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2. Outcomes after perioperative SARS-CoV-2 infection in patients with proximal femoral fractures: an international cohort study
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Khatri, C, Ward, AE, Nepogodiev, D, Ahmed, I, Chaudhry, D, Dhaif, F, Bankhad-Kendall, B, Kaafarani, H, Bretherton, C, Mahmood, A, Marais, L, Parsons, N, Bhangu, A, Metcalfe, A, Siaw-Acheampong, K, Dawson, BE, Evans, JP, Glasbey, JC, Gujjuri, RR, Heritage, E, Jones, CS, Kamarajah, SK, Keatley, JM, Lawday, S, Li, E, Mckay, SC, Pellino, G, Tiwari, A, Simoes, JFF, Trout, IM, Venn, ML, Wilkin, RJW, Ademuyiwa, AO, Agarwal, A, Al Ameer, E, Alderson, D, Alser, O, Arnaud, AP, Augestad, KM, Bankhead-Kendall, B, Benson, RA, Chakrabortee, S, Blanco-Colino, R, Brar, A, Bravo, A Minaya, Breen, KA, Buarque, I Lima, Caruana, E, Cunha, MF, Davidson, GH, Desai, A, Di Saverio, S, Edwards, J, Elhadi, M, Farik, S, Fiore, M, Fitzgerald, JE, Ford, S, Gallo, G, Ghosh, D, Gomes, GMA, Griffiths, E, Halkias, C, Harrison, EM, Hutchinson, P, Isik, A, Kolias, A, Lawani, I, Lederhuber, H, Leventoglu, S, Loffler, MW, Martin, J, Mashbari, H, Mazingi, D, Mohan, H, Moore, R, Moszkowicz, D, Ng-Kamstra, JS, Metallidis, S, Moug, S, Niquen, M, Ntirenganya, F, Outani, O, Pata, F, Pinkney, TD, Pockney, P, Radenkovic, D, Ramos-De la Medina, A, Roberts, K, Santos, I, Schache, A, Schnitzbauer, A, Stewart, GD, Shaw, R, Shu, S, Soreide, K, Spinelli, A, Sundar, S, Tabiri, S, Townend, P, Tsoulfas, G, van Ramshorst, G, Vidya, R, Vimalachandran, D, Wright, N, Mak, JKC, Kulkarni, R, Sharma, N, Nankivell, P, Tirotta, F, Parente, A, Breik, O, Kisiel, A, Cato, LD, Saeed, S, Pathanki, AM, Almond, M, Kamal, M, Chebaro, A, Lecolle, K, Truant, S, El Amrani, M, Zerbib, P, Pruvot, FR, Mathieu, D, Surmei, E, Mattei, L, Marin, H, Dudek, J, Singhal, T, El-Hasani, S, Nehra, D, Walters, A, Cuschieri, J, Ho, M, Wade, RG, Johnstone, J, Bourke, G, Brunelli, A, Elkadi, H, Otify, M, Pompili, C, Burke, JR, Bagouri, E, Chowdhury, M, Abual-Rub, Z, Kaufmann, A, Munot, S, Lo, T, Young, A, Kowal, M, Wall, J, Peckham-Cooper, A, Winter, SC, Belcher, E, Stavroulias, D, Di Chiara, F, Wallwork, K, Qureishi, A, Lami, M, Sravanam, S, Mastoridis, S, Shah, K, Chidambaram, S, Smillie, R, Shaw, AV, Bandyopadhyay, S, Cernei, C, Jeyaretna, D, Ganau, M, Piper, RJ, Duck, E, Brown, S, Jelley, C, Tucker, SC, Bond-Smith, G, Griffin, XL, Tebala, GD, Neal, N, Vatish, M, Noton, TM, Ghattaura, H, Maher, M, Fu, H, Risk, OBF, Majd, Soleymani H, Sinha, S, Shankar, S, Aggarwal, A, Kharkar, H, Lakhoo, K, Verberne, C, Senent-Boza, A, Sanchez-Arteaga, A, Benitez-Linero, I, Manresa-Manresa, F, Tallon-Aguilar, L, Melero-Cortes, L, Fernandez-Marin, MR, Duran-Munoz-Cruzado, VM, Ramallo-Solis, I, Beltran-Miranda, P, Pareja-Ciuro, F, Anton-Eguia, BT, Dawson, AC, Drane, A, Oliva