda Unit&#224, Sanitaria Locale di Ferrara, - University of Ferrara), Ampollini, L, Bellanti, L, Bergonzani, M, Bertoli, G, Bocchialini, G, Angelo, G, Lanfranco, D, Musini, L, Poli, T, Santoro, Gp, Varazzani, A (Azienda Ospedaliero-Universitaria Di Parma), Aguzzoli, L, Borgonovo, G, Castro Ruiz, C, Coiro, S, Falco, G, Mandato, Vd, Mastrofilippo, V, Montella, Mt, Annessi, V, Zizzo M (Azienda Unit&#224, Sanitaria Locale, - Irccs Di Reggio Emilia), Grossi, U, Novello, S, Romano, M, Rossi, S, Zanus, G (Ca&#8217, Foncello Treviso-DISCOG-Universit Di Padova), Esposito, G, Frongia, F, Pisanu, A, Podda, M (Cagliari University Hospital), Belluco, C, Lauretta, A, Montori, G, Moras, L, Olivieri, M (Centro Di Riferimento Oncologico Di Aviano (Cro) Irccs), Bussu, F, Carta, Ag, Cossu, Ml, Cottu, P, Fancellu, A, Feo, Cf, Ginesu, Gc, Giuliani, G, Madonia, M, Perra, T, Piras, A, Porcu, A, Rizzo, D, Scanu, Am, Tedde, A, Tedde, M (Cliniche San Pietro, Sassari), A. o. u., Delrio, P, Rega D (Colorectal Surgical Oncology Unit, - Istituto Nazionale Tumori Fondazione, Pascale-I. r. c. c. s., ), Badalamenti, G, Campisi, G, Cordova, A, Franza, M, Maniaci, G, Rinaldi, G, Toia, F (Department Of Surgical, University Of Palermo), Oncological And Oral Sciences., Calabr&#242, M, Farnesi, F, Lunghi, Eg, Muratore, A, Pipitone Federico NS (Edoardo Agnelli), B&#224, mbina, F, Andrea, G, Familiari, P, Picotti, V (Fabrizio Spaziani), De Palma, G, Luglio, G, Pagano, G, Tropeano FP (Federico Ii University Hospital), Baldari, L, Beltramini, Ga, Boni, L, Cassinotti, E, Gianni&#8217, Pignataro, L, Torretta S (Fondazione Irccs Ca&#8217, Granda, - Ospedale Maggiore Policlinico), Abatini, C, Baia, M, Biasoni, D, Bogani, G, Cadenelli, P, Capizzi, V, Cioffi, Spb, Citterio, D, Comini, Lv, Cosimelli, M, Fiore, M, Folli, S, Gennaro, M, Giannini, L, Gronchi, A, Guaglio, M, Macchi, A, Martinelli, F, Mazzaferro, V, Mosca, A, Pasquali, S, Piazza, C, Raspagliesi, F, Rolli, L, Salvioni, R, Sarpietro, G, Sarre, C, Sorrentino, L (Fondazione Irccs Istituto Nazionale Dei Tumori, Milano), Agnes, A, Alfieri, S, Belia, F, Biondi, A, Cozza, V, Amore, A, Ugo, D, De Simone, V, Fagotti, A, Gasparini, G, Gordini, L, Litta, F, Lombardi, Cp, Lorenzon, L, Marra, Aa, Marzi, F, Moro, A, Parello, A, Perrone, E, Persiani, R, Ratto, C, Rosa, F, Saponaro, G, Scambia, G, Scrima, O, Sganga, G, Tudisco, R (Fondazione Policlinico Universitario Agostino Gemelli), Belli, A, Granata, V, Izzo, F, Palaia, R, Patrone R (Hpb Surgical Oncology Unit, - Istituto Nazionale Tumori Fondazione, Pascale- I. r. c. c. s., ), Carrano, Fm, Carvello, Mm, De Virgilio, A, Di Candido, F, Ferreli, F, Gaino, F, Mercante, G, Rossi, V, Spinelli, A, Spriano, G (Humanitas Clinical And Research Center Irccs, Rozzano (Mi) &amp, Humanitas, University, Department Of Biomedical Sciences, Pieve Emanuele (Mi)), Donati, Dm, Frisoni, T, Palmerini, E (Irccs Istituto Ortopedico Rizzoli), Aprile, A, Barra, F, Batistotti, P, Ferrero, S, Fregatti, P, Scabini, S, Sparavigna, M (Irccs Ospedale Policlinico San Martino), Asti, E, Bernardi, D, Bonavina, L, Lovece, A (University of Milan, IRCCS Policlinico San Donato), Adamoli, L, Ansarin, M, Cenciarelli, S, Chu, F, De Berardinis, R, Fumagalli Romario, U, Mastrilli, F, Pietrobon, G, Tagliabue M (Istituto Europeo Di Oncologia, - Irccs -Milano), Badellino, E, Ferrero, A, Massobrio, R (Mauriziano Hospital Torino, Italy), De Manzoni Garberini, A (Ospedale Civile Spirito Santo), Federico, P, Maida, P, Marra, E, Marte, G, Petrillo, A, Tammaro, T, Tufo, A (Ospedale Del Mare), Berselli, M, Borroni, G, Cocozza, E, Conti, L, Desio, M, Livraghi, L, Quintodei, V, Rizzi, A, Zullo A (Ospedale Di Circolo, E Fondazione Macchi (Varese)), Baldi, C, Corbellini, C, Sampietro GM (Ospedale Di Rho, - Asst Rhodense), Cellerino P (Ospedale Fatebenefratelli, E Oftalmico), Baldini, E, Capelli, P, Isolani, Sm, Ribolla, M (Ospedale Guglielmo Da Saliceto Piacenza), Bondurri, A, Colombo, F, Ferrario, L, Guerci, C, Maffioli, A (Ospedale Luigi Sacco Milano), Armao, T, Ballabio, M, Bisagni, P, Gagliano, A, Longhi, M, Madonini, M, Pizzini, P (Ospedale Maggiore Di Lodi), Baietti, Am, Biasini, M, Maremonti, P, Neri, F, Prucher, Gm, Ricci, S, Ruggiero, F, Zarabini AG (Ospedale Maggiore/Bellaria Carlo Alberto Pizzardi Ausl Bologna), Barmasse, R, Mochet, S, Usai, A (Ospedale Regionale Umberto Parini), Leonardo - Asl Napoli 3 Sud, Incollingo P (Ospedale S., Castellammare Di Stabia), Mancini, S, Marino Cosentino, L, Sagnotta, A (Ospedale San Filippo Neri), Fruscio, R, Grassi, T, Nespoli, Lc, Tamini, N (Ospedale San Gerardo), Anastasi, A, Bartalucci, B, Bellacci, A, Canonico, G, Capezzuoli, L, Di Martino, C, Ipponi, P, Linari, C, Montelatici, M, Nelli, T, Spagni, G, Tirloni, L, Vitali, A (Ospedale San Giovanni Di Dio), Abate, E, Casati, M, Casiraghi, T, Laface, L, Schiavo M (Ospedale Vittorio Emanuele Iii, - Carate Brianza), Arminio, A, Cotoia, A, Lizzi, V, Vovola, F (Ospedali Riuniti Azienda Ospedaliera Universitaria Foggia), Vergari, R (Ospedali Riuniti Di Ancona), Ugo, S, Depalma, N, 8220, Vito Fazzi&#8221, Spampinato MG (P. o., Bartolucci, P, Brachini, G, Bruzzaniti, P, Chiappini, A, Chiarella, V, Ciccarone, F, Cicerchia, Pm, Cirillo, B, De Toma, G, Di bartolomeo, A, Fiori, E, Fonsi, Gb, Franco, G, Frati, A, Giugliano, M, Iannone, I, La Torre, F, Lapolla, P, Leonardo, C, Marruzzo, G, Meneghini, S, Mingoli, A, Ribuffo, D, Salvati, M, Santoro, A, Sapienza, P, Scafa, Ak, Simonelli, L, Zambon M (Policlinico Umberto, I Sapienza University Of Rome), Capolupo, Gt, Carannante, F, Caricato, M, Mascian&#224, G, Mazzotta, E (Policlinico Universitario Campus Bio Medico Of Rome), Gattolin, A, Migliore, M, Rimonda, R, Sasia, D, Travaglio, E (Regina Montis Regalis Hospital, Mondov&#236, Cervellera, M, Gori, A, Sartarelli, L, orsola-Malpighi Hospital), Tonini V (S., Giacometti, M, Zonta, S (Ospedale San Biagio, Asl, VCO), Chessa, A, Fiorini, A, Norcini, C (San Giovanni Di Dio), Colletti, G, Confalonieri, M, Costanzi, A, Frattaruolo, C, Mari, G, Monteleone, M (San Leopoldo Mandic), Bandiera, A, Bocciolone, L, Bonavina, G, Candiani, M, De Nardi, P, Gagliardi, F, Medone, M, Mortini, P, Negri, G, Ottolina, J, Parise, P, Piloni, M, Sileri, P, Vignali, A (San Raffaele Scientific Institute, Milan), Belvedere, A, Bernante, P, Bertoglio, P, Boussedra, S, Brunocilla, E, Cipriani, R, Cisternino, G, De Crescenzo, E, De Iaco, P, Dondi, G, Frio, F, Jovine, E, Mineo Bianchi, F, Neri, J, Parlanti, D, Perrone, Am, Pezzuto, Ap, Pignatti, M, Pinto, V, Poggioli, G, Ravaioli, M, Rottoli, M, Schiavina, R, Serenari, M, Serra, M, Solli, P, Taffurelli, M, Tanzanu, M, Tesei, M, Violante, T, Zanotti, S (Sant&#8217, orsola Hospital, Alma Mater Studiorum University Of Bologna, Borghi, F, Cianflocca, D, Di Maria Grimaldi, S, Donati, D, Gelarda, E, Geretto, P, Giraudo, G, Giuffrida, Mc, Marano, A, Palagi, S, Pellegrino, L, Peluso, C, Testa V (Santa Croce, E Carle Hospital, Cuneo), Agresta, F, Prando, D, Zese M (Santa Maria Degli Angeli Hospital Ulss5, - Adria), Aquila, F, Gambacciani, C, Lippa, L, Pieri, F, Santonocito OS (Spedali Riuniti Di Livorno), Armatura, G, Bertelli, G, Frena, A, Marinello, P, Notte, F, Patauner, S, Moritz Hospital), Scotton G (St., Fulginiti, Sf, Gallo, G, Sammarco, G, Vescio, G (University &#8216, Magna Graecia&#8217, Of Catanzaro), Balercia, P, Catarzi, L, Consorti G (University Hospital Umberto, I Ancona), Di Marzo, F (Valtiberina), Japan: Daiko H, Fontana T (Vittorio Emanuele)., Ishikawa, M, Ishiyama, K, Iwata, S, Kanematsu, K, Kanemitsu, Y, Kato, T, Kawai, A, Kobayashi, E, Kobayashi Kato, M, Moritani, K, Nakatani, F, Oguma, J, Tanase, Y, Jordan: Al Abdallah M, Uno M (National Cancer Center Hospital)., Ayasra, F, Ayasra, Y, Qasem, A (Al-Basheer Hospital), Abu Za&#8217, nouneh FJ, Fahmawee, T, Hmedat, A, Ibrahim, A, Obeidat, K (King Abdullah University Hospital), Abdel Al, S, Abdel Jalil, R, Abou Chaar MK, Al-Masri, M, Al-Najjar, H, Alawneh, F, Alsaraireh, O, Elayyan, M, Ghanem, R, Libya: Alkadeeki G (Al-Jalaa Hospital), Lataifeh I (King Hussein Cancer Center)., Aldokali, N, Senossi, O, Subhi MT (Alkhadra Hospital), Burgan, D, Kamoka, E, Kilani, Ai, Salamah, A, Salem, M, Shuwayyah, A (National Cancer Institute, Sabratha, - Libya), Abdulwahed, E, Alshareea, E, Aribi, N, Aribi, S, Biala, M, Ghamgh, R, Morgom, M (Tripoli Central Hospital), Aldayri, Z, Ellojli, I, Lithuania: Bradulskis S, Kredan A (Tripoli University Hospital)., Dainius, E, Kubiliute, E, Kutkevi&#269, ius, J, Parseliunas, A, Subocius, A, Madagascar: Rasoaherinomenjanahary F, Venskutonis D (Lithuanian University Of Health Sciences Kaunas Clinical Hospital)., Razafindrahita, Jb, Malaysia: Ong EC (Bintulu), Samison LH (Joseph Ravoahangy Andrianavalona Hospital)., Hamdan, Kh, Ibrahim, Mr, Tan, Ja, Thanapal MR (Hospital Kuala Lumpur), Amin Sahid, N, Hayati, F, Jayasilan, J, Sriram, Rk, Subramaniam, S (Queen Elizabeth Hospital &amp, Universiti Malaysia Sabah, Kota, Kinabalu, Sabah, Malaysia), Che Jusoh, A, Hussain, Ah, Mohamed Sidek AS, Mohd Yunus MF, Soh, Jy, Wong, Mpk, Zakaria, Ad, Zakaria, Z (School Of Medical Sciences &amp, Hospital, Universiti Sains Malaysia), Fadzli, A, Fathi, Nq, Koh, Ps, Liew, Yt, Roslani, Ac, Tang, Cy, Teoh, Ly, Wong, Wj, Mexico: Alvarez MR, Yahaya AS (University Malaya Medical Centre)., Arrangoiz, R, Cordera, F, De la Rosa Abaroa MA, G&#243, mez-Pedraza, A, Hernandez, R, Maffuz-Aziz, A, Posada JA (Abc Medical Center), Becerra Garc&#237, a FC (Hospital San &#193, ngel Inn Chapultepec), Alfaro-Goldaracena, A, Buerba, Ga, Castillejos- Molina RA, Chan, C, Dominguez-Rosado, I, Medina-Franco, H, Mercado, M&#225, Oropeza- Aguilar, M, Pe&#241, a G&#243, mez Portugal, E, Posadas-Trujillo, Oe, Rodriguez-Covarrubias, F, Salgado-Nesme, N, Morocco: Arkha Y, Vilatoba M (Instituto Nacional De Ciencias M&#233, dicas Y Nutrici&#243, n &#8220, Salvador Zubir&#225, n&#8221, Bechri, H, El Ouahabi, A, Oudrhiri MY (Centre Hospitalier Universitaire Ibn Sina Rabat), Derkaoui hassani F, El abbadi N (Cheikh Zaid International University Hospital), Amrani, L, Belkhadir, Zh, Benkabbou, A, Chakib, O, El Ahmadi, B, El Bouazizi, Y, Essangri, H, Ghannam, A, Majbar, Am, Mohsine, R, Netherlands: Hompes R, Souadka A (Institut National D&#8217, oncologie)., Meima-van Praag, E, Pronk, Ajm, Sharabiany, S (Amsterdam Umc, University Of Amsterdam), Grotenhuis, B, Hartveld, L, Reijers, S, Van Houdt, W (Antoni Van Leeuwenhoek Ziekenhuis), Baaij, J, Bolster-van Eenennaam, M, De Graaff, M, Sloothaak, D, Van Duijvendijk, P (Gelre Ziekenhuis), Posma-Bouman, L (Slingeland Ziekenhuis), Derksen, T, Franken, J, Oosterling, S (Spaarne Gasthuis), De Bree, R (University Medical Center Utrecht), Konsten, J, Nigeria: Fidelis L, Van Heinsbergen M (Viecuri Medisch Centrum)., Sholadoye, Tt, Tolani, M (Ahmadu Bello University Teaching Hospital), Olaogun, J (Ekiti State University Teaching Hospital), Egbuchulem, Ik, Lawal, Ta, Ogundoyin, O, Olulana DI (University College Hospital), Abdur-Rahman, L, Adeyeye, A, Aremu, I, Bello, J, Olasehinde, O, Oman: Massoud J, Popoola A (University Of Ilorin Teaching Hospital)., Massoud, R, Pakistan: Jamal A, Sorour TM (Khoula Hospital)., Kerawala AA (Cancer Foundation Hospital), Memon, As, Nafees Ahmed, R, Pfau Civil Hospital), Rai L (Dr Ruth K. m., Ayub, B, Hassan, N, Martins, Rs, Ramesh, P, Sayyed, R (Patel Hospital), Butt, U, Kashif, M, Khan, Wh, Qureshi, A, Umar, M, Waris Farooka, M, Wasim, T (Services Hospital Lahore), Ayubi, A, Rashid, I, Peru: Falcon GM, Waqar SH (The Pakistan Institute Of Medical Sciences)., Philippines: Jocson R, Robles R (Instituto Regional De Enfermedades Neopl&#225, sicas Del Sur)., Teh, C (National Kidney &amp, Poland: Major P (Jagiellonian University Medical College), Transplant Institute)., Bobi&#324, ski, M, Kotarski, J, Rasoul-Peli&#324, ska, K (Medical University Of Lublin, Portugal: Azevedo C, Chair And Department Of Gynaecological Oncology And Gynaecology)., Machado, D, Mendes, F (Centro Hospitalar Cova Da Beira), De Sousa, X (Centro Hospitalar De Set&#250, bal), Fernandes, U, Ferreira, C, Guidi, G, Leal, C, Mar&#231, al, A, Marques, R, Martins, D, Melo, A, Tenreiro, N, Vaz Pereira, R, Vieira B (Centro Hospitalar De Tr&#225, s-Os-Montes, E Alto Douro, E. p. e., ), Almeida, Ji, Correia de S&#225, T, Costa, Mjma, Fernandes, V, Ferraz, I, Gil, Cg, Lima da Silva, C, Lopes, L, Machado, N, Marialva, J, Nunes Coelho, M, Pedro, J, Pereira, C, Reis, R, Ribeiro, A, Santos, R, Saraiva, P, Silva, R, Tavares, F, Teixeira M (Centro Hospitalar Do Tamega, E Sousa), Almeida, Ac, Amaral, Mj, Andrade, R, Athayde Nem&#233, sio, R, Breda, D, Camacho, C, Canhoto, C, Colino, M, Correia, S, Costa, M, De Barros, J, De Oliveira L&#243, pez AL, Duque, M, Garrido, S, Guerreiro, P, Guimar&#227, es, A, L&#225, zaro, A, Lopes, C, Martins, R, Nogueira, O, Oliveira, A, Oliveira, Jm, Rodrigues, M, Ruivo, A, Santos, E, Silva, M, Sim&#245, es, J, Valente da Costa A (Centro Hospitalar, E Universit&#225, rio De Coimbra), Almeida, A, Cavaleiro, S, Devezas, V, Faria, Cs, J&#225, come, F, Magalh&#227, es Maia, M, Nogueiro, J, Pereira, A, Pereira-Neves, A, Pina-Vaz, T, Santos-Sousa, H, Silveira, H, Vaz, S, Vieira P (Centro Hospitalar, E Universit&#225, rio De S&#227, o Jo&#227, Gomes da Costa A, Lobo Antunes I (Centro Hospitalar Lisboa Norte), Pinto J, Tojal A (Centro Hospitalar Tondela-Viseu), Cardoso, N, Cardoso, P, Domingues, Jc, Henriques, P, Manso, Mi, Martins dos Santos, G, Morais, H, Pereira, R, Revez, T, Ribeiro, R, Ribeiro, Vi, Soares, A, Sousa, S, Teixeira J (Centro Hospitalar Universit&#225, rio Do Algarve, - Unidade De Faro), Amorim, E, Baptista, Vh, Cunha, Mf, Dias, B, Fazenda, A, Melo Neves JP, Policarpo, F, Sampaio da N&#243, voa Gomes Miguel II, Veiga D (Centro Hospitalar Universitario Do Algarve, - Unidade De Portim&#227, Andrade, Ak, Bandovas, Jp, Borges, N, Branquinho, A, Chumbinho, B, Correia, J, Fidalgo, H, Figueiredo de Barros, I, Frade, S, Gomes, J, Maciel, J, Pina, S, Rodrigues, A, Silva, N, Silveira Nunes, I, Sousa, R (Centro Hospitalar Universit&#225, rio Lisboa Central), Ascens&#227, o, J, Azevedo, P, Costeira, B, Cunha, C, Garrido, R, Gomes, H, Louren&#231, o, I, Mendinhos, G, Miranda, P, Nobre Pinto, A, Peralta Ferreira, M, Ribeiro, J, Rio Rodrigues, L, Sousa Fernandes, M (Hospital Beatriz Angelo), Azevedo J (Hospital Da Horta, E. p. e. ), Galv&#227, o, D, Soares, Ac, Vieira, A, Vieira, B (Hospital De Santo Espirito Da Ilha Terceira), Patr&#237, cio, B, Santos, Pmdd, Vieira Paiva Lopes AC (Hospital De Torres Vedras, - Centro Hospitalar Do Oeste), Cunha, R, Faustino, A, Freitas, A, Martins, Ab, Mendes, Jr, Parreira, R, Rosa, J, Teves, M (Hospital Do Divino Esp&#237, rito Santo), Abreu da Silva, A, Claro, M, Costa Santos, D, Deus, Ac, Grilo JV (Hospital Do Litoral Alentejano), Borges, F, Corte Real, J, Henriques, S, Lima, Mj, Matos Costa, P (Hospital Garcia De Orta), Brito da Silva, F, Caiado, A, Fonseca, F (Instituto Portugu&#234, s De Oncologia De Lisboa Francisco Gentil), 194, ngelo, M, Baiao, Jm, Martins Jord&#227, Vieira Caro&#231, o, T (Ipo Coimbra), Messias, J, Millan, A, Salgado, I, Santos, P (Ipo Lisboa), Ba&#237, a, C, Canotilho, R, Correia, Am, Ferreira Pinto AP, Peyroteo, M, Puerto Rico: Escobar P, Videira JF (Ipo Porto)., R&#233, union: Kassir R, Maldonado Santiago M (Instituto Gineco Oncologico)., Romania: Bezede C, Sauvat F (Chu Reunion)., Chitul, A, Ciofic, E, Cristian, D, Grama, F (Coltea Clinical Hospital), Pirtea L, Secosan C (Emergency Clinical City Hospital), Bonci, E, Gata, V, Ion Chiricuta Institute Of Oncology), Titu S (Prof. Dr., Ginghina, O, Iordache, N, Russia: Garmanova T, Iosifescu RV (Saint John Emergency Hospital)., Kazachenko, E, Markaryan, D, Rodimov, S, Tsarkov, P, Tulina, I (Clinic Of Coloproctology And Minimally Invasive Surgery, Sechenov Medical State University), Litvina, Y, Provozina, A (Immanuel Kant Baltic Federal University, Regional Clinical Hospital), Agapov, M, Galliamov, E, Kakotkin, V, Kubyshkin, V, 1050, 1072, 1084, 1083, 1086, 1074, &#1040, (Moscow Research And Educational Center, Saudi Arabia: Alshahrani M, Lomonosov Moscow State University)., Alsharif, F, Eskander, M (Aseer Central Hospital), Al Raddadi, R, Majrashi, S, Mashat, A (East Jeddah General Hospital), Akeel, N, Alharthi, M, Aljiffry, M, Basendowah, M, Farsi, A, Ghunaim, M, Khoja, A, Maghrabi, A, Malibary, N, Nassif, M, Nawawi, A, Saleem, A, Samkari, A, Trabulsi, N (King Abdulaziz University Hospital), Al Awwad, S, Alghamdi, M, Alnumani, T, Nasser, M, Said bayazeed, A (King Fahad General Hospital), Alhefdhi, A, Almalik, O, Alomair, A, Alotaibi, N, Alresaini, F, Alsalamah, R, Alsobhi, S, Mahasin, Z, Othman, E, Velagapudi, S (King Faisal Specialist Hospital), Al Habes, H, Alamri, A, Alkarak, S, Alqannas, M, Alyami, M, Alzamanan, M, Cort&#233, s Guiral, D, Elawad, A (King Khalid Hospital), AlAamer, O, Alriyees, L, Alselaim, N (King Saud Bin Abdulaziz University For Health Sciences, King Abdullah International Medical Research Center, Ministry Of National Guard, Health, Affairs, General Surgery Department., ), Abdulkareem, A, Ajlan, A, Akkour, K, Al-Habib, A, Al-Khayal, K, Alatar, A, Alburakan, A, Alhalal, H, Alhassan, B, Alhassan, N, Alobeed, O, Alsaif, A, Alsaif, F, Alshammari, S, Alshaygy, I, Barry, M, Bin Nasser, A, Bin Traiki, T, Bokhari, A, Elwatidy, S, Helmi, H, Madkhali, A, Nouh, T, Rabah, Pd, Serbia: Paunovic I, Zubaidi A (King Saud University)., Slijepcevic, N (Centre For Endocrine Surgery, Clinical Centre Of Serbia), Aleksi&#263, L, Antic, A, Barisic, G, Ceranic, M, Galun, D, Gruba&#269, &#381, Jelenkovic, J, Kecmanovi&#263, Kmezi&#263, Knezevic, D, Krivokapic, Z, Latin&#269, Markovic, V, Mati&#263, Miladinov, M, Pavlov, M, Pejovic, I, Radenkovic, D, Tadic, B, Vasljevi&#263, J, Velickovic, D, Zivanovic, M (Clinic For Digestive Surgery, Perovic M, Srbinovic L (Clinic For Gynecology And Obstetrics Narodni Front), Andrijasevic, S, Bozanovic, T, Cerovic Popovic, R, Dokic, M, Janjic, T, Jeremic, K, Kadija, S, Ladjevic Likic, I, Mirkovic, L, Pantovic, S, Pilic, I, Radojevic, M, Stefanovic, A, Vidakovic, S, Vilendecic, Z (Clinic For Gynecology And Obstetrics, Clinical Center Of Serbia), Antic, S, Dun&#273, erovi&#263, Jelovac, D, Jezdic, Z, Konstantinovic, V, Kotlar, B, Kuzmanovic, C, Lazi&#263, Petrovic, M, Popovic, F, Pucar, A, Romic, M, Sumrak, S, Vujanac, V (Clinic For Maxillofacial Surgery, School Of Dental Medicine, University Of Belgrade), Bascarevic, V, Bogdanovi&#263, I, Gruji&#269, Ilic, R, Mili&#263, evi&#263, Milisavljevi&#263, F, Miljkovi&#263, Paunovic, A, 352, 263, epanovi&#263, V, Stanimirovic, A, Todorovic, M (Clinic For Neurosurgery, Jotic, A, Milovanovic, J, Trivic, A (Clinic For Otorhinolaryngology And Maxillofacial Surgery, Bumbasirevic, U, Dzamic, Z, Kajmakovi&#263, B, Prijovi&#263, N, Zivkovic, M (Clinic Of Urology, Buta, M, Cvetkovic, A, Djurisic, I, Gacic, S, Goran, M, Inic, Z, Jeftic, N, Jevric, M, Jokic, V, Markovic, I, Milanovi&#263, Nikolic, S, Pejnovic, L, Savkovi&#263, Spurnic, I, Stevic, D, Stojiljkovic, D, Vucic, N, Zegarac, M (Institute For Oncology And Radiology Of Serbia), Karamarkovic, A, Kenic, M, Kovacevic, B, Krdzic, I, Singapore: Chan CW, Milutinovi&#263, V (Zvezdara University Medical Center)., Slovakia: G&#225, lis B, Lieske B (National University Hospital)., South Africa: Almgla N, &#352, imko K (University Hospital Bratislava)., Bernon, M, Boutall, A, Cairncross, L, Herman, A, Hilton, T, Jonas, E, Kloppers, C, Malherbe, F, Mugla, W, Nel, D, Rayamajhi, S, Van Wyngaard, T, Spain: Casta&#241, o-Leon AM, Vogel J (Groote Schuur Hospital)., Delgado Fernandez, J, Eiriz Fernandez, C, Espino Segura-Illa, M, Esteban Sinovas, O, Garcia Perez, D, Gomez, P, Jimenez-Roldan, L, Lagares, A, Moreno- Gomez, L, Paredes, I, P&#233, rez N&#250, 241, ez, A, S&#225, nchez Aniceto, G, Santas, M (12 De Octubre University Hospital), Fern&#225, ndez Rodr&#237, guez, P, Paniagua Garc&#237, a Se&#241, orans, M, Sanchez- Santos, R, Vigorita, V (&#193, lvaro Cunqueiro Hospital), Acrich, E, Baena Sanfeliu, E, Barrios, O, Golda, T, Santanach, C, Serrano-Navidad, M, Sorribas Grifell, M, Vives RV (Bellvitge University Hospital), Escol&#224, D, Jim&#233, nez A (Comarcal Alt Pened&#233, Cayetano Paniagua L, G&#243, mez Fern&#225, ndez L (Consorci Sanitari De Terrassa), Artigues, E, Bernal-Sprekelsen, Jc, Catal&#225, Bauset JC (Consorcio Hospital General Universitario), Collera, P, Diaz Del Gobbo, R, Farre Font, R, Flores Clotet, R, mez D&#237, az CJ, Gu&#224, rdia, N, Guariglia, Ca, Osorio, A, Sanchez Jimenez, R, Sanchon, L, Soto Montesinos C (Fundaci&#243, Althaia, - Xarxa Assistencial Universit&#224, ria De Manresa), Albi Martin B, Garc&#237, a Villayz&#225, n JE (Fundaci&#243, n Jimenez Diaz University Hospital), Alonso-Lamberti, L, Assaf, M, Baeza Pintado, N, Carabias, A, a-Quijada, J, Huertas Fernandez MA, Jimenez Miram&#243, n, J, Jimenez, V, Jover, Jm, Landeo Ag&#252, ero SA, Leon, R, Mart&#237, n Salamanca MB, rez Sim&#243, n, V, Ponce, S, Rodriguez, Jl, Salazar, A, Valle Rubio, A (Getafe University Hospital), Aguado, H (Hell&#237, n Hospital), Aldecoa Ansorregui, I, Bravo Infante, R, De Lacy FB, Di Somma, A, D&#237, az-Feijoo, B, Ense&#241, at Nora, J, Fabregas, N, Ferr&#233, s, A, Gil Iba&#241, ez, B, Gonzalez Sanchez JJ, Gracia, I, Hoyos Castro JA, Lacy, Am, Langdon, C, Mombl&#225, n, D, Morales, X, Oleaga, L, Otero, A, Pedrosa, L, Poblete Carrizo, J, Reyes Figueroa LA, Roldan Ramos, P, Rumia-Arboix, J, Tercero-Uribe, Ai, Topczewski, Te, Torales, J, Torne, A, Torn&#233, R, Turrado-Rodriguez, V, Valero, R, Valverde, S (Hospital Clinic Barcelona), Anula, R, Cano-Valderrama, O, Del Campo Mart&#237, n, M, ez-Valladares, L, Dom&#237, nguez, I, Dziakova, J, a Alonso, M, a Romero, E, mez Latorre, L, Muguerza, Jm, Pizarro, Mj, Saez Carlin, P, nchez del Pueblo, C, nchez-Pernaute, A, Sanz Ortega, G, Sanz-Lopez, R, Torres, A (Hospital Cl&#237, nico De Madrid), Garc&#233, s-Albir, M, Lopez, F, n-Ar&#233, valo, J, Moro-Valdezate, D, Pla-Marti, V (Hospital Cl&#237, nico Universitario De Valencia), Beltr&#225, n de Heredia, J, De Andr&#233, s Asenjo, B, mez Sanz, T, Jezieniecki, C, Nu&#241, ez Del Barrio, H, Ortiz de Sol&#243, rzano Aurusa FJ, Romero de Diego, A, Ruiz Soriano, M, Trujillo D&#237, az, J, Vazquez fernandez, A (Hospital Cl&#237, nico Universitario De Valladolid), Lora-Cumplido P, Sosa MV (Hospital De Cabue&#241, es), Gonzalez-Gonzalez E, Minaya Bravo AM (Hospital Del Henares), Alonso de la Fuente, N, Cazador Labat, M, Cecchini, L, Espinosa, Ca, Jimenez Toscano, M, L&#243, pez Campillo, A, Mancebo, G, Martorell, P, Munarriz, M (Hospital Del Mar), Grau-Talens EJ, Martin-Perez B (Hospital Don Benito-Villanueva), Benavides Buleje JA, Carrasco Prats, M, ndez, Pv, ndez-L&#243, pez, A, a Escudero, D, a Porcel VJ, Garcia Soria, V, Gim&#233, nez Franc&#233, s, C, Gonz&#225, lez Valverde FM, Gurrea, E, pez-Morales, P, Marco Garrido, A, nez Alonso JA, Medina, E, Mu&#241, oz Camarena JM, Parra Ba&#241, os PA, a Ros, E, Ramirez Faraco, M, Ruiz-Mar&#237, Sanchez Rodriguez, C, Valero Soriano, M (Hospital General Reina Sof&#237, Estaire G&#243, mez, M, ndez Camu&#241, as, &#193, Garcia Santos EP, Jimenez Higuera, E, nez-Pinedo, C, oz-Atienza, V, Padilla-Valverde, D, Pic&#243, n Rodr&#237, guez, R, Redondo Calvo FJ, nchez-Garc&#237, a, S, Sanchez-Pelaez, D (Hospital General Universitario De Ciudad Real), Colombari, Rc, Del valle, E, ndez, M, Lozano Lominchar, P, n, L, Rey Valcarcel, C, Steiner, Ma, Tudela, M, Zorrilla Ort&#250, zar, J (Hospital General Universitario Gregorio Mara&#241, 243, Alcaide Matas, F, a P&#233, rez JM, Troncoso Pereira, P (Hospital Mateu Orfila), Mora-Guzm&#225, n, I (Hospital Santa B&#225, rbara), Abell&#225, Achalandabaso Boira, M, Jorba, R, Memba Ikuga, R, Olona, C, Sales Mallafr&#233, R (Hospital Universitari De Tarragona Joan Xxiii), Cavall&#233, Busquets, P, Gavalda Pellice MGP, Salinas Pe&#241, a, J (Hospital Universitari Sant Joan), Aragon Achig EJ, Barbier, L, Caja Vivancos, P, Gainza, A, a Gutierrez JJ, Mallabiabarrena Ormaechea, G, Mar&#237, n, H, Martin Playa, P, Melchor Corc&#243, stegui, I, Prieto Calvo, M, Rodriguez Fraga, A, Villalabeitia Ateca, I (Hospital Universitario Cruces), De Andres Olabarria, U, Dur&#225, n Ballesteros, M, ndez Pablos FJ, Ib&#225, ez-Aguirre, Fj, Sanz Larrainzar, A, Ugarte-Sierra, B (Hospital Universitario De Galdakao), De la Hoz Rodr&#237, guez, &#193, Di Martino, M, a Septiem, J, Martin-Perez, E, oz de Nova JL (Hospital Universitario De La Princesa), Calvo Espino P, Guillamot Ruano P (Hospital Universitario De M&#243, stoles), Colao Garc&#237, a, L, az P&#233, rez, D, Esteban Agust&#237, E, Galindo Jara, P, Gutierrez Samaniego, M, Hernandez Bartolome MA, Serrano Gonz&#225, lez, J (Hospital Universitario De Torrej&#243, n De Ardoz), Alonso Poza, A, Di&#233, guez, B, a-Conde, M, Hern&#225, ndez-Garc&#237, a, M, Losada, M (Hospital Universitario Del Sureste), Chiesa-Estomba, Cm, lez Garc&#237, a J&#193, Larruscain, E, Sistiaga-Su&#225, rez JA (Hospital Universitario Donostia), Alvarez, E, Chavarrias, N, Fr&#237, as, L, a Pineda, V, Geg&#250, ndez Sim&#243, n, A, Gort&#225, zar, S, Gracia, M, Guevara, J, ndez Gutierrez, A, Loayza, A, a Dolores DT, C, Melendez, M, Moreno-Palacios, E, Perez, Y, Prieto Nieto MI, Ramos- Mart&#237, n, P, Rubio-Perez, I, Saavedra, J, Sanchez-Mendez, Ji, Siegrist Ridruejo, J, Urbieta, A, Zapardiel, I (Hospital Universitario La Paz), Cantalejo diaz, M, De Miguel Ardevines MDC, Duque-Mall&#233, Gascon Ferrer, I, lez-Nicol&#225, s Tr&#233, bol MT, Gracia-Roche, C, Herrero Lopez, M, Jariod Ferrer UM, Lanzon, A, Martinez German, A, Matute, M, Redondo, C, nchez Fuentes, N, nchez-Rubio, M, Santero-Ramirez, Ms, Saud&#237, Sim&#243, n Sanz MV, Uson-Bouthelier, T (Hospital Universitario Miguel Servet), Blazquez Martin, A, Diez Alonso, M, a Rico, E, Garcia-Loarte Gomez, E, Garcia-Moreno Nisa, F, Gutierrez Calvo, A, Hernandez, P, Lasa, I, Mendoza-Moreno, F, Morales Palacios, N, Ovejero Merino, E, Vera Mansilla, C (Hospital Universitario Principe De Asturias), Acebes Garc&#237, a, F, Bail&#243, Bueno Ca&#241, ones AD, Choolani Bhojwani, E, Marcos-Santos, P, Miguel, T, Pacheco S&#225, nchez, D, rez-Saborido, B, Sanchez Gonzalez, J, Tejero-Pintor FJ (Hospital Universitario R&#237, o Hortega), Alconchel, F, Conesa, A, Gil Mart&#237, nez, J, Guti&#233, rrez Fern&#225, ndez AI, Lopez Abad, A, Nicol&#225, s-L&#243, pez, T, Ramirez Romero, P, Roca Calvo MJ, Rodrigues, K, Ruiz Manzanera JJ, Soriano AI (Hospital Universitario Virgen De La Arrixaca), Cano, A, Capitan-Morales, L, Cintas Catena, J, Gomez-Rosado, J, Oliva Mompean, F, rez S&#225, nchez MA, R&#237, o Lafuente FD, Torres Arcos, C, Valdes-Hernandez, J (Hospital Universitario Virgen Macarena), Cholewa, H, Domingo, S, Frasson, M, Lago, V, Marina Martin, T, nez Chicote, C, Sancho-Muriel J (Hospital Universitario, Y Polit&#233, cnico La Fe), Landaluce-olavarria A, Lecumberri D (Hospital Urduliz), Abad Gurumeta, A, Abad-Motos, A, nez-Hurtado, E, Ripoll&#233, s-Melchor, J, Ruiz Escobar, A (Infanta Leonor University Hospital), Cuadrado- Garc&#237, a, A, Garcia-Sancho Tellez, L, Heras Aznar, J, Mat&#233, P, Ortega V&#225, zquez, I, Picardo, Al, Rojo L&#243, pez JA, Sanchez Cabezudo Noguera, F, Serralta de Colsa, D (Infanta Sof&#237, a University Hospital), Anchuelo Latorre, J, Cagigas Fernandez, C, Cai&#241, a Ruiz, R, Gomez Ruiz, M, Hernanz, F, Jimeno Fraile, J, nez-P&#233, rez, P, Poch, C, Santarrufina Martinez, S, Valbuena Jabares, V (Marqu&#233, s De Valdecilla University Hospital), Moliner-S&#225, nchez, C, Pingarron-Martin, L, Rey-Biel, J, Ruiz Martin, I (Rey Juan Carlos University Hospital), Blas Laina JL, Cros, B, Escartin, J, Garcia Egea, J, Nogu&#233, Talal El-Abur, I, Y&#225, nez, C (Royo Villanova), Cagigal Ortega EP, Cervera, I, az Pe&#241, a, P, Elena, Gdcr, Enjuto, D, ndez Bernab&#233, s Garc&#237, a, R, Gonzalez, J, ndez, I, Herrera-Merino, N, Marqueta De Salas, M, Martinez Pascual, P, Perez Gonzalez, M, Ramos Bonilla, A, Rodr&#237, guez G&#243, mez, L (Severo Ochoa University Hospital), Besc&#243, Blanco-Colino, R, Brana, I, Caimari, B, De Pablo Garc&#237, a-Cuenca, A, Duran-Valles, F, Espin-Basany, E, Giralt L&#243, pez de Sagredo, J, Pamias, J, Pellino, G, Prat, N, Pujol Pina, R, Sri Lanka: Arulanantham A, Saez barba M (Vall D&#8217, hebron University Hospital)., Bandara, Gbk, Jayarajah, U, Ravindrakumar, S, Rodrigo VS (District General Hospital Chilaw), Srishankar S (Teaching Hospital Anuradhapura). Sudan: Ali karar AA (Al-Rajhi). Sweden: Elbe P, Lindqvist EK (Karolinska University Hospital), Taflin, H (Sahlgrenska University Hospital), 196, lg&#229, Heinius, G, Nordberg, M, Pieniowski, E (South General Hospital), Gkekas, I, fgren, N, Ruteg&#229, rd, M, Switzerland: Arigoni M, Sund M (Umea University Hospital)., Bernasconi, M, Christoforidis, D, Di Giuseppe, M, La Regina, D, Mongelli, F (Ente Ospedaliero Cantonale), Chevallay, M, Dwidar, O, Gialamas, E, Sauvain, M (Hopital De Pourtales), Klenke, F, Koll&#224, r, A, Kurze, C (Inselspital, Bern University Hospital, University Of Bern), Adamina, M, B&#228, chler, T, Crugnale, As, Giardini, M, Guglielmetti, L, Peros, G, Turkey: Aghayeva A, Solimene F (Kantonsspital Winterthur)., Hamzaoglu, I, Sahin, I (Acibadem Altunizade Hospital), Akaydin, E, Aliyeva, Z, Aytac, E, Baca, B, D&#252, lgero&#287, lu, O, Ozben, V, Ozmen, Bb, Uras, C (Acibadem Atakent Hospital), Arikan, Ae, Bilgin, Ia, Bozk&#305, rl&#305, Ceyhan, Go, Kara, H, Karahasano&#287, lu, T, Uras, C (Acibadem Maslak Hospital), Celik, H (Adana Baskent University), Meydanli MM (Ankara City Hospital), Akilli, H, Ayhan, A, Kuscu, E (Baskent University), Onan MA (Gazi University Medical Faculty Hospital), Akgor, U, Dincer, Ha, Erol, T, Gultekin, M, Orhan, N, Ozgul, N, Salman, Mc, Soyak, B (Hacettepe University Hospital), Alhamed, A, Erg&#252, n, S, OZcel&#305, k, Mf, Sanli, An, Uluda&#287, Velidedeoglu, M, Zengin AK (Istanbul Universty, - Cerrahpa&#351, a Medical Faculty), Bozkurt, Ma, Kara, Y, Kocata&#351, A (Kanuni Sultan Suleyman Training And Research Hospital), Cimenoglu, B, Demirhan, R, Lutfi Kirdar Training And Research Hospital), Saracoglu K (Kartal Dr., Azamat, I&#775, f, Balik, E, Bu&#287, ra, D, Giray, B, Kulle, Cb, Taskiran, C, Vatansever, D (Ko&#231, University Medical School), G&#246, zal, K, G&#252, ler, Sa, ken, H, Tatar, Oc, Utkan, Nz, Y&#305, ld&#305, r&#305, m, A, Y&#252, ksel, E (Kocaeli University Teaching Hospital), Akin, E, Altintoprak, F, Bayhan, Z, Cakmak, G, 199, apo&#287, lu, R, elebi, F, Demir, H, Dikicier, E, Firat, N, n&#252, ll&#252, Kamburo&#287, lu, Mb, Kocer, B, 231, 252, k, If, Mantoglu, B (Sakarya University Faculty Of Medicine), olak, E, Kucuk, Go, Uyanik MS (Samsun Training And Research Hospital), 304, lhan Varank Training And Research Hospital), G&#246, ksoy B (Sehit Prof. dr., Bozkurt, E, Citgez, B, Mihmanli, M, Tanal, M, Yetkin, G (Sisli Hamidiye Etfal Training And Research Hospital), Akalin, M, Arican, C, Avci, Ek, Aydin, C, Demirli At&#305, c&#305, Emiroglu, M, Kaya, T, Kebab&#231, 305, Kilinc, G, Kirmizi, Y, 287, c&#252, H, Salimo&#287, lu, S, Sert, I&#775, Tugmen, C, Tuncer, K, Uslu, G, Ye&#351, ilyurt, D (University Of Health Sciences Tepecik Training And Research Hospital), Karaman, E, Kolusar&#305, A (Van Yuzuncu Yil University, Medical, Faculty), Uganda: Benson O, Yildiz A (Yildirim Beyazit University Yenimahalle Training And Research Hospital)., United Kingdom: Agilinko J, Lule H (Kampala International University Teaching Hospital)., Ahmeidat, A, Barabasz, M, Bekheit, M, Cheung, Lk, Colloc, T, Cymes, W, Elhusseini, M, Gradinariu, G, Hannah, A, Kamera, Bs, Mignot, G, Shaikh, S, Sharma, P (Aberdeen Royal Infirmary), Abu-Nayla, I, Agrawal, A, Al-Mohammad, A, Ali, S, Ashcroft, J, Azizi, A, Baker, O, Balakrishnan, A, Byrne, M, Colquhoun, A, Cotter, A, Coughlin, P, Davies, Rj, Durrani, A, Elshaer, M, Fordington, S, Forouhi, P, Georgiades, F, Grimes, H, Habeeb, A, Hudson, V, Hutchinson, P, Irune, E, Jah, A, Khan, Dz, Kolias, A, Kyriacou, H, Lamb, B, Liau, S, Luke, L, Mahmoud, R, Mannion, R, Masterson, L, Mitrofan, Cg, Mohan, M, Morris, A, Murphy, S, Neill, R, Price, S, Pushpa-rajah, J, Raby-Smith, W, Ramzi, J, Rooney, S, Santarius, T, Singh, A, Stewart, Gd, Tan, Xs, Townson, A, Tweedle, E, Walker, C, Waseem, S, Yordanov, S (Addenbrooke&#8217, Jones, T, Kattakayam, A, Loh, C, Lunevicius, R, Pringle, S, Schache, A, Shaw, R, Sheel, A (Aintree University Hospital), Rossborough, C (Altnagelvin Area Hospital), Angelou, D, Choynowski, M, McAree, B, McCanny, A, Neely, D (Antrim Area Hospital- Northern Health And Social Care Trust), Tutoveanu, G (Barnsley Hospital Nhs Foundation Trust), Ahad, S, De La Cruz Monroy MFI, Mosley, F, Oktseloglou, V (Bradford Royal Infirmary), Alanbuki, A, Patel, M, Shabana, A (Brighton And Sussex Nhs Trust, Princess Royal Hospital), Perera, E, Raveendran, D, Ravi- Shankar, K, Thiruchelvam, J (Broomfield Hospital), Arrowsmith L, Campbell W (Causeway Hospital), Grove, T, Kontovounisios, C, Warren, O (Chelsea And Westminster Hospital), Rolland, P (Cheltenham General Hospital), Aggarwal, A, Brown, S, Jelley, C, Neal, N (Churchill Hospital), Clifford, R, Eardley, N, Krishnan, E, Manu, N, Martin, E, Roy Mahapatra, S, Serevina, Ol, Smith, C, Vimalachandran, D (Countess Of Chester Hospital), Bordenave, M, Houston, R, Putnam, G, Robson, A, Tustin, H (Cumberland Infirmary), Emslie, K, Labib, Pl, Marchbank, A, Miller, D, Minto, G, Natale, J, Nwinee, H, Panahi, P, Rogers, L (Derriford Hospital), Abubakar, A, Akhter Rahman MM, Kyk, Ko, Brien, H, Sasapu, K, Woodun, H (Diana Princess Of Wales Hospital Grimsby), Inglis R, Ng HJ (Dumfries And Galloway Royal Infirmary), De Gea Rico, A, Ghazali, N, Lambert, J, Markose, G, Math, S, Sarantitis, I, Shrestha, D, Sultana, A, Taggarsi, M, Timbrell, S, Vaz, Op, Vitone, L (East Lancashire Hospitals Nhs Trust), Day, A, Dent, H, Fahim, M, Waheed, S (East Surrey Hospital), Hunt A, Laskar N (East Sussex Healthcare (Conquest Hospital And Eastbourne District General Hospital)), Gupta, A, Steinke, J, Thrumurthy, S (Epsom &amp, St Helier University Hospitals Nhs Trust), Massie, E, McGivern, K, Rutherford, D, Wilson, M (Forth Valley Royal Hospital), Hardie J, Kazzaz S (Frimley Health Nhs Ft - Frimley Park), Handa, S, Kaushal, M, Kler, A, Patel, P, Redfern, J, Tezas, S (Furness General Hospital), Aawsaj, Y, Amonkar, S, Blackwell, L, Blake, D, Carter, J, Emerson, H, Fisher, A, Katory, M, Korompelis, P, McCormick, W, Mustafa, A, Pearce, L, Ratnavelu, N, Reehal, R (Gateshead Health Nhs Foundation Trust), Kretzmer, L, Lalou, L, Manku, B, Parwaiz, I, Stafford, J (George Eliot Hospital), Abdelkarim, M, Asqalan, A, Gala, T, Ibrahim, S, Maw, A, Mithany, R, Morgan, R, Sundaram Venkatesan, G (Glan Clwyd Hospital), Ang, K, Caruana, Ej, Chowdhry, Mf, Mohammad, A, Nakas, A, Rathinam, S (Glenfield Hospital), Boal, M, Brown, O, Dwerryhouse, S, Higgs, S, Vallance, A (Gloucestershire Royal Hospital), Boyd, E, Irvine, V, Kirk, A (Golden Jubilee National Hospital), Bakolas, G, Boulton, A, Chandock, A, Khan, T, Kumar, M (Good Hope Hospital), Agoston, P, Bill&#232, Challacombe, B, Fraser, S, Harrison-Phipps, K, King, J, Mehra, G, Mills, L, Najdy, M, Nath, R, Okiror, L, Pilling, J, Rizzo, V, Routledge, T, Sayasneh, A, Stroman, L, Wali, A (Guy&#8217, Fehervari, M, Fotopoulou, C, Habib, N, Hamrang-Yousefi, S, Jawad, Z, Jiao, L, Pai, M, Ploski, J, Rajagopal, P, Saso, S, Sodergren, M, Spalding, D (Hammersmith Hospital), 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H., Charlton, G., Chen, S., Gauri, N., Hayhurst, R., Jang, S., Jia, F., Mulligan, C., Yang, W., Ye, G., Zhang, H., Ballal, M., Gibson, D., Hayne, D., Moss, J., Richards, T., Viswambaram, P., Vo, U. G., Bennetts, J., Bright, T., Brooke-Smith, M., Fong, R., Gricks, B., Lam, Y. H., Ong, B. S., Szpytma, M., Watson, D., Bagraith, K., Caird, S., Chan, E., Dawson, C., Ho, D., Jeyarajan, E., Jordan, S., Lim, A., Nolan, G. J., Oar, A., Parker, D., Puhalla, H., Quennell, A., Rutherford, L., Townend, P., Von Papen, M., Wullschleger, M., Blatt, A., Cope, D., Egoroff, N., Fenton, M., Gani, J., Lott, N., Shugg, N., Elliott, M., Phung, D., Phan, D., Townend, D., Bong, C., Gundara, J., Frankel, A., Bowman, S., Guerra, G. R., Bolt, J., Buddingh, K., Dudi-Venkata, N. N., Jog, S., Kroon, H. 