Mompean, F, Gomez-Rosado, J, Reguera-Rosal, J, Valdes-Hernandez, J, Capitan-Morales, L, del Toro Lopez, MD, Patel, M, Shabana, A, Alanbuki, A, Usman, O, Tang, A, Beamish, AJ, Price, C, Bosanquet, D, Magowan, D, Solari, F, Williams, G, Nassa, H, Smith, L, Elliott, L, Mccabe, G, Holroyd, D, Jamieson, NB, Mariani, NM, Nicastro, V, Li, Z, Parkins, K, Spencer, N, Harries, R, Egan, RJ, Motter, D, Jenvey, C, Mahoney, R, Fine, N, Minto, T, Henry, A, Gill, C, Dunne, N, Sarma, DR, Godbole, C, Carlos, W, Tewari, N, Jeevan, D, Naredla, P, Khajuria, A, Connolly, H, Robertson, S, Sweeney, C, Di Taranto, G, Shanbhag, S, Dickson, K, McEvoy, K, Skillman, J, Sait, M, Al-omishy, H, Baig, M, Heer, B, Lunevicius, R, Sheel, ARG, Sundhu, M, Santini, AJA, Fathelbab, MSAT, Hussein, KMA, Nunes, QM, Jones, RP, Shahzad, K, Haq, I, Baig, MMAS, Hughes, JL, Kattakayam, A, Rajput, K, Misra, N, Shah, SB, Clynch, AL, Georgopoulou, N, Sharples, HM, Apampa, AA, Nzenwa, IC, Sud, A, Podolsky, D, Coleman, NL, Callahan, MP, Dunstan, M, Beak, P, Gerogiannis, I, Ebrahim, A, Alwadiya, A, Goyal, A, Phillips, A, Bhalla, A, Demetriou, C, Grimley, E, Theophilidou, E, Ogden, E, Malcolm, FL, Davies-Jones, G, Ng, JCK, Mirza, M, Hassan, M, Elmaleh, N, Daliya, P, Williams, S, Bateman, A, Chia, Z, A'Court, J, Konarski, A, Faulkner, G, Talwar, R, Patel, K, Askari, A, Jambulingam, PS, Shaw, S, Maity, A, Hatzantonis, C, Sagar, J, Kudchadkar, S, Cirocchi, N, Chan, CH, Eberbach, H, Bayer, J, Erdle, B, Sandkamp, R, Breen, K, Velmahos, G, Maurer, LR, El Moheb, M, Gaitanidis, A, Naar, L, Christensen, MA, Kapoen, C, Langeveld, K, El Hechi, M, Mokhtari, A, Main, B, Maccabe, T, Newton, C, Blencowe, NS, Fudulu, DP, Bhojwani, D, Baquedano, M, Caputo, M, Rapetto, F, Flannery, O, Hassan, A, Ward, A, Tadross, D, Majkowski, L, Blundell, C, Forlani, S, Nair, R, Guha, S, Brown, SR, Steele, C, Kelty, CJ, Newman, T, Lee, M, Chetty, G, Lye, G, Balasubramanian, SP, Shah, Sureshkumar N, Sherif, M, Al-mukhtar, A, Whitehall, E, Giblin, A, Wells, F, Sharkey, A, Adamec, A, Madan, S, Konsten, J, Van Heinsbergen, M, Sou, A, Simpson, D, Hamilton, E, Blair, J, Jimeno Fraile, J, Morales-Garcia, D, Carrillo-Rivas, M, Toledo Martinez, E, Pascual, A, Landaluce-Olavarria, A, Gonzalez De Miguel, M, Gomez Cruzado, Fernandez L, Begona, E, Lecumberri, D, Calvo Rey, A, Prada Hervella, GM, Dos Santos Carregal, L, Rodriguez, Fernandez MI, Freijeiro, M, El Drubi Vega, S, Van den Eynde, J, Oosterlinck, W, Van den Eynde, R, Sermon, A, Boeckxstaens, A, Cordonnier, A, De Coster, J, Jaekers, J, Politis, C, Miserez, M, Galipienso Eri, M, Garcia Montesino, JD, Dellonder Frigole, J, Noriego Munoz, D, Lizzi, V, Vovola, F, Arminio, A, Cotoia, A, Sarni, AL, Bekheit, M, Kamera, BS, Elhusseini, M, Sharma, P, Ahmeidat, A, Gradinariu, G, Cymes, W, Hannah, A, Mignot, G, Shaikh, S, Agilinko, J, Sgro, A, Rashid, MM, Milne, K, McIntyre, J, Akhtar, MA, Turnbull, A, Brunt, A, Stewart, KE, Wilson, MSJ, Rutherford, D, McGivern, K, Massie, E, Duff, S, Moura, F, Brown, BC, Khan, A, Asaad, P, Wadham, B, Aneke, IA, Collis, J, Warburton, H, Thomas, M, Pearce, L, Fountain, DM, Laurente, R, Sigamoney, KV, Dasa, M, George, K, Naqui, Z, Galhoum, M, Lipede, C, Gabr, A, Radhakrishnan, A, Hasan, MT, Kalenderov, R, Pathmanaban, O, Colombo, F, Chelva, R, Subba, K, Abou-Foul, AK, Khalefa, M, Hossain, F, Moores, T, Pickering, L, Shah, J, Anthoney, J, Emmerson, O, Bevan, K, Makin-Taylor, R, Ong, CS, Callan, R, Bloom, O, Chauhan, G, Kaur, J, Burahee, A, Bleibleh, S, Pigadas, N, Snee, D, Bhasin, S, Crichton, A, Habeebullah, A, Bodla, AS, Yassin, N, Mondragon, M, Dewan, V, Giuffrida, MC, Marano, A, Palagi, S, Grimaldi, Di Maria S, Testa, V, Peluso, C, Borghi, F, Simonato, A, Puppo, A, D'Agruma, M, Chiarpenello, R, Pellegrino, L, Maione, F, Cianflocca, D, Pruiti, Ciarello V, Giraudo, G, Gelarda, E, Dalmasso, E, Abrate, A, Daniele, A, Ciriello, V, Rosato, F, Garnero, A, Leotta, L, Chiozza, M, Anania, G, Urbani, A, Radica, Koleva M, Carcoforo, P, Portinari, M, Sibilla, M, Archer, JE, Odeh, A, Siddaiah, N, Baumber, R, Parry, J, Carmichael, H, Velopulos, CG, Wright, FL, Urban, S, McIntyre, Jr RC, Schroeppel, TJ, Hennessy, EA, Dunn, J, Zier, L, Parmar, C, Mccluney, S, Shah, S, Munoz Vives, JM, Osorio, A, Gomez Diaz, CJ, Guariglia, CA, Soto Montesinos, C, Sanchon, L, Xicola Martinez, M, Guardia, N, Collera, P, Diaz Del Gobbo, R, Sanchez Jimenez, R, Farre Font, R, Flores Clotet, R, Brathwaite, CEM, Liu, H, Petrone, P, Hakmi, H, Sohail, AH, Baltazar, G, Heckburn, R, Aujayeb, A, Townshend, D, McLarty, N, Shenfine, A, Jackson, K, Johnson, C, Madhvani, K, Hampton, M, Hormis, AP, Young, R, Miu, V, Sheridan, K, MacDonald, L, Green, S, Onos, L, Dean, B, Luney, C, Myatt, R, Williams, MA, McVeigh, J, Alqallaf, A, Ben-Sassi, A, Mohamed, I, Mellor, K, Joshi, P, Joshi, Y, Crichton, R, Sonksen, J, Aldridge, K, Layton, GR, Karki, B, Jeong, H, Pankhania, S, Asher, S, Folorunso, A, Mistry, S, Singh, B, Winyard, J, Mangwani, J, Babu, BHB, Liyanage, ASD, Newman, S, Blake, I, Weerasinghe, C, Ballabio, M, Bisagni, P, Longhi, M, Armao, T, Madonini, M, Gagliano, A, Pizzini, P, Alga, A, Nordberg, M, Sandblom, G, Jallad, S, Lord, J, Anderson, C, El Kafsi, J, Logishetty, K, Saadya, A, Midha, R, Ip, M, Ponniah, Subbiah H, Stockdale, T, Bacarese-Hamilton, T, Foster, L, James, A, Anjarwalla, N, Henriques, Marujo D, Hettige, R, Baban, C, Tenovici, A, Salerno, G, Hardie, J, Page, S, Anazor, F, King, SD, Luck, J, Kazzaz, S, HKruijff, S, De Vries, JPPM, Steinkamp, PJ, Jonker, PKC, Van der Plas, WY, Bierman, W, Janssen, Y, Borgstein, ABJ, Gisbertz, SS, Henegouwen, van Berge MI, Enjuto, D, Perez Gonzalez, M, Diaz Pena, P, Gonzalez, J, Marqueta De Salas, M, Martinez Pascual, P, Rodriguez Gomez, L, Garces Garcia, R, Ramos