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E., AL-Sayed, M., Ashoush, F., Atta, R., Elazzazy, E., Elhoseiny, M., Elnemr, M., Elqasabi, M. S., Elsayed Hewalla, M. E., Elsherbini, I., Essam, E., Eweda, M., Ghallab, I., Hassan, E., Metwalli, M., Mourad, M., Qatora, M. S., Ragab, M., Sabry, A., Saifeldin, H., Saleh Mesbah Mohamed Elkaffas, M., Samih, A., Samir Abdelaal, A., Shehata, S., Shenit, K., Attia, D., Kamal, N., Osman, N., Abbas, A. M., Abd Elazeem, H. A. S., Abdelkarem, M. M., Alaa, S., Ali, A. K., Ayman, A., Azizeldine, M. G., Elkhayat, H., Melghazaly, S., Monib, F. A., Nageh, M. A., Saad, M. M., Salah, M., Shahine, M., Yousof, E. A., Youssef, A., Eldaly, A., Elfiky, M., Nabil, A., Amira, G., Sallam, I., Sherief, M., Abdelrahman, A., Aboulkassem, H., Ghaly, G., Hamdy, R., Morsi, A., Sherif, G., Abdeldayem, H., Abdelkader Salama, I., Balabel, M., Fayed, Y., Sherif, A. E., Bekele, D., Sarjanoja, E., Helminen, O., Huhta, H., Kauppila, J. H., Beyrne, C., Jouffret, L., Lugans, L., Marie-Macron, L., Chouillard, E., De Simone, B., Bettoni, J., Dakpe, S., Devauchelle, B., Lavagen, N., Testelin, S., Boucher, S., Breheret, R., Gueutier, A., Kahn, A., Kun-Darbois, J., Barrabe, A., Lakkis, Z., Louvrier, A., Manfredelli, S., Mathieu, P., Chebaro, A., Drubay, V., El amrani, M., Eveno, C., Lecolle, K., Legault, G., Martin, L., Piessen, G., Pruvot, F. R., Truant, S., Zerbib, P., Ballouhey, Q., Barrat, B., Laloze, J., Salle, H., Taibi, A., Usseglio, J., Bergeat, D., Merdrignac, A., Le Roy, B., Perotto, L. O., Scalabre, A., Aime, A., Ezanno, A., Malgras, B., Bouche, P., Tzedakis, S., Cotte, E., Glehen, O., Kepenekian, V., Lifante, J., Passot, G., D'Urso, A., Felli, E., Mutter, D., Pessaux, P., Seeliger, B., Bardet, J., Berry, R., Boddaert, G., Bonnet, S., Brian, E., Denet, C., Fuks, D., Gossot, D., Grigoroiu, M., Laforest, A., Levy-Zauberman, Y., Louis-Sylvestre, C., Moumen, A., Pourcher, G., Seguin-Givelet, A., Tribillon, E., Duchalais, E., Espitalier, F., Ferron, C., Malard, O., Bork, U., Distler, M., Fritzmann, J., Kirchberg, J., Praetorius, C., Riediger, C., Weitz, J., Welsch, T., Wimberger, P., Beyer, K., Kamphues, C., Lauscher, J., Loch, F. N., Schineis, C., Albertsmeier, M., Angele, M., Kappenberger, A., Niess, H., Schiergens, T., Werner, J., Becker, R., Jonescheit, J., Pergolini, I., Reim, D., Boeker, C., Hakami, I., Mall, J., Liokatis, P., Smolka, W., Nowak, K., Reinhard, T., Holzle, F., Modabber, A., Winnand, P., Knitschke, M., Kauffmann, P., Wolfer, S., Kleeff, J., Lorenz, K., Michalski, C., Ronellenfitsch, U., Schneider, R., Bertolani, E., Konigsrainer, A., Loffler, M. W., Quante, M., Steidle, C., Uberruck, L., Yurttas, C., Betz, C. S., Bewarder, J., Bottcher, A., Burg, S., Busch, C., Gosau, M., Heuer, A., Izbicki, J., Klatte, T. O., Koenig, D., Moeckelmann, N., Nitschke, C., Priemel, M., Smeets, R., Speth, U., Thole, S., Uzunoglu, F. G., Vollkommer, T., Zeller, N., Battista, M. J., Gillen, K., Hasenburg, A., Krajnak, S., Linz, V., Schwab, R., Angelou, K., Haidopoulos, D., Rodolakis, A., Antonakis, P., Bramis, K., Chardalias, L., Contis, I., Dafnios, N., Dellaportas, D., Fragulidis, G., Gklavas, A., Konstadoulakis, M., Memos, N., Papaconstantinou, I., Polydorou, A., Theodosopoulos, T., Vezakis, A., Antonopoulou, M. I., Manatakis, D. K., Tasis, N., Arkadopoulos, N., Danias, N., Economopoulou, P., Kokoropoulos, P., Larentzakis, A., Michalopoulos, N., Selmani, J., Sidiropoulos, T., Tsaousis, V., Vassiliu, P., Bouchagier, K., Klimopoulos, S., Paspaliari, D., Stylianidis, G., Baxevanidou, K., Bouliaris, K., Chatzikomnitsa, P., Efthimiou, M., Giaglaras, A., Kalfountzos, C., Koukoulis, G., Ntziovara, A. M., Petropoulos, K., Soulikia, K., Tsiamalou, I., Zervas, K., Zourntou, S., Baloyiannis, I., Diamantis, A., Gkrinia, E., Hajiioannou, J., Korais, C., Koukoura, O., Perivoliotis, K., Saratziotis, A., Skoulakis, C., Symeonidis, D., Tepetes, K., Tzovaras, G., Zacharoulis, D., Alexoudi, V., Antoniades, K., Astreidis, I., Christidis, P., Deligiannidis, D., Grivas, T., Ioannidis, O., Kalaitsidou, I., Loutzidou, L., Mantevas, A., Michailidou, D., Paraskevopoulos, K., Politis, S., Stavroglou, A., Tatsis, D., Tilaveridis, I., Vahtsevanos, K., Venetis, G., Karaitianos, I., Tsirlis, T., Charalabopoulos, A., Liakakos, T., Mpaili, E., Schizas, D., Spartalis, E., Syllaios, A., Zografos, C., Anthoulakis, C., Christou, C., Papadopoulos, V., Tooulias, A., Tsolakidis, D., Tsoulfas, G., Zouzoulas, D., Athanasakis, E., Chrysos, E., Tsiaoussis, J., Xenaki, S., Xynos, E., Futaba, K., Ho, M. F., Hon, S. F., Mak, T. W. C., Ng, S. S. M., Foo, C. C., Banky, B., Susztak, N., Aremu, M., Canas-Martinez, A., Cullivan, O., Murphy, C., Owens, P., Pickett, L., Akmenkalne, L., Byrne, J., Corrigan, M., Cullinane, C., Daly, A., Fleming, C., Jordan, P., Killeen, S., Lynch, N., Mccarthy, A., Mustafa, H., O'Brien, S., O'Leary, P., Syed, W. A. S., Vernon, L., Callanan, D., Huang, L., Ionescu, A., Sheahan, P., Balasubramanian, I., Boland, M., Conlon, K., Evoy, D., Fearon, N., Gallagher, T., Geraghty, J., Heneghan, H., Kennedy, N., Maguire, D., Mccartan, D., Mcdermott, E. W., Prichard, R. S., Winter, D., Alazawi, D., Barry, C., Boyle, T., Butt, W., Connolly, E. M., Donlon, N., Donohue, C., Fahey, B. A., Farrell, R., Fitzgerald, C., Kinsella, J., Larkin, J. O., Lennon, P., Maguire, P. J., Mccormick, P., Mehigan, B. J., Nugent, T., O'Sullivan, H., Ravi, N., Reynolds, J. V., Rogers, A., Shokuhi, P., Smith, J., Smith, L. A., Timon, C., Bashir, Y., Bass, G., Connelly, T., Creavin, B., Earley, H., Elliott, J. A., Gillis, A., Kavanagh, D., Neary, P., O'Riordan, J., Reynolds, I. S., Rice, D., Ridgway, P., Umair, M., Whelan, M., Carroll, P., Collins, C., Corless, K., Finnegan, L., Fowler, A., Hogan, A., Kerin, M., Lowery, A., Mcanena, P., Mckevitt, K., Nizami, K., Ryan, E., Samy, A., Coffey, J. C., Cunningham, R., Devine, M., Nally, D., Peirce, C., Tormey, S., Hardy, N., O'Malley, S., Ryan, M., Macina, S., Mariani, N. M., Opocher, E., Pisani Ceretti, A., Ferrari, F., Odicino, F., Sartori, E., Cotsoglou, C., Granieri, S., Bianco, F., Camillo, A., Colledan, M., Tornese, S., Zambelli, M. F., Bissolotti, G., Fusetti, S., Lemma, F., Marino, M. V., Mirabella, A., Vaccarella, G., Agostini, C., Alemanno, G., Bartolini, I., Bergamini, C., Bruscino, A., Checcucci, C., De Vincenti, R., Di Bella, A., Fambrini, M., Fortuna, L., Maltinti, G., Muiesan, P., Petraglia, F., Prosperi, P., Ringressi, M. N., Risaliti, M., Sorbi, F., Taddei, A., Tucci, R., Bassi, C., Bortolasi, L., Campagnaro, T., Casetti, L., De Pastena, M., Esposito, A., Fontana, M., Guglielmi, A., Landoni, L., Malleo, G., Marchegiani, G., Nobile, S., Paiella, S., Pedrazzani, C., Rattizzato, S., Ruzzenente, A., Salvia, R., Turri, G., Tuveri, M., Bellora, P., D'Aloisio, G., Ferrari, M., Francone, E., Gentilli, S., Nikaj, H., Bianchini, M., Chiarugi, M., Coccolini, F., Di Franco, G., Furbetta, N., Gianardi, D., Guadagni, S., Morelli, L., Palmeri, M., Tartaglia, D., Anania, G., Carcoforo, P., Chiozza, M., De Troia, A., Koleva Radica, M., Portinari, M., Sibilla, M. G., Urbani, A., Fabbri, N., Feo, C. V., Gennari, S., Parini, S., Righini, E., Ampollini, L., Bellanti, L., Bergonzani, M., Bertoli, G., Bocchialini, G., D'Angelo, G., Lanfranco, D., Musini, L., Poli, T., Santoro, G. P., Varazzani, A., Aguzzoli, L., Borgonovo, G., Castro Ruiz, C., Coiro, S., Falco, G., Mandato, V. D., Mastrofilippo, V., Montella, M. T., Annessi, V., Zizzo, M., Grossi, U., Novello, S., Romano, M., Rossi, S., Zanus, G., Esposito, G., Frongia, F., Pisanu, A., Podda, M., Belluco, C., Lauretta, A., Montori, G., Moras, L., Olivieri, M., Bussu, F., Carta, A. G., Cossu, M. L., Cottu, P., Fancellu, A., Feo, C. F., Ginesu, G. C., Giuliani, G., Madonia, M., Perra, T., Piras, A., Porcu, A., Rizzo, D., Scanu, A. M., Tedde, A., Tedde, M., Delrio, P., Rega, D., Badalamenti, G., Campisi, G., Cordova, A., Franza, M., Maniaci, G., Rinaldi, G., Toia, F., Calabro, M., Farnesi, F., Lunghi, E. G., Muratore, A., Pipitone Federico, N. S., Bambina, F., D'Andrea, G., Familiari, P., Picotti, V., De Palma, G., Luglio, G., Pagano, G., Tropeano, F. P., Baldari, L., Beltramini, G. A., Boni, L., Cassinotti, E., Gianni, A., Pignataro, L., Torretta, S., Abatini, C., Baia, M., Biasoni, D., Bogani, G., Cadenelli, P., Cioffi, S. P. B., Citterio, D., Comini, L. V., Cosimelli, M., Folli, S., Gennaro, M., Giannini, L., Gronchi, A., Guaglio, M., Macchi, A., Martinelli, F., Mazzaferro, V., Mosca, A., Pasquali, S., Piazza, C., Raspagliesi, F., Rolli, L., Salvioni, R., Sarpietro, G., Sarre, C., Sorrentino, L., Agnes, A., Alfieri, S., Belia, F., Biondi, A., Cozza, V., D'Amore, A., D'Ugo, D., De Simone, V., Fagotti, A., Gasparini, G., Gordini, L., Litta, F., Lombardi, C. P., Lorenzon, L., Marra, A. A., Marzi, F., Moro, A., Parello, A., Perrone, E., Persiani, R., Ratto, C., Rosa, F., Saponaro, G., Scambia, G., Scrima, O., Sganga, G., Tudisco, R., Belli, A., Granata, V., Izzo, F., Palaia, R., Patrone, R., Carrano, F. M., Carvello, M. M., De Virgilio, A., Di Candido, F., Ferreli, F., Gaino, F., Mercante, G., Rossi, V., Spinelli, A., Spriano, G., Donati, D. M., Frisoni, T., Palmerini, E., Aprile, A., Barra, F., Batistotti, P., Ferrero, S., Fregatti, P., Scabini, S., Sparavigna, M., Asti, E., Bernardi, D., Bonavina, L., Lovece, A., Adamoli, L., Ansarin, M., Cenciarelli, S., Chu, F., De Berardinis, R., Fumagalli Romario, U., Mastrilli, F., Pietrobon, G., Tagliabue, M., Badellino, E., Ferrero, A., Massobrio, R., De Manzoni Garberini, A., Federico, P., Maida, P., Marra, E., Marte, G., Petrillo, A., Tammaro, T., Tufo, A., Berselli, M., Borroni, G., Cocozza, E., Conti, L., Desio, M., Livraghi, L., Quintodei, V., Rizzi, A., Zullo, A., Baldi, C., Corbellini, C., Sampietro, G. M., Cellerino, P., Baldini, E., Capelli, P., Isolani, S. M., Ribolla, M., Bondurri, A., Colombo, F., Ferrario, L., Guerci, C., Maffioli, A., Armao, T., Ballabio, M., Bisagni, P., Gagliano, A., Longhi, M., Madonini, M., Pizzini, P., Baietti, A. M., Biasini, M., Maremonti, P., Neri, F., Prucher, G. M., Ricci, S., Ruggiero, F., Zarabini, A. G., Barmasse, R., Mochet, S., Usai, A., Incollingo, P., Mancini, S., Marino Cosentino, L., Sagnotta, A., Fruscio, R., Grassi, T., Nespoli, L. C., Tamini, N., Anastasi, A., Bartalucci, B., Bellacci, A., Canonico, G., Capezzuoli, L., Di Martino, C., Ipponi, P., Linari, C., Montelatici, M., Nelli, T., Spagni, G., Tirloni, L., Vitali, A., Abate, E., Casati, M., Casiraghi, T., Laface, L., Schiavo, M., Arminio, A., Cotoia, A., Lizzi, V., Vovola, F., Vergari, R., D'Ugo, S., Depalma, N., Spampinato, M. G., Bartolucci, P., Brachini, G., Bruzzaniti, P., Chiappini, A., Chiarella, V., Ciccarone, F., Cicerchia, P. M., Cirillo, B., De Toma, G., Di bartolomeo, A., Fiori, E., Fonsi, G. B., Franco, G., Frati, A., Giugliano, M., Iannone, I., La Torre, F., Lapolla, P., Leonardo, C., Marruzzo, G., Meneghini, S., Mingoli, A., Ribuffo, D., Salvati, M., Santoro, A., Sapienza, P., Scafa, A. K., Simonelli, L., Zambon, M., Capolupo, G. T., Carannante, F., Caricato, M., Masciana, G., Mazzotta, E., Gattolin, A., Migliore, M., Rimonda, R., Sasia, D., Travaglio, E., Cervellera, M., Gori, A., Sartarelli, L., Tonini, V., Giacometti, M., Zonta, S., Chessa, A., Fiorini, A., Norcini, C., Colletti, G., Confalonieri, M., Costanzi, A., Frattaruolo, C., Mari, G., Monteleone, M., Bandiera, A., Bocciolone, L., Bonavina, G., Candiani, M., Candotti, G., De Nardi, P., Gagliardi, F., Medone, M., Mortini, P., Negri, G., Parise, P., Piloni, M., Sileri, P., Vignali, A., Belvedere, A., Bernante, P., Bertoglio, P., Boussedra, S., Brunocilla, E., Cipriani, R., Cisternino, G., De Crescenzo, E., De Iaco, P., Dondi, G., Frio, F., Jovine, E., Mineo Bianchi, F., Neri, J., Parlanti, D., Perrone, A. M., Pezzuto, A. P., Pignatti, M., Pinto, V., Poggioli, G., Ravaioli, M., Rottoli, M., Schiavina, R., Serenari, M., Serra, M., Solli, P., Taffurelli, M., Tanzanu, M., Tesei, M., Violante, T., Zanotti, S., Borghi, F., Cianflocca, D., Di Maria Grimaldi, S., Gelarda, E., Geretto, P., Giraudo, G., Giuffrida, M. C., Marano, A., Palagi, S., Pellegrino, L., Peluso, C., Testa, V., Agresta, F., Prando, D., Zese, M., Aquila, F., Gambacciani, C., Lippa, L., Pieri, F., Santonocito, O. S., Armatura, G., Bertelli, G., Frena, A., Marinello, P., Notte, F., Patauner, S., Scotton, G., Fulginiti, S. F., Gallo, G., Sammarco, G., Vescio, G., Balercia, P., Catarzi, L., Consorti, G., Di Marzo, F., Fontana, T., Daiko, H., Ishikawa, M., Ishiyama, K., Iwata, S., Kanematsu, K., Kanemitsu, Y., Kato, T., Kawai, A., Kobayashi, E., Kobayashi Kato, M., Moritani, K., Nakatani, F., Oguma, J., Tanase, Y., Uno, M., Al Abdallah, M., Ayasra, F., Ayasra, Y., Qasem, A., Abu Za'nouneh, F. J., Fahmawee, T., Hmedat, A., Ibrahim, A., Obeidat, K., Abdel Al, S., Abdel Jalil, R., Abou Chaar, M. K., Al-Masri, M., Al-Najjar, H., Alawneh, F., Alsaraireh, O., Elayyan, M., Ghanem, R., Lataifeh, I., Alkadeeki, G. Z., Al Maadany, F. S., Aldokali, N., Senossi, O., Subhi, M. T., Burgan, D., Kamoka, E., Kilani, A. I., Salamah, A., Salem, M., Shuwayyah, A., Abdulwahed, E., Alshareea, E., Aribi, N., Aribi, S., Biala, M., Ghamgh, R., Morgom, M., Aldayri, Z., Ellojli, I., Kredan, A., Bradulskis, S., Dainius, E., Kubiliute, E., Kutkevicius, J., Parseliunas, A., Subocius, A., Venskutonis, D., Rasoaherinomenjanahary, F., Razafindrahita, J. B., Samison, L. H., Ong, E. C., Hamdan, K. H., Ibrahim, M. R., Tan, J. A., Thanapal, M. R., Amin Sahid, N., Hayati, F., Jayasilan, J., Sriram, R. K., Subramaniam, S., Che Jusoh, A., Hussain, A. H., Mohamed Sidek, A. S., Mohd Yunus, M. F., Soh, J. Y., Wong, M. P. K., Zakaria, A. D., Zakaria, Z., Fadzli, A., Fathi, N. Q., Koh, P. S., Liew, Y. T., Roslani, A. C., Tang, C. Y., Teoh, L. Y., Wong, W. J., Yahaya, A. S., Alvarez, M. R., Arrangoiz, R., Cordera, F., De La Rosa Abaroa, M. A., Gomez-Pedraza, A., Hernandez, R., Maffuz-Aziz, A., Posada, J. A., Becerra Garcia, F. C., Alfaro-Goldaracena, A., Buerba, G. A., Castillejos-Molina, R. A., Chan, C., Dominguez-Rosado, I., Medina-Franco, H., Mercado, M. A., Oropeza-Aguilar, M., Pena Gomez Portugal, E., Posadas-Trujillo, O. E., Rodriguez-Covarrubias, F., Salgado-Nesme, N., Vilatoba, M., Arkha, Y., Bechri, H., El Ouahabi, A., Oudrhiri, M. Y., Derkaoui hassani, F., El Abbadi, N., Amrani, L., Belkhadir, Z. H., Benkabbou, A., Chakib, O., El Ahmadi, B., El Bouazizi, Y., Essangri, H., Ghannam, A., Majbar, A. M., Mohsine, R., Souadka, A., Hompes, R., Meima-Van Praag, E. M., Pronk, A. J. M., Sharabiany, S., Grotenhuis, B., Hartveld, L., Reijers, S., Van Houdt, W., Baaij, J., Bolster-Van Eenennaam, M., De Graaff, M., Sloothaak, D., Van Duijvendijk, P., Posma-Bouman, L., Derksen, T., Franken, J., Oosterling, S., De Bree, R., Konsten, J., Van Heinsbergen, M., Fidelis, L., Sholadoye, T. T., Tolani, M. A., Olaogun, J., Egbuchulem, I. K., Lawal, T. A., Ogundoyin, O., Olulana, D. I., Abdur-Rahman, L., Adeyeye, A., Aremu, I., Bello, J., Olasehinde, O., Popoola, A., Massoud, J., Massoud, R., Sorour, T. M., Jamal, A., Kerawala, A. A., Memon, A. S., Nafees Ahmed, R., Rai, L., Ayub, B., Hassan, N., Martins, R. S., Ramesh, P., Sayyed, R., Butt, U., Kashif, M., Khan, W. H., Qureshi, A., Umar, M., Waris Farooka, M., Wasim, T., Ayubi, A., Rashid, I., Waqar, S. H., Falcon, G. M., Robles, R., Jocson, R., Teh, C., Major, P., Bobinski, M., Kotarski, J., Rasoul-Pelinska, K., Azevedo, C., Machado, D., Mendes, F., De Sousa, X., Fernandes, U., Ferreira, C., Guidi, G., Leal, C., Marcal, A., Marques, R., Martins, D., Melo, A., Tenreiro, N., Vaz Pereira, R., Vieira, B., Almeida, J. I., Correia de Sa, T., Costa, M. J. M. A., Fernandes, V., Ferraz, I., Gil, C. G., Lima Da Silva, C., Lopes, L., Machado, N., Marialva, J., Nunes Coelho, M., Pedro, J., Pereira, C., Reis, R., Ribeiro, A., Santos, R., Saraiva, P., Silva, R., Tavares, F., Teixeira, M., Almeida, A. C., Amaral, M. J., Andrade, R., Athayde Nemesio, R., Breda, D., Camacho, C., Canhoto, C., Colino, M., Correia, S., De Barros, J., De Oliveira Lopez, A. L., Duque, M., Garrido, S., Guerreiro, P., Guimaraes, A., Lazaro, A., Lopes, C., Nogueira, O., Oliveira, A., Oliveira, J. M., Rodrigues, M., Ruivo, A., Santos, E., Silva, M., Simoes, J., Valente Da Costa, A., Almeida, A., Cavaleiro, S., Devezas, V., Faria, C. S., Jacome, F., Magalhaes Maia, M., Nogueiro, J., Pereira, A., Pereira-Neves, A., Pina-Vaz, T., Santos-Sousa, H., Silveira, H., Vaz, S., Vieira, P., Gomes Da Costa, A., Lobo Antunes, I., Pinto, J., Tojal, A., Cardoso, N., Cardoso, P., Domingues, J. C., Henriques, P., Manso, M. I., Martins Dos Santos, G., Morais, H., Pereira, R., Revez, T., Ribeiro, R., Ribeiro, V. I., Sousa, S., Teixeira, J., Amorim, E., Baptista, V. H., Cunha, M. F., Dias, B., Fazenda, A., Melo Neves, J. P., Policarpo, F., Sampaio Da Novoa Gomes Miguel, I. I., Veiga, D., Andrade, A. K., Bandovas, J. P., Borges, N., Branquinho, A., Chumbinho, B., Correia, J., Fidalgo, H., Figueiredo De Barros, I., Frade, S., Gomes, J., Maciel, J., Pina, S., Rodrigues, A., Silva, N., Silveira Nunes, I., Sousa, R., Ascensao, J., Azevedo, P., Costeira, B., Cunha, C., Garrido, R., Gomes, H., Lourenco, I., Mendinhos, G., Miranda, P., Nobre Pinto, A., Peralta Ferreira, M., Ribeiro, J., Rio Rodrigues, L., Sousa Fernandes, M., Azevedo, J., Galvao, D., Soares, A. C., Vieira, A., Patricio, B., Santos, P. M. D. D., Vieira Paiva Lopes, A. C., Cunha, R., Faustino, A., Freitas, A., Martins, A. B., Mendes, J. R., Parreira, R., Rosa, J., Teves, M., Abreu Da Silva, A., Claro, M., Costa Santos, D., Deus, A. C., Grilo, J. V., Borges, F., Corte Real, J., Henriques, S., Lima, M. J., Matos Costa, P., Brito da Silva, F., Caiado, A., Fonseca, F., Angelo, M., Baiao, J. M., Martins Jordao, D., Vieira Caroco, T., Messias, J., Millan, A., Salgado, I., Baia, C., Canotilho, R., Correia, A. M., Ferreira Pinto, A. P., Peyroteo, M., Videira, J. F., Escobar, P., Maldonado Santiago, M., Kassir, R., Sauvat, F., Bezede, C., Chitul, A., Ciofic, E., Cristian, D., Grama, F., Pirtea, L., Secosan, C., Bonci, E., Gata, V., Titu, S., Ginghina, O., Iordache, N., Iosifescu, R. V., Garmanova, T., Kazachenko, E., Markaryan, D., Rodimov, S., Tsarkov, P., Tulina, I., Litvina, Y., Provozina, A., Agapov, M., Galliamov, E., Kakotkin, V., Kubyshkin, V., Alshahrani, M., Alsharif, F., Eskander, M., Al Raddadi, R., Majrashi, S., Mashat, A., Akeel, N., Alharthi, M., Aljiffry, M., Basendowah, M., Farsi, A., Ghunaim, M., Khoja, A., Maghrabi, A., Malibary, N., Nassif, M., Nawawi, A., Saleem, A., Samkari, A., Trabulsi, N., Al Awwad, S., Alghamdi, M., Alnumani, T., Nasser, M., Said bayazeed, A., Alhefdhi, A., Almalik, O., Alomair, A., Alotaibi, N., Alresaini, F., Alsalamah, R., Alsobhi, S., Mahasin, Z., Othman, E., Velagapudi, S., Ghedan, S., Alharthi, R., Awad, S., Sharara, M., Abdelrahman, S., Althobaiti, W., Al Habes, H., Alamri, A., Alkarak, S., Alqannas, M., Alyami, M., Alzamanan, M., Cortes Guiral, D., Elawad, A., Alaamer, O., Alriyees, L., Alselaim, N., Abdulkareem, A., Ajlan, A., Akkour, K., Al-Habib, A., Al-Khayal, K., Alatar, A., Alburakan, A., Alhalal, H., Alhassan, B., Alhassan, N., Alobeed, O., Alsaif, A., Alsaif, F., Alshammari, S., Alshaygy, I., Barry, M., Bin Nasser, A., Bin Traiki, T., Bokhari, A., Elwatidy, S., Helmi, H., Madkhali, A., Nouh, T., Rabah, P. D., Zubaidi, A., Paunovic, I., Slijepcevic, N., Aleksic, L., Antic, A., Barisic, G., Ceranic, M., Galun, D., Grubac, Z., Jelenkovic, J., Kecmanovic, D., Kmezic, S., Knezevic, D., Krivokapic, Z., Latincic, S., Markovic, V., Matic, S., Miladinov, M., Pavlov, M., Pejovic, I., Radenkovic, D., Tadic, B., Vasljevic, J., Velickovic, D., Zivanovic, M., Perovic, M., Srbinovic, L., Andrijasevic, S., Bozanovic, T., Cerovic Popovic, R., Dokic, M., Janjic, T., Jeremic, K., Kadija, S., Ladjevic Likic, I., Mirkovic, L., Pantovic, S., Pilic, I., Radojevic, M., Stefanovic, A., Vidakovic, S., Vilendecic, Z., Antic, S., Dunderovic, D., Jelovac, D., Jezdic, Z., Konstantinovic, V., Kotlar, B., Kuzmanovic, C., Lazic, M., Petrovic, M., Popovic, F., Pucar, A., Romic, M., Sumrak, S., Vujanac, V., Bascarevic, V., Bogdanovic, I., Grujicic, D., Ilic, R., Milicevic, M., Milisavljevic, F., Miljkovic, A., Paunovic, A., Scepanovic, V., Stanimirovic, A., Todorovic, M., Jotic, A., Milovanovic, J., Trivic, A., Bumbasirevic, U., Dzamic, Z., Kajmakovic, B., Prijovic, N., Zivkovic, M., Buta, M., Cvetkovic, A., Djurisic, I., Gacic, S., Goran, M., Inic, Z., Jeftic, N., Jevric, M., Jokic, V., Markovic, I., Milanovic, M., Nikolic, S., Pejnovic, L., Savkovic, N., Spurnic, I., Stevic, D., Stojiljkovic, D., Vucic, N., Zegarac, M., Karamarkovic, A., Kenic, M., Kovacevic, B., Krdzic, I., Milutinovic, V., Lieske, B., Galis, B., Simko, K., Almgla, N., Bernon, M., Boutall, A., Cairncross, L., Herman, A., Hilton, T., Jonas, E., Kloppers, C., Malherbe, F., Mugla, W., Nel, D., Rayamajhi, S., Van Wyngaard, T., Vogel, J., Castano-Leon, A. M., Delgado Fernandez, J., Eiriz Fernandez, C., Espino Segura-Illa, M., Esteban Sinovas, O., Garcia Perez, D., Gomez, P., Jimenez-Roldan, L., Lagares, A., Moreno-Gomez, L., Paredes, I., Perez Nunez, A., Sanchez Aniceto, G., Santas, M., Fernandez Rodriguez, P., Paniagua Garcia Senorans, M., Sanchez-Santos, R., Vigorita, V., Acrich, E., Baena Sanfeliu, E., Barrios, O., Golda, T., Santanach, C., Serrano-Navidad, M., Sorribas Grifell, M., Vives, R. V., Escola, D., Jimenez, A., Cayetano Paniagua, L., Gomez Fernandez, L., Artigues, E., Bernal-Sprekelsen, J. C., Catala Bauset, J. C., Collera, P., Diaz Del Gobbo, R., Farre Font, R., Flores Clotet, R., Gomez Diaz, C. J., Guardia, N., Guariglia, C. A., Osorio, A., Sanchez Jimenez, R., Sanchon, L., Soto Montesinos, C., Albi Martin, B., Garcia Villayzan, J. E., Alonso-Lamberti, L., Assaf, M., Baeza Pintado, N., Carabias, A., Garcia-Quijada, J., Huertas Fernandez, M. A., Jimenez Miramon, J., Jimenez, V., Jover, J. M., Landeo Aguero, S. A., Leon, R., Martin Salamanca, M. B., Perez Simon, V., Ponce, S., Rodriguez, J. L., Salazar, A., Valle Rubio, A., Aguado, H., Aldecoa Ansorregui, I., Bravo Infante, R., De Lacy, F. B., Di Somma, A., Diaz-Feijoo, B., Ensenat Nora, J., Fabregas, N., Ferres, A., Gil Ibanez, B., Gonzalez Sanchez, J. J., Gracia, I., Hoyos Castro, J. A., Lacy, A. M., Langdon, C., Momblan, D., Morales, X., Oleaga, L., Otero, A., Pedrosa, L., Poblete Carrizo, J., Reyes Figueroa, L. A., Roldan Ramos, P., Rumia-Arboix, J., Tercero-Uribe, A. I., Topczewski, T. E., Torales, J., Torne, A., Torne, R., Turrado-Rodriguez, V., Valero, R., Valverde, S., Anula, R., Cano-Valderrama, O., Del Campo Martin, M., Diez-Valladares, L., Dominguez, I., Dziakova, J., Garcia Alonso, M., Garcia Romero, E., Gomez Latorre, L., Muguerza, J. M., Pizarro, M. J., Saez Carlin, P., Sanchez Del Pueblo, C., Sanchez-Pernaute, A., Sanz Ortega, G., Sanz-Lopez, R., Torres, A., Garces-Albir, M., Lopez, F., Martin-Arevalo, J., Moro-Valdezate, D., Pla-Marti, V., Beltran De Heredia, J., De Andres Asenjo, B., Gomez Sanz, T., Jezieniecki, C., Nunez Del Barrio, H., Ortiz De Solorzano Aurusa, F. J., Romero De Diego, A., Ruiz Soriano, M., Trujillo Diaz, J., Vazquez Fernandez, A., Lora-Cumplido, P., Sosa, M. V., Gonzalez-Gonzalez, E., Minaya Bravo, A. M., Alonso de la Fuente, N., Cazador Labat, M., Cecchini, L., Espinosa, C. A., Jimenez Toscano, M., Lopez Campillo, A., Mancebo, G., Martorell, P., Munarriz, M., Grau-Talens, E. J., Martin-Perez, B., Benavides Buleje, J. A., Carrasco Prats, M., Fernandez, P. V., Fernandez-Lopez, A., Garcia Escudero, D., Garcia Porcel, V. J., Garcia Soria, V., Gimenez Frances, C., Gonzalez Valverde, F. M., Gurrea, E., Lopez-Morales, P., Marco Garrido, A., Martinez Alonso, J. A., Medina, E., Munoz Camarena, J. M., Parra Banos, P. A., Pena Ros, E., Ramirez Faraco, M., Ruiz-Marin, M., Sanchez Rodriguez, C., Valero Soriano, M., Estaire Gomez, M., Fernandez Camunas, A., Garcia Santos, E. P., Jimenez Higuera, E., Martinez-Pinedo, C., Munoz-Atienza, V., Padilla-Valverde, D., Picon Rodriguez, R., Redondo Calvo, F. J., Sanchez-Garcia, S., Sanchez-Pelaez, D., Colombari, R. C., Del valle, E., Fernandez, M., Lozano Lominchar, P., Rey Valcarcel, C., Steiner, M. A., Tudela, M., Zorrilla Ortuzar, J., Alcaide Matas, F., Garcia Perez, J. M., Troncoso Pereira, P., Mora-Guzman, I., Abellan, M., Achalandabaso Boira, M., Jorba, R., Memba Ikuga, R., Olona, C., Sales Mallafre, R., Cavalle Busquets, P., Gavalda Pellice, M. G. P., Salinas Pena, J., Aragon Achig, E. J., Barbier, L., Caja Vivancos, P., Gainza, A., Garcia Gutierrez, J. J., Mallabiabarrena Ormaechea, G., Marin, H., Martin Playa, P., Melchor Corcostegui, I., Prieto Calvo, M., Rodriguez Fraga, A., Villalabeitia Ateca, I., De Andres Olabarria, U., Duran Ballesteros, M., Fernandez Pablos, F. J., Ibanez-Aguirre, F. J., Sanz Larrainzar, A., Ugarte-Sierra, B., De La Hoz Rodriguez, A., Di Martino, M., Garcia Septiem, J., Martin-Perez, E., Munoz De Nova, J. L., Calvo Espino, P., Guillamot Ruano, P., Colao Garcia, L., Diaz Perez, D., Esteban Agusti, E., Galindo Jara, P., Gutierrez Samaniego, M., Hernandez Bartolome, M. A., Serrano Gonzalez, J., Alonso Poza, A., Dieguez, B., Garcia-Conde, M., Hernandez-Garcia, M., Losada, M., Chiesa-Estomba, C. M., Gonzalez Garcia, J. A., Larruscain, E., Sistiaga-Suarez, J. A., Alvarez, E., Chavarrias, N., Frias, L., Garcia Pineda, V., Gegundez Simon, A., Gortazar, S., Gracia, M., Guevara, J., Hernandez Gutierrez, A., Loayza, A., Maria Dolores, D. T., Marti, C., Melendez, M., Moreno-Palacios, E., Perez, Y., Prieto Nieto, M. I., Ramos-Martin, P., Rubio-Perez, I., Saavedra, J., Sanchez-Mendez, J. I., Siegrist Ridruejo, J., Urbieta, A., Zapardiel, I., Cantalejo diaz, M., De Miguel Ardevines, M. D. C., Duque-Mallen, V., Gascon Ferrer, I., Gonzalez-Nicolas Trebol, M. T., Gracia-Roche, C., Herrero Lopez, M., Jariod Ferrer, U. M., Lanzon, A., Martinez German, A., Matute, M., Redondo, C., Sanchez Fuentes, N., Sanchez-Rubio, M., Santero-Ramirez, M. S., Saudi, S., Simon Sanz, M. V., Uson-Bouthelier, T., Blazquez Martin, A., Diez Alonso, M., Garcia Rico, E., Garcia-Loarte Gomez, E., Garcia-Moreno Nisa, F., Gutierrez Calvo, A., Hernandez, P., Lasa, I., Mendoza-Moreno, F., Morales Palacios, N., Ovejero Merino, E., Vera Mansilla, C., Acebes Garcia, F., Bailon, M., Bueno Canones, A. D., Choolani Bhojwani, E., Marcos-Santos, P., Miguel, T., Pacheco Sanchez, D., Perez-Saborido, B., Sanchez Gonzalez, J., Tejero-Pintor, F. J., Alconchel, F., Conesa, A., Gil Martinez, J., Gutierrez Fernandez, A. I., Lopez Abad, A., Nicolas-Lopez, T., Ramirez Romero, P., Roca Calvo, M. J., Rodrigues, K., Ruiz Manzanera, J. J., Soriano, A. I., Cano, A., Capitan-Morales, L., Cintas Catena, J., Gomez-Rosado, J., Oliva Mompean, F., Perez Sanchez, M. A., Rio Lafuente, F. D., Torres Arcos, C., Valdes-Hernandez, J., Cholewa, H., Domingo, S., Frasson, M., Lago, V., Marina Martin, T., Martinez Chicote, C., Sancho-Muriel, J., Landaluce-Olavarria, A., Lecumberri, D., Abad Gurumeta, A., Abad-Motos, A., Martinez-Hurtado, E., Ripolles-Melchor, J., Ruiz Escobar, A., Cuadrado-Garcia, A., Garcia-Sancho Tellez, L., Heras Aznar, J., Mate, P., Ortega Vazquez, I., Picardo, A. L., Rojo Lopez, J. A., Sanchez Cabezudo Noguera, F., Serralta De Colsa, D., Anchuelo Latorre, J., Cagigas Fernandez, C., Caina Ruiz, R., Gomez Ruiz, M., Hernanz, F., Jimeno Fraile, J., Martinez-Perez, P., Poch, C., Santarrufina Martinez, S., Valbuena Jabares, V., Moliner-Sanchez, C., Pingarron-Martin, L., Rey-Biel, J., Ruiz Martin, I., Blas Laina, J. L., Cros, B., Escartin, J., Garcia Egea, J., Nogues, A., Talal El-Abur, I., Yanez, C., Cagigal Ortega, E. P., Cervera, I., Diaz Pena, P., Elena, G. D. C. R., Enjuto, D., Fernandez Bernabe, P., Garces Garcia, R., Gonzalez, J., Hernandez, I., Herrera-Merino, N., Marqueta De Salas, M., Martinez Pascual, P., Perez Gonzalez, M., Ramos Bonilla, A., Rodriguez Gomez, L., Bescos, C., Blanco-Colino, R., Brana, I., Caimari, B., De Pablo Garcia-Cuenca, A., Duran-Valles, F., Espin-Basany, E., Giralt Lopez De Sagredo, J., Pamias, J., Pellino, G., Prat, N., Pujol Pina, R., Saez Barba, M., Arulanantham, A., Bandara, G. B. K., Jayarajah, U., Ravindrakumar, S., Rodrigo, V. S., Srishankar, S., Ali Karar, A. A., Elbe, P., Lindqvist, E. K., Taflin, H., Alga, A., Heinius, G., Nordberg, M., Pieniowski, E., Gkekas, I., Lofgren, N., Rutegard, M., Sund, M., Arigoni, M., Bernasconi, M., Christoforidis, D., Di Giuseppe, M., La Regina, D., Mongelli, F., Chevallay, M., Dwidar, O., Gialamas, E., Sauvain, M., Klenke, F., Kollar, A., Kurze, C., Adamina, M., Bachler, T., Crugnale, A. S., Giardini, M., Guglielmetti, L., Peros, G., Solimene, F., Aghayeva, A., Hamzaoglu, I., Sahin, I., Akaydin, E., Aliyeva, Z., Aytac, E., Baca, B., Dulgeroglu, O., Ozben, V., Ozmen, B. B., Uras, C., Arikan, A. E., Bilgin, I. A., Bozkirli, B., Ceyhan, G. O., Kara, H., Karahasanoglu, T., Celik, H., Meydanli, M. M., Akilli, H., Ayhan, A., Kuscu, E., Onan, M. A., Akgor, U., Dincer, H. A., Erol, T., Gultekin, M., Orhan, N., Ozgul, N., Salman, M. C., Soyak, B., Alhamed, A., Ergun, S., Ozcelik, M. F., Sanli, A. N., Uludag, S. S., Velidedeoglu, M., Zengin, A. K., Bozkurt, M. A., Kara, Y., Kocatas, A., Cimenoglu, B., Demirhan, R., Saracoglu, K., Azamat, I. F., Balik, E., Bugra, D., Giray, B., Kulle, C. B., Taskiran, C., Vatansever, D., Gozal, K., Guler, S. A., Koken, H., Tatar, O. C., Utkan, N. Z., Yildirim, A., Yuksel, E., Akin, E., Altintoprak, F., Bayhan, Z., Cakmak, G., Capoglu, R., Celebi, F., Demir, H., Dikicier, E., Firat, N., Gonullu, E., Kamburoglu, M. B., Kocer, B., Kucuk, I. F., Mantoglu, B., Colak, E., Kucuk, G. O., Uyanik, M. S., Goksoy, B., Bozkurt, E., Citgez, B., Mihmanli, M., Tanal, M., Yetkin, G., Akalin, M., Arican, C., Avci, E. K., Aydin, C., Demirli Atici, S., Emiroglu, M., Kaya, T., Kebabci, E., Kilinc, G., Kirmizi, Y., Ogucu, H., Salimoglu, S., Sert, I., Tugmen, C., Tuncer, K., Uslu, G., Yesilyurt, D., Karaman, E., Kolusari, A., Yildiz, A., Benson, O., Lule, H., Agilinko, J., Ahmeidat, A., Barabasz, M., Bekheit, M., Cheung, L. K., Colloc, T., Cymes, W., Elhusseini, M., Gradinariu, G., Hannah, A., Kamera, B. S., Mignot, G., Shaikh, S., Sharma, P., Abu-Nayla, I., Agrawal, A., Al-Mohammad, A., Ali, S., Ashcroft, J., Azizi, A., Baker, O., Balakrishnan, A., Byrne, M., Colquhoun, A., Cotter, A., Coughlin, P., Davies, R. J., Durrani, A., Elshaer, M., Fordington, S., Forouhi, P., Georgiades, F., Grimes, H., Habeeb, A., Hudson, V., Hutchinson, P., Irune, E., Jah, A., Khan, D. Z., Kyriacou, H., Lamb, B., Liau, S., Luke, L., Mahmoud, R., Mannion, R., Masterson, L., Mitrofan, C. G., Mohan, M., Morris, A., Murphy, S., O'Neill, R., Price, S., Pushpa-Rajah, J., Raby-Smith, W., Ramzi, J., Rooney, S., Santarius, T., Singh, A., Tan, X. S., Townson, A., Tweedle, E., Walker, C., Waseem, S., Yordanov, S., Jones, T., Kattakayam, A., Loh, C., Lunevicius, R., Pringle, S., Schache, A., Sheel, A., Rossborough, C., Angelou, D., Choynowski, M., Mcaree, B., Mccanny, A., Neely, D., Tutoveanu, G., Ahad, S., De La Cruz Monroy, M. F. I., Mosley, F., Oktseloglou, V., Alanbuki, A., Patel, M., Shabana, A., Perera, E., Raveendran, D., Ravi-Shankar, K., Thiruchelvam, J., Arrowsmith, L., Campbell, W., Grove, T., Kontovounisios, C., Warren, O., Rolland, P., Aggarwal, A., Brown, S., Jelley, C., Neal, N., Clifford, R., Eardley, N., Krishnan, E., Manu, N., Martin, E., Roy Mahapatra, S., Serevina, O. L., Smith, C., Vimalachandran, D., Bordenave, M., Houston, R., Putnam, G., Robson, A., Tustin, H., Emslie, K., Labib, P. L., Marchbank, A., Miller, D., Minto, G., Natale, J., Nwinee, H., Panahi, P., Rogers, L., Abubakar, A., Akhter Rahman, M. M., Ko, K. Y. K., O'Brien, H., Sasapu, K., Woodun, H., Inglis, R., Ng, H. J., De Gea Rico, A., Ghazali, N., Lambert, J., Markose, G., Math, S., Sarantitis, I., Shrestha, D., Sultana, A., Taggarsi, M., Timbrell, S., Vaz, O. P., Vitone, L., Day, A., Dent, H., Fahim, M., Waheed, S., Hunt, A., Laskar, N., Gupta, A., Steinke, J., Thrumurthy, S., Massie, E., Mcgivern, K., Rutherford, D., Wilson, M., Hardie, J., Kazzaz, S., Handa, S., Kaushal, M., Kler, A., Patel, P., Redfern, J., Tezas, S., Aawsaj, Y., Amonkar, S., Blackwell, L., Blake, D., Carter, J., Emerson, H., Fisher, A., Katory, M., Korompelis, P., Mccormick, W., Mustafa, A., Pearce, L., Ratnavelu, N., Reehal, R., Kretzmer, L., Lalou, L., Manku, B., Parwaiz, I., Stafford, J., Abdelkarim, M., Asqalan, A., Gala, T., Ibrahim, S., Maw, A., Mithany, R., Morgan, R., Sundaram Venkatesan, G., Ang, K., Caruana, E. J., Chowdhry, M. F., Mohammad, A., Nakas, A., Rathinam, S., Boal, M., Brown, O., Dwerryhouse, S., Higgs, S., Vallance, A., Boyd, E., Irvine, V., Kirk, A., Bakolas, G., Boulton, A., Chandock, A., Khan, T., Kumar, M., Agoston, P., Bille, A., Challacombe, B., Fraser, S., Harrison-Phipps, K., King, J., Mehra, G., Mills, L., Najdy, M., Nath, R., Okiror, L., Pilling, J., Rizzo, V., Routledge, T., Sayasneh, A., Stroman, L., Wali, A., Fehervari, M., Fotopoulou, C., Habib, N., Hamrang-Yousefi, S., Jawad, Z., Jiao, L., Pai, M., Ploski, J., Rajagopal, P., Saso, S., Sodergren, M., Spalding, D., Laws, S., Hardie, C., Mcnaught, C., Alam, R., Budacan, A., Cahill, J., Kalkat, M., Karandikar, S., Kenyon, L., Naumann, D., Patel, A., Ayorinde, J., Chase, T., Cuming, T., Ghanbari, A., Humphreys, L., Tayeh, S., Aboelkassem Ibrahim, A., Bichoo, R., Cao, H., Chai, A. K. W., Choudhury, J., Evans, C., Fitzjohn, H., Ikram, H., Langstroth, M., Loubani, M., Mcmillan, A., Nazir, S., Qadri, S. S. A., Robinson, A., Ross, E., Sehgal, T., Wilkins, A., Dixon, J., Dunning, J., Freystaetter, K., Jha, M., Lester, S., Madhavan, A., Thulasiraman, S. V., Viswanath, Y., Curl-Roper, T., Delimpalta, C., Liao, C. C. L., Velchuru, V., Westwood, E., Belcher, E., Bond-Smith, G., Chidambaram, S., Di Chiara, F., Fasanmade, K., Fraser, L., Fu, H., Ganau, M., Gore, S., Graystone, J., Jeyaretna, D., Khatkar, H., Lami, M., Maher, M., Mastoridis, S., Mihai, R., Piper, R., Prabhu, S., Risk, O. B. F., Selbong, U., Shah, K., Smillie, R., Soleymani majd, H., Sravanam, S., Stavroulias, D., Tebala, G. D., Vatish, M., Verberne, C., Wallwork, K., Winter, S., Bhatti, M. 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Moir, J, Pandanaboyana, S, Powell, J, Rai, B, Roy, C, Sachdeva, A, Saleh, C, Tingle, S, Williams, T, Manickavasagam, J, Mcdonald, C, Mcgrath, N, Mcsorley, N, Ragupathy, K, Ramsay, L, Solth, A, Kakisi, O, Seebah, K, Shaikh, I, Sreedharan, L, Youssef, M, Shah, J, Ameerally, P, Mclarty, N, Mills, S, Shenfine, A, Sahnan, K, Abu, J, Addae-Boateng, E, Bratt, D, Brock, L, Burnside, N, Cadwell-Sneath, S, Gajjar, K, Gan, C, Grundy, C, Hallam, K, Hassell, K, Hawari, M, Joshi, A, Khout, H, Konstantinidi, K, Lee, Rxn, Nunns, D, Schiemer, R, Walton, T, Weaver, H, Whisker, L, Williamson, K, Mcveigh, J, Myatt, R, A Williams, M, Kaur, R, Leung, E, Sundar, S, Michel, M, Patil, S, Ravindran, S, Sarveswaran, J, Scott, L, Edmond, M, King, E, Almond, M, Bhangu, A, Breik, O, D Cato, L, Desai, A, Ford, S, Griffiths, E, Idle, M, Kamal, M, Kisiel, A, Kulkarni, R, Mak, Jkc, Martin, T, Nankivell, P, Parente, A, Parmar, S, M Pathanki, A, Phelan, L, Praveen, P, Saeed, S, Sharma, N, Singh, J, Tirotta, F, Vijayan, D, Geddes, A, Mccaul, J, Mcmahon, J, H Khan, A, Khan, F, Mansuri, A, Mukherjee, S, Sarigul, M, Singh, S, L Tan, K, Woodham, A, Adiamah, A, Brewer, H, Chowdhury, A, Evans, J, Humes, D, Jackman, J, Koh, A, Lewis-Lloyd, C, Oyende, O, Reilly, J, Worku, D, Cool, P, Cribb, G, Shepherd, K, Bisset, C, Moug, S, Elson, N, Faulkner, G, Saleh, P, Underwood, C, Brixton, G, Findlay, L, Klatte, T, Majkowska, A, Manson, J, Potter, R, Bhalla, A, Chia, Z, Daliya, P, Goyal, A, Grimley, E, Hamad, A, Kumar, A, L Malcolm, F, Theophilidou, E, Bowden, J, Campain, N, Daniels, I, Fowler, G, John, J, Massey, L, Mcdermott, F, Mcgrath, J, Mclennan, A, Ng, M, Pascoe, J, Rajaretnam, N, Bulathsinhala, S, Davidson, B, Fusai, G, Hidalgo Salinas, C, Machairas, N, Pissanou, T, M Pollok, J, A Raptis, D, Soggiu, F, Tzerbinis, H, E Xyda, S, Beamish, A, Davies, E, Foulkes, R, Magowan, D, Nassa, H, Ooi, R, Price, C, Smith, L, Solari, F, Tang, A, Williams, G, Al-Tamimi, Y, Bacon, A, Beasley, N, Chew, D, Crank, M, Ilenkovan, N, Macdonald, M, Narice, B, Rominiyi, O, Thompson, A, Varley, I, Drake, T, Harrison, E, Linder, G, Mayes, J, Mcgregor, R, Skipworth, R, Zamvar, V, Hawkin, P, Raymond, T, Ryska, O, Baron, R, Dunne, D, Gahunia, S, Halloran, C, Howes, N, Mckinney, R, Mcnicol, F, Russ, J, Szatmary, P, R Tan, J, Thomas, A, Whelan, P, Anzak, A, Banerjee, A, Fuwa, O, Hughes, F, D Jayasinghe, J, Knowles, C, Kocher, H, Leal Silva, I, S Ledesma, F, Minicozzi, A, Navaratne, L, Rahman, R, Ramamoorthy, R, Sohrabi, C, Thaha, M, Thakur, B, Venn, M, Yip, V, Baumber, R, Parry, J, Evans, S, Jeys, L, Morris, G, Parry, M, Ahmadi, N, Aresu, G, M Barrett-Brown, Z, S Coonar, A, Durio Yates, H, Gearon, D, Hogan, J, King, M, Peryt, A, S Pradeep, I, Adishesh, M, Atherton, R, Baxter, K, Brocklehurst, M, Chaudhury, M, Krishnamohan, N, Mcaleer, J, Owens, G, Parkin, E, Patkar, P, Phang, I, Aladeojebi, A, Ali, M, Barmayehvar, B, Gaunt, A, Gowda, M, Halliday, E, Kitchen, M, Mansour, F, Thomas, M, Zakai, D, Abbassi-Ghadi, N, Assalaarachchi, H, Currie, A, Flavin, M, Frampton, A, Hague, M, Hammer, C, Hopper, J, Horsnell, J, Humphries, S, Kamocka, A, K Madhuri, T, Preston, S, Singh, P, Stebbing, J, Tailor, A, Walker, D, Aljanadi, F, Jones, M, Mhandu, P, O'Donnell, C, Turkington, R, Al-Ishaq, Z, Bhasin, S, S Bodla, A, Burahee, A, Crichton, A, Fossett, R, Pigadas, N, Pickford, S, Rahman, E, Snee, D, Vidya, R, Yassin, N, Fountain, D, T Hasan, M, Karabatsou, K, Laurente, R, Pathmanaban, O, Al-Mukhtar, A, Edwards, J, Giblin, A, Kelty, C, Lee, M, Lye, G, Newman, T, Sharkey, A, Steele, C, Sureshkumar Shah, N, Whitehall, E, Athwal, R, Baker, A, Jones, L, Konstantinou, C, Ramcharan, S, Vatish, J, Wilkin, R, Ethunandan, M, K Sekhon, G, Shields, H, Singh, R, Wensley, F, Lawday, S, Lyons, A, Abbott, T, Anwar, S, Ghufoor, K, Chung, E, Hagger, R, Hainsworth, A, Karim, A, Owen, H, Ramwell, A, Williams, K, Baker, C, Davies, A, Gossage, J, Kelly, M, Knight, W, Hall, J, Harris, G, James, G, Kang, C, J Lin, D, D Rajgor, A, Royle, T, Scurrah, R, Steel, B, J Watson, L, Choi, D, Hutchison, R, Jain, A, Luoma, V, Marcus, H, May, R, Menon, A, Pramodana, B, Webber, L, A Aneke, I, Asaad, P, Brown, B, Collis, J, Duff, S, Khan, A, Moura, F, Wadham, B, Warburton, H, Elmoslemany, T, Jenkinson, M, Millward, C, Zakaria, R, Mccluney, S, Parmar, C, Shah, S, Allison, J, S Babar, M, Collard, B, Goodrum, S, Lau, K, Scott, R, Thomas, E, Whitmore, H, Balasubramaniam, D, Jayasankar, B, Kapoor, S, Ramachandran, A, Elhamshary, A, Imam, Smb, Kapriniotis, K, Kasivisvanathan, V, Lindsay, J, Rakhshani-Moghadam, S, Beech, N, Chand, M, Green, L, Kalavrezos, N, Kiconco, H, Mcewen, R, Schilling, C, Sinha, D, Pereca, J, Chopra, S, Egbeare, D, Thomas, R, Combellack, T, Jones, Sef, Kornaszewska, M, Mohammed, M, Sharma, A, Tahhan, G, Valtzoglou, V, Williams, J, Eskander, P, Gash, K, Gourbault, L, Hanna, M, Maccabe, T, Newton, C, Olivier, J, Rozwadowski, S, Teh, E, West, D, Al-Omishy, H, Baig, M, Bates, H, Di Taranto, G, Dickson, K, Dunne, N, Gill, C, Howe, D, Jeevan, D, Khajuria, A, Martin-Ucar AMcEvoy, K, Naredla, P, Robertson, S, Sait, M, R Sarma, D, Shanbhag, S, Shortland, T, Simmonds, S, Skillman, J, Tewari, N, Walton, G, A Akhtar, M, Brunt, A, Mcintyre, J, Milne, K, M Rashid, M, Sgro, A, E Stewart, K, Turnbull, A, Aguilar Gonzalez, M, Talukder, S, Boyle, C, Fernando, D, Gallagher, K, Laird, A, Tham, D, Bath, M, Patki, P, Tanabalan, C, Arif, T, Magee, C, Nambirajan, T, Powell, S, Vinayagam, R, Flindall, I, Hanson, A, Mahendran, V, Green, S, Lim, M, Macdonald, L, Miu, V, Onos, L, Sheridan, K, Young, R, Alam, F, Griffiths, O, Houlden, C, Jones, R, S Kolli, V, K Lala, A, Leeson, S, Peevor, R, Seymour, Z, Chen, L, Henderson, E, Loehrer, A, Brown, K, Fleming, D, Heron, C, Hill, C, Kay, H, Leede, E, Mcelhinney, K, Olson, K, C Osterberg, E, Riley, C, Srikanth, P, Thornhill, M, Blazer, D, Dilalla, G, S Hwang, E, Lee, W, Lidsky, M, Plichta, J, Rosenberger, L, Scheri, R, Turnage, K, Visgauss, J, Zani, S, Farma, J, Clark, J, Kwon, D, Etchill, E, E Gabre-Kidan AJenny, H, Kent, A, Ladd, M, Long, C, Malapati, H, Margalit, A, Rapaport, S, Rose, J, Stevens, K, Tsai, L, Vervoort, D, Yesantharao, P, Dehal, A, Klaristenfeld, D, Huynh, K, Brown, L, Ganly, I, Mullinax, J, Gusani, N, Hazelton, J, Maines, J, S Oh, J, Ssentongo, A, Ssentongo, P, Azam, M, Choudhry, A, Marx, W, Fleming, J, Fuson, A, Gigliotti, J, Ovaitt, A, Ying, Y, K Abel, M, Andaya, V, Bigay, K, A Boeck, M, Chern, H, Corvera, C, El-Sayed, I, Glencer, A, Ha, P, Hamilton, Bc, Heaton, C, Hirose, K, M Jablons, D, Kirkwood, K, Z Kornblith, L, R Kratz, J, Lee, R, N Miller, P, Nakakura, E, Nunez-Garcia, B, O'Donnell, R, Ozgediz, D, Park, P, Robinson, B, Sarin, A, Sheu, B, Varma, M, Wai, K, Wustrack, R, J Xu, M, Beswick, D, Goddard, J, Manor, J, Song, J, Fullmer, T, Gaskill, C, Gross, N, Kiong, K, L Roland, C, N Zafar, S, Abdallah, M, Abouassi, A, Almasri, M, Kulkarni, G, Marwan, H, Mehdi, M, Aoun, S, S Ban, V, H Batjer, H, Caruso, J, Abbott, D, Acher, A, Aiken, T, Barrett, J, Foley, E, Schwartz, P, Hawkins, A, Maiga, A, Laufer, J, Scasso, S, Surgery, Graduate School, Glasbey, J, Nepogodiev, D, Simoes, J, Omar, O, Li, E, Abou Chaar, M, Chaudhry, D, Videria, J, Gujjuri, R, Kaafarani, H, Minaya-Bravo, A, Mckay, S, Roberts, K, Miguel-Mendez, C, Smart, N, Stewart, G, Institut de Recherche sur les Maladies Virales et Hépatiques (IVH), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire des sciences de l'ingénieur, de l'informatique et de l'imagerie (ICube), École Nationale du Génie de l'Eau et de l'Environnement de Strasbourg (ENGEES)-Université de Strasbourg (UNISTRA)-Institut National des Sciences Appliquées - Strasbourg (INSA Strasbourg), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Les Hôpitaux Universitaires de Strasbourg (HUS)-Centre National de la Recherche Scientifique (CNRS)-Matériaux et Nanosciences Grand-Est (MNGE), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Réseau nanophotonique et optique, Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), COVIDSurg Collaborative, Kolias, Angelos [0000-0003-3992-0587], Stewart, Grant [0000-0003-3188-9140], Apollo - University of Cambridge Repository, Glasbey JC, Nepogodiev D, Simoes JFF, Omar O, Li E, Venn ML, Pgdme, Abou Chaar MK, Capizzi V, Chaudhry D, Desai A, Edwards JG, Evans JP, Fiore M, Videria JF, Ford SJ, Ganly I, Griffiths EA, Gujjuri RR, Kolias AG, Kaafarani HMA, Minaya-Bravo A, McKay SC, Mohan HM, Roberts KJ, San Miguel-Méndez C, Pockney P, Shaw R, Smart NJ, Stewart GD, Sundar Mrcog S, Vidya R, Bhangu AA, COVIDSurg Collaborative, Palmerini Emanuela, Frisoni Tommaso, Donati Davide, A Belvedere, P Bernante, P Bertoglio, S Boussedra, E Brunocilla, R Cipriani, G Cisternino, E De Crescenzo, P De Iaco, G Dondi, F Frio, E Jovine, F Mineo Bianchi, J Neri, D Parlanti, A M Perrone, A P Pezzuto, M Pignatti, V Pinto, G Poggioli, M Ravaioli, M Rottoli, R Schiavina, M Serenari, M Serra, P Solli, M Taffurelli, M Tanzanu, M Tesei, T Violante, S Zanotti, V Tonini, M Cervellera, A Gori, L Sartarelli, Glasbey, James C, Simoes, Joana F F, Venn, Mary L, Pgdme, null, Abou Chaar, Mohammad K, Edwards, Jonathan G, Evans, Jonathan P, Videria, Jose Flavio, Ford, Samuel J, Griffiths, Ewen A, Gujjuri, Rohan R, Kolias, Angelos G, Kaafarani, Haytham M A, McKay, Siobhan C, Mohan, Helen M, Roberts, Keith J, Smart, Neil J, Stewart, Grant D, Sundar Mrcog, Sudha, and Bhangu, Aneel A, Toia, F
Subjects: Male, Cancer Research, Outcome Assessment, International Cooperation, Settore MED/18 - CHIRURGIA GENERALE, Settore MED/19 - Chirurgia Plastica, 030230 surgery, Aged, Aged, 80 and over, COVID-19, Cohort Studies, Critical Care, Elective Surgical Procedures, Epidemics, Female, Humans, Logistic Models, Middle Aged, Neoplasms, Outcome Assessment, Health Care, Postoperative Complications, SARS-CoV-2, 0302 clinical medicine, Operating theater, cohort studies, Health care, middle aged, 80 and over, Medicine, Lung, Cancer, COVID-19/epidemiology, OUTCOMES, Manchester Cancer Research Centre, Pulmonary Complication, ORIGINAL REPORTS, aged, Oncology, 030220 oncology & carcinogenesis, Pneumonia & Influenza, Patient Safety, Elective Surgical Procedure, Life Sciences & Biomedicine, 6.4 Surgery, Cohort study, Human, medicine.medical_specialty, elective surgical procedures/methods, Logistic Model, Health Care, Clinical Sciences, Oncology and Carcinogenesis, Epidemic, [SDV.CAN]Life Sciences [q-bio]/Cancer, cancer surgery, SARS-CoV-2 pandemic, epidemics, COVIDSurg Collaborative, NO, outcome assessment, health care/methods, 03 medical and health sciences, male, Settore MED/28 - Malattie Odontostomatologiche, Clinical Research, 1112 Oncology and Carcinogenesis, Oncology & Carcinogenesis, Elective surgery, Elective Cancer Surgery in SARS-CoV-2, Elective Cancer Surgery in COVID-19, covid 19, sars-cov-2, Science & Technology, business.industry, Prevention, ResearchInstitutes_Networks_Beacons/mcrc, Evaluation of treatments and therapeutic interventions, 1103 Clinical Sciences, Pneumonia, Odds ratio, medicine.disease, Good Health and Well Being, neoplasms/surgery, critical care/methods, Emergency medicine, postoperative complications/prevention & control, Neoplasm, Postoperative Complication, Cohort Studie, business, aged, 80 and over, SARS-CoV-2/physiology, logistic models
Abstract: PURPOSE As cancer surgery restarts after the first COVID-19 wave, health care providers urgently require data to determine where elective surgery is best performed. This study aimed to determine whether COVID-19–free surgical pathways were associated with lower postoperative pulmonary complication rates compared with hospitals with no defined pathway. PATIENTS AND METHODS This international, multicenter cohort study included patients who underwent elective surgery for 10 solid cancer types without preoperative suspicion of SARS-CoV-2. Participating hospitals included patients from local emergence of SARS-CoV-2 until April 19, 2020. At the time of surgery, hospitals were defined as having a COVID-19–free surgical pathway (complete segregation of the operating theater, critical care, and inpatient ward areas) or no defined pathway (incomplete or no segregation, areas shared with patients with COVID-19). The primary outcome was 30-day postoperative pulmonary complications (pneumonia, acute respiratory distress syndrome, unexpected ventilation). RESULTS Of 9,171 patients from 447 hospitals in 55 countries, 2,481 were operated on in COVID-19–free surgical pathways. Patients who underwent surgery within COVID-19–free surgical pathways were younger with fewer comorbidities than those in hospitals with no defined pathway but with similar proportions of major surgery. After adjustment, pulmonary complication rates were lower with COVID-19–free surgical pathways (2.2% v 4.9%; adjusted odds ratio [aOR], 0.62; 95% CI, 0.44 to 0.86). This was consistent in sensitivity analyses for low-risk patients (American Society of Anesthesiologists grade 1/2), propensity score–matched models, and patients with negative SARS-CoV-2 preoperative tests. The postoperative SARS-CoV-2 infection rate was also lower in COVID-19–free surgical pathways (2.1% v 3.6%; aOR, 0.53; 95% CI, 0.36 to 0.76). CONCLUSION Within available resources, dedicated COVID-19–free surgical pathways should be established to provide safe elective cancer surgery during current and before future SARS-CoV-2 outbreaks. Copyright © 2020 American Society of Clinical Oncology. All rights reserved. Bowel and Cancer Research; Sarcoma UK; Yorkshire Cancer Research; European Society of Coloproctology; National Institute for Health Research: 16.136.79; Bowel Disease Research Foundation; Urology Foundation Supported by a National Institute for Health Research (NIHR) Global Health Research Unit grant (NIHR 16.136.79) using UK aid from the UK government to support global health research, Association of Coloproctology of Great Britain and Ireland, Bowel & Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, The Urology Foundation, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research. The funders had no role in the study design; data collection, analysis, and interpretation; or writing of this report. The views expressed are those of the authors and not necessarily those of the National Health Service, NIHR, or UK Department of Health and Social Care.
Published: 2021