Bonilla, A, Herrera-Merino, N, Fernandez Bernabe, P, Cagigal Ortega, EP, Hernandez, I, de Castro Rubio, Garcia E, Cervera, I, Kashora, F, Siddique, MH, Singh, A, Barmpagianni, C, Basgaran, A, Basha, A, Okechukwu, V, Bartsch, A, Gallagher, P, Maqsood, A, Sahnan, K, Leo, CA, Lewis, SE, Ubhi, HK, Exley, R, Khan, U, Shah, P, Saxena, S, Zafar, N, Abdul-Jabar, H, Mongelli, F, Bernasconi, M, Di Giuseppe, M, Christoforidis, D, La Regina, D, Arigoni, M, Liew, I, Al-Sukaini, A, Mediratta, S, Saxena, D, Brown, O, Boal, M, Dean, H, Higgs, S, Stanger, S, Abdalaziz, H, Constable, J, Ishii, H, Preece, R, Dovell, G, Reddy, Gopi R, Dehal, A, Shah, HB, Cross, GWV, Seyed-Safi, P, Smart, YW, Kuc, A, Al-Yaseen, M, Jayasankar, B, Balasubramaniam, D, Abdelsaid, K, Mundkur, N, Gallagher, B, Hine, T, Keeler, B, Soulsby, RE, Taylor, A, Davies, E, Ryska, O, Raymond, T, Rogers, S, Tong, A, Hawkin, P, Kinnaman, G, Meagher, A, Sharma, I, Holler, E, Dunning, J, Viswanath, Y, Freystaetter, K, Dixon, J, Hadfield, JN, Hilley, A, Egglestone, A, Smith, B, Arkani, S, Freedman, J, Youssef, M, Sreedharan, L, Baskaran, D, Shaikh, I, Seebah, K, Reid, J, Watts, D, Kouritas, V, Chrastek, D, Maryan, G, Gill, DF, Khatun, F, Ranjit, S, Parakh, J, Sarodaya, V, Daadipour, A, Khalifa, M, Bosch, KD, Bashkirova, V, Dvorkin, LS, Kalidindi, VK, Choudhry, A, Marx, W, Espino Segura-Illa, M, Sanchez Aniceto, G, Castano-Leon, AM, Jimenez-Roldan, L, Delgado Fernandez, J, Perez Nunez, A, Lagares, A, Garcia Perez, D, Santas, M, Paredes, I, Esteban Sinovas, O, Moreno-Gomez, L, Rubio, E, Vega, V, Vivas Lopez, A, Labalde Martinez, M, Garcia Villar, O, Pelaez Torres, PM, Garcia-Borda, J, Ferrero Herrero, E, Gomez, P, Eiriz Fernandez, C, Ojeda-Thies, C, Pardo Garcia, JM, Jones, Wynn H, Divecha, H, Whelton, C, Board, T, Hardie, C, Powell-Smith, E, Alotaibi, M, Maashi, A, Zowgar, A, Alsakkaf, M, Izquierdo, O, Ventura, D, Castellanos, J, Lara, A, Escobar, D, Arrieta, M, Garcia de Cortazar, U, Villamor Garcia, I, Cioci, A, Ruiz, G, Allen, M, Rakoczy, K, Pavlis, W, Saberi, R, Sobti, A, Khaleel, A, Unnithan, A, Memon, K, Bhaskar, Pala RR, Maqboul, F, Kamel, F, Al-Samaraee, A, Madani, R, Kumar, L, Nisar, P, Agrawal, S, Llaquet Bayo, H, Duchateau, N, De Gheldere, C, Cheng, D, Yang, H, Fayad, A, Wood, ML, Persad, A, Groot, G, Pham, H, Hakami, I, Boeker, C, Mall, J, Smith, H, Haugstvedt, AF, Jonsson, M, Caja Vivancos, P, Villalabeitia Ateca, I, Prieto Calvo, M, Martin Playa, P, Gainza, A, Aragon Achig, EJ, Rodriguez Fraga, A, Melchor Corcostegui, I, Mallabiabarrena Ormaechea, G, Garcia Gutierrez, JJ, Barbier, L, Pesantez Peralta, MA, Jimenez Jimenez, M, Municio Martin, JA, Gomez Suarez, J, Garcia Opere, G, Pascua Gomez, LA, Onate Aguirre, M, Fernandez-Colorado, A, De la