7. Акромегалія: настанови з клінічної практики ендокринологічного товариства (Частина 1)

Author: Катцнельсон, Лоренс; Stanford University School of Medicine, Stanford, California 94305, Лос мол., Едвард Р.; Brigham and Women’s Hospital (E.R.L), Boston, Massachusetts 02115, Мелмед, Шломо; Cedars-Sinai Medical Center (S.M.), Los Angeles, California 90048, Моліч, Марк Е.; Northwestern University Feinberg School of Medicine (M.E.M), Chicago, Illinois 60611, Мурад, Мохаммад Гассан; Mayo Clinic (M.H.M.), Rochester, Minnesota 55905, Утц, Андреа; Vanderbilt University (A.U.), Nashville, Tennessee 37232, Васс, Джон А.Х.; Oxford Centre Diabetes, Endocrinology, and Metabolism (J.A.H.W.), Churchill Hospital, Oxfordshire OX3 7RP, Катцнельсон, Лоренс; Stanford University School of Medicine, Stanford, California 94305, Лос мол., Едвард Р.; Brigham and Women’s Hospital (E.R.L), Boston, Massachusetts 02115, Мелмед, Шломо; Cedars-Sinai Medical Center (S.M.), Los Angeles, California 90048, Моліч, Марк Е.; Northwestern University Feinberg School of Medicine (M.E.M), Chicago, Illinois 60611, Мурад, Мохаммад Гассан; Mayo Clinic (M.H.M.), Rochester, Minnesota 55905, Утц, Андреа; Vanderbilt University (A.U.), Nashville, Tennessee 37232, and Васс, Джон А.Х.; Oxford Centre Diabetes, Endocrinology, and Metabolism (J.A.H.W.), Churchill Hospital, Oxfordshire OX3 7RP
Abstract: Мета. Мета полягала в тому, щоб сформувати настанови з клінічної практики діагностики і лікування акромегалії.Автори. До складу робочої групи ввійшли голова, обраний Підкомітетом з клінічних настанов (ПКН) Ендокринологічного товариства, п’ять експертів у галузі та методолог. Автори не отримували жодного корпоративного фінансування або винагороди. Розробка цих настанов частково фінансувалася Європейським товариством ендокринологів.Доказові дані. Ці настанови, засновані на принципах доказової медицини, розроблено з використанням системи розробки, оцінки й експертизи рекомендацій (Grading of Recommendations, Assessment, Development and Evaluation) (GRADE), яка характеризує як ступінь переконливості рекомендацій, так і якість доказових даних. Робоча група проаналізувала основні доказові дані й ініціювала підготовку двох додаткових систематичних оглядів.Процес досягнення консенсусу. Процес досягнення консенсусу включав одне засідання групи, кілька телеконференцій та листування електронною поштою. Проекти настанов переглянуто комітетами й членами Ендокринологічного товариства і Європейського товариства ендокринологів.Висновки. Використовуючи підхід, заснований на принципах доказової медицини, ці настанови розглядають важливі клінічні питання, що стосуються обстеження та ведення пацієнтів з акромегалією, в тому числі належних біохімічних аналізів, розробки алгоритмів лікування (застосування медикаментозної монотерапії або комбінованої терапії) і ведення пацієнтів під час вагітності. (J Clin Endocrinol Metab 99: 3933-3951, 2014, DOI: http://dx.doi.org/10.1210/jc.2014-2700)
Published: 2016

8. Unknown ESUR cases 2004

Author: Department of Radiology, University of Michigan Hospital, Room B1D502G, 1500 East Medical Center Drive, Ann Arbor, Michigan, 48109-0030, USA, The Churchill Hospital, Oxford University, Oxford, 0X3 7LJ, England, United Kingdom, Ann Arbor, Ellis, James H., Cohan, R. H., Cowan, N. C., Department of Radiology, University of Michigan Hospital, Room B1D502G, 1500 East Medical Center Drive, Ann Arbor, Michigan, 48109-0030, USA, The Churchill Hospital, Oxford University, Oxford, 0X3 7LJ, England, United Kingdom, Ann Arbor, Ellis, James H., Cohan, R. H., and Cowan, N. C.
Abstract: The authors present 14 cases from the film interpretation session of the 11th annual meeting of the European Society of Urogenital Radiology presented in September, 2004. The cases demonstrate the imaging findings, differential diagnoses, and clinical relevance of a wide variety of genitourinary tract diseases. The cases include examples of benign and malignant urinary tract neoplasms, inflammatory processes, vascular diseases, traumatic injuries, and congenital anomalies.
Published: 2006

9. Lymphocytic Interstitial Pneumonitis in Common Variable Immunodeficiency Disorders: A Comparison with HIV

Author: Arnold, Dilani, Fergus, Gleeson, Chapel, Helen, Davies, Robert, and Misbah, Siraj
Published: 2007
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10. Mutational spectrum in a worldwide study of 29,700 families with BRCA1 or BRCA2 mutations

Author: [ 1 ] Harvard TH Chan Sch Publ Hlth, Boston, MA USA Show more [ 2 ] Chaim Sheba Med Ctr, Inst Human Genet, Susanne Levy Gertner Oncogenet Unit, IL-52621 Ramat Gan, Israel Show more [ 3 ] Tel Aviv Univ, Sackler Sch Med, Tel Aviv, Israel Show more [ 4 ] German Canc Res Ctr, Mol Genet Breast Canc, Heidelberg, Germany Show more [ 5 ] Univ Chicago, Ctr Clin Canc Genet & Global Hlth, Chicago, IL 60637 USA [ 6 ] Hong Kong Sanat & Hosp, Canc Genet Ctr, Hong Kong Hereditary Breast Canc Family Registry, Hong Kong, Hong Kong, Peoples R China Show more [ 7 ] Natl Inst Oncol, Dept Mol Genet, Budapest, Hungary Show more [ 8 ] Univ Buenos Aires, CONICET, Fac Med, INBIOMED, Buenos Aires, DF, Argentina Show more [ 9 ] CEMIC, Dept Clin Chem, Med Direct, Buenos Aires, DF, Argentina [ 10 ] Sime Darby Med Ctr, Canc Res Initiat Fdn, Subang Jaya, Malaysia Show more [ 11 ] Odense Univ Hosp, Dept Clin Genet, Odense, Denmark Show more [ 12 ] City Hope Canc Ctr, Div Clin Canc Genom, Duarte, CA USA [ 13 ] Hong Kong Sanat & Hosp, Dept Pathol, Div Mol Pathol, Happy Valley, Hong Kong, Peoples R China [ 14 ] Dept Lab Med & Pathol, Rochester, MN USA Show more [ 15 ] Univ Utah, Sch Med, Dept Dermatol, Salt Lake City, UT USA Show more [ 16 ] Barretos Canc Hosp, Mol Oncol Res Ctr, Sao Paulo, Brazil Show more [ 17 ] Seoul Natl Univ, Coll Med, Dept Prevent Med, Seoul, South Korea Show more [ 18 ] Seoul Natl Univ, Grad Sch, Dept Biomed Sci, Seoul, South Korea Show more [ 19 ] Seoul Natl Univ, Canc Res Ctr, Seoul, South Korea Show more [ 20 ] Pontificia Univ Javeriana, Inst Human Genet, Bogota, Colombia Show more [ 21 ] Univ Pretoria, Dept Genet, Canc Genet Lab, Pretoria, South Africa Show more [ 22 ] Univ Cambridge, Dept Publ Hlth & Primary Care, Ctr Canc Genet Epidemiol, Cambridge, England Show more [ 23 ] QIMR Berghofer Med Res Inst, Genet & Computat Biol Dept, Brisbane, Qld, Australia [ 24 ] Acad Med Ctr, Dept Clin Genet, Amsterdam, Netherlands [ 25 ] City Hope Clin Canc Genom Community Res Network, D, Harvard TH Chan School of Public Health and Dana Farber Cancer Institute; Boston USA, The Susanne Levy Gertner Oncogenetics Unit; Institute of Human Genetics; Chaim Sheba Medical Center, Ramat Gan 52621, and the Sackler School of Medicine; Tel-Aviv University; Tel-Aviv Israel, Molecular Genetics of Breast Cancer; German Cancer Research Center (DKFZ); Heidelberg Germany, Center for Clinical Cancer Genetics and Global Health; University of Chicago; Chicago USA, The Hong Kong Hereditary Breast Cancer Family Registry; Cancer Genetics Center; Hong Kong Sanatorium and Hospital; Hong Kong China, Department of Molecular Genetics; National Institute of Oncology; Budapest Hungary, INBIOMED; Faculty of Medicine, University of Buenos Aires/CONICET and CEMIC, Department of Clinical Chemistry; Medical Direction; Buenos Aires Argentina, Cancer Research Initiatives Foundation; Sime Darby Medical Centre; Subang Jaya Malaysia, Department of Clinical Genetics; Odense University Hospital; Odense Denmark, Center for Familial Breast and Ovarian Cancer, Center for Integrated Oncology (CIO), Medical Faculty; University Hospital Cologne; Cologne Germany, Clinical Genetics Services; Dept. of Medicine; Memorial Sloan-Kettering Cancer Center; New York USA, Division of Gynecologic Oncology; North Shore University Health System; University of Chicago; Evanston USA, All Wales Medical Genetics Services; University Hospital of Wales; Cardiff UK, Department of Gynecology; Vilnius University Hospital Santariskiu Clinics; Centre of Woman's Health and pathology; Vilnius Lithuania, Center for Genomic Medicine; Rigshospitalet; University of Copenhagen; Copenhagen Denmark, Clinical Cancer Genetics Program; Division of Human Genetics; Department of Internal Medicine; The Comprehensive Cancer Center; The Ohio State University; Columbus USA, Cancer Genetics Laboratory, Department of Genetics; University of Pretoria; South Africa, Department of Genetics and Pathology; Pomeranian Medical University; Szczecin Poland, Department of Medicine, Abramson Cancer Center; Perelman School of Medicine at the University of Pennsylvania; Philadelphia USA, Department of Internal Medicine; Division of Oncology; University of Kansas Medical Center; Westwood USA, North East Thames Regional Genetics Service; Great Ormond Street Hospital for Children NHS Trust; London UK, Genomics Center; Centre Hospitalier Universitaire de Québec Research Center and Laval University; Quebec City Canada, Dept of OB/GYN and Comprehensive Cancer Center; Medical University of Vienna; Vienna Austria, Department of Clinical Genetics; Aarhus University Hospital; Aarhus N Denmark, Division of Clinical Cancer Genomics; City of Hope Cancer Center; California USA, Medical Genetics Unit; University of London; St George's UK, Département Oncologie Génétique; Prévention et Dépistage; Institut Paoli-Calmettes; Marseille Medical School-AM University; Marseille France, Department of Breast Medical Oncology and Clinical Cancer Genetics Program; University Of Texas MD Anderson Cancer Center; Houston USA, Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care; University of Cambridge; Cambridge UK, Department of Population Sciences; Beckman Research Institute of City of Hope; Duarte USA, Institute of Cell and Molecular Pathology; Hannover Medical School; Hannover Germany, Institute of Human Genetics; University Hospital Heidelberg; Heidelberg Germany, National Human Genome Research Institute; National Institutes of Health; Bethesda USA, Dept of OB/GYN, Comprehensive Cancer Center; Medical University of Vienna; Vienna Austria, Department of Genetics; Portuguese Oncology Institute of Porto (IPO Porto); Porto Portugal, Department of Epidemiology; Columbia University; New York USA, Genetic Counseling Unit; Hereditary Cancer Program; IDIBELL (Bellvitge Biomedical Research Institute); Catalan Institute of Oncology, CIBERONC; Gran Via de l'Hospitalet; Barcelona Spain, Department of Health Sciences Research; Mayo Clinic; Rochester USA, Genetics and Computational Biology Department; QIMR Berghofer Medical Research Institute; Brisbane Australia, Department of Medicine; Magee-Womens Hospital; University of Pittsburgh School of Medicine; Pittsburgh USA, Program in Cancer Genetics; Departments of Human Genetics and Oncology; McGill University; Montreal Canada, Immunology and Molecular Oncology Unit; Veneto Institute of Oncology IOV - IRCCS; Padua Italy, Division of Human Genetics; Departments of Internal Medicine and Cancer Biology and Genetics; Comprehensive Cancer Center; The Ohio State University; Columbus USA, Clinical Genetics Research Laboratory, Dept. of Medicine; Memorial Sloan-Kettering Cancer Center; New York USA, Parkville Familial Cancer Centre; Royal Melbourne Hospital; Melbourne Australia, Department of Medical Oncology; Beth Israel Deaconess Medical Center; Massachusetts USA, Department of Clinical Genetics; Leiden University Medical Center; Leiden The Netherlands, Department of Genetics; University Medical Center; Groningen University; Groningen The Netherlands, Family Cancer Clinic; Netherlands Cancer Institute; Amsterdam The Netherlands, Department of Medical Genetics; University Medical Center; Utrecht The Netherlands, Center for Medical Genetics; Ghent University; Gent Belgium, Unit of Hereditary Cancer; Department of Epidemiology, Prevention and Special Functions; IRCCS (Istituto Di Ricovero e Cura a Carattere Scientifico) AOU San Martino - IST Istituto Nazionale per la Ricerca sul Cancro; Genoa Italy, Institute of Human Genetics; Campus Virchov Klinikum; Berlin Germany, Fundación Pública Galega de Medicina Xenómica-SERGAS, Grupo de Medicina Xenómica-USC, CIBERER, IDIS, Santiago de Compostela; Spain, Departamento de Investigacion y de Tumores Mamarios del; Instituto Nacional de Cancerologia; Mexico City Mexico, Department of Oncology; Karolinska University Hospital; Stockholm Sweden, Institute of Genetic Medicine; Centre for Life; Newcastle Upon Tyne Hospitals NHS Trust; Newcastle upon Tyne UK, Oxford Regional Genetics Service; Churchill Hospital; Oxford UK, Department of Gynaecology and Obstetrics; University Hospital; Ulm Germany, Department of Clinical Genetics; Academic Medical Center; Amsterdam The Netherlands, Institute of Human Genetics; Regensburg University; Regensburg Germany, Molecular Diagnostics Laboratory, INRASTES (Institute of Nuclear and Radiological Sciences and Technology); National Centre for Scientific Research “Demokritos”; Athens Greece, Unit of Medical Genetics, Department of Medical Oncology and Hematology; Fondazione IRCCS (Istituto Di Ricovero e Cura a Carattere Scientifico) Instituto Nazionale Tumori (INT); Milan Italy, Institute of Oncology; Rivka Ziv Medical Center; Zefat Israel, Magee-Womens Hospital; University of Pittsburgh School of Medicine; Pittsburgh USA, Institute of Human Genetics; University Leipzig; Leipzig Germany, Center for Medical Genetics; North Shore University Health System; Evanston USA, Medical Director, Center for Medical Genetics, NorthShore University HealthSystem, Clinical Assistant Professor of Medicine; University of Chicago Pritzker School of Medicine; Evanston USA, City of Hope Clinical Cancer Genomics Community Research Network; Duarte USA, Yorkshire Regional Genetics Service; Chapel Allerton Hospital; Leeds UK, Department of Clinical Genetics; Helsinki University Hospital; Helsinki Finland, Hereditary Cancer Clinic; Prince of Wales Hospital; Randwick Australia, Lunenfeld-Tanenbaum Research Institute; Toronto Canada, Laboratory of Cell Biology, Department of Pathology, hus 9, Landspitali-LSH v/Hringbraut, 101 Reykjavik, Iceland and BMC (Biomedical Centre), Faculty of Medicine; University of Iceland; Reykjavik Iceland, Department of Gynaecology & Oncology; Medical University of Vienna; Austria, Department of Medical Oncology; Vall d'Hebron University Hospital; Barcelona Spain, Division of Cancer Prevention and Genetics; Istituto Europeo di Oncologia (IEO); Milan Italy, Department of Gynaecology and Obstetrics; University Hospital Düsseldorf, Heinrich-Heine University; Düsseldorf Germany, Human Genetics Group and Genotyping Unit (CEGEN), Human Cancer Genetics Programme; Spanish National Cancer Research Centre (CNIO); Madrid Spain, The Institute of Oncology; Chaim Sheba Medical Center; Ramat Gan Israel, UCSF Cancer Genetics and Prevention Program; San Francisco USA, Department of Clinical Genetics; Maastricht University Medical Center; Maastricht The Netherlands, Unité de Prévention et d'Epidémiologie Génétique; Centre Léon Bérard, 28 rue Laënnec; Lyon France, N.N. Petrov Institute of Oncology; St. Petersburg Russia, Department of Clinical Genetics; Royal Devon & Exeter Hospital; Exeter UK, Service de Génétique; Institut Curie, 26 rue d'Ulm; Paris France, Department of Medicine; Huntsman Cancer Institute; Salt Lake City USA, Molecular Oncology Laboratory; Hospital Clinico San Carlos; Instituto de Investigación Sanitaria San Carlos (IdISSC); Centro Investigación Biomédica en Red de Cáncer (CIBERONC); Madrid Spain, Institute of Human Genetics; University Hospital of Schleswig-Holstein; Kiel Germany, Section of Molecular Genetics, Dept. of Laboratory Medicine; University Hospital of Pisa; Pisa Italy, Research Division; Peter MacCallum Cancer Centre; Melbourne Australia, CRCHU de Quebec-oncologie, Centre des maladies du sein Deschênes-Fabia; Hôpital du Saint-Sacrement; Sainte-Foy Canada, Lombardi Comprehensive Cancer Center; Georgetown University; Washington USA, Departments of Pediatrics and Medicine; Columbia University; New York USA, Department of Clinical Genetics, Family Cancer Clinic; Erasmus University Medical Center; Rotterdam The Netherlands, Sheffield Clinical Genetics Service; Sheffield Children's Hospital; Sheffield UK, Department of Clinical Genetics; South Glasgow University Hospitals; Glasgow UK, Unité d'oncogénétique; ICO-Centre René Gauducheau; Saint Herblain France, Oncogenetics Group, Vall d'Hebron Institute of Oncology (VHIO), Clinical and Molecular Genetics Area; Vall d'Hebron University Hospital; Barcelona Spain, Department of Gynaecology and Obstetrics; Ludwig-Maximilian University; Munich Germany, Cáncer Hereditario, Instituto de Biología y Genética Molecular, IBGM; Universidad de Valladolid; Valladolid Spain, Institute of Human Genetics; University of Münster; Münster Germany, Nottingham Clinical Genetics Service; Nottingham University Hospitals NHS Trust; Nottingham UK, Oncogenetics Team; The Institute of Cancer Research and Royal Marsden NHS Foundation Trust; London UK, Department of Clinical Genetics; Lund University Hospital; Lund Sweden, Clinical Genetics; Guy's and St. Thomas’ NHS Foundation Trust; London UK, Department of Oncology, Rigshospitalet; Copenhagen University Hospital; Copenhagen Denmark, Institute for Medical Informatics, Statistics and Epidemiology; University of Leipzig; Leipzig Germany, Department of Gynaecology and Obstetrics, Division of Tumor Genetics, Klinikum rechts der Isar; Technical University; Munich Germany, Genomic Medicine, Manchester Academic Health Sciences Centre, Division of Evolution and Genomic Sciences; University of Manchester, Central Manchester University Hospitals NHS Foundation Trust; Manchester UK, Centre de Lutte Contre le Cancer Georges François Leclerc, France and Genomic and Immunotherapy Medical Institute; Dijon University Hospital; Dijon France, Molecular Diagnostic Unit, Hereditary Cancer Program, ICO-IDIBELL (Catalan Institute of Oncology-Bellvitge Biomedical Research Institute); Barcelona Spain, Laboratoire de Génétique Chromosomique; Hôtel Dieu Centre Hospitalier; Chambéry France, Department of Cancer Epidemiology and Genetics; Masaryk Memorial Cancer Institute; Brno Czech Republic, Columbus Cancer Council, Ohio State University; Columbus USA, Genetic Counseling Unit, Hereditary Cancer Program, IDIBGI (Institut d'Investigació Biomèdica de Girona); Catalan Institute of Oncology; Girona Spain, Oncogenetics Department; Barretos Cancer Hospital; Barretos Brazil, UCLA Schools of Medicine and Public Health, Division of Cancer Prevention & Control Research; Jonsson Comprehensive Cancer Center; Los Angeles USA, Cancer Risk and Prevention Clinic; Dana-Farber Cancer Institute; Boston USA, Centre of Familial Breast and Ovarian Cancer, Department of Medical Genetics, Institute of Human Genetics; University of Würzburg, Germany; Würzburg, Department of Clinical Genetics; Copenhagen Denmark, Service Régional Oncogénétique Poitou-Charentes; Centre Hospitalier; Niort France, Department of Molecular Medicine; University La Sapienza, and Istituto Pasteur - Fondazione Cenci-Bolognetti; Rome Italy, Bâtiment Cheney D; Centre Léon Bérard; Lyon France, Ontario Cancer Genetics Network: Lunenfeld-Tanenbaum Research Institute; Mount Sinai Hospital; Toronto Canada, Department of Pathology and Laboratory Medicine; University of Kansas Medical Center; Kansas City USA, Clinical Genetics Branch, DCEG, NCI; NIH; Bethesda USA, Parkville Familial Cancer Centre; Peter MacCallum Cancer Centre; Melbourne Australia, Hematology, oncology and transfusion medicine center, Dept. of Molecular and Regenerative Medicine; Vilnius University Hospital Santariskiu Clinics; Vilnius Lithuania, Department of Epidemiology, Cancer Prevention Institute of California; Fremont USA, Women's Cancer Program at the Samuel Oschin Comprehensive Cancer Institute; Cedars-Sinai Medical Center; Los Angeles USA, Division of Molecular Pathology; Department of Pathology; Hong Kong Sanatorium & Hospital; Happy Valley Hong Kong, Department of Gynecology and Obstetrics; Medical Faculty and University Hospital Carl Gustav Carus; Dresden Germany, Research Department, Peter MacCallum Cancer Centre, Melbourne, Victoria; Australia and The Sir Peter MacCallum Department of Oncology University of Melbourne; Parkville Australia, Department of Surgery; Daerim St. Mary's Hospital; Seoul Korea, The Gyneco-Oncology Department; Chaim Sheba Medical Center; Ramat Gan Israel, Servicio de Genética-CIBERER U705; Hospital de la Santa Creu i Sant Pau; Barcelona Spain, The Feinstein Institute for Medical Research; Manhasset USA, Department of Laboratory Medicine and Pathology; and Health Sciences Research; Rochester USA, Department of Surgery; Soonchunhyang University and Seoul Hospital; Seoul Korea, Inserm U900, Institut Curie; PSL Research University; Paris France, Department of Oncology Radiumhemmet and Institution of Oncology and Patology; Karolinska University Hospital and Karolinska Institutet; Solna Sweden, Department of Health Sciences Research; Mayo Clinic; Scottsdale USA, Oncogénétique; Institut Bergonié; Bordeaux France, Clinical Genetics Branch, DCEG, NCI, NIH; Bethesda USA, Department of Gynecological Oncology and Clinical Cancer Genetics Program; University Of Texas MD Anderson Cancer Center; Houston USA, Department of Dermatology; University of Utah School of Medicine; Salt Lake City USA, Centre Antoine Lacassagne; Nice France, Laboratorio de Genética Molecular, Servicio de Genética; Hospital Universitario Cruces, BioCruces Health Research Institute; Barakaldo Spain, Department of Surgery; National Institute of Oncology; Budapest Hungary, Department of Clinical Genetics; VU University Medical Center; Amsterdam The Netherlands, Department of Human Genetics; Radboud University Medical Center; Nijmegen The Netherlands, Vilnius university Santariskiu hospital; National Center of Pathology; Vilnius Lithuania, NRG Oncology; Statistics and Data Management Center; Roswell Park Cancer Institute; Buffalo USA, Department of Cancer Prevention and Control; Roswell Park Cancer Institute; Buffalo USA, Department of Laboratory Medicine and Pathobiology; University of Toronto; Toronto Canada, Department of Obstetrics and Gynecology; University of Helsinki and Helsinki University Hospital; HUS Finland, Cancer Genetics Service; Division of Medical Oncology; National Cancer Centre Singapore; Bukit Merah Singapore, Institute of Medical Genetics and Applied Genomics; University of Tuebingen; Tuebingen Germany, Molecular Oncology Research Center; Barretos Cancer Hospital; São Paulo Brazil, Cancer Genetics and Prevention Program; University of California San Francisco; San Francisco USA, Clinical Genetics Research Laboratory; Dept. of Medicine; Cancer Biology and Genetics; Memorial Sloan-Kettering Cancer Center; New York USA, Department of Clinical Genetics; Sahlgrenska University Hospital; Gothenburg Sweden, West Midlands Regional Genetics Service; Birmingham Women's Hospital Healthcare NHS Trust; Edgbaston UK, Human Genetics Group; Human Cancer Genetics Programme; Spanish National Cancer Research Centre (CNIO); Biomedical Network on Rare Diseases (CIBERER); Madrid Spain, Unit of Medical Genetics; Department of Biomedical; Experimental and Clinical Sciences; University of Florence; Florence Italy, Department of Medical Sciences; University of Turin; Turin Italy, Section of Molecular Diagnostics; Department of Biochemistry; Aalborg University Hospital; Aalborg Denmark, Department of Preventive Medicine; Seoul National University College of Medicine; Seoul Korea, IFOM; The FIRC (Italian Foundation for Cancer Research) Institute of Molecular Oncology; Milan Italy, Service de Génétique Clinique Chromosomique et Moléculaire; Hôpital Nord; St Etienne France, Unité d'Oncogénétique; CHU Arnaud de Villeneuve; Montpellier France, Unit of Molecular Bases of Genetic Risk and Genetic Testing; Department of Research; Fondazione IRCCS (Istituto Di Ricovero e Cura a Carattere Scientifico), Istituto Nazionale Tumori (INT); Milan Italy, School of Women's and Children's Health; UNSW; Sydney Australia, Department of Clinical Genetics; Karolinska University Hospital; Stockholm Sweden, Rebbeck, Timothy R., Friebel, Tara M., Friedman, Eitan, Hamann, Ute, Huo, Dezheng, Kwong, Ava, Olah, Edith, Olopade, Olufunmilayo I., Solano, Angela R., Teo, Soo-Hwang, Thomassen, Mads, Rashid, Muhammad Usman, Rhiem, Kerstin, Robson, Mark, Rodriguez, Gustavo C., Rogers, Mark T., Rudaitis, Vilius, Schmidt, Ane Y., Schmutzler, Rita Katharina, Senter, Leigha, van Rensburg, Elizabeth J., Gronwald, Jacek, Shah, Payal D., Sharma, Priyanka, Side, Lucy E., Simard, Jacques, Singer, Christian F., Skytte, Anne-Bine, Slavin, Thomas P., Snape, Katie, Sobol, Hagay, Southey, Melissa, Gutierrez-Barrera, Angelica, McGuffog, Lesley, Steele, Linda, Steinemann, Doris, Sukiennicki, Grzegorz, Sutter, Christian, Szabo, Csilla I., Tan, Yen Y., Teixeira, Manuel R., Terry, Mary Beth, Teulé, Alex, Hahnen, Eric, Thomas, Abigail, Parsons, Michael T., Thull, Darcy L., Tischkowitz, Marc, Tognazzo, Silvia, Toland, Amanda Ewart, Topka, Sabine, Trainer, Alison H, Tung, Nadine, van Asperen, Christi J., Hauke, Jan, van der Hout, Annemieke H., van der Kolk, Lizet E., Leslie, Goska, van der Luijt, Rob B., Van Heetvelde, Mattias, Varesco, Liliana, Varon-Mateeva, Raymonda, Vega, Ana, Villarreal-Garza, Cynthia, von Wachenfeldt, Anna, Henderson, Alex, Walker, Lisa, Wang-Gohrke, Shan, Wappenschmidt, Barbara, Aalfs, Cora M., Weber, Bernhard H. F., Yannoukakos, Drakoulis, Yoon, Sook-Yee, Zanzottera, Cristina, Zidan, Jamal, Zorn, Kristin K., Hentschel, Julia, Hutten Selkirk, Christina G., Hulick, Peter J., Chenevix-Trench, Georgia, Spurdle, Amanda B., Abugattas, Julio, Antoniou, Antonis C., Nathanson, Katherine L., Adlard, Julian, Agata, Simona, Aittomäki, Kristiina, Hogervorst, Frans B.L., Andrews, Lesley, Andrulis, Irene L., Arason, Adalgeir, Arnold, Norbert, Arun, Banu K., Asseryanis, Ella, Auerbach, Leo, Azzollini, Jacopo, Balmaña, Judith, Barile, Monica, Honisch, Ellen, Barkardottir, Rosa B., Barrowdale, Daniel, Benitez, Javier, Berger, Andreas, Berger, Raanan, Blanco, Amie M., Blazer, Kathleen R., Blok, Marinus J., Bonadona, Valérie, Bonanni, Bernardo, Imyanitov, Evgeny N., Bradbury, Angela R., Brewer, Carole, Buecher, Bruno, Buys, Saundra S., Caldes, Trinidad, Caliebe, Almuth, Caligo, Maria A., Campbell, Ian, Caputo, Sandrine M., Chiquette, Jocelyne, Isaacs, Claudine, Chung, Wendy K., Claes, Kathleen B.M., Collée, J. Margriet, Cook, Jackie, Davidson, Rosemarie, de la Hoya, Miguel, De Leeneer, Kim, de Pauw, Antoine, Delnatte, Capucine, Diez, Orland, Weitzel, Jeffrey N., Ding, Yuan Chun, Ditsch, Nina, Domchek, Susan M., Dorfling, Cecilia M., Velazquez, Carolina, Dworniczak, Bernd, Eason, Jacqueline, Easton, Douglas F., Eeles, Ros, Ehrencrona, Hans, Izatt, Louise, Ejlertsen, Bent, Engel, Christoph, Engert, Stefanie, Evans, D. Gareth, Faivre, Laurence, Feliubadaló, Lidia, Ferrer, Sandra Fert, Foretova, Lenka, Fowler, Jeffrey, Frost, Debra, Izquierdo, Angel, Galvão, Henrique C. R., Ganz, Patricia A., Garber, Judy, Gauthier-Villars, Marion, Gehrig, Andrea, Gerdes, Anne-Marie, Gesta, Paul, Giannini, Giuseppe, Giraud, Sophie, Glendon, Gord, Jakubowska, Anna, Godwin, Andrew K., Greene, Mark H., James, Paul, Janavicius, Ramunas, Jensen, Uffe Birk, John, Esther M., Vijai, Joseph, Kaczmarek, Katarzyna, Karlan, Beth Y., Chan, TL, Kast, Karin, Investigators, KConFab, Kim, Sung-Won, Konstantopoulou, Irene, Korach, Jacob, Laitman, Yael, Lasa, Adriana, Lasset, Christine, Lázaro, Conxi, Lee, Annette, Couch, Fergus J., Lee, Min Hyuk, Lester, Jenny, Lesueur, Fabienne, Liljegren, Annelie, Lindor, Noralane M., Longy, Michel, Loud, Jennifer T., Lu, Karen H., Lubinski, Jan, Machackova, Eva, Goldgar, David E., Manoukian, Siranoush, Mari, Véronique, Martínez-Bouzas, Cristina, Matrai, Zoltan, Mebirouk, Noura, Meijers-Heijboer, Hanne E.J., Meindl, Alfons, Mensenkamp, Arjen R., Mickys, Ugnius, Miller, Austin, Kruse, Torben A., Montagna, Marco, Moysich, Kirsten B., Mulligan, Anna Marie, Musinsky, Jacob, Neuhausen, Susan L., Nevanlinna, Heli, Ngeow, Joanne, Nguyen, Huu Phuc, Niederacher, Dieter, Nielsen, Henriette Roed, Palmero, Edenir Inêz, Nielsen, Finn Cilius, Nussbaum, Robert L., Offit, Kenneth, Öfverholm, Anna, Ong, Kai-ren, Osorio, Ana, Papi, Laura, Papp, Janos, Pasini, Barbara, Pedersen, Inge Sokilde, Park, Sue Kyung, Peixoto, Ana, Peruga, Nina, Peterlongo, Paolo, Pohl, Esther, Pradhan, Nisha, Prajzendanc, Karolina, Prieur, Fabienne, Pujol, Pascal, Radice, Paolo, Ramus, Susan J., Torres, Diana, Rantala, Johanna, [ 1 ] Harvard TH Chan Sch Publ Hlth, Boston, MA USA Show more [ 2 ] Chaim Sheba Med Ctr, Inst Human Genet, Susanne Levy Gertner Oncogenet Unit, IL-52621 Ramat Gan, Israel Show more [ 3 ] Tel Aviv Univ, Sackler Sch Med, Tel Aviv, Israel Show more [ 4 ] German Canc Res Ctr, Mol Genet Breast Canc, Heidelberg, Germany Show more [ 5 ] Univ Chicago, Ctr Clin Canc Genet & Global Hlth, Chicago, IL 60637 USA [ 6 ] Hong Kong Sanat & Hosp, Canc Genet Ctr, Hong Kong Hereditary Breast Canc Family Registry, Hong Kong, Hong Kong, Peoples R China Show more [ 7 ] Natl Inst Oncol, Dept Mol Genet, Budapest, Hungary Show more [ 8 ] Univ Buenos Aires, CONICET, Fac Med, INBIOMED, Buenos Aires, DF, Argentina Show more [ 9 ] CEMIC, Dept Clin Chem, Med Direct, Buenos Aires, DF, Argentina [ 10 ] Sime Darby Med Ctr, Canc Res Initiat Fdn, Subang Jaya, Malaysia Show more [ 11 ] Odense Univ Hosp, Dept Clin Genet, Odense, Denmark Show more [ 12 ] City Hope Canc Ctr, Div Clin Canc Genom, Duarte, CA USA [ 13 ] Hong Kong Sanat & Hosp, Dept Pathol, Div Mol Pathol, Happy Valley, Hong Kong, Peoples R China [ 14 ] Dept Lab Med & Pathol, Rochester, MN USA Show more [ 15 ] Univ Utah, Sch Med, Dept Dermatol, Salt Lake City, UT USA Show more [ 16 ] Barretos Canc Hosp, Mol Oncol Res Ctr, Sao Paulo, Brazil Show more [ 17 ] Seoul Natl Univ, Coll Med, Dept Prevent Med, Seoul, South Korea Show more [ 18 ] Seoul Natl Univ, Grad Sch, Dept Biomed Sci, Seoul, South Korea Show more [ 19 ] Seoul Natl Univ, Canc Res Ctr, Seoul, South Korea Show more [ 20 ] Pontificia Univ Javeriana, Inst Human Genet, Bogota, Colombia Show more [ 21 ] Univ Pretoria, Dept Genet, Canc Genet Lab, Pretoria, South Africa Show more [ 22 ] Univ Cambridge, Dept Publ Hlth & Primary Care, Ctr Canc Genet Epidemiol, Cambridge, England Show more [ 23 ] QIMR Berghofer Med Res Inst, Genet & Computat Biol Dept, Brisbane, Qld, Australia [ 24 ] Acad Med Ctr, Dept Clin Genet, Amsterdam, Netherlands [ 25 ] City Hope Clin Canc Genom Community Res Network, D, Harvard TH Chan School of Public Health and Dana Farber Cancer Institute; Boston USA, The Susanne Levy Gertner Oncogenetics Unit; Institute of Human Genetics; Chaim Sheba Medical Center, Ramat Gan 52621, and the Sackler School of Medicine; Tel-Aviv University; Tel-Aviv Israel, Molecular Genetics of Breast Cancer; German Cancer Research Center (DKFZ); Heidelberg Germany, Center for Clinical Cancer Genetics and Global Health; University of Chicago; Chicago USA, The Hong Kong Hereditary Breast Cancer Family Registry; Cancer Genetics Center; Hong Kong Sanatorium and Hospital; Hong Kong China, Department of Molecular Genetics; National Institute of Oncology; Budapest Hungary, INBIOMED; Faculty of Medicine, University of Buenos Aires/CONICET and CEMIC, Department of Clinical Chemistry; Medical Direction; Buenos Aires Argentina, Cancer Research Initiatives Foundation; Sime Darby Medical Centre; Subang Jaya Malaysia, Department of Clinical Genetics; Odense University Hospital; Odense Denmark, Center for Familial Breast and Ovarian Cancer, Center for Integrated Oncology (CIO), Medical Faculty; University Hospital Cologne; Cologne Germany, Clinical Genetics Services; Dept. of Medicine; Memorial Sloan-Kettering Cancer Center; New York USA, Division of Gynecologic Oncology; North Shore University Health System; University of Chicago; Evanston USA, All Wales Medical Genetics Services; University Hospital of Wales; Cardiff UK, Department of Gynecology; Vilnius University Hospital Santariskiu Clinics; Centre of Woman's Health and pathology; Vilnius Lithuania, Center for Genomic Medicine; Rigshospitalet; University of Copenhagen; Copenhagen Denmark, Clinical Cancer Genetics Program; Division of Human Genetics; Department of Internal Medicine; The Comprehensive Cancer Center; The Ohio State University; Columbus USA, Cancer Genetics Laboratory, Department of Genetics; University of Pretoria; South Africa, Department of Genetics and Pathology; Pomeranian Medical University; Szczecin Poland, Department of Medicine, Abramson Cancer Center; Perelman School of Medicine at the University of Pennsylvania; Philadelphia USA, Department of Internal Medicine; Division of Oncology; University of Kansas Medical Center; Westwood USA, North East Thames Regional Genetics Service; Great Ormond Street Hospital for Children NHS Trust; London UK, Genomics Center; Centre Hospitalier Universitaire de Québec Research Center and Laval University; Quebec City Canada, Dept of OB/GYN and Comprehensive Cancer Center; Medical University of Vienna; Vienna Austria, Department of Clinical Genetics; Aarhus University Hospital; Aarhus N Denmark, Division of Clinical Cancer Genomics; City of Hope Cancer Center; California USA, Medical Genetics Unit; University of London; St George's UK, Département Oncologie Génétique; Prévention et Dépistage; Institut Paoli-Calmettes; Marseille Medical School-AM University; Marseille France, Department of Breast Medical Oncology and Clinical Cancer Genetics Program; University Of Texas MD Anderson Cancer Center; Houston USA, Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care; University of Cambridge; Cambridge UK, Department of Population Sciences; Beckman Research Institute of City of Hope; Duarte USA, Institute of Cell and Molecular Pathology; Hannover Medical School; Hannover Germany, Institute of Human Genetics; University Hospital Heidelberg; Heidelberg Germany, National Human Genome Research Institute; National Institutes of Health; Bethesda USA, Dept of OB/GYN, Comprehensive Cancer Center; Medical University of Vienna; Vienna Austria, Department of Genetics; Portuguese Oncology Institute of Porto (IPO Porto); Porto Portugal, Department of Epidemiology; Columbia University; New York USA, Genetic Counseling Unit; Hereditary Cancer Program; IDIBELL (Bellvitge Biomedical Research Institute); Catalan Institute of Oncology, CIBERONC; Gran Via de l'Hospitalet; Barcelona Spain, Department of Health Sciences Research; Mayo Clinic; Rochester USA, Genetics and Computational Biology Department; QIMR Berghofer Medical Research Institute; Brisbane Australia, Department of Medicine; Magee-Womens Hospital; University of Pittsburgh School of Medicine; Pittsburgh USA, Program in Cancer Genetics; Departments of Human Genetics and Oncology; McGill University; Montreal Canada, Immunology and Molecular Oncology Unit; Veneto Institute of Oncology IOV - IRCCS; Padua Italy, Division of Human Genetics; Departments of Internal Medicine and Cancer Biology and Genetics; Comprehensive Cancer Center; The Ohio State University; Columbus USA, Clinical Genetics Research Laboratory, Dept. of Medicine; Memorial Sloan-Kettering Cancer Center; New York USA, Parkville Familial Cancer Centre; Royal Melbourne Hospital; Melbourne Australia, Department of Medical Oncology; Beth Israel Deaconess Medical Center; Massachusetts USA, Department of Clinical Genetics; Leiden University Medical Center; Leiden The Netherlands, Department of Genetics; University Medical Center; Groningen University; Groningen The Netherlands, Family Cancer Clinic; Netherlands Cancer Institute; Amsterdam The Netherlands, Department of Medical Genetics; University Medical Center; Utrecht The Netherlands, Center for Medical Genetics; Ghent University; Gent Belgium, Unit of Hereditary Cancer; Department of Epidemiology, Prevention and Special Functions; IRCCS (Istituto Di Ricovero e Cura a Carattere Scientifico) AOU San Martino - IST Istituto Nazionale per la Ricerca sul Cancro; Genoa Italy, Institute of Human Genetics; Campus Virchov Klinikum; Berlin Germany, Fundación Pública Galega de Medicina Xenómica-SERGAS, Grupo de Medicina Xenómica-USC, CIBERER, IDIS, Santiago de Compostela; Spain, Departamento de Investigacion y de Tumores Mamarios del; Instituto Nacional de Cancerologia; Mexico City Mexico, Department of Oncology; Karolinska University Hospital; Stockholm Sweden, Institute of Genetic Medicine; Centre for Life; Newcastle Upon Tyne Hospitals NHS Trust; Newcastle upon Tyne UK, Oxford Regional Genetics Service; Churchill Hospital; Oxford UK, Department of Gynaecology and Obstetrics; University Hospital; Ulm Germany, Department of Clinical Genetics; Academic Medical Center; Amsterdam The Netherlands, Institute of Human Genetics; Regensburg University; Regensburg Germany, Molecular Diagnostics Laboratory, INRASTES (Institute of Nuclear and Radiological Sciences and Technology); National Centre for Scientific Research “Demokritos”; Athens Greece, Unit of Medical Genetics, Department of Medical Oncology and Hematology; Fondazione IRCCS (Istituto Di Ricovero e Cura a Carattere Scientifico) Instituto Nazionale Tumori (INT); Milan Italy, Institute of Oncology; Rivka Ziv Medical Center; Zefat Israel, Magee-Womens Hospital; University of Pittsburgh School of Medicine; Pittsburgh USA, Institute of Human Genetics; University Leipzig; Leipzig Germany, Center for Medical Genetics; North Shore University Health System; Evanston USA, Medical Director, Center for Medical Genetics, NorthShore University HealthSystem, Clinical Assistant Professor of Medicine; University of Chicago Pritzker School of Medicine; Evanston USA, City of Hope Clinical Cancer Genomics Community Research Network; Duarte USA, Yorkshire Regional Genetics Service; Chapel Allerton Hospital; Leeds UK, Department of Clinical Genetics; Helsinki University Hospital; Helsinki Finland, Hereditary Cancer Clinic; Prince of Wales Hospital; Randwick Australia, Lunenfeld-Tanenbaum Research Institute; Toronto Canada, Laboratory of Cell Biology, Department of Pathology, hus 9, Landspitali-LSH v/Hringbraut, 101 Reykjavik, Iceland and BMC (Biomedical Centre), Faculty of Medicine; University of Iceland; Reykjavik Iceland, Department of Gynaecology & Oncology; Medical University of Vienna; Austria, Department of Medical Oncology; Vall d'Hebron University Hospital; Barcelona Spain, Division of Cancer Prevention and Genetics; Istituto Europeo di Oncologia (IEO); Milan Italy, Department of Gynaecology and Obstetrics; University Hospital Düsseldorf, Heinrich-Heine University; Düsseldorf Germany, Human Genetics Group and Genotyping Unit (CEGEN), Human Cancer Genetics Programme; Spanish National Cancer Research Centre (CNIO); Madrid Spain, The Institute of Oncology; Chaim Sheba Medical Center; Ramat Gan Israel, UCSF Cancer Genetics and Prevention Program; San Francisco USA, Department of Clinical Genetics; Maastricht University Medical Center; Maastricht The Netherlands, Unité de Prévention et d'Epidémiologie Génétique; Centre Léon Bérard, 28 rue Laënnec; Lyon France, N.N. Petrov Institute of Oncology; St. Petersburg Russia, Department of Clinical Genetics; Royal Devon & Exeter Hospital; Exeter UK, Service de Génétique; Institut Curie, 26 rue d'Ulm; Paris France, Department of Medicine; Huntsman Cancer Institute; Salt Lake City USA, Molecular Oncology Laboratory; Hospital Clinico San Carlos; Instituto de Investigación Sanitaria San Carlos (IdISSC); Centro Investigación Biomédica en Red de Cáncer (CIBERONC); Madrid Spain, Institute of Human Genetics; University Hospital of Schleswig-Holstein; Kiel Germany, Section of Molecular Genetics, Dept. of Laboratory Medicine; University Hospital of Pisa; Pisa Italy, Research Division; Peter MacCallum Cancer Centre; Melbourne Australia, CRCHU de Quebec-oncologie, Centre des maladies du sein Deschênes-Fabia; Hôpital du Saint-Sacrement; Sainte-Foy Canada, Lombardi Comprehensive Cancer Center; Georgetown University; Washington USA, Departments of Pediatrics and Medicine; Columbia University; New York USA, Department of Clinical Genetics, Family Cancer Clinic; Erasmus University Medical Center; Rotterdam The Netherlands, Sheffield Clinical Genetics Service; Sheffield Children's Hospital; Sheffield UK, Department of Clinical Genetics; South Glasgow University Hospitals; Glasgow UK, Unité d'oncogénétique; ICO-Centre René Gauducheau; Saint Herblain France, Oncogenetics Group, Vall d'Hebron Institute of Oncology (VHIO), Clinical and Molecular Genetics Area; Vall d'Hebron University Hospital; Barcelona Spain, Department of Gynaecology and Obstetrics; Ludwig-Maximilian University; Munich Germany, Cáncer Hereditario, Instituto de Biología y Genética Molecular, IBGM; Universidad de Valladolid; Valladolid Spain, Institute of Human Genetics; University of Münster; Münster Germany, Nottingham Clinical Genetics Service; Nottingham University Hospitals NHS Trust; Nottingham UK, Oncogenetics Team; The Institute of Cancer Research and Royal Marsden NHS Foundation Trust; London UK, Department of Clinical Genetics; Lund University Hospital; Lund Sweden, Clinical Genetics; Guy's and St. Thomas’ NHS Foundation Trust; London UK, Department of Oncology, Rigshospitalet; Copenhagen University Hospital; Copenhagen Denmark, Institute for Medical Informatics, Statistics and Epidemiology; University of Leipzig; Leipzig Germany, Department of Gynaecology and Obstetrics, Division of Tumor Genetics, Klinikum rechts der Isar; Technical University; Munich Germany, Genomic Medicine, Manchester Academic Health Sciences Centre, Division of Evolution and Genomic Sciences; University of Manchester, Central Manchester University Hospitals NHS Foundation Trust; Manchester UK, Centre de Lutte Contre le Cancer Georges François Leclerc, France and Genomic and Immunotherapy Medical Institute; Dijon University Hospital; Dijon France, Molecular Diagnostic Unit, Hereditary Cancer Program, ICO-IDIBELL (Catalan Institute of Oncology-Bellvitge Biomedical Research Institute); Barcelona Spain, Laboratoire de Génétique Chromosomique; Hôtel Dieu Centre Hospitalier; Chambéry France, Department of Cancer Epidemiology and Genetics; Masaryk Memorial Cancer Institute; Brno Czech Republic, Columbus Cancer Council, Ohio State University; Columbus USA, Genetic Counseling Unit, Hereditary Cancer Program, IDIBGI (Institut d'Investigació Biomèdica de Girona); Catalan Institute of Oncology; Girona Spain, Oncogenetics Department; Barretos Cancer Hospital; Barretos Brazil, UCLA Schools of Medicine and Public Health, Division of Cancer Prevention & Control Research; Jonsson Comprehensive Cancer Center; Los Angeles USA, Cancer Risk and Prevention Clinic; Dana-Farber Cancer Institute; Boston USA, Centre of Familial Breast and Ovarian Cancer, Department of Medical Genetics, Institute of Human Genetics; University of Würzburg, Germany; Würzburg, Department of Clinical Genetics; Copenhagen Denmark, Service Régional Oncogénétique Poitou-Charentes; Centre Hospitalier; Niort France, Department of Molecular Medicine; University La Sapienza, and Istituto Pasteur - Fondazione Cenci-Bolognetti; Rome Italy, Bâtiment Cheney D; Centre Léon Bérard; Lyon France, Ontario Cancer Genetics Network: Lunenfeld-Tanenbaum Research Institute; Mount Sinai Hospital; Toronto Canada, Department of Pathology and Laboratory Medicine; University of Kansas Medical Center; Kansas City USA, Clinical Genetics Branch, DCEG, NCI; NIH; Bethesda USA, Parkville Familial Cancer Centre; Peter MacCallum Cancer Centre; Melbourne Australia, Hematology, oncology and transfusion medicine center, Dept. of Molecular and Regenerative Medicine; Vilnius University Hospital Santariskiu Clinics; Vilnius Lithuania, Department of Epidemiology, Cancer Prevention Institute of California; Fremont USA, Women's Cancer Program at the Samuel Oschin Comprehensive Cancer Institute; Cedars-Sinai Medical Center; Los Angeles USA, Division of Molecular Pathology; Department of Pathology; Hong Kong Sanatorium & Hospital; Happy Valley Hong Kong, Department of Gynecology and Obstetrics; Medical Faculty and University Hospital Carl Gustav Carus; Dresden Germany, Research Department, Peter MacCallum Cancer Centre, Melbourne, Victoria; Australia and The Sir Peter MacCallum Department of Oncology University of Melbourne; Parkville Australia, Department of Surgery; Daerim St. Mary's Hospital; Seoul Korea, The Gyneco-Oncology Department; Chaim Sheba Medical Center; Ramat Gan Israel, Servicio de Genética-CIBERER U705; Hospital de la Santa Creu i Sant Pau; Barcelona Spain, The Feinstein Institute for Medical Research; Manhasset USA, Department of Laboratory Medicine and Pathology; and Health Sciences Research; Rochester USA, Department of Surgery; Soonchunhyang University and Seoul Hospital; Seoul Korea, Inserm U900, Institut Curie; PSL Research University; Paris France, Department of Oncology Radiumhemmet and Institution of Oncology and Patology; Karolinska University Hospital and Karolinska Institutet; Solna Sweden, Department of Health Sciences Research; Mayo Clinic; Scottsdale USA, Oncogénétique; Institut Bergonié; Bordeaux France, Clinical Genetics Branch, DCEG, NCI, NIH; Bethesda USA, Department of Gynecological Oncology and Clinical Cancer Genetics Program; University Of Texas MD Anderson Cancer Center; Houston USA, Department of Dermatology; University of Utah School of Medicine; Salt Lake City USA, Centre Antoine Lacassagne; Nice France, Laboratorio de Genética Molecular, Servicio de Genética; Hospital Universitario Cruces, BioCruces Health Research Institute; Barakaldo Spain, Department of Surgery; National Institute of Oncology; Budapest Hungary, Department of Clinical Genetics; VU University Medical Center; Amsterdam The Netherlands, Department of Human Genetics; Radboud University Medical Center; Nijmegen The Netherlands, Vilnius university Santariskiu hospital; National Center of Pathology; Vilnius Lithuania, NRG Oncology; Statistics and Data Management Center; Roswell Park Cancer Institute; Buffalo USA, Department of Cancer Prevention and Control; Roswell Park Cancer Institute; Buffalo USA, Department of Laboratory Medicine and Pathobiology; University of Toronto; Toronto Canada, Department of Obstetrics and Gynecology; University of Helsinki and Helsinki University Hospital; HUS Finland, Cancer Genetics Service; Division of Medical Oncology; National Cancer Centre Singapore; Bukit Merah Singapore, Institute of Medical Genetics and Applied Genomics; University of Tuebingen; Tuebingen Germany, Molecular Oncology Research Center; Barretos Cancer Hospital; São Paulo Brazil, Cancer Genetics and Prevention Program; University of California San Francisco; San Francisco USA, Clinical Genetics Research Laboratory; Dept. of Medicine; Cancer Biology and Genetics; Memorial Sloan-Kettering Cancer Center; New York USA, Department of Clinical Genetics; Sahlgrenska University Hospital; Gothenburg Sweden, West Midlands Regional Genetics Service; Birmingham Women's Hospital Healthcare NHS Trust; Edgbaston UK, Human Genetics Group; Human Cancer Genetics Programme; Spanish National Cancer Research Centre (CNIO); Biomedical Network on Rare Diseases (CIBERER); Madrid Spain, Unit of Medical Genetics; Department of Biomedical; Experimental and Clinical Sciences; University of Florence; Florence Italy, Department of Medical Sciences; University of Turin; Turin Italy, Section of Molecular Diagnostics; Department of Biochemistry; Aalborg University Hospital; Aalborg Denmark, Department of Preventive Medicine; Seoul National University College of Medicine; Seoul Korea, IFOM; The FIRC (Italian Foundation for Cancer Research) Institute of Molecular Oncology; Milan Italy, Service de Génétique Clinique Chromosomique et Moléculaire; Hôpital Nord; St Etienne France, Unité d'Oncogénétique; CHU Arnaud de Villeneuve; Montpellier France, Unit of Molecular Bases of Genetic Risk and Genetic Testing; Department of Research; Fondazione IRCCS (Istituto Di Ricovero e Cura a Carattere Scientifico), Istituto Nazionale Tumori (INT); Milan Italy, School of Women's and Children's Health; UNSW; Sydney Australia, Department of Clinical Genetics; Karolinska University Hospital; Stockholm Sweden, Rebbeck, Timothy R., Friebel, Tara M., Friedman, Eitan, Hamann, Ute, Huo, Dezheng, Kwong, Ava, Olah, Edith, Olopade, Olufunmilayo I., Solano, Angela R., Teo, Soo-Hwang, Thomassen, Mads, Rashid, Muhammad Usman, Rhiem, Kerstin, Robson, Mark, Rodriguez, Gustavo C., Rogers, Mark T., Rudaitis, Vilius, Schmidt, Ane Y., Schmutzler, Rita Katharina, Senter, Leigha, van Rensburg, Elizabeth J., Gronwald, Jacek, Shah, Payal D., Sharma, Priyanka, Side, Lucy E., Simard, Jacques, Singer, Christian F., Skytte, Anne-Bine, Slavin, Thomas P., Snape, Katie, Sobol, Hagay, Southey, Melissa, Gutierrez-Barrera, Angelica, McGuffog, Lesley, Steele, Linda, Steinemann, Doris, Sukiennicki, Grzegorz, Sutter, Christian, Szabo, Csilla I., Tan, Yen Y., Teixeira, Manuel R., Terry, Mary Beth, Teulé, Alex, Hahnen, Eric, Thomas, Abigail, Parsons, Michael T., Thull, Darcy L., Tischkowitz, Marc, Tognazzo, Silvia, Toland, Amanda Ewart, Topka, Sabine, Trainer, Alison H, Tung, Nadine, van Asperen, Christi J., Hauke, Jan, van der Hout, Annemieke H., van der Kolk, Lizet E., Leslie, Goska, van der Luijt, Rob B., Van Heetvelde, Mattias, Varesco, Liliana, Varon-Mateeva, Raymonda, Vega, Ana, Villarreal-Garza, Cynthia, von Wachenfeldt, Anna, Henderson, Alex, Walker, Lisa, Wang-Gohrke, Shan, Wappenschmidt, Barbara, Aalfs, Cora M., Weber, Bernhard H. F., Yannoukakos, Drakoulis, Yoon, Sook-Yee, Zanzottera, Cristina, Zidan, Jamal, Zorn, Kristin K., Hentschel, Julia, Hutten Selkirk, Christina G., Hulick, Peter J., Chenevix-Trench, Georgia, Spurdle, Amanda B., Abugattas, Julio, Antoniou, Antonis C., Nathanson, Katherine L., Adlard, Julian, Agata, Simona, Aittomäki, Kristiina, Hogervorst, Frans B.L., Andrews, Lesley, Andrulis, Irene L., Arason, Adalgeir, Arnold, Norbert, Arun, Banu K., Asseryanis, Ella, Auerbach, Leo, Azzollini, Jacopo, Balmaña, Judith, Barile, Monica, Honisch, Ellen, Barkardottir, Rosa B., Barrowdale, Daniel, Benitez, Javier, Berger, Andreas, Berger, Raanan, Blanco, Amie M., Blazer, Kathleen R., Blok, Marinus J., Bonadona, Valérie, Bonanni, Bernardo, Imyanitov, Evgeny N., Bradbury, Angela R., Brewer, Carole, Buecher, Bruno, Buys, Saundra S., Caldes, Trinidad, Caliebe, Almuth, Caligo, Maria A., Campbell, Ian, Caputo, Sandrine M., Chiquette, Jocelyne, Isaacs, Claudine, Chung, Wendy K., Claes, Kathleen B.M., Collée, J. Margriet, Cook, Jackie, Davidson, Rosemarie, de la Hoya, Miguel, De Leeneer, Kim, de Pauw, Antoine, Delnatte, Capucine, Diez, Orland, Weitzel, Jeffrey N., Ding, Yuan Chun, Ditsch, Nina, Domchek, Susan M., Dorfling, Cecilia M., Velazquez, Carolina, Dworniczak, Bernd, Eason, Jacqueline, Easton, Douglas F., Eeles, Ros, Ehrencrona, Hans, Izatt, Louise, Ejlertsen, Bent, Engel, Christoph, Engert, Stefanie, Evans, D. Gareth, Faivre, Laurence, Feliubadaló, Lidia, Ferrer, Sandra Fert, Foretova, Lenka, Fowler, Jeffrey, Frost, Debra, Izquierdo, Angel, Galvão, Henrique C. R., Ganz, Patricia A., Garber, Judy, Gauthier-Villars, Marion, Gehrig, Andrea, Gerdes, Anne-Marie, Gesta, Paul, Giannini, Giuseppe, Giraud, Sophie, Glendon, Gord, Jakubowska, Anna, Godwin, Andrew K., Greene, Mark H., James, Paul, Janavicius, Ramunas, Jensen, Uffe Birk, John, Esther M., Vijai, Joseph, Kaczmarek, Katarzyna, Karlan, Beth Y., Chan, TL, Kast, Karin, Investigators, KConFab, Kim, Sung-Won, Konstantopoulou, Irene, Korach, Jacob, Laitman, Yael, Lasa, Adriana, Lasset, Christine, Lázaro, Conxi, Lee, Annette, Couch, Fergus J., Lee, Min Hyuk, Lester, Jenny, Lesueur, Fabienne, Liljegren, Annelie, Lindor, Noralane M., Longy, Michel, Loud, Jennifer T., Lu, Karen H., Lubinski, Jan, Machackova, Eva, Goldgar, David E., Manoukian, Siranoush, Mari, Véronique, Martínez-Bouzas, Cristina, Matrai, Zoltan, Mebirouk, Noura, Meijers-Heijboer, Hanne E.J., Meindl, Alfons, Mensenkamp, Arjen R., Mickys, Ugnius, Miller, Austin, Kruse, Torben A., Montagna, Marco, Moysich, Kirsten B., Mulligan, Anna Marie, Musinsky, Jacob, Neuhausen, Susan L., Nevanlinna, Heli, Ngeow, Joanne, Nguyen, Huu Phuc, Niederacher, Dieter, Nielsen, Henriette Roed, Palmero, Edenir Inêz, Nielsen, Finn Cilius, Nussbaum, Robert L., Offit, Kenneth, Öfverholm, Anna, Ong, Kai-ren, Osorio, Ana, Papi, Laura, Papp, Janos, Pasini, Barbara, Pedersen, Inge Sokilde, Park, Sue Kyung, Peixoto, Ana, Peruga, Nina, Peterlongo, Paolo, Pohl, Esther, Pradhan, Nisha, Prajzendanc, Karolina, Prieur, Fabienne, Pujol, Pascal, Radice, Paolo, Ramus, Susan J., Torres, Diana, and Rantala, Johanna
Abstract: To access publisher's full text version of this article click on the hyperlink below, The prevalence and spectrum of germline mutations in BRCA1 and BRCA2 have been reported in single populations, with the majority of reports focused on White in Europe and North America. The Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA) has assembled data on 18,435 families with BRCA1 mutations and 11,351 families with BRCA2 mutations ascertained from 69 centers in 49 countries on six continents. This study comprehensively describes the characteristics of the 1,650 unique BRCA1 and 1,731 unique BRCA2 deleterious (disease-associated) mutations identified in the CIMBA database. We observed substantial variation in mutation type and frequency by geographical region and race/ethnicity. In addition to known founder mutations, mutations of relatively high frequency were identified in specific racial/ethnic or geographic groups that may reflect founder mutations and which could be used in targeted (panel) first pass genotyping for specific populations. Knowledge of the population-specific mutational spectrum in BRCA1 and BRCA2 could inform efficient strategies for genetic testing and may justify a more broad-based oncogenetic testing in some populations.

11. International consensus on initial screening and follow-up of asymptomatic SDHx mutation carriers

Author: Camilo Jimenez, Henricus P. M. Kunst, Eric Baudin, Nicola Tufton, Philippe Herman, Rodney J. Hicks, Simon Aylwin, Mercedes Robledo, Henri J L M Timmers, Anne Paule Gimenez-Roqueplo, William F. Young, Massimo Mannelli, Roderick J. Clifton-Bligh, Patricia L. M. Dahia, Mitsuhide Naruse, Alexandre Buffet, Andrzej Januszewicz, Olivier Steichen, Scott Akker, Charlotte Lussey-Lepoutre, Karel Pacak, Martin Fassnacht, David R Taylor, Laurence Amar, Ashley B. Grossman, Giorgio Treglia, Jacques W.M. Lenders, Dylan Lewis, Nelly Burnichon, David Taïeb, Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Paris-Centre de Recherche Cardiovasculaire (PARCC (UMR_S 970/ U970)), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), Service de Médecine Interne [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), St Bartholomew's Hospital, King's College Hospital (KCH), Institut Gustave Roussy (IGR), Médecine nucléaire, Département d'imagerie médicale [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Royal North Shore Hospital (RNSH), The University of Sydney, The University of Texas at San Antonio (UTSA), University of Würzburg, Churchill Hospital, Churchill Hospital Oxford Centre for Haematology, Royal Free Hospital [London, UK], Barts & The London School of Medicine and Dentistry, Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), University of Melbourne, Institute of Cardiology (WARSAW - Cardiology), Institute of Cardiology, The University of Texas M.D. Anderson Cancer Center [Houston], Radboud University Medical Center [Nijmegen], Maastricht University Medical Centre (MUMC), Maastricht University [Maastricht], Università degli Studi di Firenze = University of Florence [Firenze] (UNIFI), Kyoto Medical Center, National Hospital Organization, Spanish National Cancer Research Center (CNIO), Centro de Investigación Biomédica en Red de Enfermedades Raras - CIBERER [Santiago de Compostela, Spain] (Grupo de Medicina Xenómica), Universidade de Santiago de Compostela [Spain] (USC ), Hôpital de la Timone [CHU - APHM] (TIMONE), Ente Ospedaliero Cantonale (EOC), Lausanne University Hospital, Università della Svizzera italiana = University of Italian Switzerland (USI), Mayo Clinic, Technische Universität Dresden = Dresden University of Technology (TU Dresden), Service de médecine nucléaire [CHU Pitié-Salpétrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), RS: MHeNs - R1 - Cognitive Neuropsychiatry and Clinical Neuroscience, KNO, and MUMC+: MA Keel Neus Oorheelkunde (9)
Subjects: 0301 basic medicine, PHEOCHROMOCYTOMA, Pediatrics, Internationality, SDHB, Endocrinology, Diabetes and Metabolism, Vascular damage Radboud Institute for Health Sciences [Radboudumc 16], 0302 clinical medicine, Endocrinology, Mass Screening, CAROTID-BODY TUMORS, Child, HIGH-ALTITUDE, Molecular medicine, medicine.diagnostic_test, Genetic Carrier Screening, GASTROINTESTINAL STROMAL TUMORS, Vascular damage Radboud Institute for Molecular Life Sciences [Radboudumc 16], [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, Penetrance, 3. Good health, Succinate Dehydrogenase, PARAGANGLIOMA, 030220 oncology & carcinogenesis, Mutation (genetic algorithm), Algorithms, Rare cancers Radboud Institute for Health Sciences [Radboudumc 9], Adult, Heterozygote, PENETRANCE, medicine.medical_specialty, Consensus, Genetic counseling, Adrenal tumours, 03 medical and health sciences, Germline mutation, medicine, Humans, Genetic Testing, Germ-Line Mutation, Mass screening, Aged, Monitoring, Physiologic, Genetic testing, business.industry, CLINICAL UTILITY, GENE, METANEPHRINES, 030104 developmental biology, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, Asymptomatic Diseases, MATERNAL TRANSMISSION, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, SDHD, business
Abstract: Approximately 20% of patients diagnosed with a phaeochromocytoma or paraganglioma carry a germline mutation in one of the succinate dehydrogenase (SDHx) genes (SDHA, SDHB, SDHC and SDHD), which encode the four subunits of the SDH enzyme. When a pathogenic SDHx mutation is identified in an affected patient, genetic counselling is proposed for first-degree relatives. Optimal initial evaluation and follow-up of people who are asymptomatic but might carry SDHx mutations have not yet been agreed. Thus, we established an international consensus algorithm of clinical, biochemical and imaging screening at diagnosis and during surveillance for both adults and children. An international panel of 29 experts from 12 countries was assembled, and the Delphi method was used to reach a consensus on 41 statements. This Consensus Statement covers a range of topics, including age of first genetic testing, appropriate biochemical and imaging tests for initial tumour screening and follow-up, screening for rare SDHx-related tumours and management of elderly people who have an SDHx mutation. This Consensus Statement focuses on the management of asymptomatic SDHx mutation carriers and provides clinicians with much-needed guidance. The standardization of practice will enable prospective studies in the near future.
Published: 2021

12. HIST1H1E heterozygous protein‐truncating variants cause a recognizable syndrome with intellectual disability and distinctive facial gestalt: A study to clarify the HIST1H1E syndrome phenotype in 30 individuals

Author: John M. Graham, Anna Ardissone, Dieter Kotzot, Paul R. Mark, Anna Zachariou, Guillermo Lay-Son, Allyn McConkie-Rosell, John Pappas, Karen Low, Fiona Stewart, Chey Loveday, Brian G. Skotko, Melissa Lees, Helen Stewart, Ho Ming Luk, Cheryl Cytrynbaum, Rachel Horton, Siddharth Banka, Gerard Marion, Deborah J. Shears, Marie T. McDonald, Ricardo A. Verdugo, Christine Coubes, Yuri A. Zarate, Christophe Phillipe, Katrina Tatton-Brown, Clare Allen, Deepika D.Cunha Burkardt, Rosanna Weksberg, I. Karen Temple, Alexia Bourgois, David J. Amor, Frédéric Tran Mau-Them, Laurence Faivre, Case Western Reserve University [Cleveland], The institute of cancer research [London], University College London Hospitals (UCLH), Murdoch Children's Research Institute (MCRI), University of Melbourne, Fondazione IRCCS Istituto Neurologico 'Carlo Besta', University of Manchester [Manchester], Manchester University NHS Foundation Trust (MFT), Service de Génétique [CHU Caen], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Université de Caen Normandie (UNICAEN), Normandie Université (NU), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), The Hospital for sick children [Toronto] (SickKids), Hôpital d'Enfants [CHU Dijon], Hôpital du Bocage, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Biologie, génétique et thérapies ostéoarticulaires et respiratoires (BIOTARGEN), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU), University Hospital Southampton NHS Foundation Trust, Paracelsus Medizinische Privatuniversität = Paracelsus Medical University (PMU), Pontificia Universidad Católica de Chile (UC), Great Ormond Street Hospital for Children [London] (GOSH), University Hospitals Bristol, Department of Health Clinical Genetic Service Centre, Spectrum Health [Grand Rapids], Department of Molecular Genetics and Microbiology [Durham] (MGM), Duke University [Durham], New York University School of Medicine (NYU), New York University School of Medicine, NYU System (NYU)-NYU System (NYU), Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Department of Clinical Genetics [Churchill Hospital], Churchill Hospital Oxford Centre for Haematology, Harvard Medical School [Boston] (HMS), Belfast City Hospital, Oxford University Hospitals NHS Trust, University of Oxford [Oxford], University of Southampton, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Universitad de Chile, Arkansas Children's Hospital, Cedars-Sinai Medical Center, St George’s University Hospitals, and Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Heterozygote, Bioinformatics, Corpus callosum, Rahman syndrome, Histones, 03 medical and health sciences, Frontal Bossing, 0302 clinical medicine, HIST1H1E, Gene cluster, Intellectual disability, Genetics, Humans, Learning, Medicine, Epigenetics, Genetics (clinical), 030304 developmental biology, Behavior, [SDV.GEN]Life Sciences [q-bio]/Genetics, 0303 health sciences, epigenetic regulator gene, biology, business.industry, Facies, Heterozygote advantage, Syndrome, medicine.disease, Phenotype, Histone, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, intellectual disability, Mutation, biology.protein, Growth and Development, business, 030217 neurology & neurosurgery
Abstract: International audience; Histone Gene Cluster 1 Member E, HIST1H1E, encodes Histone H1.4, is one of a family of epigenetic regulator genes, acts as a linker histone protein, and is responsible for higher order chromatin structure. HIST1H1E syndrome (also known as Rahman syndrome, OMIM #617537) is a recently described intellectual disability (ID) syndrome. Since the initial description of five unrelated individuals with three different heterozygous protein-truncating variants (PTVs) in the HIST1H1E gene in 2017, we have recruited 30 patients, all with HIST1H1E PTVs that result in the same shift in frame and that cluster to a 94-base pair region in the HIST1H1E carboxy terminal domain. The identification of 30 patients with HIST1H1E variants has allowed the clarification of the HIST1H1E syndrome phenotype. Major findings include an ID and a recognizable facial appearance. ID was reported in all patients and is most frequently of moderate severity. The facial gestalt consists of a high frontal hairline and full lower cheeks in early childhood and, in later childhood and adulthood, affected individuals have a strikingly high frontal hairline, frontal bossing, and deep-set eyes. Other associated clinical features include hypothyroidism, abnormal dentition, behavioral issues, cryptorchidism, skeletal anomalies, and cardiac anomalies. Brain magnetic resonance imaging (MRI) is frequently abnormal with a slender corpus callosum a frequent finding.
Published: 2019

13. SARS-CoV-2 elimination, not mitigation, creates best outcomes for health, the economy, and civil liberties

Author: Ilona Kickbusch, Philippe Aghion, Devi Sridhar, Patrick Artus, Miquel Oliu-Barton, Samantha Vanderslott, Jeffrey V. Lazarus, Bary S. R. Pradelski, Université Paris Dauphine-PSL, Université Paris sciences et lettres (PSL), Performance analysis and optimization of LARge Infrastructures and Systems (POLARIS), Inria Grenoble - Rhône-Alpes, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Laboratoire d'Informatique de Grenoble (LIG), Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP ), Université Grenoble Alpes (UGA)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP ), Université Grenoble Alpes (UGA), Oxford-Man Institute of Quantitative Finance (Oxford-Man), University of Oxford [Oxford], Collège de France (CdF (institution)), London School of Economics and Political Science (LSE), Institut Européen d'administration des Affaires (INSEAD), Natixis, Paris School of Economics (PSE), École des Ponts ParisTech (ENPC)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris 1 Panthéon-Sorbonne (UP1)-Centre National de la Recherche Scientifique (CNRS)-École des hautes études en sciences sociales (EHESS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Graduate Institute of International and Development studies (IHEID), Instituto de Salud Global - Institute For Global Health [Barcelona] (ISGlobal), Usher Institute of Population Health Sciences and Informatics [Edinburgh, U.K.], University of Edinburgh, Oxford Vaccine Group, University of Oxford [Oxford]-Oxford NIHR Biomedical Research Centre-The Churchill hospital, University of Oxford, Université Paris 1 Panthéon-Sorbonne (UP1)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École des hautes études en sciences sociales (EHESS)-École des Ponts ParisTech (ENPC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Paris Jourdan Sciences Economiques (PJSE), and University of Oxford-Oxford NIHR Biomedical Research Centre-The Churchill hospital
Subjects: medicine.medical_specialty, 2019-20 coronavirus outbreak, Economic growth, Coronavirus disease 2019 (COVID-19), Gross Domestic Product, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Civil liberties, Gross domestic product, [SHS]Humanities and Social Sciences, 03 medical and health sciences, 0302 clinical medicine, Civil rights, Political science, medicine, Civil Rights, Humans, 030212 general & internal medicine, ComputingMilieux_MISCELLANEOUS, SARS-CoV-2, Public health, Comment, COVID-19, General Medicine, Communicable Disease Control, Public Health, 030217 neurology & neurosurgery
Abstract: International audience
Published: 2021

14. Long-term real-world experience with ipilimumab and non-ipilimumab therapies in advanced melanoma: the IMAGE study

Author: Michal Lotem, T. Kim Le, Jane Brokaw, Srividya Kotapati, Ana Arance, Brian Buysse, Jennifer Lord-Bessen, Frank Meiss, Laurent Mortier, Andriy Moshyk, Pippa Corrie, Stéphane Dalle, Ruth E Board, Susan D. Mathias, Kelly Oh, Ralf Gutzmer, Mark R. Middleton, Julie Scotto, Patrick Terheyden, Apollo - University of Cambridge Repository, Hospices Civils de Lyon (HCL), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Thérapies Laser Assistées par l'Image pour l'Oncologie - U 1189 (ONCO-THAI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Cambridge University Hospitals NHS Foundation Trust, Cambridge University Hospitals - NHS (CUH), University of Cambridge [UK] (CAM), Hadassah Hebrew University Hospital, The Hebrew University of Jerusalem (HUJ), Hadassah Hebrew University Medical Center [Jerusalem], Royal Preston Hospital [Preston, UK] (RPH), Hospital Clinic [Barcelona, Spain], University of Freiburg [Freiburg], Universität zu Lübeck = University of Lübeck [Lübeck], Medizinische Hochschule Hannover (MHH), Syneos Health [Morrisville, NC, USA] (SH), Bristol-Myers Squibb [Princeton], Health Outcomes Solutions [Winter Park, FL, USA] (HOS), Churchill Hospital [Breast Care Unit], Churchill Hospital Oxford Centre for Haematology, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Universität zu Lübeck [Lübeck], and Malbec, Odile
Subjects: Male, Cancer Research, Skin Neoplasms, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Systemic therapy, 0302 clinical medicine, hemic and lymphatic diseases, Antineoplastic Combined Chemotherapy Protocols, Medicine, Overall survival, 030212 general & internal medicine, Prospective Studies, Immune Checkpoint Inhibitors, Melanoma, RC254-282, Aged, 80 and over, education.field_of_study, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Chemoradiotherapy, Middle Aged, Advanced melanoma, 3. Good health, [SDV] Life Sciences [q-bio], Treatment Outcome, Oncology, 030220 oncology & carcinogenesis, Cohort, Female, medicine.drug, Research Article, Subsequent therapy, Quality of life, Adult, medicine.medical_specialty, Population, Ipilimumab, Radiosurgery, 03 medical and health sciences, Young Adult, Internal medicine, Genetics, Humans, Adverse effect, education, Aged, Chemotherapy, business.industry, Survival Analysis, Clinical trial, Radiation therapy, Real-world, business, Follow-Up Studies
Abstract: Background Ipilimumab has shown long-term overall survival (OS) in patients with advanced melanoma in clinical trials, but robust real-world evidence is lacking. We present long-term outcomes from the IMAGE study (NCT01511913) in patients receiving ipilimumab and/or non-ipilimumab (any approved treatment other than ipilimumab) systemic therapies. Methods IMAGE was a multinational, prospective, observational study assessing adult patients with advanced melanoma treated with ipilimumab or non-ipilimumab systemic therapies between June 2012 and March 2015 with ≥3 years of follow-up. Adjusted OS curves based on multivariate Cox regression models included covariate effects. Safety and patient-reported outcomes were assessed. Results Among 1356 patients, 1094 (81%) received ipilimumab and 262 (19%) received non-ipilimumab index therapy (systemic therapy [chemotherapy, anti–programmed death 1 antibodies, or BRAF ± MEK inhibitors], radiotherapy, and radiosurgery). In the overall population, median age was 64 years, 60% were male, 78% were from Europe, and 78% had received previous treatment for advanced melanoma. In the ipilimumab-treated cohort, 780 (71%) patients did not receive subsequent therapy (IPI-noOther) and 314 (29%) received subsequent non-ipilimumab therapy (IPI-Other) on study. In the non-ipilimumab–treated cohort, 205 (78%) patients remained on or received other subsequent non-ipilimumab therapy (Other-Other) and 57 (22%) received subsequent ipilimumab therapy (Other-IPI) on study. Among 1151 patients who received ipilimumab at any time during the study (IPI-noOther, IPI-Other, and Other-IPI), 296 (26%) reported CTCAE grade ≥ 3 treatment-related adverse events, most occurring in year 1. Ipilimumab-treated and non-ipilimumab–treated patients who switched therapy (IPI-Other and Other-IPI) had longer OS than those who did not switch (IPI-noOther and Other-Other). Patients with prior therapy who did not switch therapy (IPI-noOther and Other-Other) showed similar OS. In treatment-naive patients, those in the IPI-noOther group tended to have longer OS than those in the Other-Other group. Patient-reported outcomes were similar between treatment cohorts. Conclusions With long-term follow-up (≥ 3 years), safety and OS in this real-world population of patients treated with ipilimumab 3 mg/kg were consistent with those reported in clinical trials. Patient-reported quality of life was maintained over the study period. OS analysis across both pretreated and treatment-naive patients suggested a beneficial role of ipilimumab early in treatment. Trial registration ClinicalTrials.gov, NCT01511913. Registered January 19, 2012 – Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT01511913
Published: 2021

15. Estimating the effect size of the 15Q11.2 BP1–BP2 deletion and its contribution to neurodevelopmental symptoms: recommendations for practice

Author: Jacques Puechberty, Charlotte Brasch-Andersen, Aurélie Pain, Sonia Richetin, Sébastien Jacquemont, Usha Kini, Anke Van Dijck, Christiane Zweier, Elise Douard, Lilian Bomme Ousager, Aia E. Jønch, Cédric Le Caignec, Anders Bojesen, Bertrand Isidor, Damien Sanlaville, Carolyn Campbell, James Lespinasse, Anne-Bine Skytte, Henrietta Lefroy, Helle Hjalgrim, Marie Ange Delrue, Marzia Passeggeri, Clara Moreau, Emmanuelle Lemyre, Rikke S. Møller, R. Frank Kooy, Jean-Hubert Caberg, David Geneviève, University of Southern Denmark (SDU), Centre Hospitalier de l'Université de Montréal (CHUM), Université de Montréal (UdeM), Antwerp University Hospital [Edegem] (UZA), Service of Neurology [CHUV, Lausanne, Switzerland], Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV), Institut de génétique humaine (IGH), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Oxford University Hospitals NHS Trust, University of Oxford [Oxford], Centre de recherche en neurosciences de Lyon (CRNL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Department of Clinical Genetics [Churchill Hospital], Churchill Hospital Oxford Centre for Haematology, unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Centre hospitalier universitaire de Nantes (CHU Nantes), Centre Hospitalier Métropole Savoie [Chambéry], Aarhus University Hospital, Service de génétique médicale - Unité de génétique clinique [Nantes], Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), Friedrich-Alexander Universität Erlangen-Nürnberg (FAU), Centre Hospitalier Universitaire de Liège (CHU-Liège), Service de génétique médicale, Université de Bordeaux (UB)-CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, The Danish Epilepsy Centre Filadelfia [Dianalund, Denmark], and 15q11.2 Working Group
Subjects: Male, Pediatrics, Heart malformation, 15q11.2 copy-number variants, [SDV]Life Sciences [q-bio], Neurodevelopmental Disorders/genetics, Epilepsy/genetics, Cohort Studies, Epilepsy, 0302 clinical medicine, Loss of Function Mutation, Gene duplication, Genetics (clinical), Sequence Deletion, 0303 health sciences, loss-of-function intolerance, neurodevelopmental disorders, Microdeletion syndrome, congenital heart disease, Schizophrenia, Female, Autistic Disorder/genetics, medicine.medical_specialty, Heart Diseases, DNA Copy Number Variations, Genetic counseling, 03 medical and health sciences, Intellectual Disability, Genetics, medicine, Humans, Autistic Disorder, Biology, 030304 developmental biology, Heart Diseases/congenital, [SDV.GEN]Life Sciences [q-bio]/Genetics, business.industry, medicine.disease, Intellectual Disability/genetics, Case-Control Studies, Autism, epilepsy, Clinical case, Human medicine, Copy-Number Variation, business, 030217 neurology & neurosurgery, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: BackgroundThe 15q11.2 deletion is frequently identified in the neurodevelopmental clinic. Case–control studies have associated the 15q11.2 deletion with neurodevelopmental disorders, and clinical case series have attempted to delineate a microdeletion syndrome with considerable phenotypic variability. The literature on this deletion is extensive and confusing, which is a challenge for genetic counselling. The aim of this study was to estimate the effect size of the 15q11.2 deletion and quantify its contribution to neurodevelopmental disorders.MethodsWe performed meta-analyses on new and previously published case–control studies and used statistical models trained in unselected populations with cognitive assessments. We used new (n=241) and previously published (n=150) data from a clinically referred group of deletion carriers. 15q11.2 duplications (new n=179 and previously published n=35) were used as a neutral control variant.ResultsThe deletion decreases IQ by 4.3 points. The estimated ORs and respective frequencies in deletion carriers for intellectual disabilities, schizophrenia and epilepsy are 1.7 (3.4%), 1.5 (2%) and 3.1 (2.1%), respectively. There is no increased risk for heart malformations and autism. In the clinically referred group, the frequency and nature of symptoms in deletions are not different from those observed in carriers of the 15q11.2 duplication suggesting that most of the reported symptoms are due to ascertainment bias.ConclusionsWe recommend that the deletion should be classified as ‘pathogenic of mild effect size’. Since it explains only a small proportion of the phenotypic variance in carriers, it is not worth discussing in the developmental clinic or in a prenatal setting.
Published: 2019