Rosa-Estadella, M, Gasulla-Rodriguez, A, Serrano-Martin, M, Peig-Font, A, Junca-Marti, S, Juarez-Pomes, M, Garrido-Ondono, S, Blasco-Torres, L, Molina-Corbacho, M, Maldonado-Sotoca, Y, Gasset-Teixidor, A, Blasco-Moreu, J, Turrado-Rodriguez, V, Lacy, AM, de Lacy, FB, Morales, X, Carreras-Castaner, A, Torner, P, Jornet-Gibert, M, Balaguer-Castro, M, Renau-Cerrillo, M, Camacho-Carrasco, P, Vives-Barquiel, M, Campuzano-Bitterling, B, Gracia, I, Pujol-Muncunill, R, Estaire Gomez, M, Padilla-Valverde, D, Sanchez-Garcia, S, Sanchez-Pelaez, D, Jimenez Higuera, E, Picon Rodriguez, R, Fernandez Camunas, A, Martinez-Pinedo, C, Garcia Santos, EP, Munoz-Atienza, V, Moreno Perez, A, de la Manzanara Cano, Lopez CA, Crego-Vita, D, Huecas-Martinez, M, Domenech, J, Rosello Anon, A, Sanguesa, MJ, Bernal-Sprekelsen, JC, Catala Bauset, JC, Renovell Ferrer, P, Martinez Perez, C, Gil-Albarova, O, Gilabert Estelles, J, Aghababyan, K, Rivas, R, Rivas, F, Escartin, J, Blas Laina, JL, Nogues, A, Cros, B, Talal El-Abur, I, Garcia Egea, J, Yanez, C, Kauppila, JH, Sarjanoja, E, Tzedakis, S, Bouche, PA, Gaujoux, S, Gossot, D, Seguin-Givelet, A, Fuks, D, Grigoroiu, M, Salas, Sanchez R, Cathelineau, X, Macek, P, Barbe, Y, Rozet, F, Barret, E, Mombet, A, Cathala, N, Brian, E, Zadegan, F, Conso, C, Baldwin, AJ, West, R, Gammeri, E, Catton, A, Kouris, Marinos S, Pereca, J, Singh, J, Patel, P, Handa, S, Kaushal, M, Kler, A, Reghuram, V, Tezas, S, Oktseloglou, V, Mosley, F, Monroy, De La Cruz MFI, Bobak, P, Omar, I, Ahad, S, Langlands, F, Brown, V, Hashem, M, Williams, A, Ridgway, A, Pournaras, D, Britton, E, Lostis, E, Ambler, GK, Chu, H, Hopkins, J, Manara, J, Chan, M, Doe, M, Moon, RDC, Jichi, T, Singleton, W, Mannion, R, Ramzi, J, Mohan, M, Singh, AA, Ashcroft, J, Baker, OJ, Coughlin, P, Davies, RJ, Durst, AZED, Abood, A, Habeeb, A, Hudson, VE, Lamb, B, Luke, L, Mitrasinovic, S, Murphy, S, Ngu, AWT, O'Neill, JR, Waseem, S, Wong, K, Georgiades, F, Hutchinson, PJ, Tan, XS, Pushpa-rajah, J, Colquhoun, A, Masterson, L, Abu-Nayla, I, Walker, C, Balakrishnan, A, Rooney, S, Irune, E, Byrne, MHV, Durrani, A, Richards, T, Venkatesan, Sethuraman A, Combellack, T, Williams, J, Tahhan, G, Mohammed, M, Kornaszewska, M, Valtzoglou, V, Deglurkar, I, Rahman, M, Von Oppell, U, Mehta, D, Koutentakis, M, Chek, Syed Nong SAH, Hill, G, Morris, C, Shinkwin, M, Torkington, J, Cornish, J, Houston, R, Mannan, S, Ayeni, F, Tustin, H, Bordenave, M, Robson, A, Manu, N, Eardley, N, Krishnan, E, Serevina, OL, Martin, E, Smith, C, Jones, A, Mahapatra, Roy S, Clifford, R, Matthews, W, Mohankumar, K, Khawaja, I, Palepa, A, Doulias, T, Premakumar, Y, Jauhari, Y, Koshnow, Z, Bowen, D, Uberai, A, Hirri, F, Stubbs, BM, McDonald, C, Manickavasagam, J, Ragupathy, K, Davison, S, Dalgleish, S, McGrath, N, Kanitkar, R, Payne, CJ, Ramsay, L, Ng, CE, Collier, T, Khan, K, Evans, R, 