16. Heterozygous Variants in KMT2E Cause a Spectrum of Neurodevelopmental Disorders and Epilepsy

Author: Anne H. O’Donnell-Luria, Lynn S. Pais, Víctor Faundes, Jordan C. Wood, Abigail Sveden, Victor Luria, Rami Abou Jamra, Andrea Accogli, Kimberly Amburgey, Britt Marie Anderlid, Silvia Azzarello-Burri, Alice A. Basinger, Claudia Bianchini, Lynne M. Bird, Rebecca Buchert, Wilfrid Carre, Sophia Ceulemans, Perrine Charles, Helen Cox, Lisa Culliton, Aurora Currò, Florence Demurger, James J. Dowling, Benedicte Duban-Bedu, Christèle Dubourg, Saga Elise Eiset, Luis F. Escobar, Alessandra Ferrarini, Tobias B. Haack, Mona Hashim, Solveig Heide, Katherine L. Helbig, Ingo Helbig, Raul Heredia, Delphine Héron, Bertrand Isidor, Amy R. Jonasson, Pascal Joset, Boris Keren, Fernando Kok, Hester Y. Kroes, Alinoë Lavillaureix, Xin Lu, Saskia M. Maas, Gustavo H.B. Maegawa, Carlo L.M. Marcelis, Paul R. Mark, Marcelo R. Masruha, Heather M. McLaughlin, Kirsty McWalter, Esther U. Melchinger, Saadet Mercimek-Andrews, Caroline Nava, Manuela Pendziwiat, Richard Person, Gian Paolo Ramelli, Luiza L.P. Ramos, Anita Rauch, Caitlin Reavey, Alessandra Renieri, Angelika Rieß, Amarilis Sanchez-Valle, Shifteh Sattar, Carol Saunders, Niklas Schwarz, Thomas Smol, Myriam Srour, Katharina Steindl, Steffen Syrbe, Jenny C. Taylor, Aida Telegrafi, Isabelle Thiffault, Doris A. Trauner, Helio van der Linden, Silvana van Koningsbruggen, Laurent Villard, Ida Vogel, Julie Vogt, Yvonne G. Weber, Ingrid M. Wentzensen, Elysa Widjaja, Jaroslav Zak, Samantha Baxter, Siddharth Banka, Lance H. Rodan, Jeremy F. McRae, Stephen Clayton, Tomas W. Fitzgerald, Joanna Kaplanis, Elena Prigmore, Diana Rajan, Alejandro Sifrim, Stuart Aitken, Nadia Akawi, Mohsan Alvi, Kirsty Ambridge, Daniel M. Barrett, Tanya Bayzetinova, Philip Jones, Wendy D. Jones, Daniel King, Netravathi Krishnappa, Laura E. Mason, Tarjinder Singh, Adrian R. Tivey, Munaza Ahmed, Uruj Anjum, Hayley Archer, Ruth Armstrong, Jana Awada, Meena Balasubramanian, Diana Baralle, Angela Barnicoat, Paul Batstone, David Baty, Chris Bennett, Jonathan Berg, Birgitta Bernhard, A. Paul Bevan, Maria Bitner-Glindzicz, Edward Blair, Moira Blyth, David Bohanna, Louise Bourdon, David Bourn, Lisa Bradley, Angela Brady, Simon Brent, Carole Brewer, Kate Brunstrom, David J. Bunyan, John Burn, Natalie Canham, Bruce Castle, Kate Chandler, Elena Chatzimichali, Deirdre Cilliers, Angus Clarke, Susan Clasper, Jill Clayton-Smith, Virginia Clowes, Andrea Coates, Trevor Cole, Irina Colgiu, Amanda Collins, Morag N. Collinson, Fiona Connell, Nicola Cooper, Lara Cresswell, Gareth Cross, Yanick Crow, Mariella D’Alessandro, Tabib Dabir, Rosemarie Davidson, Sally Davies, Dylan de Vries, John Dean, Charu Deshpande, Gemma Devlin, Abhijit Dixit, Angus Dobbie, Alan Donaldson, Dian Donnai, Deirdre Donnelly, Carina Donnelly, Angela Douglas, Sofia Douzgou, Alexis Duncan, Jacqueline Eason, Sian Ellard, Ian Ellis, Frances Elmslie, Karenza Evans, Sarah Everest, Tina Fendick, Richard Fisher, Frances Flinter, Nicola Foulds, Andrew Fry, Alan Fryer, Carol Gardiner, Lorraine Gaunt, Neeti Ghali, Richard Gibbons, Harinder Gill, Judith Goodship, David Goudie, Emma Gray, Andrew Green, Philip Greene, Lynn Greenhalgh, Susan Gribble, Rachel Harrison, Lucy Harrison, Victoria Harrison, Rose Hawkins, Liu He, Stephen Hellens, Alex Henderson, Sarah Hewitt, Lucy Hildyard, Emma Hobson, Simon Holden, Muriel Holder, Susan Holder, Georgina Hollingsworth, Tessa Homfray, Mervyn Humphreys, Jane Hurst, Ben Hutton, Stuart Ingram, Melita Irving, Lily Islam, Andrew Jackson, Joanna Jarvis, Lucy Jenkins, Diana Johnson, Elizabeth Jones, Dragana Josifova, Shelagh Joss, Beckie Kaemba, Sandra Kazembe, Rosemary Kelsell, Bronwyn Kerr, Helen Kingston, Usha Kini, Esther Kinning, Gail Kirby, Claire Kirk, Emma Kivuva, Alison Kraus, Dhavendra Kumar, V. K. Ajith Kumar, Katherine Lachlan, Wayne Lam, Anne Lampe, Caroline Langman, Melissa Lees, Derek Lim, Cheryl Longman, Gordon Lowther, Sally A. Lynch, Alex Magee, Eddy Maher, Alison Male, Sahar Mansour, Karen Marks, Katherine Martin, Una Maye, Emma McCann, Vivienne McConnell, Meriel McEntagart, Ruth McGowan, Kirsten McKay, Shane McKee, Dominic J. McMullan, Susan McNerlan, Catherine McWilliam, Sarju Mehta, Kay Metcalfe, Anna Middleton, Zosia Miedzybrodzka, Emma Miles, Shehla Mohammed, Tara Montgomery, David Moore, Sian Morgan, Jenny Morton, Hood Mugalaasi, Victoria Murday, Helen Murphy, Swati Naik, Andrea Nemeth, Louise Nevitt, Ruth Newbury-Ecob, Andrew Norman, Rosie O’Shea, Caroline Ogilvie, Kai-Ren Ong, Soo-Mi Park, Michael J. Parker, Chirag Patel, Joan Paterson, Stewart Payne, Daniel Perrett, Julie Phipps, Daniela T. Pilz, Martin Pollard, Caroline Pottinger, Joanna Poulton, Norman Pratt, Katrina Prescott, Sue Price, Abigail Pridham, Annie Procter, Hellen Purnell, Oliver Quarrell, Nicola Ragge, Raheleh Rahbari, Josh Randall, Julia Rankin, Lucy Raymond, Debbie Rice, Leema Robert, Eileen Roberts, Jonathan Roberts, Paul Roberts, Gillian Roberts, Alison Ross, Elisabeth Rosser, Anand Saggar, Shalaka Samant, Julian Sampson, Richard Sandford, Ajoy Sarkar, Susann Schweiger, Richard Scott, Ingrid Scurr, Ann Selby, Anneke Seller, Cheryl Sequeira, Nora Shannon, Saba Sharif, Charles Shaw-Smith, Emma Shearing, Debbie Shears, Eamonn Sheridan, Ingrid Simonic, Roldan Singzon, Zara Skitt, Audrey Smith, Kath Smith, Sarah Smithson, Linda Sneddon, Miranda Splitt, Miranda Squires, Fiona Stewart, Helen Stewart, Volker Straub, Mohnish Suri, Vivienne Sutton, Ganesh Jawahar Swaminathan, Elizabeth Sweeney, Kate Tatton-Brown, Cat Taylor, Rohan Taylor, Mark Tein, I. Karen Temple, Jenny Thomson, Marc Tischkowitz, Susan Tomkins, Audrey Torokwa, Becky Treacy, Claire Turner, Peter Turnpenny, Carolyn Tysoe, Anthony Vandersteen, Vinod Varghese, Pradeep Vasudevan, Parthiban Vijayarangakannan, Emma Wakeling, Sarah Wallwark, Jonathon Waters, Astrid Weber, Diana Wellesley, Margo Whiteford, Sara Widaa, Sarah Wilcox, Emily Wilkinson, Denise Williams, Nicola Williams, Louise Wilson, Geoff Woods, Christopher Wragg, Michael Wright, Laura Yates, Michael Yau, Chris Nellåker, Michael Parker, Helen V. Firth, Caroline F. Wright, David R. FitzPatrick, Jeffrey C. Barrett, Matthew E. Hurles, Department of Medicine 1, Friedrich-Alexander Universität Erlangen-Nürnberg (FAU), Center for Medical Genetics, Istituto di Scienze e Tecnologie della Cognizione, Consiglio Nazionale delle Ricerche (ISTC, CNR), Istituto di Scienze e Tecnologie della Cognizione, Station biologique de Roscoff [Roscoff] (SBR), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Génétique médicale [Centre Hospitalier de Vannes], Centre hospitalier Bretagne Atlantique (Morbihan) (CHBA), Department of Pediatrics, University of Michigan [Ann Arbor], University of Michigan System-University of Michigan System, Centre de Génétique Chromosomique [Hôpital Saint Vincent de Paul], Hôpital Saint Vincent de Paul-Groupement des Hôpitaux de l'Institut Catholique de Lille (GHICL), Université catholique de Lille (UCL)-Université catholique de Lille (UCL), Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Service de génétique médicale, Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV), Institute of Human Genetics, Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM)-Helmholtz Zentrum München = German Research Center for Environmental Health, Groupe de Recherche Clinique : Déficience Intellectuelle et Autisme (GRC), Université Pierre et Marie Curie - Paris 6 (UPMC), Children’s Hospital of Philadelphia (CHOP ), Service de Génétique Médicale, Centre hospitalier universitaire de Nantes (CHU Nantes), Department of Public Health Sciences, Karolinska Institutet [Stockholm], Department of Molecular and Human Genetics, Baylor College of Medicine (BCM), Baylor University-Baylor University, Institute of Medical Genetics, Universität Zürich [Zürich] = University of Zurich (UZH), Università degli Studi di Camerino = University of Camerino (UNICAM), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), University of Oxford, GeneDx [Gaithersburg, MD, USA], Department of Clinical Genetics (Academic Medical Center, University of Amsterdam), VU University Medical Center [Amsterdam], Marseille medical genetics - Centre de génétique médicale de Marseille (MMG), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Clinical Genetics, Aarhus University Hospital, Boston Children's Hospital, Wellcome Trust Genome Campus, The Wellcome Trust Sanger Institute [Cambridge], Institute of Biomedical Engineering [Oxford] (IBME), Climatic Research Unit, University of East Anglia [Norwich] (UEA), Imperial College London, St Mary's Hospital, East Anglian Medical Genetics Service, Cytogenetics Laboratory, Addenbrooke's Hospital, Sheffield Children's NHS Foundation Trust, Regional Genetic Service, St Mary's Hospital, Manchester, Genetics, University of Southampton, Great Ormond Street Hospital for Children [London] (GOSH), Yorkshire Regional Clinical Genetics Service, Chapel Allerton Hospital, Molecular and Clinical Medicine [Dundee, UK] (School of Medicine), University of Dundee [UK]-Ninewells Hospital & Medical School [Dundee, UK], Department of Clinical Genetics, Oxford Regional Genetics Service, The Churchill hospital, North West Thames Regional Genetics, Northwick Park Hospital, Royal Devon & Exeter Hospital, Wessex Clinical Genetics Service, Wessex clinical genetics service, Manchester University NHS Foundation Trust (MFT), West Midlands Regional Genetics Service, Birmingham Women's and Children's NHS Foundation Trust, Our Lady's hospital for Sick Children, Our Lady's Hospital for Sick Children, Guy's Hospital [London], University Hospitals Leicester, University of Edinburgh, Belfast City Hospital, Ferguson-Smith Centre for Clinical Genetics, Yorkhill Hospitals, Institute of Medical Genetics, Heath Park, Cardiff, The London Clinic, Nottingham City Hospital, Clinical Genetics Department, St Michael's Hospital, Department of Genetic Medicine, Nottingham Clinical Genetics Service, Nottingham University Hospitals NHS Trust (NUH), Royal Devon and Exeter Foundation Trust, Histopathology, St. George's Hospital, Teesside Genetics Unit, James Cook University (JCU), Kansas State University, Liverpool Women's NHS Foundation Trust, Department of Medical Genetics, HMNC Brain Health, North West Thames Regional Genetics Service, Northwick Park Hospital, Harrow, Leicester Royal Infirmary, University Hospitals Leicester-University Hospitals Leicester, Ninewells Hospital and Medical School [Dundee], Academic Centre on Rare Diseases (ACoRD), University College Dublin [Dublin] (UCD), Oxford Brookes University, Institute of medicinal plant development, Chinese Academy of Medical Sciences, Newcastle Upon Tyne Hospitals NHS Trust, Service d'explorations fonctionnelles respiratoires [Lille], Department of Computer Science - Trinity College Dublin, University of Dublin, Department of Clinical Genetics (Sheffield Children’s NHS Foundation Trust), Division of Medical & Molecular Genetics, NHS Greater Glasgow & Clyde [Glasgow] (NHSGGC), Department of Clinical Genetics [Churchill Hospital], Churchill Hospital Oxford Centre for Haematology, Weizmann Institute of Science [Rehovot, Israël], Southampton General Hospital, Western General Hospital, Head of the Department of Medical Genetics, University of Birmingham [Birmingham], SW Thames Regional Genetics Service, St Georgeâ™s University of London, London, Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), All Wales Medical Genetics Services, Singleton Hospital, Central Manchester University Hospitals NHS Foundation Trust, University of North Texas (UNT), Clinical Genetics, Northern Genetics Service, Newcastle University [Newcastle], United Kingdom Met Office [Exeter], Institute of Medical Genetics (University Hospital of Wales), University Hospital of Wales (UHW), West Midlands Regional Genetics Laboratory and Clinical Genetics Unit, Birmingham Women's Hospital, Laboratory of Molecular Genetics, National Institute of Child Health and Human Development, National Institutes of Health, Department of Genetics, Cell- and Immunobiology, Semmelweis University, University Hospitals Bristol, Marketing (MKT), EESC-GEM Grenoble Ecole de Management, Addenbrookes Hospital, West of Scotland Genetics Service (Queen Elizabeth University Hospital), University Hospital Birmingham Queen Elizabeth, Department of Clnical Genetics, Chapel Allerton Hospital, Department of Clinical Genetics, Northampton General Hospital, Northampton, Royal Devon and Exeter Hospital [Exeter, UK] (RDEH), Guy's and St Thomas' Hospital [London], School of Computer Science, Bangor University, University Hospital Southampton, Clinical Genetics Unit, St Georges, University of London, Medical Genetics, Cardiff University, Research and Development, Futurelab, Nottingham Regional Genetics Service [Nottingham, UK], Nottingham University Hospitals NHS Trust (NUH)-City Hospital Campus [Nottingham, UK], University of St Andrews [Scotland], Clinical Genetics Service, Nottingham University Hospitals NHS Trust - City Hospital Campus, West Midlands Regional Genetics Unit, Department of Neurology, Johns Hopkins University (JHU), Oxford University Hospitals NHS Trust, St James's University Hospital, Leeds Teaching Hospitals NHS Trust, Addenbrooke's Hospital, Cambridge University NHS Trust, Institute of Human Genetics, Newcastle, Division of Biological Stress Response [Amsterdam, The Netherlands], The Netherlands Cancer Institute [Amsterdam, The Netherlands], Johns Hopkins Bloomberg School of Public Health [Baltimore], Birmingham Women’s Hospital, Department of Genetics, Portuguese Oncology Institute, Molecular Genetics, IWK Health Centre, IWK health centre, North West london hospitals NHS Trust, Department of Clinical Genetics (Queen Elizabeth University Hospital, Glasgow), Queen Elizabeth University Hospital (Glasgow), Birmingham women's hospital, Birmingham, Ethox Centre, Department of Public Health and Primary Health Care, University of Oxford, Badenoch Building, Old Road Campus, Headington, R01 HD091846, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Human Genome Research Institute, National Institutes of Health’s National Institute of Child Health and Human Development, Boston Children’s Hospital Faculty Development Fellowship, UM1HG008900, Broad Center for Mendelian Genomics, Chile’s National Commission for Scientific and Technological Research, DFG WE4896/3-1, German Research Society, WT 100127, Health Innovation Challenge Fund, Comprehensive Clinical Research Network, Skaggs-Oxford Scholarship, 10/H0305/83, Cambridge South REC, REC GEN/284/12, Republic of Ireland, WT098051, Wellcome Sanger Institute, 72160007, Comisión Nacional de Investigación Científica y Tecnológica, Children's Hospital of Philadelphia, Technische Universität Kaiserslautern, 1DH1813319, Dietmar Hopp Stiftung, National Institute for Health Research, Department of Health & Social Care, Service de neurologie 1 [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Hôpital Saint Vincent de Paul-GHICL, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM)-Helmholtz-Zentrum München (HZM)-German Research Center for Environmental Health, Service de Génétique Cytogénétique et Embryologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Università degli Studi di Camerino (UNICAM), University of Oxford [Oxford], Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU), Nottingham University Hospitals NHS Trust, Nottingham University Hospitals, SW Thames Regional Genetics Service, St Georgeâ™s University of London, London, University Hospital of Wales, Grenoble Ecole de Management, Royal Devon and Exeter Hospital, City Hospital Campus [Nottingham, UK]-Nottingham University Hospitals NHS Trust [UK], ANS - Complex Trait Genetics, Human Genetics, ARD - Amsterdam Reproduction and Development, ACS - Pulmonary hypertension & thrombosis, Service de Neurologie [CHU Pitié-Salpêtrière], IFR70-CHU Pitié-Salpêtrière [AP-HP], GHICL-Hôpital Saint Vincent de Paul, Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Friedrich-Alexander d'Erlangen-Nuremberg, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Centre Hospitalier Bretagne Atlantique [Vannes], Technische Universität München [München] (TUM)-Helmholtz-Zentrum München (HZM)-German Research Center for Environmental Health, Service de Génétique et Cytogénétique [CHU Pitié-Salpêtrière], University of Zürich [Zürich] (UZH), Università di Camerino (UNICAM), Birmingham Women's Hospital Healthcare NHS Trust, University Hospitals of Leicester, Sheffield Children’s Hospital, Weizmann Institute of Science, and Grenoble Ecole de Management (GEM)
Subjects: 0301 basic medicine, Male, Microcephaly, [SDV]Life Sciences [q-bio], Haploinsufficiency, autism, epilepsy, epileptic encephalopathy, global developmental delay, H3K4 methylation, intellectual disability, KMT2E, neurodevelopmental disorder, Adolescent, Adult, Child, Child, Preschool, DNA-Binding Proteins, Epilepsy, Female, Humans, Infant, Neurodevelopmental Disorders, Pedigree, Phenotype, Young Adult, Genetic Variation, Heterozygote, 0302 clinical medicine, Neurodevelopmental disorder, Intellectual disability, Global developmental delay, Genetics (clinical), ComputingMilieux_MISCELLANEOUS, Genetics, 0303 health sciences, Hypotonia, 030220 oncology & carcinogenesis, medicine.symptom, Rare cancers Radboud Institute for Health Sciences [Radboudumc 9], 03 medical and health sciences, Report, medicine, Journal Article, Expressivity (genetics), Preschool, 030304 developmental biology, [SDV.GEN]Life Sciences [q-bio]/Genetics, business.industry, Macrocephaly, medicine.disease, 030104 developmental biology, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, Autism, business, 030217 neurology & neurosurgery
Abstract: Contains fulltext : 206572.pdf (Publisher’s version ) (Open Access) We delineate a KMT2E-related neurodevelopmental disorder on the basis of 38 individuals in 36 families. This study includes 31 distinct heterozygous variants in KMT2E (28 ascertained from Matchmaker Exchange and three previously reported), and four individuals with chromosome 7q22.2-22.23 microdeletions encompassing KMT2E (one previously reported). Almost all variants occurred de novo, and most were truncating. Most affected individuals with protein-truncating variants presented with mild intellectual disability. One-quarter of individuals met criteria for autism. Additional common features include macrocephaly, hypotonia, functional gastrointestinal abnormalities, and a subtle facial gestalt. Epilepsy was present in about one-fifth of individuals with truncating variants and was responsive to treatment with anti-epileptic medications in almost all. More than 70% of the individuals were male, and expressivity was variable by sex; epilepsy was more common in females and autism more common in males. The four individuals with microdeletions encompassing KMT2E generally presented similarly to those with truncating variants, but the degree of developmental delay was greater. The group of four individuals with missense variants in KMT2E presented with the most severe developmental delays. Epilepsy was present in all individuals with missense variants, often manifesting as treatment-resistant infantile epileptic encephalopathy. Microcephaly was also common in this group. Haploinsufficiency versus gain-of-function or dominant-negative effects specific to these missense variants in KMT2E might explain this divergence in phenotype, but requires independent validation. Disruptive variants in KMT2E are an under-recognized cause of neurodevelopmental abnormalities.
Published: 2019

17. Competing risk events in antimalarial drug trials in uncomplicated Plasmodium falciparum malaria: a WorldWide Antimalarial Resistance Network individual participant data meta-analysis

Author: Pedro Rafael Dimbu, Marit De Wit, Kamala L. Thriemer, Sarah G. Staedke, Filomeno Fortes, Salim Abdulla, Julie A. Simpson, Oliver James Pratt, Bart Janssens, Andreas Mårtensson, Veronique Sinou, Steffen Borrmann, Walter R. J. Taylor, Ingrid van der Broek, Christopher J. M. Whitty, Meghna Desai, François Bompart, Zulfikarali Premji, Theonest K. Mutabingwa, Aarti Agarwal, Anupkumar R. Anvikar, Emmanuel Arinaitwe, Petra F. Mens, Piero Olliaro, François Nosten, Maman Laminou Ibrahim, Birgit Schramm, Hasifa Bukirwa, Michèle van Vugt, Jane Achan, J. Pedro Gil, Timothy M. E. Davis, Ogobara K. Doumbo, Michel Cot, Grant Dorsey, Michael Ramharter, Sue J. Lee, Sodiomon B. Sirima, Ambrose O. Talisuna, Poul-Erik Kofoed, Brian Greenwood, Catherine O. Falade, Valerie Lameyre, Mayfong Mayxay, Andre Toure Offianan, Hervé Ei Menan, Teun Bousema, Erasmus Kamugisha, Chris J. Drakeley, Elizabeth Juma, Johan Ursing, Abul Faiz, Emmanuel Temu, Carol Hopkins Sibley, Patrice Piola, Philip J. Rosenthal, Frank Smithuis, Mateusz M. Plucinski, Marco Corsi, Anastasia Grivoyannis, Richard Allan, Elizabeth A. Ashley, Harald Noedl, Jean François Faucher, Issaka Zongo, Corine Karema, Cornelis Winnips, Kamal Hamed, Umberto D'Alessandro, Venkatachalam Udhayakumar, Michael D. Edstein, Fred Kironde, Harin Karunajeewa, Philippe Deloron, Quique Bassat, Patrick Sawa, David P. Hughes, Ishag Adam, Michel Van Herp, Christopher V. Plowe, Ghulam Rahim Awab, Caterina I. Fanello, Joel Tarning, Stephan Duparc, Jean Bosco Ouedraogo, Emmanuelle Espie, Tran Tinh Hien, Jean R. Kiechel, Anders Björkman, Abdoulaye Djimde, Billy E. Ngasala, Nahla B. Gadalla, Prabin Dahal, Kasia Stepniewska, Lars Rombo, Nhien Nguyen Thuy, Philippe J Guerin, Verena I. Carrara, Babacar Faye, Christophe Rogier, Peter G. Kremsner, Oumar Gaye, Inge Sutanto, Jean-Louis A Ndiaye, Bernhards Ogutu, Mary Oguike, Vincent Jullien, Jimee Hwang, Kevin Marsh, Djibrine Djalle, Ric N. Price, Yavo William, Georgina S Humphreys, WorldWide Antimalarial Resistance Network (WWARN), University of Oxford [Oxford]-Churchill Hospital Oxford Centre for Haematology, Neuroépidémiologie Tropicale (NET), Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM)-CHU Limoges-Institut d'Epidémiologie Neurologique et de Neurologie Tropicale-Institut National de la Santé et de la Recherche Médicale (INSERM), Service des Maladies infectieuses et tropicales [CHU Limoges], CHU Limoges, Membranes et cibles thérapeutiques (MCT), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Recherche Biomédicale des Armées (IRBA), University of Oxford-Churchill Hospital Oxford Centre for Haematology, CHU Limoges-Institut d'Epidémiologie Neurologique et de Neurologie Tropicale-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Recherche Biomédicale des Armées [Brétigny-sur-Orge] (IRBA), Infectious diseases, AII - Infectious diseases, APH - Global Health, and APH - Quality of Care
Subjects: [SDV]Life Sciences [q-bio], Network Meta-Analysis, Infektionsmedicin, Plasmodium falciparum/drug effects, Polymerase Chain Reaction, 0302 clinical medicine, Dihydroartemisinin/piperaquine, Recurrence, Cumulative incidence, 030212 general & internal medicine, Antimalarials/pharmacology, Malaria, Falciparum, biology, Malaria, Falciparum/drug therapy, food and beverages, 3. Good health, Infectious Diseases, Meta-analysis, Regression Analysis, Competing risk even, Risk, Treatment efficacy study, Infectious Medicine, medicine.medical_specialty, lcsh:Arctic medicine. Tropical medicine, lcsh:RC955-962, 030231 tropical medicine, Plasmodium falciparum, Malària, Competing risks, lcsh:Infectious and parasitic diseases, Antimalarials, 03 medical and health sciences, Internal medicine, parasitic diseases, medicine, Humans, lcsh:RC109-216, business.industry, Methodology, medicine.disease, biology.organism_classification, Malaria, Competing risk event, Parasitology, Tropical medicine, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business
Abstract: Background Therapeutic efficacy studies in uncomplicated Plasmodium falciparum malaria are confounded by new infections, which constitute competing risk events since they can potentially preclude/pre-empt the detection of subsequent recrudescence of persistent, sub-microscopic primary infections. Methods Antimalarial studies typically report the risk of recrudescence derived using the Kaplan–Meier (K–M) method, which considers new infections acquired during the follow-up period as censored. Cumulative Incidence Function (CIF) provides an alternative approach for handling new infections, which accounts for them as a competing risk event. The complement of the estimate derived using the K–M method (1 minus K–M), and the CIF were used to derive the risk of recrudescence at the end of the follow-up period using data from studies collated in the WorldWide Antimalarial Resistance Network data repository. Absolute differences in the failure estimates derived using these two methods were quantified. In comparative studies, the equality of two K–M curves was assessed using the log-rank test, and the equality of CIFs using Gray’s k-sample test (both at 5% level of significance). Two different regression modelling strategies for recrudescence were considered: cause-specific Cox model and Fine and Gray’s sub-distributional hazard model. Results Data were available from 92 studies (233 treatment arms, 31,379 patients) conducted between 1996 and 2014. At the end of follow-up, the median absolute overestimation in the estimated risk of cumulative recrudescence by using 1 minus K–M approach was 0.04% (interquartile range (IQR): 0.00–0.27%, Range: 0.00–3.60%). The overestimation was correlated positively with the proportion of patients with recrudescence [Pearson’s correlation coefficient (ρ): 0.38, 95% Confidence Interval (CI) 0.30–0.46] or new infection [ρ: 0.43; 95% CI 0.35–0.54]. In three study arms, the point estimates of failure were greater than 10% (the WHO threshold for withdrawing antimalarials) when the K–M method was used, but remained below 10% when using the CIF approach, but the 95% confidence interval included this threshold. Conclusions The 1 minus K–M method resulted in a marginal overestimation of recrudescence that became increasingly pronounced as antimalarial efficacy declined, particularly when the observed proportion of new infection was high. The CIF approach provides an alternative approach for derivation of failure estimates in antimalarial trials, particularly in high transmission settings. Electronic supplementary material The online version of this article (10.1186/s12936-019-2837-4) contains supplementary material, which is available to authorized users.
Published: 2019

18. Outcomes of unrelated cord blood transplantation in patients with multiple myeloma: a survey on behalf of Eurocord, the Cord Blood Committee of Cellular Therapy and Immunobiology Working Party, and the Chronic Leukemia Working Party of the EBMT

Author: Erick Xavier, Annalisa Paviglianiti, Eliane Gluckman, E. Deconinck, Pierre-Simon Rohrlich, Vanderson Rocha, Fernanda Volt, Annalisa Ruggeri, Nicolaus Kroeger, Laurent Garderet, Patrice Ceballos, Nathalie Fegueux, Guillermo Sanz, Jan J. Cornelissen, Mohamad Mohty, Natacha Maillard, Stephanie Nguyen-Quoc, France Monacord, Centre Scientifique de Monaco (CSM), Eurocord, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut Universitaire d'Hématologie (IUH), Université Paris Diderot - Paris 7 (UPD7)-Université Paris Diderot - Paris 7 (UPD7), Service d'hématologie clinique et de thérapie cellulaire [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Hôpital Lapeyronie [Montpellier] (CHU), Service d'Hématologie [CHRU Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Erasmus University Medical Center [Rotterdam] (Erasmus MC), Service d'Hématologie clinique [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital de la Milétrie, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Hospital La Fe [Valencia, Spain], Hôpital l'Archet, Churchill Hospital, Churchill Hospital Oxford Centre for Haematology, Universität Hamburg (UHH), Centre de Recherche Saint-Antoine (UMRS893), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Hematology
Subjects: Adult, Male, medicine.medical_specialty, Graft vs Host Disease, Cord Blood Stem Cell Transplantation, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Recurrence, Internal medicine, Medicine, Humans, Registries, Mortality, Multiple myeloma, Aged, Retrospective Studies, Plasma cell leukemia, Neutrophil Engraftment, business.industry, Umbilical Cord Blood Transplantation, Graft Survival, Hematology, Articles, Middle Aged, medicine.disease, Combined Modality Therapy, 3. Good health, Surgery, Transplantation, Treatment Outcome, Chronic leukemia, 030220 oncology & carcinogenesis, Cord blood, Female, business, Multiple Myeloma, Unrelated Donors, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, 030215 immunology, Follow-Up Studies
Abstract: International audience; Although allogeneic stem cell transplantation is not a standard therapy for multiple myeloma, some patients can benefit from this intense therapy. There are few reports on outcomes after umbilical cord blood transplantation in multiple myeloma, and investigation of this procedure is warranted. We retrospectively analyzed 95 patients, 85 with multiple myeloma and 10 with plasma cell leukemia, receiving single or double umbilical cord blood transplantation from 2001 to 2013. Median follow up was 41 months. The majority of patients received a reduced intensity conditioning. The cumulative incidence of neutrophil engraftment was 97%±3% at 60 days, and that of 100-day acute graft-versus-host disease grade II-IV was 41%±5%. Chronic graft-versus-host disease at two years was 22%±4%. Relapse and non-relapse mortality was 47%±5% and 29%±5% at three years, respectively. Three-year progression-free survival and overall survival were 24%±5% and 40%±5%, respectively. Anti-thymocyte globulin was associated with decreased incidence of acute graft-versus-host disease, higher non-relapse mortality, decreased overall and progression-free survival. Patients with high cytogenetic risk had higher relapse, and worse overall and progression-free survival. In conclusion, umbilical cord blood transplantation is feasible for multiple myeloma patients.
Published: 2016

19. A novel strategy combining array-CGH, whole-exome sequencing and in utero electroporation in rodents to identify causative genes for brain malformations

Author: Conti, V, Carabalona, A, Pallesi-Pocachard, E, Leventer, R, Schaller, F, Parrini, E, Deparis, A, Watrin, F, Buhler, E, Novara, F, Lise, S, Pagnamenta, A, Kini, U, Taylor, J, Zuffardi, O, Represa, A, Keays, D, Guerrini, R, Falace, A, Cardoso, C, Institut de Biologie du Développement de Marseille (IBDM), Aix Marseille Université (AMU)-Collège de France (CdF (institution))-Centre National de la Recherche Scientifique (CNRS), Institut de Neurobiologie de la Méditerranée [Aix-Marseille Université] (INMED - INSERM U901), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Pediatric Neurology Unit and Laboratories, Università degli Studi di Firenze = University of Florence (UniFI)-Children's Hospital A. Meyer, Cytogenetics, The Wellcome Trust Centre for Human Genetics [Oxford], University of Oxford, Department of Clinical Genetics [Churchill Hospital], Churchill Hospital Oxford Centre for Haematology, Biologia Generale e Genetica Medica, Università degli Studi di Pavia = University of Pavia (UNIPV), Epilepsie et ischémie cérébrale, Université de la Méditerranée - Aix-Marseille 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Istituto Di Ricovero e Cura a Carattere Scientifico (IRCCS), Stella Maris Foundation, Children's Hospital A. Meyer-Università degli Studi di Firenze = University of Florence [Firenze] (UNIFI), University of Oxford [Oxford], Università degli Studi di Pavia, and Università degli Studi di Firenze = University of Florence [Firenze] (UNIFI)-Children's Hospital A. Meyer
Subjects: Brain Chemistry, Comparative Genomic Hybridization, [SDV]Life Sciences [q-bio], [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Brain, DNA, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Rats, Malformations of Cortical Development, Disease Models, Animal, Electroporation, Pregnancy, Exome Sequencing, Animals, Humans, Female, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], [SDV.BDD]Life Sciences [q-bio]/Development Biology, ComputingMilieux_MISCELLANEOUS, Neuroscience
Abstract: Birth defects that involve the cerebral cortex - also known as malformations of cortical development (MCD) - are important causes of intellectual disability and account for 20-40% of drug-resistant epilepsy in childhood. High-resolution brain imaging has facilitated in vivo identification of a large group of MCD phenotypes. Despite the advances in brain imaging, genomic analysis and generation of animal models, a straightforward workflow to systematically prioritize candidate genes and to test functional effects of putative mutations is missing. To overcome this problem, an experimental strategy enabling the identification of novel causative genes for MCD was developed and validated. This strategy is based on identifying candidate genomic regions or genes via array-CGH or whole-exome sequencing and characterizing the effects of their inactivation or of overexpression of specific mutations in developing rodent brains via in utero electroporation. This approach led to the identification of the C6orf70 gene, encoding for a putative vesicular protein, to the pathogenesis of periventricular nodular heterotopia, a MCD caused by defective neuronal migration.
Published: 2018

20. Oral Contraceptive Use and Breast Cancer Risk: Retrospective and Prospective Analyses From a BRCA1 and BRCA2 Mutation Carrier Cohort Study

Author: Christian F. Singer, Louise Izatt, Yen Y. Tan, Emmanuelle Mouret-Fourme, Embrace, Genepso, Bcfr, Hebon, kConFab, Marie Navratilova, Lucy Side, Trinidad Caldés, Rosemarie Davidson, Kelly-Anne Phillips, Saundra S. Buys, Dominique Leroux, Mary B. Daly, Melissa C. Southey, Marian J.E. Mourits, Brita Arver, Theo A. M. van Os, Anne-Marie Gerdes, Douglas F. Easton, Marie-José Roos-Blom, Michael Friedlander, Lieske H. Schrijver, David E. Goldgar, Anna Jakubowska, Roger L. Milne, Håkan Olsson, Lisa Walker, Ros Eeles, Flora E. van Leeuwen, Mary Porteous, Sue-Anne McLachlan, Pascaline Berthet, Lenka Foretova, Catherine Noguès, Matti A. Rookus, Debra Frost, Daniel Barrowdale, Esther M. John, Julian Adlard, Encarna B. Gomez Garcia, Nadine Andrieu, Laurence Venat-Bouvet, Anita Bane, John L. Hopper, Mary Beth Terry, Jacques Simard, Ana Osorio, Antonis C. Antoniou, Christoph Engel, Wendy K. Chung, Karin Kast, Ibccs, D. Gareth Evans, Valérie Bonadona, Edith Olah, Steve Ellis, Christi J. van Asperen, T.M. Mooij, Human Genetics, APH - Methodology, APH - Quality of Care, Netherlands Cancer Institute (NKI), Antoni van Leeuwenhoek Hospital, Skane University Hospital [Lund], Lund University [Lund], University of Melbourne, Columbia Mailman School of Public Health, University of Utah School of Medicine [Salt Lake City], Technische Universität Dresden = Dresden University of Technology (TU Dresden), Department of Clinical Sciences [Lund], University of Leipzig [Leipzig, Allemagne], Chapel Allerton Hospital, University of Cambridge [UK] (CAM), Queen Elizabeth University Hospital (Glasgow), Royal Marsden NHS Foundation Trust, University of Manchester [Manchester], Guy's and St Thomas NHS Foundation Trust [London], Western General Hospital [Edinburgh, UK], Great Ormond Street Hospital for Children NHS Foundation Trust [London, UK], Churchill Hospital [Breast Care Unit], Churchill Hospital Oxford Centre for Haematology, Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Centre Hospitalier Universitaire [Grenoble] (CHU), hôpital couple-enfant [CHU Grenoble Alpes], Hôpital René HUGUENIN (Saint-Cloud), Hôpital Dupuytren [CHU Limoges], Huntsman Cancer Institute [Salt Lake City], University of Utah, Monash University [Melbourne], Stanford University School of Medicine [CA, USA], California Sciences Institute, Columbia University [New York], Fox Chase Cancer Center, McMaster University [Hamilton, Ontario], Karolinska Institutet [Stockholm], Leiden University Medical Center (LUMC), School for Oncology and Developmental Biology [Maastricht] (GROW), Maastricht University [Maastricht]-Maastricht University Medical Centre (MUMC), Maastricht University [Maastricht], University Medical Center Groningen [Groningen] (UMCG), Academic Medical Center - Academisch Medisch Centrum [Amsterdam] (AMC), University of Amsterdam [Amsterdam] (UvA), University of New South Wales [Sydney] (UNSW), Prince of Wales Hospital, St. Vincent's Hospital, Sydney, Medizinische Universität Wien = Medical University of Vienna, Masaryk Memorial Cancer Institute (RECAMO), University Hospital of Cologne [Cologne], Copenhagen University Hospital, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos [Madrid, Spain] (IdISSC), Université Laval [Québec] (ULaval), National Institute of Oncology [Budapest, Hungary], Pomeranian Medical University [Szczecin, Poland] (PMU), Spanish National Cancer Centre, Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale (SESSTIM - U1252 INSERM - Aix Marseille Univ - UMR 259 IRD), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Cancer et génome: Bioinformatique, biostatistiques et épidémiologie d'un système complexe, MINES ParisTech - École nationale supérieure des mines de Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Cancer Epidemiology Centre & Cancer Council Victoria [Melbourne, Australia], Melbourne School for Population and Global Health-University of Melbourne, Leipzig University, Great Ormond Street Hospital for Children NHS Foundation Trust [London, UK] (GOSHC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), Masaryk Memorial Cancer Institute (MMCI), Pomeranian Medical University [Szczecin] (PUM), Mines Paris - PSL (École nationale supérieure des mines de Paris), University of Melbourne-Melbourne School for Population and Global Health, Malbec, Odile, Universiteit Leiden, RS: GROW - R4 - Reproductive and Perinatal Medicine, MUMC+: DA KG Polikliniek (9), Klinische Genetica, MUMC+: DA KG Lab Centraal Lab (9), Damage and Repair in Cancer Development and Cancer Treatment (DARE), Targeted Gynaecologic Oncology (TARGON), Life Course Epidemiology (LCE), and Basic and Translational Research and Imaging Methodology Development in Groningen (BRIDGE)
Subjects: 0301 basic medicine, Cancer Research, medicine.medical_specialty, [SDV]Life Sciences [q-bio], Article, OVARIAN-CANCER, 03 medical and health sciences, 0302 clinical medicine, Breast cancer, medicine, Prospective cohort study, skin and connective tissue diseases, Pregnancy, Proportional hazards model, Obstetrics, business.industry, Hazard ratio, CONSORTIUM, WOMEN, medicine.disease, PREVENTION, Confidence interval, KCONFAB, [SDV] Life Sciences [q-bio], 030104 developmental biology, Oncology, 030220 oncology & carcinogenesis, Cohort, business, Cohort study
Abstract: Background For BRCA1 and BRCA2 mutation carriers, the association between oral contraceptive preparation (OCP) use and breast cancer (BC) risk is still unclear. Methods Breast camcer risk associations were estimated from OCP data on 6030 BRCA1 and 3809 BRCA2 mutation carriers using age-dependent Cox regression, stratified by study and birth cohort. Prospective, left-truncated retrospective and full-cohort retrospective analyses were performed. Results For BRCA1 mutation carriers, OCP use was not associated with BC risk in prospective analyses (hazard ratio [HR] = 1.08, 95% confidence interval [CI] = 0.75 to 1.56), but in the left-truncated and full-cohort retrospective analyses, risks were increased by 26% (95% CI = 6% to 51%) and 39% (95% CI = 23% to 58%), respectively. For BRCA2 mutation carriers, OCP use was associated with BC risk in prospective analyses (HR = 1.75, 95% CI = 1.03 to 2.97), but retrospective analyses were inconsistent (left-truncated: HR = 1.06, 95% CI = 0.85 to 1.33; full cohort: HR = 1.52, 95% CI = 1.28 to 1.81). There was evidence of increasing risk with duration of use, especially before the first full-term pregnancy (BRCA1: both retrospective analyses, P < .001 and P = .001, respectively; BRCA2: full retrospective analysis, P = .002). Conclusions Prospective analyses did not show that past use of OCP is associated with an increased BC risk for BRCA1 mutation carriers in young middle-aged women (40–50 years). For BRCA2 mutation carriers, a causal association is also not likely at those ages. Findings between retrospective and prospective analyses were inconsistent and could be due to survival bias or a true association for younger women who were underrepresented in the prospective cohort. Given the uncertain safety of long-term OCP use for BRCA1/2 mutation carriers, indications other than contraception should be avoided and nonhormonal contraceptive methods should be discussed.
Published: 2018

21. Natural immunity against capsular group X N. meningitidis following an outbreak in Togo, 2007

Author: Andrew J. Pollard, Tsidi Agbeko Tamekloe, Gunnstein Norheim, Berthe-Marie Njanpop-Lafourcade, Roshan Ramasamy, Ray Borrow, Jerry C. Nagaputra, Lisbeth Meyer Næss, Christine S. Rollier, Hilary Watt, Helen Findlow, Judith E. Mueller, Ouli Xie, Abiba Banla Kere, Christina Dold, Isabelle Delrieu, Norwegian Institute of Public Health [Oslo] (NIPH), Oxford Vaccine Group, University of Oxford [Oxford]-Oxford NIHR Biomedical Research Centre-The Churchill hospital, École des Hautes Études en Santé Publique [EHESP] (EHESP), Département Méthodes quantitatives en santé publique (METIS), Epidémiologie des Maladies Emergentes - Emerging Diseases Epidemiology, Pasteur-Cnam Risques infectieux et émergents (PACRI), Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM), Agence de Médecine Préventive, Public Health England [London], Ministry of Health [Togo], Imperial College London, Institut National d’Hygiene [Togo], This work was funded by a research grant from the Meningitis Research Foundation, U.K. (Grant number 0906.1) and supported by the Oxford Partnership Comprehensive Biomedical Research Centre with funding from the NIHR Biomedical Research Centre Programme., University of Oxford-Oxford NIHR Biomedical Research Centre-The Churchill hospital, Institut Pasteur [Paris] (IP), Institut Pasteur [Paris] (IP)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Institut Pasteur [Paris] (IP)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), and HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)
Subjects: Male, [SDV]Life Sciences [q-bio], Physiology, Neisseria meningitidis, medicine.disease_cause, MESH: Meningococcal Vaccines, Disease Outbreaks, 0302 clinical medicine, Seroepidemiologic Studies, MESH: Child, MESH: Antibodies, Bacterial, 030212 general & internal medicine, MESH: Disease Outbreaks, Child, Polysaccharide, MESH: Immunoglobulin G, Meningococcal, biology, MESH: Meningitis, Meningococcal, Age Factors, 11 Medical And Health Sciences, Antibodies, Bacterial, 3. Good health, Titer, Infectious Diseases, MESH: Young Adult, Child, Preschool, Population Surveillance, Togo, Molecular Medicine, MESH: Immunity, Innate, Female, Antibody, Adult, Adolescent, 030231 tropical medicine, Meningococcal Vaccines, Meningitis, Meningococcal, MESH: Neisseria meningitidis, Antibodies, MESH: Population Surveillance, Capsular group X, Young Adult, 03 medical and health sciences, Immune system, Antigen, Conjugate vaccine, Virology, medicine, Humans, MESH: Adolescent, MESH: Age Factors, Antigens, Bacterial, MESH: Humans, MESH: Seroepidemiologic Studies, Innate immune system, General Veterinary, General Immunology and Microbiology, business.industry, MESH: Child, Preschool, Public Health, Environmental and Occupational Health, Outbreak, MESH: Adult, 06 Biological Sciences, MESH: Male, Immunity, Innate, MESH: Togo, Immunoglobulin G, biology.protein, Bactericidal, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, 07 Agricultural And Veterinary Sciences, business, MESH: Female, MESH: Antigens, Bacterial
Abstract: Background Capsular group X N. meningitidis (MenX) has emerged as a cause of localized disease outbreaks in sub-Saharan Africa, but the human immune response following exposure to MenX antigens is poorly described. We therefore assessed the natural immunity against MenX in individuals who were living in an area affected by a MenX outbreak during 2007 in Togo, West Africa. During 2009, 300 healthy individuals (100 aged 3–5 years, 100 aged 13–19 years and 100 aged 20–25 years) were included in the study, and serum responses were compared with sera from age-matched controls from the U.K. and Burkina Faso. Methods MenX serum bactericidal antibody (SBA) was measured using rabbit complement, and antibodies against MenX polysaccharide (XPS) and outer membrane vesicles (XOMVs) were quantified by ELISA. Results The proportion of Togolese individuals with an SBA titer of ≥8 against the MenX strain was 29% (95% confidence interval (CI) 18–41) among those aged 3–5 years, 34% (95% CI 9–60) among those aged 13–19 years and 32% (95% CI 24–40) among those aged 20–25 years. These were significantly higher than observed in the control populations from the U.K (range 13–16%) and Burkina Faso (range 2–6%). Conclusion In Togolese individuals, the concentration of serum IgG against XPS was higher among the two older age groups as compared to the youngest age group. Antibody concentrations against MenX PS correlated significantly with SBA titers. This supports further development of a MenX PS based conjugate vaccine. Further studies are needed to verify the ability of MenX PS to induce SBA in humans.
Published: 2018

22. Cord Blood Unit Dominance Analysis and Effect of the Winning Unit on Outcomes after Double-Unit Umbilical Cord Blood Transplantation in Adults with Acute Leukemia: A Retrospective Study on Behalf of Eurocord, the Cord Blood Committee of Cellular Therapy, Immunobiology Working Party, and the Acute Leukemia Working Party of the European Group for Blood and Marrow Transplantation

Author: Charles Craddock, Nigel H. Russell, Henrik Sengeloev, Thierry Lamy, Pierre-Simon Rohrlich, Maud D'Aveni, Vanderson Rocha, Mauricette Michallet, Arnon Nagler, Karina Tozatto-Maio, Eric Deconinck, Eliane Gluckman, Edouard Forcade, Annalisa Ruggeri, Chantal Kenzey, Hiromi Hayashi, Jan J. Cornelissen, Regis Peffault de la Tour, Federica Giannotti, Fernanda Volt, Annalisa Paviglianiti, Didier Blaise, Myriam Labopin, Eefke Petersen, Dimitrios Karakasis, Eurocord, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut Universitaire d'Hématologie (IUH), Université Paris Diderot - Paris 7 (UPD7)-Université Paris Diderot - Paris 7 (UPD7), Centre International des greffes [CHU Saint-Antoine] (EBMT), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Service d'hématologie clinique et de thérapie cellulaire [CHU Saint-Antoine], France Monacord, Centre Scientifique de Monaco (CSM), Erasmus University Medical Center [Rotterdam] (Erasmus MC), Service d'hématologie [Hôpital Edouard Herriot - HCL], Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Hôpital l'Archet, Service d'hématologie greffe [Saint-Louis], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Haut-Lévêque, Université Sciences et Technologies - Bordeaux 1-CHU Bordeaux [Bordeaux], University Medical Center [Utrecht], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Ingénierie Moléculaire et Physiopathologie Articulaire (IMoPA), Centre National de la Recherche Scientifique (CNRS)-Université de Lorraine (UL), Rigshospitalet [Copenhagen], Copenhagen University Hospital, CHU Pontchaillou [Rennes], Composantes innées de la réponse immunitaire et différenciation (CIRID), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique (CNRS), Centre for Clinical Haematology [Birmingham, UK], Queen Elizabeth Hospital [Birmingham, UK], Churchill Hospital, Churchill Hospital Oxford Centre for Haematology, and Hematology
Subjects: Adult, Male, medicine.medical_specialty, [SDV.CAN]Life Sciences [q-bio]/Cancer, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Medicine, Humans, Retrospective Studies, Transplantation, Acute leukemia, Transplantation Chimera, Neutrophil Engraftment, Leukemia, Umbilical Cord Blood Transplantation, business.industry, Hazard ratio, Retrospective cohort study, Hematology, HLA Mismatch, Survival Analysis, HLA, 030220 oncology & carcinogenesis, Cord blood, Double-Unit Umbilical Cord Blood Transplantation, Histocompatibility, Acute Disease, Double cord blood transplantation, Winning cord blood unit, Female, Cord Blood Stem Cell Transplantation, business, SOBREVIDA, 030215 immunology, Unit dominance
Abstract: International audience; Usually, after double umbilical cord blood transplantation (DUCBT), only 1 of the transplanted units persists in the long term. The characteristics of the winning cord blood unit (W-CBU) that determine unit dominance and how they influence the outcomes of DUCBT remain unclear. We retrospectively analyzed 347 patients with acute leukemia transplanted with a DUCBT (694 CBU) from 2005 to 2013 who had documented neutrophil engraftment and a W-CBU identified by chimerism analysis, to identify unit characteristics impacting on dominance. Median age at DUCBT was 40 years and median follow-up was 35 months. Among W-CBUs, 41% were ≥5/6 HLA matched to the recipient and 59% were ≤4/6. Multivariate analysis indicated that ≤4/6 HLA-matched W-CBUs led to lower leukemia-free survival (44% versus 56%; hazard ratio [HR], 1.5; P = .032) and overall survival (49% versus 62%; HR, 1.5; P = .028), increased nonrelapse mortality (26% versus 18%; HR, 1.9; P = .027), and acute graft-versus-host disease (46% versus 35%; HR, 1.7; P = .013). We were unable to predict unit dominance, but we demonstrated that outcomes were strongly influenced by the degree of HLA mismatch between W-CBU and recipient. Therefore, selection of both units with the lower number of HLA mismatches with the recipient is indicated.
Published: 2017

23. Mutations in the HECT domain of NEDD4L lead to AKT-mTOR pathway deregulation and cause periventricular nodular heterotopia

Author: Broix, L, Jagline, H, L Ivanova, E, Schmucker, S, Drouot, N, Clayton-Smith, J, Pagnamenta, A, Metcalfe, K, Isidor, B, Louvier, U, Poduri, A, Taylor, J, Tilly, P, Poirier, K, Saillour, Y, Lebrun, N, Stemmelen, T, Rudolf, G, Muraca, G, Saintpierre, B, Elmorjani, A, study, Deciphering Developmental Disorders, Moïse, M, Weirauch, N, Guerrini, R, Boland, A, Olaso, R, Masson, C, Tripathy, R, Keays, D, Beldjord, C, Nguyen, L, Godin, J, Kini, U, Nischké, P, Deleuze, J, Bahi-Buisson, N, Sumara, I, Hinckelmann, M, Chelly, J, Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Regional Genetic Service, St Mary's Hospital, Manchester, The Wellcome Trust Centre for Human Genetics [Oxford], University of Oxford [Oxford], Central Manchester University Hospitals NHS Foundation Trust, Service de génétique médicale - Unité de génétique clinique [Nantes], Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), Institut de génétique et biologie moléculaire et cellulaire (IGBMC), Université Louis Pasteur - Strasbourg I-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-CHU Pitié-Salpêtrière [APHP], Pediatric Neurology & Neurogenetics Unit and Laboratories, Children's Hospital A. Meyer-University of Florence (UNIFI), Centre National de Génotypage (CNG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Plate Forme Paris Descartes de Bioinformatique (BIP-D), Université Paris Descartes - Paris 5 (UPD5), Institut Cochin (UMR_S567 / UMR 8104), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5), Department of Clinical Genetics [Churchill Hospital], Churchill Hospital Oxford Centre for Haematology, Service de neurologie pédiatrique [CHU Necker], CHU Necker - Enfants Malades [AP-HP]-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Institute of Biochemistry (IBC), Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology in Zürich [Zürich] (ETH Zürich), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Università degli Studi di Firenze = University of Florence [Firenze] (UNIFI)-Children's Hospital A. Meyer, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich), University of Oxford, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), and Università degli Studi di Firenze = University of Florence (UniFI)-Children's Hospital A. Meyer
Subjects: 0301 basic medicine, HECT domain, Male, Nedd4 Ubiquitin Protein Ligases, Ubiquitin-Protein Ligases, [SDV]Life Sciences [q-bio], Mutation, Missense, mTORC1, Bioinformatics, medicine.disease_cause, Article, 03 medical and health sciences, Mice, 0302 clinical medicine, Ubiquitin, Periventricular Nodular Heterotopia, Protein Domains, hemic and lymphatic diseases, Genetics, medicine, Animals, Humans, Protein kinase B, PI3K/AKT/mTOR pathway, Cells, Cultured, ComputingMilieux_MISCELLANEOUS, Mutation, biology, Endosomal Sorting Complexes Required for Transport, TOR Serine-Threonine Kinases, DAB1, Cell biology, Ubiquitin ligase, 030104 developmental biology, biology.protein, Female, Proto-Oncogene Proteins c-akt, 030217 neurology & neurosurgery, Signal Transduction
Abstract: Neurodevelopmental disorders with periventricular nodular heterotopia (PNH) are etiologically heterogeneous, and their genetic causes remain in many cases unknown. Here we show that missense mutations in the HECT domain of the E3 ubiquitin ligase NEDD4L lead to PNH associated with toes syndactyly, cleft palate and neurodevelopmental delay. Cellular and expression data showed a sensitivity of PNH-associated mutants to proteasome degradation. Moreover, in utero electroporation approach showed that PNH-related mutants and excess of wild type (WT) NEDD4L affect neurogenesis, neuronal positioning and terminal translocation. Further investigations, including rapamycin based experiments, revealed differential deregulation of pathways involved. Excess of WT NEDD4L leads to a disruption of Dab1 and mTORC1 pathways, while PNH-related mutations are associated with a deregulation of mTORC1 and AKT activities. Altogether, these data provide insights to better understand the critical role of NEDD4L in the regulation of mTOR pathways and their contributions in cortical development.
Published: 2017