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Tustin, H, Bordenave, M, Robson, A, Manu, N, Eardley, N, Krishnan, E, Serevina, OL, Martin, E, Smith, C, Jones, A, Mahapatra, SR, Clifford, R, Matthews, W, Mohankumar, K, Khawaja, I, Palepa, A, Doulias, T, Premakumar, Y, Jauhari, Y, Koshnow, Z, Bowen, D, Uberai, A, Hirri, F, Stubbs, BM, McDonald, C, Manickavasagam, J, Ragupathy, K, Davison, S, Dalgleish, S, McGrath, N, Kanitkar, R, Payne, CJ, Ramsay, L, Ng, CE, Collier, T, Khan, K, Evans, R, Brennan, C, Henshall, DE, Drake, T, Zamvar, V, Tambyraja, A, Skipworth, RJE, Linder, G, McGregor, R, Brennan, P, Mayes, J, Ross, L, Smith, S, White, T, Jamjoom, AAB, Pasricha, R, Holme, T, Abbott, S, Razik, A, Thrumurthy, S, Steinke, J, Baker, M, Howden, D, Baxter, Z, Osagie, L, Bence, M, Fowler, GE, Massey, L, Rajaretnam, N, Evans, J, John, J, Goubran, A, Campain, N, McDermott, FD, McGrath, JS, Ng, M, Pascoe, J, Phillips, JRA, Daniels, IR, Raptis, DA, Pollok, JM, Machairas, N, Davidson, B, Fusai, G, Soggiu, F, Xyda, S, Salinas, CH, Tzerbinis, H, Pissanou, T, Gilliland, J, Chowdhury, S, Varcada, M, Hart, C, Mirnezami, R, Knowles, J, Angamuthu, N, Vijay, V, Shakir, T, Hasan, R, Tansey, R, Ross, E, Loubani, M, Wilkins, A, Cao, H, Capitelli-McMahon, H, Hitchman, L, Ikram, H, Andronic, A, Ibrahim, AA, Totty, J, Tayeh, S, Chase, T, Humphreys, L, Ayorinde, J, Ghanbari, A, Cuming, T, Williams, K, Chung, E, Hagger, R, Karim, A, Hainsworth, A, Flatman, M, Trompeter, A, Hing, C, Tsinaslanidis, P, Benjamin, MW, Leyte, A, Tan, C, Smelt, J, Vaughan, P, Santhirakumaran, G, Hunt, I, Raza, M, Labib, A, Luo, X, Sudarsanam, A, Rolls, A, Lyons, O, Onida, S, Shalhoub, J, Sugand, K, Park, C, Sarraf, KM, Erridge, S, Kinross, J, Denning, M, Yalamanchili, S, Abuown, A, Ibrahim, M, Martin, G, Davenport, D, Wheatstone, S, Andreani, S, Bath, MF, Sahni, A, Judkins, N, Springford, LR, Sohrabi, C, Bacarese-Hamilton, J, Taylor, FG, Patki, P, Tanabalan, C, Reynolds, J, Alexander, ME, Smart, CJ, Stylianides, N, Abdalla, M, Newton, K, Bhatia, K, Edmondson, R, Abdeh, L, Jones, D, Zeiton, M, Ismail, O, Naseem, H, Advani, R, Fell, A, Smith, A, Nikolaou, S, English, C, Kristinsson, S, Oni, T, Ilahi, N, Ballantyne, K, Woodward, Z, Merh, R, Robertson-Smith, B, Mahmoud, A, Ameerally, P, Finch, JG, Gnanachandran, C, Pop, I, Rogers, M, Yousef, Y, Woods, R, Zahid, H, Mundy, G, Dass, D, Ford, D, Khan, J, Thiruchandran, G, Toh, SKC, Ahmad, Y, Allana, A, Bellis, C, Babawale, O, Phan, YC, Lokman, U, Ismail, M, Koc, T, Witek, A, Duggleby, L, Shamoon, S, Stefan, S, Clancy, H, Singh, S, Mukherjee, S, Ferguson, D, Mansuri, A, Thakrar, A, Wickramarachchi, L, Cuthbert, R, Sivayoganathan, S, Chui, K, Karam, E, Dott, C, Singh, R, Lane, J, Colvin, HV, Badran, A, Cadersa, A, Cumpstey, A, Hamady, Z, Aftab, R, Wensley, F, Byrne, J, Morrison-Jones, V, Sekhon, GK, Shields, H, Shakoor, Z, Yener, A, Talbot, T, Alzetani, A, Cresner, R, Johnson, D, Hughes, I, Hall, J, Rooney, J, Chatterji, S, Zhang, Y, Owen, R, Rudic, M, Hunt, J, Zakai, D, Aladeojebi, A, Ali, M, Gaunt, A, Barmayehvar, B, Kitchen, M, Gowda, M, Mansour, F, Jarvis, M, Halliday, E, Lefroy, R, Nanjaiah, P, Ali, S, Lin, DJ, Rajgor, AD, Scurrah, RJ, Kang, C, Watson, LJ, Harris, G, Royle, T, Cunningham, Y, James, G, Steel, B, Luk, ACO, Stables, G, Doorgakant, A, Thiruvasagam, VG, Carter, J, Reid, S, Mohammed, R, Marlow, W, Ferguson, H, Wilkin, R, Konstantinou, C, Yershov, D, Vatish, J, Denning, A, Das, R, Powell, S, Magee, C, Agarwal, K, Mangos, E, Nambirajan, T, Flindall, I, Mahendran, V, Hanson, A, De Marchi, J, Hill, A, Farrell, T, Davis, NF, Kearney, D, Nelson, T, Picciariello, A, Papagni, V, Altomare, DF, Granieri, S, Cotsoglou, C, Cabeleira, A, Branco, C, Serralheiro, P, Alves, R, Teles, T, Lazaro, A, Canhoto, C, Simoes, J, Costa, M, Almeida, AC, Nogueira, O, Oliveira, A, Nemesio, RA, Silva, M, Lopes, C, Amaral, MJ, da Costa, AV, Andrade, R, Martins, R, Guimaraes, A, Guerreiro, P, Ruivo, A, Camacho, C, Duque, M, Santos, E, Breda, D, Oliveira, JM, Lopez, ALD, Garrido, S, Colino, M, De Barros, J, Correia, S, Rodrigues, M, Cardoso, P, Teixeira, J, Soares, AP, Morais, H, Pereira, R, Revez, T, Manso, MI, Domingues, JC, Henriques, P, Ribeiro, R, Ribeiro, VI, Cardoso, N, Sousa, S, dos Santos, SM, Miranda, P, Garrido, R, Ferreira, MP, Ascensao, J, Costeira, B, Cunha, C, Rodrigues, LR, Fernandes, MS, Azevedo, P, Ribeiro, J, Lourenco, I, Gomes, H, Mendinhos, G, Pinto, AN, dos Santos, GM, Taflin, H, Abdou, H, Diaz, J, Richmond, M, Clark, J, O'Meara, L, Hanna, N, Cooper, Z, Salim, A, Hirji, SA, Brown, A, Chung, C, Hansen, L, Okafor, BU, Roxo, V, Raut, CP, Jolissaint, JS, Mahvi, DA, Reinke, C, Ross, S, Thompson, K, Manning, D, Perkins, R, Volpe, A, Merola, S, Ssentongo, A, Ssentongo, P, Oh, JS, Hazelton, J, Maines, J, Gusani, N, Garner, M, Horvath, S, Martin, RCG, Bhutiani, N, Choron, R, Peck, G, Soliman, F, Rehman, S, Abbas, A, Soliman, A, Kim, B, Jones, C, Dauer, MDE, Renza-Stingone, E, Hernandez, E, Gokcen, E, Kropf, E, Sufrin, H, Hirsch, H, Ross, H, Engel, J, Sewards, J, Poggio, J, Sanserino, K, Rae, L, Philp, M, Metro, M, McNelis, P, Petrov, R, Pazionis, T, Quintana, M, Jackson, H, Lumenta, DB, Nischwitz, SP, Richtig, E, Pau, M, Srekl-Filzmaier, P, Eibinger, N, Michelitsch, B, Fediuk, M, Papinutti, A, Seidel, G, Kahn, J, Cohnert, TU, Kantor, E, Kahiu, J, Hossain, N, Hosny, S, Sultana, A, Taggarsi, M, Vitone, L, Lambert, J, Vaz, OP, Sarantitis, I, Shrestha, D, Timbrell, S, Shugaba, A, Jones, GP, Gardner, A, Tripathi, SS, Greenhalgh, MS, Emerson, H, Vejsbjerg, K, McCormick, W, Fisher, A, Singisetti, K, Aawsaj, Y, Barry, C, Blanco, J, Vanker, R, Ghobrial, M, Jones, G, Kanthasamy, S, Fawi, H, Awadallah, M, Chen, F, Cheung, J, Tingle, S, Abbadessa, F, Sachdeva, A, Rai, B, Chan, CD, McPherson, I, Booth, K, Ali, FM, Pandanaboyana, S, Grainger, T, Nandhra, S, Patience, A