24. Sickle cell disease: An international survey of results of HLA-identical sibling hematopoietic stem cell transplantation

Author: Gluckman, E., Cappelli, B., Bernaudin, F., Labopin, M., Volt, F., Carreras, J., Simoes, B. P., Ferster, A., Dupont, S., De La Fuente, J., Dalle, J. -H., Zecca, M., Walters, M. C., Krishnamurti, L., Bhatia, M., Leung, K., Yanik, G., Kurtzberg, J., Dhedin, N., Kuentz, M., Michel, G., Apperley, J., Lutz, P., Neven, B., Bertrand, Y., Vannier, J. P., Ayas, M., Cavazzana, M., Matthes-Martin, S., Rocha, V., Elayoubi, H., Kenzey, C., Bader, P., Locatelli, Franco, Ruggeri, A., Eapen, M., Bordon, V., Labarque, V., Pereira, M., Bittencourt, H., Petersen, H., Deconninck, E., Jubert, C., Perrin, J., Cahn, J. Y., Bruno, B., Bordigoni, P., Mechinaud, F., Vernant, J. P., Stephan, J. L., Suttorp, M., Strahm, B., Da Cunha, C. B., Garwer, B., Rothmayer, M., Wendelin, K., Graphakos, S., Tbakhi, A., Naeimi, N., Zuckerman, T., Sharon, P. B., Yaniv, I., Amos, T., Prete, A., Lo Nigro, L., Lanino, E., Faraci, M., Ciceri, F., Marktel, S., De Simone, G., Messina, C., Bartolomeo, P. D. I., Santarone, S., Vallisa, D., Bertaina, A., Arcese, W., Foa, R., Berger, M., Maximova, N., Wallet, S., Bazuaye, G. N., Maschan, A., De Heredia, C. D., Bieler, C. B., Pato, J. R., Heras, I., Trevor, R., Abayomi, K., Thomson, J., Fasth, A., Frodin, U., Ljugman, P., Ansari, M., Gungor, T., Unal, E., Pehlivan, M., Anak, S., Ozturk, G., Unal, A., Lawson, S., Keshani, J., Drake, A., Wynn, R., Williams, J., Jagsia, M., Leung, W., Abraham, A., Sahdey, I., Margolis, D., Eames, G., Horwitz, E., Cowan, M., Kapoor, N., Rowley, S., Megason, G., Rogers, Z., Bolanos-Meade, J., Hudspeth, M., Rosenthal, J., Olson, T., Kassow, K., Selby, G., Haines, H., Chaudhury, S., Gluckman, E., Cappelli, B., Bernaudin, F., Labopin, M., Volt, F., Carreras, J., Simoes, B. P., Ferster, A., Dupont, S., De La Fuente, J., Dalle, J. -H., Zecca, M., Walters, M. C., Krishnamurti, L., Bhatia, M., Leung, K., Yanik, G., Kurtzberg, J., Dhedin, N., Kuentz, M., Michel, G., Apperley, J., Lutz, P., Neven, B., Bertrand, Y., Vannier, J. P., Ayas, M., Cavazzana, M., Matthes-Martin, S., Rocha, V., Elayoubi, H., Kenzey, C., Bader, P., Locatelli, F., Ruggeri, A., Eapen, M., Bordon, V., Labarque, V., Pereira, M., Bittencourt, H., Petersen, H., Deconninck, E., Jubert, C., Perrin, J., Cahn, J. Y., Bruno, B., Bordigoni, P., Mechinaud, F., Vernant, J. P., Stephan, J. L., Suttorp, M., Strahm, B., Da Cunha, C. B., Garwer, B., Rothmayer, M., Wendelin, K., Graphakos, S., Tbakhi, A., Naeimi, N., Zuckerman, T., Sharon, P. B., Yaniv, I., Amos, T., Prete, A., Lo Nigro, L., Lanino, E., Faraci, M., Ciceri, F., Marktel, S., De Simone, G., Messina, C., Bartolomeo, P. D. I., Santarone, S., Vallisa, D., Bertaina, A., Arcese, W., Foa, R., Berger, M., Maximova, N., Wallet, S., Bazuaye, G. N., Maschan, A., De Heredia, C. D., Bieler, C. B., Pato, J. R., Heras, I., Trevor, R., Abayomi, K., Thomson, J., Fasth, A., Frodin, U., Ljugman, P., Ansari, M., Gungor, T., Unal, E., Pehlivan, M., Anak, S., Ozturk, G., Unal, A., Lawson, S., Keshani, J., Drake, A., Wynn, R., Williams, J., Jagsia, M., Leung, W., Abraham, A., Sahdey, I., Margolis, D., Eames, G., Horwitz, E., Cowan, M., Kapoor, N., Rowley, S., Megason, G., Rogers, Z., Bolanos-Meade, J., Hudspeth, M., Rosenthal, J., Olson, T., Kassow, K., Selby, G., Haines, H., Chaudhury, S., France Monacord, Centre Scientifique de Monaco (CSM), CHI Créteil, Centre de Recherche Saint-Antoine (CR Saint-Antoine), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Eurocord, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Institut Universitaire d'Hématologie (IUH), Université Paris Diderot - Paris 7 (UPD7)-Université Paris Diderot - Paris 7 (UPD7), Hôpital Universitaire des Enfants - Reine Fabiola, Université Libre de Bruxelles, Equipe NEMESIS - Centre de Recherches de l'Institut du Cerveau et de la Moelle épinière (NEMESIS-CRICM), Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière (CRICM), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Unité d'Hémato-Immunologie pédiatrique [Hôpital Robert Debré, Paris], Service d'Immuno-hématologie pédiatrique [Hôpital Robert Debré, Paris], Hôpital Robert Debré-Hôpital Robert Debré, Duke University Medical Center, Service de Greffe de Moelle - Unité AJA, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Service d'hématologie clinique, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Hôpital de la Timone [CHU - APHM] (TIMONE), Department of Haematology, Hôpital Civil, Hopital Civil, Département d'Immunologie, hématologie et rhumatologie pédiatriques [Hôpital Necker-Enfants malades - APHP], CHU Necker - Enfants Malades [AP-HP], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Hemostase, Endothelium, Angiogenese (UMR_S_553), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Diderot - Paris 7 (UPD7), Physiopathologie, Autoimmunité, maladies Neuromusculaires et THErapies Régénératrices (PANTHER), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Imagine - Institut des maladies génétiques (IMAGINE - U1163), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Churchill Hospital [Breast Care Unit], Churchill Hospital Oxford Centre for Haematology, Santa Lucia Foundation, IRCSS, Rome, Medical College of Wisconsin, National Institute for Health Research, Centre de Recherche Saint-Antoine (UMRS893), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut Universitaire d'Hématologie (IUH), Hôpital Universitaire des Enfants Reine Fabiola [Bruxelles, Belgique] (HUDERF), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), UCL - SSS/IREC/PEDI - Pôle de Pédiatrie, and UCL - (SLuc) Service d'hématologie et d'oncologie pédiatrique
Subjects: Male, HYDROXYUREA, Transplantation Conditioning, [SDV]Life Sciences [q-bio], medicine.medical_treatment, CHILDREN, Hematopoietic stem cell transplantation, Biochemistry, THALASSEMIA, 0302 clinical medicine, HLA Antigens, Surveys and Questionnaires, 1114 Paediatrics And Reproductive Medicine, Child, ComputingMilieux_MISCELLANEOUS, CÉLULAS-TRONCO, Hazard ratio, Graft Survival, BONE-MARROW TRANSPLANT, Hematopoietic Stem Cell Transplantation, Hematology, Sickle cell anemia, 3. Good health, Survival Rate, medicine.anatomical_structure, Treatment Outcome, Settore MED/38 - PEDIATRIA GENERALE E SPECIALISTICA, 030220 oncology & carcinogenesis, Child, Preschool, Histocompatibility, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, Life Sciences & Biomedicine, medicine.medical_specialty, Adolescent, Anemia, Immunology, Anemia, Sickle Cell, 1102 Cardiovascular Medicine And Haematology, Disease-Free Survival, 03 medical and health sciences, Internal medicine, MANAGEMENT, medicine, Humans, ANEMIA, Survival rate, Transplantation, Science & Technology, business.industry, Siblings, Sickle cell disease, Infant, 1103 Clinical Sciences, ADULTS, Cell Biology, medicine.disease, LIFE, EXPERT PANEL, Bone marrow, FOLLOW-UP, business, 030215 immunology
Abstract: Despite advances in supportive therapy to prevent complications of sickle cell disease (SCD), access to care is not universal. Hematopoietic cell transplantation is, to date, the only curative therapy for SCD, but its application is limited by availability of a suitable HLA-matched donor and lack of awareness of the benefits of transplant. Included in this study are 1000 recipients of HLA-identical sibling transplants performed between 1986 and 2013 and reported to the European Society for Blood and Marrow Transplantation, Eurocord, and the Center for International Blood and Marrow Transplant Research. The primary endpoint was event-free survival, defined as being alive without graft failure; risk factors were studied using a Cox regression models. The median age at transplantation was 9 years, and the median follow-up was longer than 5 years. Most patients received a myeloablative conditioning regimen (n = 873; 87%); the remainder received reduced-intensity conditioning regimens (n = 125; 13%). Bone marrow was the predominant stem cell source (n = 839; 84%); peripheral blood and cord blood progenitors were used in 73 (7%) and 88 (9%) patients, respectively. The 5-year event-free survival and overall survival were 91.4% (95% confidence interval, 89.6%-93.3%) and 92.9% (95% confidence interval, 91.1%-94.6%), respectively. Event-free survival was lower with increasing age at transplantation (hazard ratio [HR], 1.09; P < .001) and higher for transplantations performed after 2006 (HR, 0.95; P = .013). Twenty-three patients experienced graft failure, and 70 patients (7%) died, with the most common cause of death being infection. The excellent outcome of a cohort transplanted over the course of 3 decades confirms the role of HLA-identical sibling transplantation for children and adults with SCD.
Published: 2017

25. Defining the next generation of Plasmodium vivax diagnostic tests for control and elimination: Target product profiles

Author: Naomi W. Lucchi, Jack S. Richards, Xavier C. Ding, Maria Paz Ade, Arsène Ratsimbason, Sócrates Herrera, Mehul Dhorda, Iveth J. González, Ivo Mueller, Jetsumon Sattabongkot, Alfredo Mayor, Jane Cunningham, Marcel Tanner, Matthias Harbers, Chris Drakeley, Dionicia Gamboa, Ingrid Felger, Qin Cheng, J. Kevin Baird, Foundation for Innovative New Diagnostics (FIND), Pan American Health Organization, World Health Organization (PANAFTOSA), Eijkman Institute for Molecular Biology [Jakarta], Australian Army Malaria Institute, Global Malaria Programme, Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), University of Oxford, Churchill Hospital [Breast Care Unit], Churchill Hospital Oxford Centre for Haematology, London School of Hygiene and Tropical Medicine (LSHTM), Swiss Tropical and Public Health Institute [Basel], Universidad Peruana Cayetano Heredia (UPCH), RIKEN Center for Life Science Technologies (RIKEN CLST), RIKEN - Institute of Physical and Chemical Research [Japon] (RIKEN), Caucaseco scientific research center = Centro de Investigación Científica Caucaseco, Centers for Disease Control and Prevention [Atlanta] (CDC), Centers for Disease Control and Prevention, Barcelona Centre for International Health Research, Hospital Clinic (CRESIB), Universitat de Barcelona (UB), The Walter and Eliza Hall Institute of Medical Research (WEHI), Département Parasites et Insectes vecteurs - Department of Parasites and Insect Vectors, Institut Pasteur [Paris] (IP), Mahidol University [Bangkok], Université d'Antananarivo, Burnet Institute [Melbourne, Victoria], University of Melbourne, University of Basel (Unibas), This work was supported by funds from the Department of Foreign Affairs and Trade, Australian Government., University of Oxford [Oxford], and Institut Pasteur [Paris]
Subjects: Plasmodium, Physiology, Plasmodium vivax, Psychological intervention, Plasmodium vivax/isolation & purification, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Epidemiology, Medicine and Health Sciences, 030212 general & internal medicine, Malaria, Falciparum, MESH: Plasmodium falciparum, Protozoans, biology, lcsh:Public aspects of medicine, MESH: Malaria, Falciparum, Malarial Parasites, Parasitic diseases, 3. Good health, MESH: Plasmodium vivax, MESH: Point-of-Care Systems, Body Fluids, Malalties parasitàries, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Blood, Infectious Diseases, Malaria, Vivax/diagnosis/parasitology/prevention & control, Anatomy, purl.org/pe-repo/ocde/ford#3.03.06 [https], Research Article, medicine.medical_specialty, lcsh:Arctic medicine. Tropical medicine, Infectious Disease Control, lcsh:RC955-962, Point-of-Care Systems, 030231 tropical medicine, Plasmodium falciparum, 03 medical and health sciences, Species Specificity, Diagnostic Medicine, parasitic diseases, Parasite Groups, medicine, Gametocyte, Malaria, Vivax, Parasitic Diseases, MESH: Species Specificity, Humans, Malaria, Falciparum/diagnosis/parasitology/prevention & control, Intensive care medicine, MESH: Diagnostic Tests, Routine, MESH: Humans, Plasmodium falciparum/isolation & purification, Diagnostic Tests, Routine, Public health, Public Health, Environmental and Occupational Health, Organisms, MESH: Malaria, Vivax, Biology and Life Sciences, lcsh:RA1-1270, medicine.disease, biology.organism_classification, Tropical Diseases, Parasitic Protozoans, Malaria, Parasitology, Immunology, Apicomplexa
Abstract: The global prevalence of malaria has decreased over the past fifteen years, but similar gains have not been realized against Plasmodium vivax because this species is less responsive to conventional malaria control interventions aimed principally at P. falciparum. Approximately half of all malaria cases outside of Africa are caused by P. vivax. This species places dormant forms in human liver that cause repeated clinical attacks without involving another mosquito bite. The diagnosis of acute patent P. vivax malaria relies primarily on light microscopy. Specific rapid diagnostic tests exist but typically perform relatively poorly compared to those for P. falciparum. Better diagnostic tests are needed for P. vivax. To guide their development, FIND, in collaboration with P. vivax experts, identified the specific diagnostic needs associated with this species and defined a series of three distinct target product profiles, each aimed at a particular diagnostic application: (i) point-of-care of acutely ill patients for clinical care purposes; (ii) point-of-care asymptomatic and otherwise sub-patent residents for public health purposes, e.g., mass screen and treat campaigns; and (iii) ultra-sensitive not point-of-care diagnosis for epidemiological research/surveillance purposes. This report presents and discusses the rationale for these P. vivax-specific diagnostic target product profiles. These contribute to the rational development of fit-for-purpose diagnostic tests suitable for the clinical management, control and elimination of P. vivax malaria., Author summary Plasmodium vivax is the second most prevalent Plasmodium species amongst the five that can infect humans and cause malaria. The control and elimination of P. vivax is complicated by its specific biology, such as hard-to-detect low densities of blood-circulating parasites in infected individuals, the existence of persistent liver forms causing relapse, or the early appearance of sexual stages of the parasite during the course of an infection, which facilitates its transmission. These difficulties are reinforced by the fact that most antimalarial tools have been developed primarily for P. falciparum, the most prevalent malaria species, and are not always as effective for P. vivax. Current tools for the diagnosis of P. vivax are of limited effectiveness. Rapid diagnostic tests exist but show, in average, lower performance than similar test for P. falciparum. P. vivax diagnosis often relies on light microscopy which is challenging to maintain at a high quality and not sensitive enough to detect a large fraction of all infections. Recognizing that better diagnostic tools for P. vivax are needed, we report in this study the development of new target product profiles to define the specific characteristics of such tests. The establishment of these consensus-based documents is an important first step to guide research and development efforts toward better diagnostic solutions for P. vivax malaria and to accelerate the elimination of this species alongside P. falciparum.
Published: 2016

26. TBC1D24 genotype-phenotype correlation: Epilepsies and other neurologic features

Author: Balestrini, Simona, Milh, Mathieu, Castiglioni, Claudia, Lüthy, Kevin, Finelli, Mattea J, Verstreken, Patrik, Cardon, Aaron, Stražišar, Barbara Gnidovec, Holder, J Lloyd, Lesca, Gaetan, Mancardi, Maria M, Poulat, Anne L, Repetto, Gabriela M, Banka, Siddharth, Bilo, Leonilda, Birkeland, Laura E, Bosch, Friedrich, Brockmann, Knut, Cross, J Helen, Doummar, Diane, Félix, Temis M, Giuliano, Fabienne, Hori, Mutsuki, Hüning, Irina, Kayserili, Hulia, Kini, Usha, Lees, Melissa M, Meenakshi, Girish, Mewasingh, Leena, Pagnamenta, Alistair T, Peluso, Silvio, Mey, Antje, Rice, Gregory M, Rosenfeld, Jill A, Taylor, Jenny C, Troester, Matthew M, Stanley, Christine M, Ville, Dorothee, Walkiewicz, Magdalena, Falace, Antonio, Fassio, Anna, Lemke, Johannes R, Biskup, Saskia, Tardif, Jessica, Ajeawung, Norbert F, Tolun, Aslihan, Corbett, Mark, Gecz, Jozef, Afawi, Zaid, Howell, Katherine B, Oliver, Karen L, Berkovic, Samuel F, Scheffer, Ingrid E, de Falco, Fabrizio A, Oliver, Peter L, Striano, Pasquale, Zara, Federico, Campeau, Phillipe M, Sisodiya, S M, Service de pédiatrie et neurologie pédiatrique, Université de la Méditerranée - Aix-Marseille 2-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Génétique Médicale et Génomique Fonctionnelle (GMGF), Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Centre National de la Recherche Scientifique (CNRS), Servicio di Neurologia, Clinica Las Condes, Centre de recherche en neurosciences de Lyon (CRNL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Lyon, Regional Genetic Service, St Mary's Hospital, Manchester, Department of Pediatrics and Neuropediatrics, Georg-August-University [Göttingen], CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de génétique médicale, Hôpital l'Archet, Department of Clinical Genetics [Churchill Hospital], Churchill Hospital Oxford Centre for Haematology, Baylor College of Medicine (BCM), Baylor University, Service de Neurologie Pédiatrique [CHU Lyon], Hôpital Femme Mère Enfant [CHU - HCL] (HFME), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Institut de Biologie du Développement de Marseille (IBDM), Aix Marseille Université (AMU)-Collège de France (CdF (institution))-Centre National de la Recherche Scientifique (CNRS), University of Genova, Universita degli studi di Genova, Institute of Medical Genetics, Department of Neurodegenerative Diseases, Eberhard Karls Universität Tübingen = Eberhard Karls University of Tuebingen, Department of Molecular Biology and Genetics, Boaziçi University, University of Adelaide, Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Georg-August-University = Georg-August-Universität Göttingen, Università degli studi di Genova = University of Genoa (UniGe), Balestrini, Simona, Milh, Mathieu, Castiglioni, Claudia, Lüthy, Kevin, Finelli, Mattea J, Verstreken, Patrik, Cardon, Aaron, Stražišar, Barbara Gnidovec, Holder, J. Lloyd, Lesca, Gaetan, Mancardi, Maria M, Poulat, Anne L, Repetto, Gabriela M, Banka, Siddharth, Bilo, Leonilda, Birkeland, Laura E, Bosch, Friedrich, Brockmann, Knut, Cross, J. Helen, Doummar, Diane, Félix, Temis M, Giuliano, Fabienne, Hori, Mutsuki, Hüning, Irina, Kayserili, Hulia, Kini, Usha, Lees, Melissa M, Meenakshi, Girish, Mewasingh, Leena, Pagnamenta, Alistair T, Peluso, Silvio, Mey, Antje, Rice, Gregory M, Rosenfeld, Jill A, Taylor, Jenny C, Troester, Matthew M, Stanley, Christine M, Ville, Dorothee, Walkiewicz, Magdalena, Falace, Antonio, Fassio, Anna, Lemke, Johannes R, Biskup, Saskia, Tardif, Jessica, Ajeawung, Norbert F, Tolun, Aslihan, Corbett, Mark, Gecz, Jozef, Afawi, Zaid, Howell, Katherine B, Oliver, Karen L, Berkovic, Samuel F, Scheffer, Ingrid E, de Falco, Fabrizio A, Oliver, Peter L, Striano, Pasquale, Zara, Federico, Campeau, Phillipe M, and Sisodiya, S. M.
Subjects: TBC1D24-related epilepsy syndromes, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Journal Article
Abstract: OBJECTIVE: To evaluate the phenotypic spectrum associated with mutations in TBC1D24.METHODS: We acquired new clinical, EEG, and neuroimaging data of 11 previously unreported and 37 published patients. TBC1D24 mutations, identified through various sequencing methods, can be found online (http://lovd.nl/TBC1D24).RESULTS: Forty-eight patients were included (28 men, 20 women, average age 21 years) from 30 independent families. Eighteen patients (38%) had myoclonic epilepsies. The other patients carried diagnoses of focal (25%), multifocal (2%), generalized (4%), and unclassified epilepsy (6%), and early-onset epileptic encephalopathy (25%). Most patients had drug-resistant epilepsy. We detail EEG, neuroimaging, developmental, and cognitive features, treatment responsiveness, and physical examination. In silico evaluation revealed 7 different highly conserved motifs, with the most common pathogenic mutation located in the first. Neuronal outgrowth assays showed that some TBC1D24 mutations, associated with the most severe TBC1D24-associated disorders, are not necessarily the most disruptive to this gene function.CONCLUSIONS: TBC1D24-related epilepsy syndromes show marked phenotypic pleiotropy, with multisystem involvement and severity spectrum ranging from isolated deafness (not studied here), benign myoclonic epilepsy restricted to childhood with complete seizure control and normal intellect, to early-onset epileptic encephalopathy with severe developmental delay and early death. There is no distinct correlation with mutation type or location yet, but patterns are emerging. Given the phenotypic breadth observed, TBC1D24 mutation screening is indicated in a wide variety of epilepsies. A TBC1D24 consortium was formed to develop further research on this gene and its associated phenotypes.
Published: 2016

27. Single- vs double-unit cord blood transplantation for children and young adults with acute leukemia or myelodysplastic syndrome

Author: Mohamad Mohty, Fanny Rialland, Patrick Lutz, Karine Baumstarck, Anderson Loundou, Sophie Esmiol, Charlotte Jubert, Claire Galambrun, Ibrahim Yakoub-Agha, Mauricette Michallet, Didier Blaise, Cécile Pochon, Anne Sirvent, Jean-Hugues Dalle, Gérard Michel, Claire Oudin, Bénédicte Bruno, Virginie Gandemer, Aude Marie-Cardine, Vanderson Rocha, Mylène Seux, Noel Milpied, Cecile Renard, Pédiatrie et oncologie pédiatrique [Hôpital de la Timone - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Service d'Hématologie pédiatrique, Hôpital de la Timone, Marseille, Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Institut Gustave Roussy (IGR), Unité d'Aide Méthodologique, Assistance Publique - Hôpitaux de Marseille (APHM)-CHU Marseille, Lille Inflammation Research International Center - U 995 (LIRIC), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Service de pédiatrie, CHU Grenoble, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble, Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), CHU Pontchaillou [Rennes], Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Service d’Hématologie [Centre Hospitalier Lyon Sud - HCL], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Service d'Hématologie Clinique [Nantes], Hôpital Hôtel Dieu-Centre hospitalier universitaire de Nantes (CHU Nantes), Service d'hématologie pédiatrique, Université de la Méditerranée - Aix-Marseille 2-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Stress Cellulaire, Université de la Méditerranée - Aix-Marseille 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire Chimie Provence (LCP), Université de Provence - Aix-Marseille 1-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Aix Marseille Université (AMU), Service d'Hématologie [Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Centre d'investigation clinique en cancérologie (CI2C), Centre de Recherche Saint-Antoine (UMRS893), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Pierre et Marie Curie - Paris 6 (UPMC), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Churchill Hospital, Churchill Hospital Oxford Centre for Haematology, Eurocord, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut Universitaire d'Hématologie (IUH), Université Paris Diderot - Paris 7 (UPD7)-Université Paris Diderot - Paris 7 (UPD7), France Monacord, Centre Scientifique de Monaco (CSM), Hôpital Robert Debré Paris, Hôpital Robert Debré, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), and Centre National de la Recherche Scientifique (CNRS)-Université de Provence - Aix-Marseille 1-Institut de Chimie du CNRS (INC)
Subjects: Male, Transplantation Conditioning, [SHS.PSY]Humanities and Social Sciences/Psychology, Graft vs Host Disease, Biochemistry, Gastroenterology, 0302 clinical medicine, Child, Acute leukemia, Leukemia, Hematology, Total body irradiation, [SHS.ECO]Humanities and Social Sciences/Economics and Finance, Quality, 3. Good health, Survival Rate, surgical procedures, operative, 030220 oncology & carcinogenesis, Child, Preschool, Acute Disease, Female, Cord Blood Stem Cell Transplantation, Whole-Body Irradiation, medicine.drug, Adult, medicine.medical_specialty, Adolescent, Immunology, Disease-Free Survival, 03 medical and health sciences, Young Adult, Internal medicine, medicine, Humans, Survival rate, Antilymphocyte Serum, business.industry, Myelodysplastic syndromes, Cell Biology, medicine.disease, Surgery, Transplantation, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Myelodysplastic Syndromes, Chronic Disease, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, Busulfan, 030215 immunology
Abstract: Transplantation of 2 unrelated cord blood (UCB) units instead of 1 has a been proposed to increase the cell dose. We report a prospective a randomized study, designed to compare single-vs double-UCB a transplantation in children and young adults with acute leukemia in a remission or myelodysplasia. Eligible patients had at least two 4-6 a HLA-identical UCBs with >3x10(7) nucleated cells/kg for the first and a >1.5x10(7) for the second. The primary end point was the 2-year a cumulative incidence of transplantation strategy failure, a composite a end point including transplant-related mortality (TRM), engraftment a failure, and autologous recovery. Randomized patients who did not a proceed to transplantation due to refractory disease were considered a transplantation failures. A total of 151 patients were randomized and a included in the intent-to-treat analysis; 137 were transplanted. a Double-UCB transplantation did not decrease transplantation strategy a failure (23.4% 6 4.9% vs 14.9% +/- 4.2%). Two-year posttransplant a survival, disease-free survival, and TRM were 68.8% +/- 6.0%, 67.6% a +/- 6.0%, and 5.9% +/- 2.9% after single-unit transplantation a compared with 74.8% +/- 5.5%, 68.1% +/- 6.0%, and 11.6% +/- 3.9% a after double-unit transplantation. The final relapse risk did not a significantly differ, but relapses were delayed after double-unit a transplantation. Overall incidences of graft-versus-host disease (GVHD) a were similar, but chronic GVHD was more frequently extensive after a double-UCB transplantation (31.9% +/- 5.7% vs 14.7% +/- 4.3%, a P=.02). In an exploratory subgroup analysis, we found a significantly a lower relapse risk after double-unit transplantation in patients a receiving total body irradiation without antithymocyte globulin (ATG), a whereas the relapse risk was similar in the group treated with busulfan, a cyclophosphamide, and ATG. Single-UCB transplantation with adequate cell a dose remains the standard of care and leads to low TRM. Double-unit a transplantation should be reserved for patients who lack such units. a This trial was registered at www. clinicaltrials. gov as #NCT01067300.
Published: 2016

28. Impact of cord blood banking technologies on clinical outcome: a Eurocord/Cord Blood Committee (CTIWP), European Society for Blood and Marrow Transplantation and NetCord retrospective analysis

Author: Saccardi, Riccardo, Tucunduva, Luciana, Ruggeri, Annalisa, Ionescu, Irina, Koegler, Gesine, Querol, Sergio, Grazzini, Giuliano, Lecchi, Lucilla, Nanni Costa, Alessandro, Navarrete, Cristina, Pouthiers, Fabienne, Larghero, Jerome, Regan, Donna, Freeman, Taryn, Bittencourt, Henrique, Kenzey, Chantal, Labopin, Myriam, Baudoux, Etienne, Rocha, Vanderson, Gluckman, Eliane, Careggi University Hospital, Eurocord, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut Universitaire d'Hématologie (IUH), Université Paris Diderot - Paris 7 (UPD7)-Université Paris Diderot - Paris 7 (UPD7), Centre de Recherche Saint-Antoine (UMRS893), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Agence de la Biomedicine, Dusseldorf Cord Blood Bank, University of Düsseldorf, Barcelona Cord Blood Bank, Centro Nazionale Sangue, Milano Cord Blood Bank, Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, Centro Nazionale Trapianti, NHS Cord Blood Bank, Etablissement français du sang [Besançon] (EFS), Paris Cord Blood Bank, Hôpital Saint-Louis, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), St Louis Cord Blood Bank & Cellular Therapy Laboratory, Sydney Cord Blood Bank, CHU Sainte Justine [Montréal], NetCord Foundation and Liege Cord Blood Bank, Université de Liège, Churchill Hospital [Breast Care Unit], Churchill Hospital Oxford Centre for Haematology, France Monacord, Centre Scientifique de Monaco (CSM), Heinrich Heine Universität Düsseldorf = Heinrich Heine University [Düsseldorf], and d'Eggis, Gilles
Subjects: [SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology
Abstract: International audience; BACKGROUNDTechniques for banking cord blood units (CBUs) as source for hematopoietic stem cell transplantation have been developed over the past 20 years, aimed to improve laboratory efficiency without altering the biologic properties of the graft. A large-scale, registry-based assessment of the impact of the banking variables on the clinical outcome is currently missing.STUDY DESIGN AND METHODSA total of 677 single cord blood transplants (CBTs) carried out for acute leukemia in complete remission in centers affiliated with the European Society for Blood and Marrow Transplantation were selected. An extensive set of data concerning CBU banking were collected and correlations with clinical outcome were assessed. Clinical endpoints were transplant-related mortality, engraftment, and graft-versus-host disease (GVHD).RESULTSThe median time between collection and CBT was 4.1 years (range, 0.2-16.3 years). Volume reduction (VR) of CBUs before freezing was performed in 59.2% of available reports; in half of these the frozen volume was less than 30 mL. Cumulative incidences of neutrophil engraftment on Day 60, 100-day acute GVHD (II-IV), and 4-year chronic GVHD were 87, 29, and 21 ± 2%. The cumulative incidence of nonrelapse mortality (NRM) at 100 days and 4-year NRM were, respectively, 16 ± 2 and 30 ± 2%. Neither the variables related to banking procedures nor the interval between collection and CBT influenced the clinical outcome.CONCLUSIONThese findings indicate a satisfactory validation of the techniques associated with CBU VR across the banks. Cell viability assessment varied among the banks, suggesting that efforts to improve the standardization of CBU quality controls are needed.
Published: 2016

29. Plasmodium falciparum dihydroartemisinin-piperaquine failures in Cambodia are associated with mutant K13 parasites presenting high survival rates in novel piperaquine in vitro assays: retrospective and prospective investigations

Author: Anais Domergue, Odile Mercereau-Puijalon, Rithea Leang, Malen Ken, Dysoley Lek, Johann Beghain, Benoit Witkowski, Nimol Khim, Kaknika Loch, Rekol Huy, Frédéric Ariey, Saorin Kim, Chanra Khean, Nimol Kloeung, Valentine Duru, Rotha Eam, Philippe J Guerin, Sophy Chy, Didier Menard, Sopheakvatey Ke, Institut Pasteur du Cambodge, Réseau International des Instituts Pasteur (RIIP), National Center for Parasitology, Entomology and Malaria Control [Phnom Penh, Cambodia] (CNM), Département Parasites et Insectes vecteurs - Department of Parasites and Insect Vectors, Institut Pasteur [Paris], WorldWide Antimalarial Resistance Network (WWARN), University of Oxford [Oxford]-Churchill Hospital Oxford Centre for Haematology, Centre for Tropical Medicine and Global Health [Oxford, UK], Nuffield Department of Medicine [Oxford, UK] (Big Data Institute), University of Oxford [Oxford]-University of Oxford [Oxford], This work was funded by grants from Institut Pasteur du Cambodge, USAID and BMGF through the World Health Organization, and Institut Pasteur Paris. PJG is member of the Worldwide Antimalarial Resistance Network supported by the Bill and Melinda Gates Foundation. VD is supported by a doctoral fellowship from the International Division, Institut Pasteur., We thank all patients enrolled in the therapeutic efficacy studies, the health centres staff and the staff from the National Center for Parasitology, Entomology and Malaria Control in Cambodia for their support. We are grateful to Joel Tarning (Mahidol Oxford Tropical Medicine Research Unit, Bangkok, Thailand, Centre for Tropical Medicine, University of Oxford, Oxford, United Kingdom) who performed the piperaquine concentration measurements., Institut Pasteur [Paris] (IP), University of Oxford-Churchill Hospital Oxford Centre for Haematology, and University of Oxford-University of Oxford
Subjects: Male, Oncology, MESH: Treatment Failure, Piperaquine resistance, Pharmacology, Dihydroartemisinin/piperaquine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, MESH: Animals, Prospective Studies, Malaria, Falciparum, Artemisinin, Prospective cohort study, Ex vivo testing, MESH: Plasmodium falciparum, Artemisinin combination therapies, MESH: Treatment Outcome, Medicine(all), 0303 health sciences, biology, MESH: Malaria, Falciparum, General Medicine, Artemisinins, 3. Good health, Survival Rate, Treatment Outcome, Artemisinin resistance, MESH: Young Adult, Quinolines, Female, Cambodia, MESH: Quinolines, Research Article, medicine.drug, Adult, Falciparum, medicine.medical_specialty, Adolescent, MESH: Survival Rate, Plasmodium falciparum, Antimalarials, Young Adult, 03 medical and health sciences, Internal medicine, Piperaquine, parasitic diseases, MESH: Artemisinins, medicine, Animals, Humans, Parasites, Survival rate, In-vitro testing, MESH: Parasites, Retrospective Studies, 030304 developmental biology, MESH: Adolescent, MESH: Humans, 030306 microbiology, business.industry, MESH: Cambodia, MESH: Adult, MESH: Retrospective Studies, medicine.disease, biology.organism_classification, MESH: Antimalarials, MESH: Male, MESH: Prospective Studies, Malaria, Treatment failure, business, MESH: Female, Ex vivo
Abstract: Background The declining efficacy of dihydroartemisinin-piperaquine against Plasmodium falciparum in Cambodia, along with increasing numbers of recrudescent cases, suggests resistance to both artemisinin and piperaquine. Available in vitro piperaquine susceptibility assays do not correlate with treatment outcome. A novel assay using a pharmacologically relevant piperaquine dose/time exposure was designed and its relevance explored in retrospective and prospective studies. Methods The piperaquine survival assay (PSA) exposed parasites to 200 nM piperaquine for 48 hours and monitored survival 24 hours later. The retrospective study tested 32 culture-adapted, C580Y-K13 mutant parasites collected at enrolment from patients treated with a 3-day course of dihydroartemisinin-piperaquine and having presented or not with a recrudescence at day 42 (registered ACTRN12615000793516). The prospective study assessed ex vivo PSA survival rate alongside K13 polymorphism of isolates collected from patients enrolled in an open-label study with dihydroartemisinin-piperaquine for uncomplicated P. falciparum malaria in Cambodia (registered ACTRN12615000696594). Results All parasites from recrudescent cases had in vitro or ex vivo PSA survival rates ≥10 %, a relevant cut-off value for piperaquine-resistance. Ex vivo PSA survival rates were higher for recrudescent than non-recrudescent cases (39.2 % vs. 0.17 %, P
Published: 2015

30. Refinement of Genotype-Phenotype Correlation in 18 Patients Carrying a 1q24q25 Deletion

Author: Caroline Schluth-Bolard, Claudia A. L. Ruivenkamp, Brigitte Benzacken, Zeynep Tümer, Joris Andrieux, Nicole Bain, Kerry Fagan, Nicolas Chatron, Marianne Till, Damien Sanlaville, Clarisse Baumann, Odile Boute, P. Edery, Laura Bernardini, Céline Bonnet, Anna Hackett, Massimiliano Rossi, Bruno Leheup, Julie Désir, Arie van Haeringen, Séverine Drunat, Yves Alembik, Véronique Haddad, Marion Gérard, Pia Castelluccio, Anne Dieux, Helen Stewart, Azzedine Aboura, Elisabeth Flori, Laura Roos, Joanna McParland, Laboratoire de Cytogénétique Constitutionnelle [Hospices civils de Lyon], Hospices Civils de Lyon (HCL), Unité de Cytogénétique [CHU Debré], AP-HP Hôpital universitaire Robert-Debré [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Laboratoire de Génétique Médicale, Hôpital Jeanne de Flandre [Lille]-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Institut de Pathologie et Génétique [Gosselies] (I.P.G.), Service de Génétique clinique, Unité de Génétique Clinique [CHU Debré], Service de Génétique [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Service de Médecine Infantile III et Génétique Clinique [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Service de génétique [Hôpial Louis Pradel - HCL], Hôpital Louis Pradel [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Centre de recherche en neurosciences de Lyon (CRNL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Cytogénétique, CHU Strasbourg-Hôpital de Hautepierre [Strasbourg], Service de Génétique Clinique [Hautepierre Strasbourg], Hôpital de Hautepierre [Strasbourg], Department of Clinical Genetics [Churchill Hospital], Churchill Hospital Oxford Centre for Haematology, Mendel Laboratory, Istituto di Ricovero e Cura a Carattere Scientifico, Ospedale Casa Sollievo della Sofferenza [San Giovanni Rotondo] (IRCCS), Ospedale Cardarelli, Department of Clinical Genetics [Copenhagen], Rigshospitalet [Copenhagen], Copenhagen University Hospital-Copenhagen University Hospital, University of Newcastle [Australia] (UoN), Department of Clinical Genetics, Leiden University Medical Centre, Clinical Cytogeneticist Laboratory for Diagnostic Genome Analysis [Leiden University Medical Center], Leiden University Medical Center (LUMC), Physiopathologie, conséquences fonctionnelles et neuroprotection des atteintes du cerveau en développement, Université Paris Diderot - Paris 7 (UPD7)-IFR2-Institut National de la Santé et de la Recherche Médicale (INSERM), Unité de Cytogénétiqué, Hôpital Jean-Verdier, Laboratoire de Biologie Moléculaire de la Cellule (LBMC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), University of Newcastle [Callaghan, Australia] (UoN), Universiteit Leiden-Universiteit Leiden, École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Adult, Male, Microcephaly, Pathology, medicine.medical_specialty, Microarray, Adolescent, [SDV]Life Sciences [q-bio], growth retardation, Biology, Single transverse palmar crease, Genetics, medicine, Humans, 1q24q25 deletion, Sex organ, Abnormalities, Multiple, 10. No inequality, Child, Genetics (clinical), Genetic Association Studies, In Situ Hybridization, Fluorescence, Aged, Comparative Genomic Hybridization, Brachydactyly, Infant, Newborn, brachydactyly, Chromosome, Infant, Middle Aged, DNM3, medicine.disease, Phenotype, Chromosomes, Human, Pair 1, intellectual disability, Child, Preschool, Female, medicine.symptom, Chromosome Deletion
Abstract: International audience; Interstitial deletion 1q24q25 is a rare rearrangement associated with intellectual disability, growth retardation, abnormal extremities and facial dysmorphism. In this study, we describe the largest series reported to date, including 18 patients (4M/14F) aged from 2 days to 67 years and comprising two familial cases. The patients presented with a characteristic phenotype including mild to moderate intellectual disability (100%), intrauterine (92%) and postnatal (94%) growth retardation, microcephaly (77%), short hands and feet (83%), brachydactyly (70%), fifth finger clinodactyly (78%) and facial dysmorphism with a bulbous nose (72%), abnormal ears (67%) and micrognathia (56%). Other findings were abnormal palate (50%), single transverse palmar crease (53%), renal (38%), cardiac (38%), and genital (23%) malformations. The deletions were characterized by chromosome microarray. They were of different sizes (490 kb to 20.95 Mb) localized within chromosome bands 1q23.3-q31.2 (chr1:160797550-192912120, hg19). The 490 kb deletion is the smallest deletion reported to date associated with this phenotype. We delineated three regions that may contribute to the phenotype: a proximal one (chr1:164,501,003-167,022,133), associated with cardiac and renal anomalies, a distal one (chr1:178,514,910-181,269,712) and an intermediate 490 kb region (chr1:171970575-172460683, hg19), deleted in the most of the patients, and containing DNM3, MIR3120 and MIR214 that may play an important role in the phenotype. However, this genetic region seems complex with multiple regions giving rise to the same phenotype.
Published: 2015

31. The effect of dosing strategies on the therapeutic efficacy of artesunate-amodiaquine for uncomplicated malaria: a meta-analysis of individual patient data

Author: Ouédraogo J-B., Bertrand Lell, Sanjeev Krishna, Ogobara K. Doumbo, Mbaye Pene, Emiliana Tjitra, Ric N. Price, I Van den Broek, Jennifer A. Flegg, Christian Nsanzabana, Faucher J-F., Jean-René Kiechel, Sue J. Lee, Nicholas J. White, Issaka Zongo, Adoke Yeka, Sodiomon B. Sirima, Halidou Tinto, Michel Vaillant, Etard J-F., K Sylla, Sarah G. Staedke, Andreas Mårtensson, Louis K. Penali, Meghna Desai, Martin M Meremikwu, M A Adjuik, Elizabeth A. Ashley, Peter W. Gething, Sally Hamour, Claude Rwagacondo, Clarissa Moreira, Moses R. Kamya, François Bompart, Julie Thwing, Prabin Dahal, Armedy Ronny Hasugian, Elizabeth Juma, Francesco Grandesso, Hasifa Bukirwa, Loretxu Pinoges, Vincent Jullien, Philip J. Rosenthal, Simon I. Hay, Ndiaye J-L., Raquel González, Bhawna Sharma, D Sow, Anup Anvikar, Neena Valecha, E Espié, Frank Smithuis, Didier Menard, Philippe Deloron, Carol Hopkins Sibley, Peter G. Kremsner, M S Ba, Anders Björkman, Albert Same-Ekobo, Todd D. Swarthout, G Diap, Taylor Wrj., Michael Nambozi, Georgina S Humphreys, Caterina I. Fanello, Tine Rck., Karen I. Barnes, Carolyn Nabasumba, Achille Massougbodji, Hervé Ei Menan, Jeff Smith, A Seck, Patrice Piola, Babacar Faye, Richard Allan, Philippe J Guerin, Corine Karema, Frederic Nikiema, Ambrose O. Talisuna, Véronique Sinou, E A Temu, Lyda Osorio, Gaye O, Piero Olliaro, Francine Ntoumi, Michel Cot, Grant Dorsey, Maryline Bonnet, Hubert Barennes, Birgit Schramm, Umberto D'Alessandro, Kasia Stepniewska, Elisabeth Baudin, Steffen Borrmann, Abdoulaye Djimde, Bernards Ogutu, Guthmann J-P., L M Ibrahim, Francesco Checchi, Fabrice A. Somé, Valerie Lameyre, Clara Menéndez, Quique Bassat, Philippe Brasseur, Cally Roper, Joel Tarning, WorldWide Antimalarial Resistance Network (WWARN), University of Washington [Seattle], National Institute of Malaria Research [New Dehli, Inde] (NIMR), Indian Council of Medical Research [New Dehli] (ICMR), Epicentre [Paris] [Médecins Sans Frontières], Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD), Centre Muraz [Bobo-Dioulasso, Burkina Faso], Universitat de Barcelona (UB), Karolinska Institutet [Stockholm], Recherches Translationnelles sur le VIH et les maladies infectieuses endémiques et émergentes (TransVIHMI), Institut de Recherche pour le Développement (IRD)-Université de Yaoundé I-Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), German Center for Infection Research - partner site Hannover-Braunschweig (DZIF), Centre Lillois d’Études et de Recherches Sociologiques et Économiques - UMR 8019 (CLERSÉ), Université de Lille-Centre National de la Recherche Scientifique (CNRS), Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine (LSHTM), Institut de Recherche pour le Développement (IRD), University of Oxford-Churchill Hospital Oxford Centre for Haematology, Centre for Tropical Medicine and Global Health [Oxford, UK], Nuffield Department of Medicine [Oxford, UK] (Big Data Institute), University of Oxford-University of Oxford, Mère et enfant en milieu tropical : pathogènes, système de santé et transition épidémiologique (MERIT - UMR_D 216), Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5), Mère et enfant en milieu tropical : pathogènes, système de santé et transition épidémiologique (MERIT - UMR_D 261), Institut de Recherche pour le Développement (IRD)-Université Paris Cité (UPCité), Département d'épidémiologie des affections parasitaires (DEAP), Université de Bamako-Malaria Research and Training Center (MRTC)-Facultés de Médecine, de Pharmacie et d'Odonto-Stomatologie-Centre National de la Recherche Scientifique (CNRS), University of California [San Francisco] (UC San Francisco), University of California (UC), Malaria Research and Training Centre, Université de Bamako-Faculty of Medicine, Pharmacy, Institut Pasteur de Dakar, Réseau International des Instituts Pasteur (RIIP), Mahidol Oxford Tropical Medicine Research Unit, University of Oxford-Mahidol University [Bangkok], Neuroépidémiologie Tropicale (NET), CHU Limoges-Institut d'Epidémiologie Neurologique et de Neurologie Tropicale-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM), Génétique, Reproduction et Développement (GReD), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), WorldWide Antimalarial Resistance Network (WWARN) (WWARN), University of Oxford, Università degli Studi di Milano = University of Milan (UNIMI), Institut de Veille Sanitaire (INVS), Institute for Health Metrics and Evaluation [University of Washington], Pharmacologie clinique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Descartes - Paris 5 (UPD5), University of Tübingen, Division of Cellular and Molecular Medicine, St George's University of London, Sanofi-Aventis R&D, SANOFI Recherche, Mahidol Oxford Tropical Medicine Research Unit (MORU), University of Oxford-Mahidol University [Bangkok]-Wellcome Trust, Department of Microbiology, Tumour and Cell biology [Stockholm, Sweden] (Malaria Research), Faculté des Sciences de la Santé de Cotonou (Faculté des Sciences de la Santé de Cotonou), Université d’Abomey-Calavi = University of Abomey Calavi (UAC), Centre de recherche et de Diagnostic sur le Sida [Abidjan, Côte d'Ivoire] (CeDreS), Centre Hospitalier Universitaire de Treichville [Abidjan, Côte d'Ivoire] (CHU de Treichville), Institut Pasteur du Cambodge, Universidad de la República [Montevideo] (UDELAR), Nuffield Department of Clinical Medicine [Oxford], Epicentre Ouganda [Mbarara] [Médecins Sans Frontières], Tropical Diseases Research Center (TDRC), Université Marien Ngouabi, Kenya Medical Research Institute (KEMRI), WHO-TDR Suisse, WHO-TDR Suisse-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Universidad del Valle [Cali] (Univalle), Institut de Recherche en Sciences de la Santé Bobo Dioulasso (INSSA), Université Polytechnique Nazi Boni Bobo-Dioulasso (UNB), World Wide Antimalarial Resistance Network [West Africa] (WWARN-West Africa Regional Centre), University of Washington [Seattle]-University of Washington [Seattle], Institut Pasteur de Madagascar, Global Health Division, Menzies School of Health Research, Infections Parasitaires : Transmission, Physiopathologie et Thérapeutiques (IP-TPT), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Service de Santé des Armées, Centre National de Recherche et de Formation sur le Paludisme [Ouagadougou, Burkina Faso] (CNRFP), Myanmar Oxford Clinical Research Unit [Yangon, Myanmar], Service de Parasitologie-Mycologie Médicale, Institut de Recherche en Sciences de la Santé (IRSS) / Centre Muraz, Université de Bordeaux Ségalen [Bordeaux 2], WWARN is funded by a Bill and Melinda Gates Foundation grant., The WorldWide Antimalarial Resistance Network (WWARN) AS-AQ Study Group, We thank the patients and all the staff who participated in these clinical trials at all the sites and the WWARN team for technical and administrative support., Université de Washington Seattle, Recherches Translationnelles sur le VIH et les maladies infectieuses endémiques er émergentes (TransVIHMI), Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Institut de Recherche pour le Développement (IRD)-Université de Yaoundé I-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Université Montpellier 1 (UM1), University of Oxford [Oxford]-Churchill Hospital Oxford Centre for Haematology, University of Oxford [Oxford]-University of Oxford [Oxford], Institut de Recherche pour le Développement (IRD)-Université de Paris (UP), University of California [San Francisco] (UCSF), University of California, University of Oxford [Oxford]-Mahidol University [Bangkok], Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM)-CHU Limoges-Institut d'Epidémiologie Neurologique et de Neurologie Tropicale-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Oxford [Oxford], Università degli Studi di Milano [Milano] (UNIMI), Wellcome Trust-Mahidol University [Bangkok]-University of Oxford [Oxford], University of Abomey Calavi (UAC), Universidad de la República [Montevideo] (UCUR), Université de Washington Seattle-Université de Washington Seattle, and Université Montpellier 1 (UM1)-Institut de Recherche pour le Développement (IRD)-Université de Yaoundé I-Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)
Subjects: Male, Artemether/lumefantrine, Artesunate, Infektionsmedicin, MESH: Africa, Pharmacology, Gastroenterology, MESH: Dose-Response Relationship, Drug, Efficacy, chemistry.chemical_compound, MESH: Risk Factors, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Recurrence, Risk Factors, Malaria, Falciparum, MESH: Treatment Outcome, MESH: Middle Aged, MESH: Malaria, Falciparum, Artesunate/amodiaquine, Hazard ratio, General Medicine, Middle Aged, Artemisinins, 3. Good health, Drug Combinations, Dosing, Treatment Outcome, Female, medicine.drug, Research Article, medicine.medical_specialty, Infectious Medicine, Fixed-dose combination, Plasmodium falciparum, Amodiaquine, Antimalarials, Internal medicine, MESH: Artemisinins, medicine, Humans, MESH: Amodiaquine, MESH: Drug Combinations, MESH: Humans, Dose-Response Relationship, Drug, business.industry, MESH: Antimalarials, MESH: Male, MESH: Recurrence, Malaria, chemistry, Drug resistance, Africa, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Commentary, business, MESH: Female
Abstract: Background Artesunate-amodiaquine (AS-AQ) is one of the most widely used artemisinin-based combination therapies (ACTs) to treat uncomplicated Plasmodium falciparum malaria in Africa. We investigated the impact of different dosing strategies on the efficacy of this combination for the treatment of falciparum malaria. Methods Individual patient data from AS-AQ clinical trials were pooled using the WorldWide Antimalarial Resistance Network (WWARN) standardised methodology. Risk factors for treatment failure were identified using a Cox regression model with shared frailty across study sites. Results Forty-three studies representing 9,106 treatments from 1999-2012 were included in the analysis; 4,138 (45.4%) treatments were with a fixed dose combination with an AQ target dose of 30 mg/kg (FDC), 1,293 (14.2%) with a non-fixed dose combination with an AQ target dose of 25 mg/kg (loose NFDC-25), 2,418 (26.6%) with a non-fixed dose combination with an AQ target dose of 30 mg/kg (loose NFDC-30), and the remaining 1,257 (13.8%) with a co-blistered non-fixed dose combination with an AQ target dose of 30 mg/kg (co-blistered NFDC). The median dose of AQ administered was 32.1 mg/kg [IQR: 25.9-38.2], the highest dose being administered to patients treated with co-blistered NFDC (median = 35.3 mg/kg [IQR: 30.6-43.7]) and the lowest to those treated with loose NFDC-25 (median = 25.0 mg/kg [IQR: 22.7-25.0]). Patients treated with FDC received a median dose of 32.4 mg/kg [IQR: 27-39.0]. After adjusting for reinfections, the corrected antimalarial efficacy on day 28 after treatment was similar for co-blistered NFDC (97.9% [95% confidence interval (CI): 97.0-98.8%]) and FDC (98.1% [95% CI: 97.6%-98.5%]; P = 0.799), but significantly lower for the loose NFDC-25 (93.4% [95% CI: 91.9%-94.9%]), and loose NFDC-30 (95.0% [95% CI: 94.1%-95.9%]) (P
Published: 2015

32. Changes in epicardial and visceral adipose tissue depots following bariatric surgery and their effect on cardiac geometry

Author: Henry, J. A., Abdesselam, I., Deal, O., Lewis, A. J., Rayner, J., Bernard, M., Dutour, A., Gaborit, B., Kober, F., Soghomonian, A., Sgromo, B., Byrne, J., Bege, T., Neubauer, S., Borlaug, B. A., Rider, O. J., University of Oxford, Centre de résonance magnétique biologique et médicale (CRMBM), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Centre National de la Recherche Scientifique (CNRS), Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Assistance Publique - Hôpitaux de Marseille (APHM), The Churchill Hospital, University Hospital Southampton NHS Foundation Trust, Hôpital Nord [CHU - APHM], Aix Marseille Université (AMU), and Mayo Clinic [Rochester]
Subjects: obesity, Endocrinology, Diabetes and Metabolism, bariatric surgery, cardiac geometry, cardiac remodelling, epicardiac adipose tissue, weight loss, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: IntroductionObesity affects cardiac geometry, causing both eccentric (due to increased cardiac output) and concentric (due to insulin resistance) remodelling. Following bariatric surgery, reversal of both processes should occur. Furthermore, epicardial adipose tissue loss following bariatric surgery may reduce pericardial restraint, allowing further chamber expansion. We investigated these changes in a serial imaging study of adipose depots and cardiac geometry following bariatric surgery.Methods62 patients underwent cardiac magnetic resonance (CMR) before and after bariatric surgery, including 36 with short-term (median 212 days), 37 medium-term (median 428 days) and 32 long-term (median 1030 days) follow-up. CMR was used to assess cardiac geometry (left atrial volume (LAV) and left ventricular end-diastolic volume (LVEDV)), LV mass (LVM) and LV eccentricity index (LVei – a marker of pericardial restraint). Abdominal visceral (VAT) and epicardial (EAT) adipose tissue were also measured.ResultsPatients on average had lost 21kg (38.9% excess weight loss, EWL) at 212 days and 36kg (64.7% EWL) at 1030 days following bariatric surgery. Most VAT and EAT loss (43% and 14%, pConclusionsCardiac volumes show a biphasic response to weight loss, initially becoming smaller and then returning to pre-operative sizes by 1030 days. We propose this is due to an initial reversal of eccentric remodelling followed by reversal of concentric remodelling. Furthermore, we provide evidence for a role of EAT contributing to pericardial restraint, with EAT loss improving markers of pericardial restraint.
Published: 2023

33. Engraftment kinetics and graft failure after single umbilical cord blood transplantation using a myeloablative conditioning regimen

Author: Eliane Gluckman, Tracey A. O'Brien, Cristina Navarrete, Maria Pia Sormani, Mary Eapen, Gesine Kögler, Myriam Labopin, Juliana Ruiz Fernandes, Anna Paola Iori, Federico Garnier, Jaime Sanz, Fernanda Volt, Guillermo Sanz, Lucilla Lecchi, Chantal Kenzey, Riccardo Saccardi, Fabienne Pouthier, Cristina Díaz de Heredia, Franco Locatelli, Sergi Querol, Vanderson Rocha, Etienne Baudoux, Annalisa Ruggeri, Gérard Michel, William Arcese, Centre de Recherche Saint-Antoine (UMRS893), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Eurocord, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut Universitaire d'Hématologie (IUH), Université Paris Diderot - Paris 7 (UPD7)-Université Paris Diderot - Paris 7 (UPD7), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Cord blood committee EBMT, Università degli studi di Genova = University of Genoa (UniGe), Hospital La Fe, Hôpital de la Timone [CHU - APHM] (TIMONE), Santa Lucia Foundation, IRCSS, Rome, Vall d'Hebron University Hospital [Barcelona], Sydney Children's hospital, Rome transplant network, Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome] (UNIROMA), Barcelona Cord Blood Bank, Heinrich Heine Universität Düsseldorf = Heinrich Heine University [Düsseldorf], Maggiore Hospital, IRCCS Foundation, Milano, Etablissement français du sang [Besançon] (EFS), Agence de la biomédecine [Saint-Denis la Plaine], NHSBT, Université de Liège, Medical College of Wisconsin, France Monacord, Centre Scientifique de Monaco (CSM), Churchill Hospital, Churchill Hospital Oxford Centre for Haematology, Careggi University Hospital, HAL UPMC, Gestionnaire, Service d'hématologie clinique et de thérapie cellulaire [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Universita degli studi di Genova, Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome], and Dusseldorf University
Subjects: Graft Rejection, Myeloid, Male, [SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology, Time Factors, Transplantation Conditioning, Neutrophils, Graft vs Host Disease, Umbilical cord, 0302 clinical medicine, Cumulative incidence, Child, Adolescent, Adult, Child, Preschool, Female, Follow-Up Studies, Humans, Infant, Leukemia, Myeloid, Acute, Middle Aged, Myeloablative Agonists, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Remission Induction, Survival Analysis, Transplantation, Homologous, Cord Blood Stem Cell Transplantation, Acute leukemia, Leukemia, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Articles, Hematology, 3. Good health, medicine.anatomical_structure, surgical procedures, operative, N/A, Settore MED/38 - PEDIATRIA GENERALE E SPECIALISTICA, 030220 oncology & carcinogenesis, Homologous, medicine.medical_specialty, Acute, 03 medical and health sciences, medicine, Preschool, Transplantation, Neutrophil Engraftment, business.industry, Umbilical Cord Blood Transplantation, Settore MED/15, Surgery, business, 030215 immunology
Abstract: on behalf of Eurocord, Cord Blood Committee EBMT and Netcord; International audience; Umbilical cord blood transplant recipients are exposed to an increased risk of graft failure, a complication leading to a higher rate of transplant-related mortality. The decision and timing to offer a second transplant after graft failure is challenging. With the aim of addressing this issue, we analyzed engraftment kinetics and outcomes of 1268 patients (73% children) with acute leukemia (64% acute lymphoblastic leukemia, 36% acute myeloid leukemia) in remission who underwent single-unit umbilical cord blood transplantation after a myeloablative conditioning regimen. The median follow-up was 31 months. The overall survival rate at 3 years was 47%; the 100-day cumulative incidence of transplant-related mortality was 16%. Longer time to engraftment was associated with increased transplant-related mortality and shorter overall survival. The cumulative incidence of neutrophil engraftment at day 60 was 86%, while the median time to achieve engraftment was 24 days. Probability density analysis showed that the likelihood of engraftment after umbilical cord blood transplantation increased after day 10, peaked on day 21 and slowly decreased to 21% by day 31. Beyond day 31, the probability of engraftment dropped rapidly, and the residual probability of engrafting after day 42 was 5%. Graft failure was reported in 166 patients, and 66 of them received a second graft (allogeneic, n=45). Rescue actions, such as the search for another graft, should be considered starting after day 21. A diagnosis of graft failure can be established in patients who have not achieved neutrophil recovery by day 42. Moreover, subsequent transplants should not be postponed after day 42.
Published: 2014

34. Intravenous Busulfan for Autologous Stem Cell Transplantation in Adult Patients with Acute Myeloid Leukemia: a Survey of 952 Patients on Behalf of the Acute Leukemia Working Party of the European Group for Blood and Marrow Transplantation

Author: Myriam Labopin, Vanderson Rocha, Depei Wu, Giuseppe Irrera, Arnon Nagler, Aida Botelho Sousa, Avichai Shimoni, Mohamad Mohty, Antonio P. Torres Gomez, Miguel A. Sanz, Raanan Berger, William Arcese, Norbert Claude Gorin, Jose E. Guimaraes, Simona Lapusan, Norbert Vey, Felicetto Ferrara, Angelo Michele Carella, Chaim Sheba Medical Center, Acute Leukemia Working Party of EBMT, European Society for Blood and Marrow Transplantation (EBMT), Centre de Recherche Saint-Antoine (UMRS893), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'hématologie clinique et de thérapie cellulaire [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Ospedale Cardarelli, Hospital La Fe, Soochow University, Hospital Reina Sofia, Cordoba, Azienda Ospedaleria Universitaria di Modena, Hospital de São João [Porto], Hospital de St. António dos Capuchos, University of Genova, San Martino Hospital, Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Rome transplant network, Churchill Hospital, Churchill Hospital Oxford Centre for Haematology, HAL UPMC, Gestionnaire, CHU Saint-Antoine [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: Myeloid, Male, [SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology, Bone Marrow Transplantation/mortality, medicine.medical_treatment, Leukemia, Myeloid, Acute/therapy, Hematopoietic stem cell transplantation, Antineoplastic Agents, Alkylating/administration & dosage, Leukemia, Myeloid, Acute/mortality, Gastroenterology, HSAC ONC, Autologous stem-cell transplantation, Hematopoietic Stem Cell Transplantation/mortality, Infusions, Intravenous, Bone Marrow Transplantation, Acute leukemia, Survival Rate/trends, Transplantation, Autologous/mortality, Leukemia, Data Collection, Hematopoietic Stem Cell Transplantation, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Articles, Hematology, Middle Aged, Alkylating, 3. Good health, Europe, Survival Rate, Leukemia, Myeloid, Acute, Female, Intravenous, Autologous, medicine.drug, Adult, Busulfan/administration & dosage, Infusions, medicine.medical_specialty, Adolescent, Cyclophosphamide, Antineoplastic Agents, Acute, Transplantation, Autologous, Europe/epidemiology, Data Collection/methods, Young Adult, Internal medicine, medicine, Humans, Antineoplastic Agents, Alkylating, Busulfan, Survival rate, Aged, Retrospective Studies, Transplantation, business.industry, Settore MED/15, medicine.disease, Immunology, business
Abstract: Oral busulfan is the historical backbone of the busulfan+cyclophosphamide regimen for autologous stem cell transplantation. However intravenous busulfan has more predictable pharmacokinetics and less toxicity than oral busulfan; we, therefore, retrospectively analyzed data from 952 patients with acute myeloid leukemia who received intravenous busulfan for autologous stem cell transplantation. Most patients were male (n=531, 56%), and the median age at transplantation was 50.5 years. Two-year overall survival, leukemia-free survival, and relapse incidence were 67 +/- 2%, 53 +/- 2%, and 40 +/- 2%, respectively. The non-relapse mortality rate at 2 years was 7 +/- 1%. Five patients died from veno-occlusive disease. Overall leukemia-free survival and relapse incidence at 2 years did not differ significantly between the 815 patients transplanted in first complete remission (52 +/- 2% and 40 +/- 2%, respectively) and the 137 patients transplanted in second complete remission (58 +/- 5% and 35 +/- 5%, respectively). Cytogenetic risk classification and age were significant prognostic factors: the 2-year leukemia-free survival was 63 +/- 4% in patients with good risk cytogenetics, 52 +/- 3% in those with intermediate risk cytogenetics, and 37 +/- 10% in those with poor risk cytogenetics (P=0.01); patients
Published: 2014

35. Cost-effectiveness and clinical outcomes of double versus single cord blood transplantation in adults with acute leukemia in France

Author: Eliane Gluckman, Vanderson Rocha, Mauricette Michallet, Norbert Claude Gorin, Catherine Faucher, Didier Blaise, Gérard Socié, Nathalie Fegueux, Myriam Labopin, Jean-Yves Cahn, Stéphanie Nguyen, Eric Deconinck, Federico Garnier, Dominique Bertrand, Thierry de Revel, Fernanda Volt, Chantal Kenzey, Namik Taright, Noel Milpied, Lionel Mannone, Mohamad Mohty, Ibrahim Yakoub Agha, Annalisa Ruggeri, Service d'hématologie clinique et de thérapie cellulaire [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Centre de Recherche Saint-Antoine (UMRS893), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Eurocord, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut Universitaire d'Hématologie (IUH), Université Paris Diderot - Paris 7 (UPD7)-Université Paris Diderot - Paris 7 (UPD7), Università degli Studi di Roma Tor Vergata [Roma], CEREST-TC [CHU Saint-Antoine], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Hôpital l'Archet, Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Hôpital Claude Huriez [Lille], CHU Lille, Hôpital JeanMinjoz, Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Hôpital Lapeyronie [Montpellier] (CHU), Hôpital Saint-Louis, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Michallon, Hôpital d'Instruction des Armées Percy, Service de Santé des Armées, Agence de la biomédecine [Saint-Denis la Plaine], DIM Paris, Centre national gestion Paris, Churchill Hospital, Churchill Hospital Oxford Centre for Haematology, HAL UPMC, Gestionnaire, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and CHU Saint-Antoine [AP-HP]
Subjects: Adult, [SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology, medicine.medical_specialty, Transplantation Conditioning, Cord, Adolescent, Cost effectiveness, Cost-Benefit Analysis, Graft vs Host Disease, [SDV.CAN]Life Sciences [q-bio]/Cancer, Cord Blood Stem Cell Transplantation, Young Adult, 03 medical and health sciences, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, Recurrence, Risk Factors, medicine, Humans, Transplantation, Homologous, Aged, Acute leukemia, Leukemia, business.industry, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Hematology, Middle Aged, medicine.disease, 3. Good health, Surgery, Transplantation, Treatment Outcome, 030220 oncology & carcinogenesis, Cord blood, Acute Disease, France, business, 030215 immunology
Abstract: on behalf of Eurocord and Société Française de Greffe de Moelle et de Thérapie Cellulaire (SFGM-TC); International audience; Double cord blood transplantation extends the use of cord blood to adults for whom a single unit is not available, but the procedure is limited by its cost. To evaluate outcomes and cost-effectiveness of double compared to single cord blood transplantation, we analyzed 134 transplants in adults with acute leukemia in first remission. Transplants were performed in France with reduced intensity or myeloablative conditioning regimens. Costs were estimated from donor search to 1 year after transplantation. A Markov decision analysis model was used to calculate quality-adjusted life-years and cost-effectiveness ratio within 4 years. The overall survival at 2 years after single and double cord blood transplants was 42% versus 62%, respectively (P=0.03), while the leukemia-free-survival was 33% versus 53%, respectively (P=0.03). The relapse rate was 21% after double transplants and 42% after a single transplant (P=0.006). No difference was observed for non-relapse mortality or chronic graft-versus-host-disease. The estimated costs up to 1 year after reduced intensity conditioning for single and double cord blood transplantation were € 165,253 and €191,827, respectively. The corresponding costs after myeloablative conditioning were € 192,566 and € 213,050, respectively. Compared to single transplants, double cord blood transplantation was associated with supplementary costs of € 21,302 and € 32,420 up to 4 years, but with increases in quality-adjusted life-years of 0.616 and 0.484, respectively, and incremental cost-effectiveness ratios of € 34,581 and €66,983 in the myeloablative and reduced intensity conditioning settings, respectively. Our results showed that for adults with acute leukemia in first complete remission in France, double cord transplantation is more cost-effective than single cord blood transplantation, with better outcomes, including quality-adjusted life-years.
Published: 2014

36. Alternative donor hematopoietic stem cell transplantation for mature lymphoid malignancies after reduced-intensity conditioning regimen: similar outcomes with umbilical cord blood and unrelated donor peripheral blood

Author: Stephen D. Robinson, Celso Arrais Rodrigues, Jan J. Cornelissen, Vanderson Rocha, Peter Dreger, Carmen Canals, Eliane Gluckman, Arnon Nagler, Pavel Jindra, Mohamad Mohty, Hélène Schoemans, Bernard Rio, Henrik Sengeloev, Dietger Niederwieser, Annalisa Ruggeri, Claudio G. Brunstein, Eefke Petersen, Juergen Finke, Nathalie Fegueux, Anna Sureda, François Guilhot, Hematology, Universidade de São Paulo = University of São Paulo (USP), Hospital Sírio-Libanês, Churchill Hospital, Churchill Hospital Oxford Centre for Haematology, Eurocord, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut Universitaire d'Hématologie (IUH), Université Paris Diderot - Paris 7 (UPD7)-Université Paris Diderot - Paris 7 (UPD7), Heidelberg University Hospital [Heidelberg], University of Minnesota [Twin Cities] (UMN), University of Minnesota System, Rigshospitalet [Copenhagen], Copenhagen University Hospital, University Hospital Freiburg, CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre hospitalier universitaire de Nantes (CHU Nantes), Université Pierre et Marie Curie - Paris 6 (UPMC), Centre de Recherche Saint-Antoine (UMRS893), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), University Medical Center [Utrecht], INSERM CIC 0802 (INSERM - CHU de Poitiers), Université de Poitiers-Centre hospitalier universitaire de Poitiers (CHU Poitiers)-Institut National de la Santé et de la Recherche Médicale (INSERM), Universität Leipzig, ErasmusMC, Charles University Hospital Pilsen, Chaim Sheba Medical Center, Hôpital Lapeyronie [Montpellier] (CHU), University Hospitals Leuven [Leuven], Avon haematology unit Bristol, Hospital de la Santa Creu i Sant Pau, Addenbrooke's Hospital, Cambridge University NHS Trust, Universidade de São Paulo (USP), Service d'hématologie clinique et de thérapie cellulaire [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre hospitalier universitaire de Poitiers (CHU Poitiers)-Université de Poitiers, Universität Leipzig [Leipzig], and HAL UPMC, Gestionnaire
Subjects: Adult, Male, [SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology, medicine.medical_specialty, Transplantation Conditioning, Adolescent, medicine.medical_treatment, Graft vs Host Disease, Cord Blood Stem Cell Transplantation, Hematopoietic stem cell transplantation, Lower risk, Gastroenterology, Umbilical cord, Disease-Free Survival, Risk Factors, Internal medicine, medicine, Humans, Survival rate, Aged, Retrospective Studies, Neutrophil Engraftment, business.industry, Hematopoietic Stem Cell Transplantation, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Hematology, Articles, Middle Aged, 3. Good health, Transplantation, Survival Rate, medicine.anatomical_structure, Cord blood, Hematologic Neoplasms, Immunology, Female, business, Unrelated Donors, Follow-Up Studies
Abstract: on behalf of Eurocord-Netcord and the Lymphoma Working Party and the Chronic Leukemia Working Party of the European Group for Blood and Marrow Transplantation; International audience; We have reported encouraging results of unrelated cord blood transplantation for patients with lymphoid malignancies. Whether those outcomes are comparable to matched unrelated donor transplants remains to be defined. We studied 645 adult patients with mature lymphoid malignancies who received an allogeneic unrelated donor transplant using umbilical cord blood (n=104) or mobilized peripheral blood stem cells (n=541) after a reduced-intensity conditioning regimen. Unrelated cord blood recipients had more refractory disease. Median follow-up time was 30 months. Neutrophil engraftment (81% vs. 97%, respectively; P
Published: 2014

37. Made in Europe: will artemisinin resistance emerge in French Guiana?

Author: Bernard Carme, Félix Djossou, Philippe J Guerin, François Nosten, Magalie Demar-Pierre, Mathieu Nacher, EA 3593 Université des Antilles et de la Guyane, Centre d'investigation clinique Antilles-Guyane (CIC - Antilles Guyane), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU de la Martinique [Fort de France]-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française]-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU de la Martinique [Fort de France]-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française]-Infectious and Tropical Diseases Department, Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française], WorldWide Antimalarial Resistance Network (WWARN), University of Oxford [Oxford]-Churchill Hospital Oxford Centre for Haematology, Infectious and Tropical Diseases Department, Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française]-Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française]-Unité des Maladies Infectieuses et Tropicales (UMIT), Unité des Maladies Infectieuses et Tropicales (UMIT), Shoklo Malaria Research Unit [Mae Sot, Thailand] (SMRU), Mahidol Oxford Tropical Medicine Research Unit (MORU), Wellcome Trust-Mahidol University [Bangkok]-University of Oxford [Oxford]-Wellcome Trust-Mahidol University [Bangkok]-University of Oxford [Oxford], Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU de la Martinique [Fort de France]-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française], Laboratoire de Parasitologie Mycologie, ADENIS, ANTOINE, Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -CHU de la Martinique [Fort de France]-Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française]-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -CHU de la Martinique [Fort de France]-Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française]-Infectious and Tropical Diseases Department, University of Oxford-Churchill Hospital Oxford Centre for Haematology, University of Oxford-Mahidol University [Bangkok]-Wellcome Trust-University of Oxford-Mahidol University [Bangkok]-Wellcome Trust, and Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -CHU de la Martinique [Fort de France]-Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française]
Subjects: Difficult problem, Opinion, medicine.medical_specialty, 030231 tropical medicine, Drug Resistance, Antimalarials, 03 medical and health sciences, 0302 clinical medicine, Environmental protection, Political science, parasitic diseases, Development economics, medicine, Humans, Health policy, 030304 developmental biology, Shadow (psychology), 0303 health sciences, Amazon rainforest, Health Policy, Public health, Artemisinin resistance, Legislature, medicine.disease, Artemisinins, French Guiana, Malaria, 3. Good health, Europe, Infectious Diseases, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Parasitology
Abstract: International audience; Resistance to artemisinin casts a shadow on the fight against malaria. The importance of illegal gold miners and of malaria in isolated regions of French Guiana constitutes a threat that endangers the fight against malaria in the Amazon. The hurdles of French laws and the remoteness of the territory from France make it impossible for the system to adapt to the problem of total inaccessibility of an important part of the malaria problem. Transmission is high in these areas and gold miners self-medicate with erratic regimens of artemisinin combinations, thus creating perfect conditions for the emergence of resistance. What needs to be done is being done, but within the limits of national law, with some results. However, facing the same difficult problem, Suriname shows more flexibility and is doing much better than French Guiana despite having lower resources. Local authorities in French Guiana cannot overrule the laws that block appropriate malaria care from reaching a third of malaria-exposed persons. Thus the health authorities in France should take immediate calibrated legislative and financial measures to avoid a predictable disaster.
Published: 2013

38. Emergence of serogroup X meningococcal disease in Africa: need for a vaccine

Author: Gunnstein Norheim, Ouli Xie, Andrew J. Pollard, Judith E. Mueller, Oxford Vaccine Group, University of Oxford-Oxford NIHR Biomedical Research Centre-The Churchill hospital, Epidémiologie des Maladies Emergentes - Emerging Diseases Epidemiology, Pasteur-Cnam Risques infectieux et émergents (PACRI), Institut Pasteur [Paris] (IP)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Institut Pasteur [Paris] (IP)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM), École des Hautes Études en Santé Publique [EHESP] (EHESP), Département Méthodes quantitatives en santé publique (METIS), Institut Pasteur [Paris] (IP), Norwegian Institute of Public Health [Oslo] (NIPH), University of Oxford [Oxford]-Oxford NIHR Biomedical Research Centre-The Churchill hospital, Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM), and Institut Pasteur [Paris]
Subjects: Biomedical Research, Epidemiology, Meningococcal Vaccines, Biology, Meningitis, Meningococcal, Neisseria meningitidis, medicine.disease_cause, Meningococcal disease, Microbiology, Disease Outbreaks, Serogroup X, 03 medical and health sciences, 0302 clinical medicine, Conjugate vaccine, parasitic diseases, medicine, Serogroup c, Humans, 030212 general & internal medicine, Africa South of the Sahara, 2. Zero hunger, 0303 health sciences, Vaccines, Vaccines, Conjugate, General Veterinary, General Immunology and Microbiology, 030306 microbiology, Incidence (epidemiology), Incidence, Public Health, Environmental and Occupational Health, Outbreak, medicine.disease, bacterial infections and mycoses, Virology, 3. Good health, Infectious Diseases, Molecular Medicine, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Meningitis, MenAfriVac
Abstract: International audience; Neisseria meningitidis is responsible for the seasonal burden and recurrent epidemics of meningitis in an area of sub-Saharan Africa known as the meningitis belt. Historically, the majority of the cases in the meningitis belt are caused by serogroup A meningococci. Serogroup C meningococci were responsible for outbreaks in the meningitis belt in the 1980s, while serogroup W (formerly W-135) has emerged as a cause of epidemic meningitis since 2000. Serogroup X meningococci have previously been considered a rare cause of sporadic meningitis, but during 2006–2010, outbreaks of serogroup X meningitis occurred in Niger, Uganda, Kenya,Togo and Burkina Faso, the latter with at least 1300 cases of serogroup X meningitis among the 6732 reported annual cases. While serogroup X has not yet caused an epidemic wave of the scale of serogroup A in 1996–1997 or serogroup W in Burkina Faso during 2002, the existing reports suggest a similar seasonal hyperendemicity and capacity for localised epidemics. Serogroup X incidence appears to follow a pattern of highly localised clonal waves, and in affected districts, other meningococcal serogroups are usually absent from disease. Currently, no licensed vaccine is available against serogroup X meningococci. Following the introduction of a monovalent serogroup A conjugate vaccine (MenAfriVac®) in the meningitis belt and the upcoming introduction of pneumococcal conjugate vaccines, vaccine-based prevention of serogroup X may become a public health need. The serogroup X polysaccharide capsule is the most likely target for vaccine development, but recent data also indicate a potential role for protein-based vaccines. A multivalent vaccine, preferably formulated as a conjugate vaccine and covering at least serogroups A, W, and X is needed, and the efforts for vaccine development should be intensified.
Published: 2013

39. NOTCH, a new signaling pathway implicated in holoprosencephaly

Author: Valérie Dupé, Véronique David, Isabelle Gicquel, Christèle Dubourg, Yann Le Pétillon, Claude Bendavid, Timothy P. Bohan, Sandra Mercier, Usha Kini, Georges Bourrouillou, Sylvie Odent, Christel Thauvin-Robinet, Lucie Rochard, Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Génétique Moléculaire, Hôpital Pontchaillou, Service de génétique médicale, CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Department of Clinical Genetics [Churchill Hospital], Churchill Hospital Oxford Centre for Haematology, Centre de génétique - Centre de référence des maladies rares, anomalies du développement et syndromes malformatifs (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Department of Molecular and Human Genetics, Baylor College of Medicine (BCM), Baylor University-Baylor University, Service de génétique clinique, hôpital Sud, Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de génétique moléculaire et génomique médicale [CHU Rennes], CHU Pontchaillou [Rennes], Service Génétique Médicale [CHU Toulouse], Institut Fédératif de Biologie (IFB), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle Biologie [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Service de génétique clinique [Rennes], Université de Rennes (UR)-CHU Pontchaillou [Rennes]-hôpital Sud, and De Villemeur, Hervé
Subjects: Male, MESH: Signal Transduction, Candidate gene, [SDV.GEN] Life Sciences [q-bio]/Genetics, Chick Embryo, MESH: Amino Acid Sequence, MESH: Base Sequence, Holoprosencephaly, MESH: Animals, [SDV.BDD]Life Sciences [q-bio]/Development Biology, Genetics (clinical), Sequence Deletion, Genetics, 0303 health sciences, Receptors, Notch, MESH: Androstenediols, 030305 genetics & heredity, MESH: Infant, Newborn, Intracellular Signaling Peptides and Proteins, General Medicine, MESH: Sequence Deletion, MESH: Chick Embryo, Cell biology, embryonic structures, Female, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], MESH: Membrane Proteins, Signal transduction, MESH: Holoprosencephaly, Signal Transduction, Adult, musculoskeletal diseases, Cell signaling, congenital, hereditary, and neonatal diseases and abnormalities, animal structures, Molecular Sequence Data, Notch signaling pathway, MESH: Sequence Alignment, Biology, Article, 03 medical and health sciences, FGF8, [SDV.BDD] Life Sciences [q-bio]/Development Biology, Androstenediols, medicine, Animals, Humans, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Amino Acid Sequence, Molecular Biology, 030304 developmental biology, [SDV.GEN]Life Sciences [q-bio]/Genetics, MESH: Molecular Sequence Data, MESH: Humans, Base Sequence, Infant, Newborn, Membrane Proteins, MESH: Adult, medicine.disease, MESH: Male, Forebrain, Mutation testing, MESH: Receptors, Notch, Sequence Alignment, MESH: Female
Abstract: International audience; Genetics of Holoprosencephaly (HPE), a congenital malformation of the developing human forebrain, is due to multiple genetic defects. Most genes that have been implicated in HPE belong to the sonic hedgehog signaling pathway. Here we describe a new candidate gene isolated from array comparative genomic hybridization redundant 6qter deletions, DELTA Like 1 (DLL1), which is a ligand of NOTCH. We show that DLL1 is co-expressed in the developing chick forebrain with Fgf8. By treating chick embryos with a pharmacological inhibitor, we demonstrate that DLL1 interacts with FGF signaling pathway. Moreover, a mutation analysis of DLL1 in HPE patients revealed a three-nucleotide deletion. These various findings implicate DLL1 in early patterning of the forebrain and identify NOTCH as a new signaling pathway involved in HPE.
Published: 2011

40. Plasmodium falciparum msp1, msp2 and glurp allele frequency and diversity in sub-Saharan Africa

Author: Kefas Mugittu, Ingrid Felger, Piero Olliaro, Georges Snounou, Deborah Sumari, Felista Mwingira, Hans-Peter Beck, Gamba Nkwengulila, Sonja Schoepflin, Dares Salaam University College of Education, Department of Zoology and Wildlife Conservation, University of Dar es Salaam (UDSM), Swiss Tropical and Public Health Institute [Basel], University of Basel (Unibas), Ifakara Health Institute, Immunité et Infection, Université Pierre et Marie Curie - Paris 6 (UPMC)-IFR113-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), UNICEF/UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases, Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Centre for Tropical Medicine and Vaccinology, University of Oxford [Oxford]-Churchill Hospital Oxford Centre for Haematology-Nuffield Department of Medicine, These studies were funded by UNICEF/UNDP/World Bank/WHO Special program for Research and Training in Tropical Diseases (TDR) and Novartis pharmaceutical company. IHI receives core financial support from the Swiss Agency for Development and Co-operation (SDC) and Department for International Development (DFID). Felista Mwingira's MSc project was jointly sponsored by TDR, IHI and Dar Es Salaam University College of Education (DUCE), a constituent college of the University of Dar es salaam - Tanzania., Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Nuffield Department of Clinical Medicine [Oxford], University of Oxford, University of Oxford-Churchill Hospital Oxford Centre for Haematology-Nuffield Department of Medicine, and BMC, Ed.
Subjects: Molecular biology, Protozoan Proteins, MESH: Base Sequence, Polymerase Chain Reaction, MESH: Gene Amplification, MESH: Genotype, 0302 clinical medicine, Gene Frequency, Recurrence, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, MESH: Child, Genotype, MESH: Genetic Variation, Malaria, Falciparum, Child, MESH: Protozoan Proteins, Merozoite Surface Protein 1, Diagnosis & treatment, MESH: Plasmodium falciparum, MESH: Merozoite Surface Protein 1, Genetics, 0303 health sciences, biology, MESH: Malaria, Falciparum, 3. Good health, Drug Combinations, Infectious Diseases, Child, Preschool, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, lcsh:Arctic medicine. Tropical medicine, lcsh:RC955-962, Plasmodium falciparum, 030231 tropical medicine, Antigens, Protozoan, lcsh:Infectious and parasitic diseases, Antimalarials, 03 medical and health sciences, Genetic variation, parasitic diseases, medicine, MESH: Gene Frequency, Humans, lcsh:RC109-216, MESH: Africa South of the Sahara, Genotyping, Allele frequency, Africa South of the Sahara, MESH: Drug Combinations, Genetic diversity, MESH: Humans, Base Sequence, 030306 microbiology, Research, MESH: Child, Preschool, Gene Amplification, Genetic Variation, MESH: Polymerase Chain Reaction, medicine.disease, biology.organism_classification, MESH: Antimalarials, MESH: Recurrence, Parasitology, Malaria, MESH: Antigens, Protozoan
Abstract: Background The efficacy of anti-malarial drugs is assessed over a period of 28-63 days (depending on the drugs' residence time) following initiation of treatment in order to capture late failures. However, prolonged follow-up increases the likelihood of new infections depending on transmission intensity. Therefore, molecular genotyping of highly polymorphic regions of Plasmodium falciparum msp1, msp2 and glurp loci is usually carried out to distinguish recrudescence (true failures) from new infections. This tool has now been adopted as an integral part of anti-malarial efficacy studies and clinical trials. However, there are concerns over its utility and reliability because conclusions drawn from molecular typing depend on the genetic profile of the respective parasite populations, but this profile is not systematically documented in most endemic areas. This study presents the genetic diversity of P. falciparum msp1, msp2 and glurp markers in selected sub-Saharan Africa countries with varying levels of endemicity namely Malawi, Tanzania, Uganda, Burkina Faso and São Tomé. Methods A total 780 baseline (Day 0) blood samples from children less than seven years, recruited in a randomized controlled clinical trials done between 1996 and 2000 were genotyped. DNA was extracted; allelic frequency and diversity were investigated by PCR followed by capillary electrophoresis for msp2 and fragment sizing by a digitalized gel imager for msp1 and glurp. Results and Conclusion Plasmodium falciparum msp1, msp2 and glurp markers were highly polymorphic with low allele frequencies. A total of 17 msp1 genotypes [eight MAD20-, one RO33- and eight K1-types]; 116 msp2 genotypes [83 3D7 and 33 FC27- types] and 14 glurp genotypes were recorded. All five sites recorded very high expected heterozygosity (HE) values (0.68 - 0.99). HE was highest in msp2 locus (HE = 0.99), and lowest for msp1 (HE = 0.68) (P < 0.0001). The genetic diversity and allelic frequency recorded were independent of transmission intensity (P = 0.84, P = 0.25 respectively. A few genotypes had particularly high frequencies; however the most abundant showed only a 4% probability that a new infection would share the same genotype as the baseline infection. This is unlikely to confound the distinction of recrudescence from new infection, particularly if more than one marker is used for genotyping. Hence, this study supports the use of msp1, msp2 and glurp in malaria clinical trials in sub-Saharan Africa to discriminate new from recrudescent infections.
Published: 2011

41. A Biologically Inspired Algorithm for Microcalcification Cluster Detection

Author: Michael Brady, Marius George Linguraru, Kostas Marias, Ruth English, Wolfson Medical Vision Laboratory (MVL), University of Oxford [Oxford], Harvard John A. Paulson School of Engineering and Applied Sciences (SEAS), Harvard University [Cambridge], Institute of Computer Science (ICS-FORTH), Foundation for Research and Technology - Hellas (FORTH), Churchill Hospital [Breast Care Unit], and Churchill Hospital Oxford Centre for Haematology
Subjects: Anisotropic diffusion, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, microcalcification clusters, Health Informatics, Breast Neoplasms, X-ray mammography, 02 engineering and technology, human visual system, 030218 nuclear medicine & medical imaging, Image (mathematics), Phase congruency, 03 medical and health sciences, image normalization, 0302 clinical medicine, [INFO.INFO-TS]Computer Science [cs]/Signal and Image Processing, Image Interpretation, Computer-Assisted, 0202 electrical engineering, electronic engineering, information engineering, Cluster (physics), medicine, [INFO.INFO-IM]Computer Science [cs]/Medical Imaging, Humans, Radiology, Nuclear Medicine and imaging, Computer vision, Selection (genetic algorithm), Mathematics, Radiological and Ultrasound Technology, business.industry, Calcinosis, anisotropic diffusion, Pattern recognition, Computer Graphics and Computer-Aided Design, [INFO.INFO-MO]Computer Science [cs]/Modeling and Simulation, ROC Curve, Human visual system model, 020201 artificial intelligence & image processing, Female, Computer Vision and Pattern Recognition, Artificial intelligence, Microcalcification, medicine.symptom, business, Algorithm, [SPI.SIGNAL]Engineering Sciences [physics]/Signal and Image processing, Energy (signal processing), Algorithms, Mammography
Abstract: International audience; The early detection of breast cancer greatly improves prognosis. One of the earliest signs of cancer is the formation of clusters of microcalcifications. We introduce a novel method for microcalcification detection based on a biologically inspired adaptive model of contrast detection. This model is used in conjunction with image filtering based on anisotropic diffusion and curvilinear structure removal using local energy and phase congruency. An important practical issue in automatic detection methods is the selection of parameters: we show that the parameter values for our algorithm can be estimated automatically from the image. This way, the method is made robust and essentially free of parameter tuning. We report results on mammograms from two databases and show that the detection performance can be improved by first including a normalisation scheme.
Published: 2006

42. Response to Letter to the Editor: 'Prevention of Adrenal Crisis: Cortisol Response to Major Stress Compared to Stress Dose Hydrocortisone Delivery'

Author: David J. Smith, Christopher J Mowatt, Angela E Taylor, Sibylle Kohler, Alessandro Prete, Radu Mihai, John Komninos, Niki Karavitaki, Dimitra Vassiliadi, Mark A. Foster, Violet Fazal-Sanderson, Brian G. Keevil, Joanne L. Fallowfield, Janet M. Lord, Donna M. O'Neil, Wiebke Arlt, Irina Bancos, John A.H. Wass, Djillali Annane, Merlan, Justine, University of Birmingham [Birmingham], Department of Internal Medicine, Division of Endocrinology, Diabetes, Metabolism, Nutrition, Mayo Clinic, School of Mathematics [Birmingham], Queens Elizabeth Hospital [Birmingham], Oxford Centre for Diabetes, Endocrinology and Metabolism (OCDEM), University of Oxford, Evangelismos Athens General Hospital, Royal Shrewsbury Hospital, Churchill Hospital Oxford Centre for Haematology, Hôpital Raymond Poincaré [AP-HP], Infection et inflammation (2I), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM), and University Hospital of South Manchester
Subjects: medicine.medical_specialty, Letter to the editor, Hydrocortisone, [SDV]Life Sciences [q-bio], Endocrinology, Diabetes and Metabolism, Clinical Biochemistry, Adrenocorticotropic hormone, Biochemistry, Endocrinology, Adrenocorticotropic Hormone, Internal medicine, Humans, Medicine, Online Only Articles, ComputingMilieux_MISCELLANEOUS, business.industry, Biochemistry (medical), Letters to the Editor Responses, Adrenal crisis, [SDV] Life Sciences [q-bio], Acute Disease, Cosyntropin, medicine.symptom, business, AcademicSubjects/MED00250, Adrenal Insufficiency, medicine.drug
Abstract: International audience
Published: 2020

43. nab-Paclitaxel Plus Durvalumab in Patients With Previously Treated Advanced Stage Non-small Cell Lung Cancer (ABOUND.2L+)

Author: Morgensztern, D., Dols, M.C., Aix, S.P., Postmus, P.E., Bennouna, J., Fischer, J.R., Juan-Vidal, O., Stewart, D.J., Ardizzoni, A., Bhore, R., Wolfsteiner, M., Reck, M., Talbot, D., Govindan, R., Ong, T.J., ABOUND2L Investigators, Morgensztern D., Dols M.C., Ponce Aix S., Postmus P.E., Bennouna J., Fischer J.R., Juan-Vidal O., Stewart D.J., Ardizzoni A., Bhore R., Wolfsteiner M., Reck M., Talbot D., Govindan R., Ong T.J., ABOUND.2L+, [Morgensztern,D, Govindan,R] Washington University School of Medicine, St Louis, MO, United States. [Cobo Dols,Manuel] Hospital Universitario Málaga Regional, Instituto de Investigación Biomédica de Málaga (IBIMA), Málaga, Spain. [Ponce Aix,S] Unidad de Investigación Clínica de Cáncer Pulmón H12O-CNIO, Madrid, Spain. [Postmus,PE] Clatterbridge Cancer Center, Liverpool, United Kingdom. [Bennouna,J] Centre René Gauducheau Centre de Lutte Contre Le Cancer Nantes Atlantique, Nantes, France. [Fischer,JR] Lungenklinik Löwenstein gGmbH, Löwenstein, Germany. [Juan-Vidal,O] Universitari i Politécnic La Fe, Valencia, Spain. [Stewart,DJ] Ottawa Hospital, Ottawa, ON, Canada. [Ardizzoni,A] Azienda Ospedaliero Universitaria Di Bologna—Policlinico S. Orsola-Malpighi, Bologna, Italy. [Bhore,R] Bristol Myers Squibb, Princeton, NJ, United States. [Wolfsteiner,M] Pharmaceutical Research Associates Inc. (PRA) Health Sciences, Lenexa, KS, United States. [Reck,M] LungenClinic, Grosshansdorf, Germany. [Talbot,D] Churchill Hospital, Oxford, United Kingdom, and This work was supported by Bristol Myers Squibb Company, Princeton, New Jersey. The sponsor was involved in the design of the study as well as in the collection, analysis, and interpretation of the data. The sponsor agreed to the decision to submit the article for publication.
Subjects: Oncology, Cancer Research, medicine.medical_specialty, Phenomena and Processes::Genetic Phenomena::Genetic Variation::Mutation [Medical Subject Headings], Durvalumab, durvalumab, medicine.medical_treatment, Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Transferases::Phosphotransferases::Phosphotransferases (Alcohol Group Acceptor)::Protein Kinases::Protein-Tyrosine Kinases::Receptor Protein-Tyrosine Kinases [Medical Subject Headings], Carcinoma de pulmón de células no pequeñas, Diseases::Neoplasms::Neoplasms by Site::Thoracic Neoplasms::Respiratory Tract Neoplasms::Lung Neoplasms [Medical Subject Headings], lcsh:RC254-282, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], second-line therapy, 03 medical and health sciences, nab-paclitaxel, 0302 clinical medicine, immune checkpoint blocker plus chemotherapy, Internal medicine, medicine, Clinical endpoint, 030212 general & internal medicine, Adverse effect, Lung cancer, advanced stage non-small cell lung cancer, Original Research, Diseases::Neoplasms::Neoplasms by Site::Thoracic Neoplasms::Respiratory Tract Neoplasms::Lung Neoplasms::Bronchial Neoplasms::Carcinoma, Bronchogenic::Carcinoma, Non-Small-Cell Lung [Medical Subject Headings], Chemotherapy, business.industry, Persons::Persons::Age Groups::Adult::Middle Aged [Medical Subject Headings], advanced stage non-small cell lung cancer, durvalumab, immune checkpoint blocker plus chemotherapy, nab-paclitaxel, second-line therapy, medicine.disease, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Clinical trial, Puntos de control inmunológico, Check Tags::Female [Medical Subject Headings], Docetaxel, Diseases::Pathological Conditions, Signs and Symptoms::Signs and Symptoms::Signs and Symptoms, Digestive::Diarrhea [Medical Subject Headings], Tumor progression, 030220 oncology & carcinogenesis, Quimioterapia, business, Diseases::Pathological Conditions, Signs and Symptoms::Signs and Symptoms::Asthenia [Medical Subject Headings], medicine.drug
Abstract: Background: The standard therapy for advanced stage non-small cell lung cancer (NSCLC) with no actionable gene alterations is a platinum-based chemotherapy doublet and immune checkpoint blocker (ICB), either concurrently or sequentially, followed by docetaxel at the time of tumor progression. However, more effective treatments are needed. We evaluated the nab-paclitaxel and durvalumab combination in patients with previously treated advanced stage NSCLC.Methods: Patients with advanced stage NSCLC previously treated with one line of platinum-based doublet with or without an ICB and no activating EGFR mutations or ALK translocations received nab-paclitaxel 100 mg/m2 (days 1 and 8) plus durvalumab 1,125 mg (day 15) every 21 days. The primary endpoint was progression-free survival (PFS). Key secondary endpoints included overall survival (OS) and safety.Results: Between February 2016 and December 2016, 79 patients were enrolled. The median age was 63 years. Most patients were males (68.4%), had non-squamous histology (69.6%), and had no prior ICB treatment (88.6%). The median PFS was 4.5 months; median OS was 10.1 months. A post hoc analysis of survival by prior ICB treatment revealed a median PFS and OS of 4.4 and 9.9 months, respectively, in ICB-naive patients and 6.9 months and not estimable, respectively, in patients previously treated with ICB. The most common treatment-emergent adverse events were asthenia (46.2%) and diarrhea (34.6%); four treatment-related deaths (5.1%) occurred.Conclusions: The nab-paclitaxel and durvalumab combination is feasible and demonstrated antitumor activity without new safety signals. Additional studies using taxanes and ICB in patients with previously treated NSCLC are warranted.Clinical Trial Registration:ClinicalTrials.gov registration (NCT02250326).EudraCT number: 2014-001105-41
Published: 2021

44. COVID-19 infection in adult patients with hematological malignancies:a European Hematology Association Survey (EPICOVIDEHA)

Author: Pagano, Livio, Salmanton-García, Jon, Marchesi, Francesco, Busca, Alessandro, Corradini, Paolo, Hoenigl, Martin, Klimko, Nikolai, Koehler, Philipp, Pagliuca, Antonio, Passamonti, Francesco, Verga, Luisa, Víšek, Benjamin, Ilhan, Osman, Nadali, Gianpaolo, Weinbergerová, Barbora, Córdoba-Mascuñano, Raúl, Marchetti, Monia, Collins, Graham P., Farina, Francesca, Cattaneo, Chiara, Cabirta, Alba, Gomes-Silva, Maria, Itri, Federico, van Doesum, Jaap, Ledoux, Marie-Pierre, Čerňan, Martin, Jakšić, Ozren, Duarte, Rafael F., Magliano, Gabriele, Omrani, Ali S., Fracchiolla, Nicola S., Kulasekararaj, Austin, Valković, Toni, Poulsen, Christian Bjørn, Machado, Marina, Glenthøj, Andreas, Stoma, Igor, Ráčil, Zdeněk, Piukovics, Klára, Navrátil, Milan, Emarah, Ziad, Sili, Uluhan, Maertens, Johan, Blennow, Ola, Bergantim, Rui, García-Vidal, Carolina, Prezioso, Lucia, Guidetti, Anna, del Principe, Maria Ilaria, Popova, Marina, de Jonge, Nick, Ormazabal-Vélez, Irati, Fernández, Noemí, Falces-Romero, Iker, Cuccaro, Annarosa, Meers, Stef, Buquicchio, Caterina, Antić, Darko, Al-Khabori, Murtadha, García-Sanz, Ramón, Biernat, Monika M., Tisi, Maria Chiara, Sal, Ertan, Rahimli, Laman, Čolović, Natasa, Schönlein, Martin, Calbacho, Maria, Tascini, Carlo, Miranda-Castillo, Carolina, Khanna, Nina, Méndez, Gustavo-Adolfo, Petzer, Verena, Novák, Jan, Besson, Caroline, Duléry, Rémy, Lamure, Sylvain, Nucci, Marcio, Zambrotta, Giovanni, Žák, Pavel, Seval, Guldane Cengiz, Bonuomo, Valentina, Mayer, Jiří, López-García, Alberto, Sacchi, Maria Vittoria, Booth, Stephen, Ciceri, Fabio, Oberti, Margherita, Salvini, Marco, Izuzquiza, Macarena, Nunes-Rodrigues, Raquel, Ammatuna, Emanuele, Obr, Aleš, Herbrecht, Raoul, Núñez-Martín-Buitrago, Lucía, Mancini, Valentina, Shwaylia, Hawraa, Sciumè, Mariarita, Essame, Jenna, Nygaard, Marietta, Batinić, Josip, Gonzaga, Yung, Regalado-Artamendi, Isabel, Karlsson, Linda Katharina, Shapetska, Maryia, Hanakova, Michaela, El-Ashwah, Shaimaa, Borbényi, Zita, Çolak, Gökçe Melis, Nordlander, Anna, Dragonetti, Giulia, Maraglino, Alessio Maria Edoardo, Rinaldi, Amelia, De Ramón-Sánchez, Cristina, Cornely, Oliver A., Finizio, Olimpia, Fazzi, Rita, Sapienza, Giuseppe, Chauchet, Adrien, Van Praet, Jens, Prattes, Juergen, Dargenio, Michelina, Rossi, Cédric, Shirinova, Ayten, Malak, Sandra, Tafuri, Agostino, Ommen, Hans-Beier, Bologna, Serge, Khedr, Reham Abdelaziz, Choquet, Sylvain, Joly, Bertrand, Ceesay, M. Mansour, Philippe, Laure, Kho, Chi Shan, Desole, Maximilian, Tsirigotis, Panagiotis, Otašević, Vladimir, Borducchi, Davimar M. M., Antoniadou, Anastasia, Gaziev, Javid, Almaslamani, Muna A., García-Poutón, Nicole, Paterno, Giovangiacinto, Torres-López, Andrea, Tarantini, Giuseppe, Mellinghoff, Sibylle, Gräfe, Stefanie, Börschel, Niklas, Passweg, Jakob, Merelli, Maria, Barać, Aleksandra, Wolf, Dominik, Shaikh, Mohammad Usman, Thiéblemont, Catherine, Bernard, Sophie, Funke, Vaneuza Araújo Moreira, Daguindau, Etienne, Khostelidi, Sofya, Nucci, Fabio Moore, Martín-González, Juan-Alberto, Landau, Marianne, Soussain, Carole, Laureana, Cécile, Lacombe, Karine, Kohn, Milena, Aliyeva, Gunay, Piedimonte, Monica, Fouquet, Guillemette, Rêgo, Mayara, Hoell-Neugebauer, Baerbel, Cartron, Guillaume, Pinto, Fernando, Alburquerque, Ana Munhoz, Passos, Juliana, Yilmaz, Asu Fergun, Redondo-Izal, Ana-Margarita, Altuntaş, Fevzi, Heath, Christopher, Kolditz, Martin, Schalk, Enrico, Guolo, Fabio, Karthaus, Meinolf, Della Pepa, Roberta, Vinh, Donald, Noël, Nicolas, Deau Fischer, Bénédicte, Drenou, Bernard, Mitra, Maria Enza, Meletiadis, Joseph, Bilgin, Yavuz M., Jindra, Pavel, Espigado, Ildefonso, Drgoňa, Ľuboš, Serris, Alexandra, Di Blasi, Roberta, Ali, Natasha, EPICOVIDEHA working group, [missing], Pagano, Livio, Salmanton-Garcia, Jon, Marchesi, Francesco, Busca, Alessandro, Corradini, Paolo, Hoenigl, Martin, Klimko, Nikolai, Koehler, Philipp, Pagliuca, Antonio, Passamonti, Francesco, Verga, Luisa, Visek, Benjamin, Ilhan, Osman, Nadali, Gianpaolo, Weinbergerova, Barbora, Cordoba-Mascunano, Raul, Marchetti, Monia, Collins, Graham P., Farina, Francesca, Cattaneo, Chiara, Cabirta, Alba, Gomes-Silva, Maria, Itri, Federico, van Doesum, Jaap, Ledoux, Marie-Pierre, Cernan, Martin, Jaksic, Ozren, Duarte, Rafael F., Magliano, Gabriele, Omrani, Ali S., Fracchiolla, Nicola S., Kulasekararaj, Austin, Valkovic, Toni, Poulsen, Christian Bjorn, Machado, Marina, Glenthoj, Andreas, Stoma, Igor, Racil, Zdenek, Piukovics, Klara, Navratil, Milan, Emarah, Ziad, Sili, Uluhan, Maertens, Johan, Blennow, Ola, Bergantim, Rui, Garcia-Vidal, Carolina, Prezioso, Lucia, Guidetti, Anna, del Principe, Maria Ilaria, Popova, Marina, de Jonge, Nick, Ormazabal-Velez, Irati, Fernandez, Noemi, Falces-Romero, Iker, Cuccaro, Annarosa, Meers, Stef, Buquicchio, Caterina, Antic, Darko, Al-Khabori, Murtadha, Garcia-Sanz, Ramon, Biernat, Monika M., Tisi, Maria Chiara, Sal, Ertan, Rahimli, Laman, Colovic, Natasa, Schonlein, Martin, Calbacho, Maria, Tascini, Carlo, Miranda-Castillo, Carolina, Khanna, Nina, Mendez, Gustavo-Adolfo, Petzer, Verena, Novak, Jan, Besson, Caroline, Dulery, Remy, Lamure, Sylvain, Nucci, Marcio, Zambrotta, Giovanni, Zak, Pavel, Seval, Guldane Cengiz, Bonuomo, Valentina, Mayer, Jiri, Lopez-Garcia, Alberto, Sacchi, Maria Vittoria, Booth, Stephen, Ciceri, Fabio, Oberti, Margherita, Salvini, Marco, Izuzquiza, Macarena, Nunes-Rodrigues, Raquel, Ammatuna, Emanuele, Obr, Ales, Herbrecht, Raoul, Nunez-Martin-Buitrago, Lucia, Mancini, Valentina, Shwaylia, Hawraa, Sciume, Mariarita, Essame, Jenna, Nygaard, Marietta, Batinic, Josip, Gonzaga, Yung, Regalado-Artamendi, Isabel, Karlsson, Linda Katharina, Shapetska, Maryia, Hanakova, Michaela, El-Ashwah, Shaimaa, Borbenyi, Zita, Colak, Gokce Melis, Nordlander, Anna, Dragonetti, Giulia, Maraglino, Alessio Maria Edoardo, Rinaldi, Amelia, De Ramon-Sanchez, Cristina, Cornely, Oliver A., Pagano, L., Salmanton-Garcia, J., Marchesi, F., Busca, A., Corradini, P., Hoenigl, M., Klimko, N., Koehler, P., Pagliuca, A., Passamonti, F., Verga, L., Visek, B., Ilhan, O., Nadali, G., Weinbergerova, B., Cordoba-Mascunano, R., Marchetti, M., Collins, G. P., Farina, F., Cattaneo, C., Cabirta, A., Gomes-Silva, M., Itri, F., van Doesum, J., Ledoux, M. -P., Cernan, M., Jaksic, O., Duarte, R. F., Magliano, G., Omrani, A. S., Fracchiolla, N. S., Kulasekararaj, A., Valkovic, T., Poulsen, C. B., Machado, M., Glenthoj, A., Stoma, I., Racil, Z., Piukovics, K., Navratil, M., Emarah, Z., Sili, U., Maertens, J., Blennow, O., Bergantim, R., Garcia-Vidal, C., Prezioso, L., Guidetti, A., del Principe, M. I., Popova, M., de Jonge, N., Ormazabal-Velez, I., Fernandez, N., Falces-Romero, I., Cuccaro, A., Meers, S., Buquicchio, C., Antic, D., Al-Khabori, M., Garcia-Sanz, R., Biernat, M. M., Tisi, M. C., Sal, E., Rahimli, L., Colovic, N., Schonlein, M., Calbacho, M., Tascini, C., Miranda-Castillo, C., Khanna, N., Mendez, G. -A., Petzer, V., Novak, J., Besson, C., Dulery, R., Lamure, S., Nucci, M., Zambrotta, G., Zak, P., Seval, G. C., Bonuomo, V., Mayer, J., Lopez-Garcia, A., Sacchi, M. V., Booth, S., Ciceri, F., Oberti, M., Salvini, M., Izuzquiza, M., Nunes-Rodrigues, R., Ammatuna, E., Obr, A., Herbrecht, R., Nunez-Martin-Buitrago, L., Mancini, V., Shwaylia, H., Sciume, M., Essame, J., Nygaard, M., Batinic, J., Gonzaga, Y., Regalado-Artamendi, I., Karlsson, L. K., Shapetska, M., Hanakova, M., El-Ashwah, S., Borbenyi, Z., Colak, G. M., Nordlander, A., Dragonetti, G., Maraglino, A. M. E., Rinaldi, A., De Ramon-Sanchez, C., Cornely, O. A., Finizio, O., Fazzi, R., Sapienza, G., Chauchet, A., Van Praet, J., Prattes, J., Dargenio, M., Rossi, C., Shirinova, A., Malak, S., Tafuri, A., Ommen, H. -B., Bologna, S., Khedr, R. A., Choquet, S., Joly, B., Ceesay, M. M., Philippe, L., Kho, C. S., Desole, M., Tsirigotis, P., Otasevic, V., Borducchi, D. M. M., Antoniadou, A., Gaziev, J., Almaslamani, M. A., Garcia-Pouton, N., Paterno, G., Torres-Lopez, A., Tarantini, G., Mellinghoff, S., Grafe, S., Borschel, N., Passweg, J., Merelli, M., Barac, A., Wolf, D., Shaikh, M. U., Thieblemont, C., Bernard, S., Funke, V. A. M., Daguindau, E., Khostelidi, S., Nucci, F. M., Martin-Gonzalez, J. -A., Landau, M., Soussain, C., Laureana, C., Lacombe, K., Kohn, M., Aliyeva, G., Piedimonte, M., Fouquet, G., Rego, M., Hoell-Neugebauer, B., Cartron, G., Pinto, F., Alburquerque, A. M., Passos, J., Yilmaz, A. F., Redondo-Izal, A. -M., Altuntas, F., Heath, C., Kolditz, M., Schalk, E., Guolo, F., Karthaus, M., Della Pepa, R., Vinh, D., Noel, N., Deau Fischer, B., Drenou, B., Mitra, M. E., Meletiadis, J., Bilgin, Y. M., Jindra, P., Espigado, I., Drgona, L., Serris, A., Di Blasi, R., Ali, N., Stem Cell Aging Leukemia and Lymphoma (SALL), Salvy-Córdoba, Nathalie, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Università cattolica del Sacro Cuore = Catholic University of the Sacred Heart [Roma] (Unicatt), University Hospital of Cologne [Cologne], Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, IFO - Istituto Nazionale Tumori Regina Elena [Roma] (IRE), Città della Salute e della Scienza University-Hospital, IRCCS Istituto Nazionale dei Tumori [Milano], University of California [San Diego] (UC San Diego), University of California (UC), Medical University of Graz, Odessa National I.I.Mechnikov University, Faculty of Medicine [Cologne], University Hospital of Cologne [Cologne]-University of Cologne, King's College Hospital (KCH), Universitá degli Studi dell’Insubria = University of Insubria [Varese] (Uninsubria), Dipartimento di Medicina e Chirurgia = School of Medicine and Surgery [Monza], Università degli Studi di Milano-Bicocca = University of Milano-Bicocca (UNIMIB), Faculty of Medicine in Hradec Kralove [Republique Tchèque], Charles University [Prague] (CU), Ankara University School of Medicine [Turkey], Azienda Ospedaliera Universitaria Integrata of Verona, Masaryk University [Brno] (MUNI), Fundación Jiménez Díaz, Fundacion Jimenez Diaz [Madrid] (FJD), Ospedale SS Antonio e Biagio e Cesare Arrigo, Churchill Hospital Oxford Centre for Haematology, IRCCS San Raffaele Scientific Institute [Milan, Italie], ASST Spedali Civili of Brescia, Vall d'Hebron Institute of Oncology [Barcelone] (VHIO), Vall d'Hebron University Hospital [Barcelona], Universitat Autònoma de Barcelona (UAB), Instituto Português de Oncologia de Lisboa Francisco Gentil, Ospedale San Luigi Gonzaga, University Medical Center Groningen [Groningen] (UMCG), Institut de Cancérologie de Strasbourg Europe (ICANS), Palacky University Olomouc, Zagreb School of Medicine [Zagreb, Croatia] (Dubrava University Hospital), University of Zagreb, Hospital Universitario Puerta de Hierro-Majadahonda [Madrid, Spain], ASST Great Metropolitan Niguarda / ASST Grande Ospedale Metropolitano Niguarda [Milan, Italia], Hamad Medical Corporation [Doha, Qatar], Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, University of Rijeka, Croatian Cooperative Group for Hematological Diseases (CROHEM), Zealand University Hospital [Roskilde, Denmark], Hospital General Universitario 'Gregorio Marañón' [Madrid], Department of Clinical Microbiology [Rigshospitalet], Rigshospitalet [Copenhagen], Copenhagen University Hospital-Copenhagen University Hospital, Homieĺ State Medical University (GSMU), Institute of Hematology and Blood Transfusion [Prague, Czech Republic], University of Szeged [Szeged], University Hospital Ostrava, Mansoura University [Egypt], Marmara University [Kadıköy - İstanbul], Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Karolinska University Hospital [Stockholm], Instituto de Investigação e Inovação em Saúde (I3S), Universidade do Porto = University of Porto, Instituto de Patologia e Imunologia Molecular da Universidade do Porto (IPATIMUP), Hospital de São João [Porto], Faculdade de Medicina da Universidade do Porto (FMUP), Clinic Barcelona Hospital Universitari, Department of Public Health and Cell Biology, University of Rome Tor Vergata, Via Montpellier 1, 00133 Rome, Italy, Pavlov First Saint Petersburg State Medical University [St. Petersburg], Vrije Universiteit Medical Centre (VUMC), Vrije Universiteit Amsterdam [Amsterdam] (VU), Complejo Hospitalario de Navarra, Hospital Universitario Marqués de Valdecilla [Santander], La Paz University Hospital, Azienda Usl Toscana centro [Firenze], AZ Klina, Clinical Center of Serbia (KCS), University of Belgrade [Belgrade], Sultan Qaboos University Hospital, Partenaires INRAE, Hospital Universitario de Salamanca, Servicio de Haematologia, Centro de Investigación del Cáncer-IBMCC (USAL-CSIC), University of Wrocław [Poland] (UWr), San Bortolo Hospital, Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg] (UKE), Hospital Universitario 12 de Octubre [Madrid], Azienda Sanitaria Universitaria Friuli Centrale (ASU FC), Universidad Rey Juan Carlos [Madrid] (URJC), University of Basel (Unibas), Innsbruck Medical University = Medizinische Universität Innsbruck (IMU), University Hospital Kralovské Vinohrady, Centre Hospitalier de Versailles André Mignot (CHV), Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Institut de Génétique Moléculaire de Montpellier (IGMM), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Département Hématologie biologique [CHRU Montpellier], Pôle Biologie-Pathologie [CHRU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Universidade Federal do Estado do Rio de Janeiro (UNIRIO), San Gerardo Hospital of Monza, Oxford NIHR Biomedical Research Centre, IRCCS Ospedale San Raffaele [Milan, Italy], Assi Sette Llaghi Varese, Instituto Português de Oncologia do Porto / Portuguese Oncology Institute of Porto (IPO Porto), University Hospital Olomouc [Czech Republic], ASST Grande Ospedale Metropolitano Niguarda, University Hospital Centre Zagreb, Instituto Nacional do Câncer, Copenhagen University Hospital, Republican Scientific and Practical Center (RSPC) for organ and Tissue Transplantation, Minsk, Republican Scientific and Practical Center (RSPC) for Organ and Transplantation, German Centre for Infection Research (DZIF), Gilead Sciences, Pagano, Livio [0000-0001-8287-928X], Salmanton-García, Jon [0000-0002-6766-8297], Marchesi, Francesco [0000-0001-6353-2272], Busca, Alessandro [0000-0001-5361-5613], Corradini, Paolo [0000-0002-9186-1353], Hoenigl, Martin [0000-0002-1653-2824], Klimko, Nikolay [0000-0001-6095-7531], Koehler, Philipp [0000-0002-7386-7495], Pagliuca, Antonio [0000-0003-2519-0333], Passamonti, Francesco [0000-0001-8068-5289], Verga, Luisa [0000-0003-1142-8435], Víšek, Benjamin [0000-0001-8268-452X], Ilhan, Osman [0000-0003-1665-372X], Weinbergerová, Barbora [0000-0001-6460-2471], Córdoba, Raúl [0000-0002-7654-8836], Marchetti, Monia [0000-0001-7615-0572], Farina, Francesca [0000-0002-5124-6970], Cattaneo, Chiara [0000-0003-0031-3237], Cabirta, Alba [0000-0001-7198-8894], Gomes-Silva, Maria [0000-0002-6993-2450], Itri, Federico [0000-0002-3532-5281], Doesum, Jaap van [0000-0003-0214-3219], Ledoux, Marie-Pierre [0000-0002-3261-3616], Čerňan, Martin [0000-0003-2345-1229], Jakšić, Ozren [0000-0003-4026-285X], Magliano, Gabriel [0000-0002-9129-1530], Omrani, Ali S. [0000-0001-5309-6358], Fracchiolla, Nicola S. [0000-0002-8982-8079], Kulasekararaj, Austin G. [0000-0003-3180-3570], Valković, Toni [0000-0001-6083-8815], Poulsen, Christian Bjørn [0000-0001-9785-1378], Machado, Marina [0000-0002-8370-2248], Glenthøj, Andrea [0000-0003-2082-0738], Stoma, Igor [0000-0003-0483-7329], Ráčil, Zdeněk [0000-0003-3511-4596], Piukovics, Klára [0000-0003-4480-3131], Emarah, Ziad [0000-0003-0622-2598], Sili, Uluhan [0000-0002-9939-9298], Maertens, Johan [0000-0003-4257-5980], Bergantim, Rui [0000-0002-7811-9509], García-Vidal, Carolina [0000-0002-8915-0683], Prezioso, Lucia [0000-0003-1660-4960], Principe, Maria Ilaria del [0000-0002-3958-0669], Popova, Marina [0000-0001-8536-5495], Jonge, Nick de [0000-0002-9901-0887], Ormazabal-Vélez, Irati [0000-0003-1141-5546], Falces-Romero, Iker [0000-0001-5888-7706], Cuccaro, Annarosa [0000-0002-0237-1839], Meers, Stef [0000-0003-1754-2175], Buquicchio, Caterina [0000-0002-3683-5953], Antić, Darko [0000-0002-2608-1342], Al-Khabori, Murtadha [0000-0002-2937-8838], García-Sanz, Ramón [0000-0003-4120-2787], Biernat, Monika [0000-0003-3161-3398], Tisi, Maria Chiara [0000-0001-8231-6700], Sal, Ertan [0000-0003-2761-2675], Rahimli, Laman [0000-0003-2266-445X], Schönlein, Martin [0000-0002-1010-0975], Calbacho, María [0000-0001-8106-4863], Tascini, Carlo [0000-0001-9625-6024], Miranda-Castillo, Carolina [0000-0001-8763-9576], Khanna, Nina [0000-0002-2642-419X], Méndez, Gustavo-Adolfo [0000-0003-0514-7004], Petzer, Verena [0000-0002-9205-1440], Besson, Caroline [0000-0003-4364-7173], Duléry, Rémy [0000-0002-5024-1713], Lamure, Sylvain [0000-0001-5980-305X], Nucci, Marcio [0000-0003-4867-0014], Zambrotta, Giovanni [0000-0002-8612-2994], Žák, Pavel [0000-0003-4465-5343], Cengiz Seval, Guldane [0000-0001-9433-2054], Bonuomo, Valentina [0000-0001-6491-8337], Mayer, Jiří [0000-0003-0567-9887], López-García, Alberto [0000-0002-5354-5261], Sacchi, Maria Vittoria [0000-0001-8133-3357], Booth, Stephen [0000-0003-2687-0234], Ciceri, Fabio [0000-0003-0873-0123], Nunes-Rodrigues, Raquel [0000-0002-8347-4281], Ammatuna, Emanuele [0000-0001-8247-4901], Obr, Aleš [0000-0002-6758-3074], Herbrecht, Raoul [0000-0002-9381-4876], Shwaylia, Hawraa [0000-0002-4098-6092], Sciumè, Mariarita [0000-0001-7958-4966], Essame, Jenna [0000-0003-0926-5577], Batinić, Josip [0000-0001-5595-9911], Gonzaga, Yung [0000-0003-1416-2118], Regalado-Artamendi, Isabel [0000-0002-9673-9015], Karlsson, Linda Katharina [0000-0003-3317-7550], Shapetska, Maryia [0000-0002-1223-9161], El-Ashwah, Shaimaa [0000-0003-2210-1534], Çolak, Gökçe Melis [0000-0002-7662-7454], Dragonetti, Giulia [0000-0003-1775-6333], Rinaldi, Amelia [0000-0002-8211-5076], Ramón, Cristina de [0000-0002-8167-6410], Cornely, Oliver A. [0000-0001-9599-3137], Institut Català de la Salut, [Pagano L] Hematology, Fondazione Policlinico Universitario Agostino Gemelli - IRCCS – Università Cattolica del Sacro Cuore, Rome, Italy. Università Cattolica del Sacro Cuore, Rome, Italy. [Salmanton-García J] Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, Excellence Center for Medical Mycology (ECMM), University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, Germany. Cologne Excellence Cluster On Cellular Stress Responses in Aging Associated Diseases (CECAD), University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, Germany. [Marchesi F] Hematology and Stem Cell Transplant Unit, IRCCS Regina Elena National Cancer Institute, Rome, Italy. [Busca A] Stem Cell Transplant Center, AOU Citta’ Della Salute E Della Scienza, Turin, Italy. [Corradini P] University of Milan and Fondazione IRCCS Istituto Nazionale Dei Tumori, Milan, Italy. [Hoenigl M] Division of Infectious Diseases and Global Public Health, Department of Medicine, University of California San Diego, San Diego, CA, USA. Clinical and Translational Fungal Working Group, University of California San Diego, La Jolla, CA, USA. Section of Infectious Diseases and Tropical Medicine, Department of Internal Medicine, Medical University of Graz, Graz, Austria. [Cabirta A, Izuzquiza M] Servei d’Hematologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Experimental Hematology, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Departament de Medicina, Universitat Autònoma de Barcelona, Bellaterra, Spain, Vall d'Hebron Barcelona Hospital Campus, Hematology, Salmanton-García, Jon, Klimko, Nikolay, Víšek, Benjamin, Weinbergerová, Barbora, Córdoba, Raúl, Doesum, Jaap van, Čerňan, Martin, Jakšić, Ozren, Magliano, Gabriel, Kulasekararaj, Austin G., Valković, Toni, Poulsen, Christian Bjørn, Glenthøj, Andrea, Ráčil, Zdeněk, Piukovics, Klára, García-Vidal, Carolina, Principe, Maria Ilaria del, Jonge, Nick de, Ormazabal-Vélez, Irati, Antić, Darko, García-Sanz, Ramón, Biernat, Monika, Schönlein, Martin, Calbacho, María, Méndez, Gustavo-Adolfo, Duléry, Rémy, Žák, Pavel, Cengiz Seval, Guldane, Mayer, Jiří, López-García, Alberto, Obr, Aleš, Sciumè, Mariarita, Batinić, Josip, Çolak, Gökçe Melis, Ramón, Cristina de, and Universidad de Sevilla. Departamento de Medicina
Subjects: [SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology, Male, Cancer Research, MESH: Registries, Epidemiology, MESH: Hospitalization, Hematological malignancies, Otros calificadores::Otros calificadores::/complicaciones [Otros calificadores], MESH: Aged, 80 and over, MESH: Risk Factors, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Risk Factors, Malalties - Factors de risc, Risk of mortality, Medicine and Health Sciences, virosis::infecciones por virus ARN::infecciones por Nidovirales::infecciones por Coronaviridae::infecciones por Coronavirus [ENFERMEDADES], 80 and over, Medicine, MESH: COVID-19, Registries, Sang - Malalties - Complicacions, RC254-282, Cause of death, BIOMEDICINA I ZDRAVSTVO. Kliničke medicinske znanosti. Interna medicina, MESH: Aged, Aged, 80 and over, Hematology, MESH: Middle Aged, Mortality rate, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Myeloid leukemia, Virus Diseases::RNA Virus Infections::Nidovirales Infections::Coronaviridae Infections::Coronavirus Infections [DISEASES], [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Middle Aged, CANCER, Europe, Hospitalization, Intensive Care Units, Oncology, MESH: Young Adult, Hematologic Neoplasms, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Female, BIOMEDICINA I ZDRAVSTVO. Kliničke medicinske znanosti. Infektologija, Life Sciences & Biomedicine, Adult, medicine.medical_specialty, [SDV.CAN]Life Sciences [q-bio]/Cancer, COVID-19, EHA, Pandemic, Aged, Humans, SARS-CoV-2, Young Adult, técnicas de investigación::métodos epidemiológicos::estadística como asunto::probabilidad::riesgo::factores de riesgo [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], [SDV.CAN] Life Sciences [q-bio]/Cancer, Intensive care, Internal medicine, Diseases of the blood and blood-forming organs, MESH: SARS-CoV-2, neoplasias::neoplasias por localización::neoplasias hematológicas [ENFERMEDADES], Molecular Biology, BIOMEDICINE AND HEALTHCARE. Clinical Medical Sciences. Internal Medicine, pandemic, hematological malignancies, epidemiology, MESH: Humans, Science & Technology, business.industry, Myelodysplastic syndromes, Research, MESH: Adult, Neoplasms::Neoplasms by Site::Hematologic Neoplasms [DISEASES], medicine.disease, BIOMEDICINE AND HEALTHCARE. Clinical Medical Sciences. Infectology, Settore MED/15, MESH: Male, Settore MED/15 - MALATTIE DEL SANGUE, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, COVID-19 (Malaltia) - Diagnòstic, MESH: Intensive Care Units, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Probability::Risk::Risk Factors [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT], MESH: Europe, RC633-647.5, business, MESH: Female, Other subheadings::Other subheadings::/complications [Other subheadings], MESH: Hematologic Neoplasms
Abstract: Background Patients with hematological malignancies (HM) are at high risk of mortality from SARS-CoV-2 disease 2019 (COVID-19). A better understanding of risk factors for adverse outcomes may improve clinical management in these patients. We therefore studied baseline characteristics of HM patients developing COVID-19 and analyzed predictors of mortality. Methods The survey was supported by the Scientific Working Group Infection in Hematology of the European Hematology Association (EHA). Eligible for the analysis were adult patients with HM and laboratory-confirmed COVID-19 observed between March and December 2020. Results The study sample includes 3801 cases, represented by lymphoproliferative (mainly non-Hodgkin lymphoma n = 1084, myeloma n = 684 and chronic lymphoid leukemia n = 474) and myeloproliferative malignancies (mainly acute myeloid leukemia n = 497 and myelodysplastic syndromes n = 279). Severe/critical COVID-19 was observed in 63.8% of patients (n = 2425). Overall, 2778 (73.1%) of the patients were hospitalized, 689 (18.1%) of whom were admitted to intensive care units (ICUs). Overall, 1185 patients (31.2%) died. The primary cause of death was COVID-19 in 688 patients (58.1%), HM in 173 patients (14.6%), and a combination of both COVID-19 and progressing HM in 155 patients (13.1%). Highest mortality was observed in acute myeloid leukemia (199/497, 40%) and myelodysplastic syndromes (118/279, 42.3%). The mortality rate significantly decreased between the first COVID-19 wave (March–May 2020) and the second wave (October–December 2020) (581/1427, 40.7% vs. 439/1773, 24.8%, p value, EPICOVIDEHA has received funds from Optics COMMITTM (COVID-19 Unmet Medical Needs and Associated Research Extension) COVID-19 RFP program by GILEAD Science, United States (Project 2020-8223).
Published: 2021

45. Monitoring Linear Accelerator Output Constancy Using the PTW Linacheck

Author: Buckle, Andrew [Radiotherapy Physics Section, Department of Medical Physics and Clinical Engineering, Churchill Hospital (Oxford Radcliffe NHS Hospitals Trust), Headington, Oxford (United Kingdom)]
Published: 2011
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46. Alcohol consumption, cigarette smoking, and risk of breast cancer for BRCA1 and BRCA2 mutation carriers: results from The BRCA1 and BRCA2 Cohort Consortium

Author: Terry, Mary Beth, Noguès, Catherine, Barrowdale, Daniel, Frost, Debra, Brewer, Carole, Evans, D. Gareth, Izatt, Louise, Side, Lucy, Walker, Lisa, Tischkowitz, Marc, Rogers, Mark, Porteous, Mary, Meijers-Heijboer, Hanne E.J., Gille, Johan JP, Blok, Marinus, Hoogerbrugge, Nicoline, Daly, Mary, Andrulis, Irene, Buys, Saundra, John, Esther, McLachlan, Sue-Anne, Friedlander, Michael, Tan, Yen, Osorio, Ana, Caldés, Trinidad, Jakubowska, Anna, Simard, Jacques, Singer, Christian, Olah, Edith, Navratilova, Marie, Foretova, Lenka, Gerdes, Anne-Marie, Roos-Blom, Marie-José, Arver, Brita, Olsson, Håkan, Schmutzler, Rita, Hopper, John, Milne, Roger, Easton, Douglas, Van Leeuwen, Flora, Rookus, Matti, Andrieu, Nadine, Goldgar, David, Huntsman Cancer Institute [Salt Lake City], University of Utah, Laboratoire d'Oncogénétique, CRLCC René Huguenin, Centre for Cancer Genetic Epidemiology, University of Cambridge [UK] (CAM), Department of Clinical Genetics, Royal Devon & Exeter Hospital, Genetic Medicine, St Mary's Hospital, Manchester Academic Health Sciences Centre, University of Manchester, Clinical Genetics, Guy's and St. Thomas' NHS Foundation Trust, Department of Clinical Genetics, The Churchill, Oxford, Oxford Regional Genetics Service [Oxford, UK], Churchill Hospital Oxford Centre for Haematology, Department of Genetics, Portuguese Oncology Institute, Department of Computer Science [Colorado State University], Colorado State University [Fort Collins] (CSU), West General Hospital, VU University Medical Center [Amsterdam], University Hospital Maastricht, Department of Human Genetics, Radboud University Medical Center [Nijmegen], Division of Population Science, Fox Chase Cancer Center, Department of Laboratory Medicine and Pathobiology, University of Toronto, Department of Internal Medicine, Huntsman Cancer Institute, Department of Epidemiology, Cancer Prevention Institute of California, St. Vincent's Hospital, Sydney, Dept of Medical Oncology, Division of Medicine, University of New South Wales [Sydney] (UNSW)-Prince of Wales Hospital Randwick, Medical University of Vienna, Human Genetics Group, Spanish National Cancer Research Centre, Molecular Oncology Laboratory, Hospital Clínico San Carlos, Department of Genetics and Pathology, Pomeranian Medical University-International Hereditary Cancer Centre, Laboratoire de Génomique des Cancers, Laval University [Québec], Division of Special Gynecology, Medizinische Universität Wien = Medical University of Vienna-Department of OB/GYN, National Institute of Oncology, Masaryk Memorial Cancer Institute (RECAMO), Odense University Hospital, Netherlands Cancer Institute (NKI), Antoni van Leeuwenhoek Hospital, Radiumhemmet, Karolinska University Hospital [Stockholm], Department of Oncology, Lund University Hospital, Division of Molecular Gyneco-Oncology, Department of Gynaecology and Obstetrics, Clinical Center Un, Centre for MEGA Epidemiology, The University of Melbourne, Victoria, Australia, Cancer Epidemiology Centre, Cancer Council Victoria, Centre for Cancer Genetic Epidemiology [Cambridge], Department of Oncology-University of Cambridge [UK] (CAM), Departments of Epidemiology and Molecular Pathology, The Netherlands Cancer Institute, Netherlands Cancer Institute, Innovation et Développement dans l'Agriculture et l'Agro-alimentaire (Innovation), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Centre national d'études agronomiques des régions chaudes (CNEARC)-Institut National de la Recherche Agronomique (INRA)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Centre International de Hautes Etudes Agronomiques Méditerranéennes - Institut Agronomique Méditerranéen de Montpellier (CIHEAM-IAMM), Centre International de Hautes Études Agronomiques Méditerranéennes (CIHEAM)-Centre International de Hautes Études Agronomiques Méditerranéennes (CIHEAM)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Department of Dermatology [Salt Lake City, UT, USA], University of Utah School of Medicine [Salt Lake City], This work was supported by grants to kConFab and the kConFab Follow-Up Study from Cancer Australia (809195, 1100868), the Australian National Breast Cancer Foundation (IF 17), the National Health and Medical Research Council (454508, 288704, 145684), the National Institute of Health U.S.A. (1RO1CA159868), the Queensland Cancer Fund, the Cancer Councils of New South Wales, Victoria, Tasmania and South Australia, and the Cancer Foundation of Western Australia. Kelly Phillips is an Australian National Breast Cancer Foundation fellow.Lenka Foretova was supported by MH CZ - DRO (MMCI, 00209805) and by MEYS - NPS I- LO1413 to LF, MN. Edith Olah and The Hungarian Breast and Ovarian Cancer Study was supported by Hungarian Research Grants KTIA-OTKA CK-80745, NKFI OTKA K-112228 and the Norwegian EEA Financial Mechanism HU0115/NA/2008-3/ÖP-9. Hakan Olsson and Lund-BRCA collaborators are supported by the Swedish Cancer Society, Lund Hospital Funds, and European Research Council Advanced Grant ERC-2011-294576. Stockholm-BRCA collaborators are supported by the Swedish Cancer Society., Medizinische Universität Wien = Medical University of Vienna, Université Laval [Québec] (ULaval), Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Curie [Paris], MINES ParisTech - École nationale supérieure des mines de Paris, and Université Paris sciences et lettres (PSL)
Subjects: breast cancer, endocrine system diseases, alcohol, cigarette smoking, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, skin and connective tissue diseases, BRCA1, BRCA2
Abstract: International audience; BACKGROUND:Tobacco smoking and alcohol consumption have been intensively studied in the general population to assess their effects on the risk of breast cancer (BC), but very few studies have examined these effects in BRCA1 and BRCA2 mutation carriers. Given the high BC risk for mutation carriers and the importance of BRCA1 and BRCA2 in DNA repair, better evidence on the associations of these lifestyle factors with BC risk is essential.METHODS:Using a large international pooled cohort of BRCA1 and BRCA2 mutation carriers, we conducted retrospective (5,707 BRCA1 mutation carriers; 3,525 BRCA2 mutation carriers) and prospective (2,276 BRCA1 mutation carriers; 1,610 BRCA2 mutation carriers) analyses of alcohol and tobacco consumption using Cox proportional hazards models.RESULTS:For both BRCA1 and BRCA2 mutation carriers, none of the smoking-related variables was associated with BC risk, except smoking for more than five years before a first full-term pregnancy (FFTP) when compared to parous women who never smoked. For BRCA1 mutation carriers, the HR from retrospective analysis (HRR) was 1.19 (95%CI:1.02,1.39) and the HR from prospective analysis (HRP) was 1.36 (95%CI:0.99,1.87). For BRCA2 mutation carriers, smoking for more than five years before a FFTP showed an association of a similar magnitude, but the confidence limits were wider (HRR=1.25,95%CI:1.01,1.55 and HRP=1.30,95%CI:0.83,2.01). For both carrier groups, alcohol consumption was not associated with BC risk.CONCLUSIONS:The finding that smoking during the pre-reproductive years increases BC risk for mutation carriers warrants further investigation.IMPACT:This is the largest prospective study of BRCA mutation carriers to assess these important risk factors.
Published: 2019

47. The selective peroxisome proliferator-activated receptor alpha modulator (SPPARMα) paradigm: conceptual framework and therapeutic potential

Author: Fruchart, Jean-Charles, Santos, Raul D., Aguilar-Salinas, Carlos, Aikawa, Masanori, Al Rasadi, Khalid, Amarenco, Pierre, Barter, Philip J., Ceska, Richard, Corsini, Alberto, Després, Jean-Pierre, Duriez, Patrick, Eckel, Robert H., Ezhov, Marat V., Farnier, Michel, Ginsberg, Henry N., Hermans, Michel P., Ishibashi, Shun, Karpe, Fredrik, Kodama, Tatsuhiko, Koenig, Wolfgang, Krempf, Michel, Lim, Soo, Lorenzatti, Alberto J., McPherson, Ruth, Nuñez-Cortes, Jesus Millan, Nordestgaard, Børge G., Ogawa, Hisao, Packard, Chris J., Plutzky, Jorge, Ponte-Negretti, Carlos I., Pradhan, Aruna, Ray, Kausik K., Reiner, Zeljko, Ridker, Paul M., Ruscica, Massimiliano, Sadikot, Shaukat, Shimano, Hitoshi, Sritara, Piyamitr, Stock, Jane K., Su, Ta-Chen, Susekov, Andrey V., Tartar, André, Taskinen, Marja-Riitta, Tenenbaum, Alexander, Tokgözoğlu, Lale S., Tomlinson, Brian, Tybjærg-Hansen, Anne, Valensi, Paul, Vrablik, Michal, Wahli, Walter, Watts, Gerald F., Yamashita, Shizuya, Yokote, Koutaro, Zambon, Alberto, Libby, Peter, R3i Foundation, Partenaires INRAE, Hospital Israelita Albert Einstein [São Paulo, Brazil], Lipid Clinic Heart Institute (InCor), Universidade de São Paulo = University of São Paulo (USP), Instituto Nacional de Ciencias Médicas y Nutrición 'Salvador Zubirán', Tecnológico de Monterrey (ITESM), Brigham and Women's Hospital [Boston], Sultan Qaboos University Hospital, Department of Neurology and Stroke Center, Universität Duisburg-Essen = University of Duisburg-Essen [Essen], University of New South Wales [Sydney] (UNSW), General University Hospital in Prague, Università degli Studi di Milano = University of Milan (UNIMI), Université Laval [Québec] (ULaval), Université de Lille, University of Colorado Cancer Center [Aurora, CO, USA], Russian Cardiology Research Center, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Columbia University [New York], Cliniques Universitaires Saint Luc, Institut de Recherche Expérimentale et Clinique (IREC), Jichi Medical University [Tochigi-Ken, Japan], University of Oxford, The Churchill hospital, The University of Tokyo (UTokyo), Deutsches Herzzentrum München (DHM), DZHK (German Centre for Cardiovascular Research), Partner site Heidelberg/Mannheim, Heidelberg, Universität Ulm - Ulm University [Ulm, Allemagne], Physiopathologie des Adaptations Nutritionnelles (PhAN), Institut National de la Recherche Agronomique (INRA)-Université de Nantes (UN), Department of Endocrinology, Metabolic Diseases and Nutrition, Hôpital Guillaume et René Laennec - Centre Hospitalier Universitaire de Nantes, Centre de recherche en nutrition humaine Ouest, Seoul National University Bundang Hospital (SNUBH), Seoul National University [Seoul] (SNU), Rusculleda Foundation for Research, Hospital Córdoba, University of Ottawa [Ottawa], Hospital General Universitario 'Gregorio Marañón', Universidad Complutense de Madrid = Complutense University of Madrid [Madrid] (UCM), Instituto de Investigaciones Sanitarias Gregorio Marañón, University Hospital Herlev Gentofte, Faculty of Health and Medical Sciences, University of Copenhagen = Københavns Universitet (UCPH), National Cerebral and Cardiovascular Center (NCCC - OSAKA), Osaka University [Osaka], Institute of Cardiovascular and Medical Sciences, University of Glasgow, Brigham and Women's Hospital, Hospital El Pino, Boston University Medical Center, Imperial College London, School of Medicine, University of Zagreb, University Hospital Centre Zagreb, Harvard Medical School [Boston] (HMS), Massachusetts General Hospital, Massachusetts General Hospital [Boston], Jaslok Hospital & Research Centre, Université de Tsukuba = University of Tsukuba, Mahidol University [Bangkok], National Taiwan University, Faculty of Clinical Pharmacology and Therapeutics, Faculté de Pharmacie, Clinical Research Institute HUCH, Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Tel Aviv University (TAU), Chaim Sheba Medical Center, Hacettepe University = Hacettepe Üniversitesi, Chinese University of Hong Kong, Copenhagen University Hospitals, Hôpital Jean Verdier [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Charles University [Prague] (CU), ToxAlim (ToxAlim), Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Ecole d'Ingénieurs de Purpan (INP - PURPAN), Université de Toulouse (UT)-Université de Toulouse (UT), Center for Integrative Genomics - Institute of Bioinformatics, Génopode (CIG), Swiss Institute of Bioinformatics [Lausanne] (SIB), Université de Lausanne = University of Lausanne (UNIL)-Université de Lausanne = University of Lausanne (UNIL), Lee Kong Chian School of Medicine, Nanyang Technological University [Singapour], Royal Perth Hospital, The University of Western Australia (UWA), Medical Center, Osaka University, Chiba University, Department of Medicine (DIMED), R3i, Hospital Israelita Albert Einstein, University of São Paulo, Universität Duisburg-Essen [Essen], Università degli Studi di Milano [Milano] (UNIMI), Jichi Medical University, University of Oxford [Oxford], Institute of Epidemiology and Medical Biometry, Université de Nantes (UN)-Institut National de la Recherche Agronomique (INRA), Seoul National University, University of Copenhagen = Københavns Universitet (KU), University of Helsinki, Tel Aviv University [Tel Aviv], Charles University in Prague, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Université de Lausanne (UNIL)-Université de Lausanne (UNIL), Nanyang Technological University (NTU), University of Western Australia, and Lee Kong Chian School of Medicine (LKCMedicine)
Subjects: Inflammation, SPPARMalpha, lcsh:Diseases of the circulatory (Cardiovascular) system, Pemafibrate (K-877), Remnant cholesterol, Visceral Obesity, Diabetes, Atherogenic dyslipidemia, PROMINENT, Visceral obesity, Selective peroxisome proliferator-activated receptor alpha modulator, Residual Cardiovascular Risk, lcsh:RC666-701, Residual cardiovascular risk, Medicine [Science], Triglycerides, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; In the era of precision medicine, treatments that target specific modifiable characteristics of high-risk patients have the potential to lower further the residual risk of atherosclerotic cardiovascular events. Correction of atherogenic dyslipidemia, however, remains a major unmet clinical need. Elevated plasma triglycerides, with or without low levels of high-density lipoprotein cholesterol (HDL-C), offer a key modifiable component of this common dyslipidemia, especially in insulin resistant conditions such as type 2 diabetes mellitus. The development of selective peroxisome proliferator-activated receptor alpha modulators (SPPARMα) offers an approach to address this treatment gap. This Joint Consensus Panel appraised evidence for the first SPPARMα agonist and concluded that this agent represents a novel therapeutic class, distinct from fibrates, based on pharmacological activity, and, importantly, a safe hepatic and renal profile. The ongoing PROMINENT cardiovascular outcomes trial is testing in 10,000 patients with type 2 diabetes mellitus, elevated triglycerides, and low levels of HDL-C whether treatment with this SPPARMα agonist safely reduces residual cardiovascular risk.
Published: 2019

48. Defective tubulin detyrosination causes structural brain abnormalities with cognitive deficiency in humans and mice

Author: Pagnamenta, AT, Heemeryck, P, Martin, HC, Bosc, C, Peris, L, Uszynski, I, Gory-Fauré, S, Couly, S, Deshpande, C, Siddiqui, A, Elmonairy, AA, Consortium, WGS500, Consortium, Genomics England Research, Jayawant, S, Murthy, S, Walker, I, Loong, L, Bauer, P, Vossier, F, Denarier, E, Maurice, T, Barbier, EL, Deloulme, J-C, Taylor, JC, Blair, EM, Andrieux, A, Moutin, M-J, Oxford NIHR Biomedical Research Centre, [GIN] Grenoble Institut des Neurosciences (GIN), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), The Wellcome Trust Sanger Institute [Cambridge], Groupe Physiopathologie du Cytosquelette (GPC), Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), Mécanismes moléculaires dans les démences neurodégénératives (MMDN), Université de Montpellier (UM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL), Guy's Hospital [London], Kings College Hospital, Ministry of Health [Koweït], John Radcliffe Hospital [Oxford University Hospital], Upton Hospital [Slough, Royaume-uni], Wexham Park Hospital [Slough, Royaume-Uni], Oxford University Hospitals NHS Trust, University of Oxford [Oxford], CENTOGENE AG, Department of Clinical Genetics, Oxford Regional Genetics Service, The Churchill hospital, ANR-19-P3IA-0003,MIAI,MIAI @ Grenoble Alpes(2019), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), and University of Oxford
Subjects: Neurons, Immunoblotting, Brain, [SDV.BDD.MOR]Life Sciences [q-bio]/Development Biology/Morphogenesis, Cell Cycle Proteins, Magnetic Resonance Imaging, Mice, Tubulin, Microcephaly, Animals, Humans, Tyrosine, Cognitive Dysfunction, Female, General Article, Carrier Proteins, ComputingMilieux_MISCELLANEOUS
Abstract: Reversible detyrosination of tubulin, the building block of microtubules, is crucial for neuronal physiology. Enzymes responsible for detyrosination were recently identified as complexes of vasohibins (VASHs) one or two with small VASH-binding protein (SVBP). Here we report three consanguineous families, each containing multiple individuals with biallelic inactivation of SVBP caused by truncating variants (p.Q28(*) and p.K13Nfs(*)18). Affected individuals show brain abnormalities with microcephaly, intellectual disability and delayed gross motor and speech development. Immunoblot testing in cells with pathogenic SVBP variants demonstrated that the encoded proteins were unstable and non-functional, resulting in a complete loss of VASH detyrosination activity. Svbp knockout mice exhibit drastic accumulation of tyrosinated tubulin and a reduction of detyrosinated tubulin in brain tissue. Similar alterations in tubulin tyrosination levels were observed in cultured neurons and associated with defects in axonal differentiation and architecture. Morphological analysis of the Svbp knockout mouse brains by anatomical magnetic resonance imaging showed a broad impact of SVBP loss, with a 7% brain volume decrease, numerous structural defects and a 30% reduction of some white matter tracts. Svbp knockout mice display behavioural defects, including mild hyperactivity, lower anxiety and impaired social behaviour. They do not, however, show prominent memory defects. Thus, SVBP-deficient mice recapitulate several features observed in human patients. Altogether, our data demonstrate that deleterious variants in SVBP cause this neurodevelopmental pathology, by leading to a major change in brain tubulin tyrosination and alteration of microtubule dynamics and neuron physiology.
Published: 2019

49. Global emergence and population dynamics of divergent serotype 3 CC180 pneumococci

Author: Jennifer E. Cornick, Robert F. Breiman, Benjamin J. Metcalf, Raymond Reid, Martin Antonio, Anna Skoczynska, Ewa Sadowy, Rebecca A. Gladstone, Katherine L O'Brien, Jennifer C. Moïsi, Lesley McGee, Claudette M. Thompson, Andrew J. Pollard, Amel Ghouila, Maria Georgieva, Waleria Hryniewicz, Bernard Beall, Pak-Leung Ho, Dean Everett, William P. Hanage, Brenda Kwambana-Adams, Mignon du Plessis, Stuart C. Clarke, Taj Azarian, Patrick K. Mitchell, Anne von Gottberg, Stephen D. Bentley, Harvard University [Cambridge], Laboratoire de Transmission, Contrôle et Immunobiologie des Infections - Laboratory of Transmission, Control and Immunobiology of Infection (LR11IPT02), Institut Pasteur de Tunis, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Oxford Vaccine Group, University of Oxford [Oxford]-Oxford NIHR Biomedical Research Centre-The Churchill hospital, National Institute for Communicable Diseases [Johannesburg] (NICD), Medical Research Council Unit The Gambia (MRC), University of Southampton, University of Edinburgh, University of Liverpool, National Medicines Institute - Narodowy Instytut Leków [Warsaw] (NIL), Pfizer Ltd France, Pfizer, Centers for Disease Control and Prevention [Atlanta] (CDC), Centers for Disease Control and Prevention, Emory Global Health Institute [Atlanta] (EGHI), Emory University [Atlanta, GA], Department of Microbiology [HKU], The University of Hong Kong (HKU), Johns Hopkins Bloomberg School of Public Health [Baltimore], Johns Hopkins University (JHU), The Wellcome Trust Sanger Institute [Cambridge], and The study was funded in part by National Institute of Allergy and Infectious Disease award to WPH (R01 AI106786). The Global Pneumococcal Sequencing project is funded by The Bill and Melinda Gates Foundation (Grant OPP1034556).
Subjects: Serotype, MESH: Vaccines, Conjugate, Physiology, [SDV]Life Sciences [q-bio], Population Dynamics, Glycobiology, Biochemistry, Pneumococcal conjugate vaccine, Coalescent theory, Pneumococcal Vaccines, MESH: Pneumococcal Vaccines/immunology, Immune Physiology, Mobile Genetic Elements, MESH: Serotyping/methods, Genotype, Prevalence, Medicine and Health Sciences, MESH: Carrier State/epidemiology, MESH: Streptococcus pneumoniae/pathogenicity, Biology (General), MESH: Phylogeny, Clade, Phylogeny, MESH: Evolution, Molecular, Data Management, Genetics, Vaccines, 0303 health sciences, education.field_of_study, Immune System Proteins, Geography, MESH: Streptococcus pneumoniae/immunology, Genomics, Antigenic Variation, Recombinant Proteins, 3. Good health, Phylogenetics, Phylogeography, Streptococcus pneumoniae, Infectious Diseases, Biogeography, Carrier State, Research Article, medicine.drug, Computer and Information Sciences, Infectious Disease Control, Tetracycline, QH301-705.5, MESH: Bayes Theorem, Immunology, Population, Biology, Serogroup, Microbiology, Pneumococcal Infections, Evolution, Molecular, 03 medical and health sciences, Genetic Elements, MESH: Whole Genome Sequencing/methods, Polysaccharides, Microbial Control, MESH: Streptococcus pneumoniae/genetics, medicine, Humans, Evolutionary Systematics, MESH: Genetics, Population/methods, Serotyping, Antigens, education, MESH: Prevalence, Taxonomy, 030304 developmental biology, Pharmacology, Evolutionary Biology, Vaccines, Conjugate, MESH: Humans, Whole Genome Sequencing, Population Biology, 030306 microbiology, Ecology and Environmental Sciences, Transposable Elements, Biology and Life Sciences, Proteins, Bayes Theorem, MESH: Serogroup, MESH: Population Dynamics, RC581-607, MESH: Pneumococcal Infections/transmission, Genetics, Population, Carriage, Antibiotic Resistance, Earth Sciences, MESH: Pneumococcal Infections/immunology, Antimicrobial Resistance, Immunologic diseases. Allergy, Population Genetics
Abstract: Streptococcus pneumoniae serotype 3 remains a significant cause of morbidity and mortality worldwide, despite inclusion in the 13-valent pneumococcal conjugate vaccine (PCV13). Serotype 3 increased in carriage since the implementation of PCV13 in the USA, while invasive disease rates remain unchanged. We investigated the persistence of serotype 3 in carriage and disease, through genomic analyses of a global sample of 301 serotype 3 isolates of the Netherlands3–31 (PMEN31) clone CC180, combined with associated patient data and PCV utilization among countries of isolate collection. We assessed phenotypic variation between dominant clades in capsule charge (zeta potential), capsular polysaccharide shedding, and susceptibility to opsonophagocytic killing, which have previously been associated with carriage duration, invasiveness, and vaccine escape. We identified a recent shift in the CC180 population attributed to a lineage termed Clade II, which was estimated by Bayesian coalescent analysis to have first appeared in 1968 [95% HPD: 1939–1989] and increased in prevalence and effective population size thereafter. Clade II isolates are divergent from the pre-PCV13 serotype 3 population in non-capsular antigenic composition, competence, and antibiotic susceptibility, the last of which resulting from the acquisition of a Tn916-like conjugative transposon. Differences in recombination rates among clades correlated with variations in the ATP-binding subunit of Clp protease, as well as amino acid substitutions in the comCDE operon. Opsonophagocytic killing assays elucidated the low observed efficacy of PCV13 against serotype 3. Variation in PCV13 use among sampled countries was not independently correlated with the CC180 population shift; therefore, genotypic and phenotypic differences in protein antigens and, in particular, antibiotic resistance may have contributed to the increase of Clade II. Our analysis emphasizes the need for routine, representative sampling of isolates from disperse geographic regions, including historically under-sampled areas. We also highlight the value of genomics in resolving antigenic and epidemiological variations within a serotype, which may have implications for future vaccine development., Author summary Streptococcus pneumoniae is a leading cause of bacterial pneumoniae, meningitis, and otitis media. Despite its inclusion in the most recent pneumococcal conjugate vaccine, PCV13, serotype 3 remains epidemiologically important globally. We investigated the persistence of serotype 3 using whole-genome sequencing data from 301 isolates collected among 24 countries from 1993–2014. Through phylogenetic analysis, we identified three distinct lineages within a single clonal complex, CC180, and found one that has recently emerged and grown in prevalence. We then compared genomic difference among lineages as well as variations in pneumococcal vaccine use among sampled countries. We found that the recently emerged lineage, termed Clade II, has a higher prevalence of antibiotic resistance compared to other lineages, diverse surface protein antigens, and a higher rate of recombination, a process by which bacteria can uptake and incorporate genetic material from its surroundings. Differences in vaccine use among sampled countries did not appear to be associated with the emergence of Clade II. We highlight the need for routine, representative sampling of bacterial isolates from diverse geographic areas and show the utility of genomic data in resolving epidemiological differences within a pathogen population.
Published: 2018

50. Molecular mapping of uncharacteristically small 5q deletions in two patients with the 5q-syndrome: Delineation of the critical region on 5q and identification of a 5q-breakout

Author: Sheridan, H [Churchill Hospital, Oxford (United Kingdom)]
Published: 1994
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