, Rogers, A, Roy, C, Williams, T, Dawe, N, McCaffer, C, Riches, J, Bhattacharya, S, Moir, J, Kalson, NS, Ahmed, HE, Mellor, C, Saleh, C, Koshy, RM, Hammond, J, Sanderson, L, Wahed, S, Phillips, AW, Ghosh, K, Rogers, LJ, Labib, PL, Miller, D, Minto, G, Hope, N, Marchbank, A, Emslie, K, Panahi, P, Ho, B, Perkins, C, Clough, E, Roy, H, Enemosah, I, Campbell, R, Natale, J, Gohil, K, Rela, M, Raza, N, Menakaya, C, Webb, JI, Antar, M, Modi, N, Sofat, R, Noel, J, Nunn, R, Adegbola, S, Eriberto, F, Sharma, V, Tanna, R, Lodhia, S, Carvalho, L, Osorio, C, Antunes, J, Lourenco, S, Balau, P, Godinho, M, Pereira, A, Keller, DS, Smart, NJ, Apollo - University of Cambridge Repository, Collaborative, COVIDSurg, and Robotics and image-guided minimally-invasive surgery (ROBOTICS)
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Male ,medicine.medical_specialty ,Multivariate analysis ,MORTALITY-RATES ,hip ,SURGERY ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,MULTICENTER ,COVIDSurg Collaborative ,1117 Public Health and Health Services ,Cohort Studies ,Medicine, General & Internal ,Internal medicine ,General & Internal Medicine ,medicine ,Dementia ,Humans ,Prospective Studies ,Aged, 80 and over ,COMPLICATIONS ,Science & Technology ,HIP-FRACTURES ,business.industry ,Hip Fractures ,SARS-CoV-2 ,COVID-19 ,1103 Clinical Sciences ,General Medicine ,Femoral fracture ,Perioperative ,medicine.disease ,Heart failure ,trauma management ,Medicine ,Surgery ,business ,Life Sciences & Biomedicine ,Femoral Fractures ,Kidney disease ,Cohort study ,1199 Other Medical and Health Sciences - Abstract
ObjectivesStudies have demonstrated high rates of mortality in people with proximal femoral fracture and SARS-CoV-2, but there is limited published data on the factors that influence mortality for clinicians to make informed treatment decisions. This study aims to report the 30-day mortality associated with perioperative infection of patients undergoing surgery for proximal femoral fractures and to examine the factors that influence mortality in a multivariate analysis.SettingProspective, international, multicentre, observational cohort study.ParticipantsPatients undergoing any operation for a proximal femoral fracture from 1 February to 30 April 2020 and with perioperative SARS-CoV-2 infection (either 7 days prior or 30-day postoperative).Primary outcome30-day mortality. Multivariate modelling was performed to identify factors associated with 30-day mortality.ResultsThis study reports included 1063 patients from 174 hospitals in 19 countries. Overall 30-day mortality was 29.4% (313/1063). In an adjusted model, 30-day mortality was associated with male gender (OR 2.29, 95% CI 1.68 to 3.13, p80 years (OR 1.60, 95% CI 1.1 to 2.31, p=0.013), preoperative diagnosis of dementia (OR 1.57, 95% CI 1.15 to 2.16, p=0.005), kidney disease (OR 1.73, 95% CI 1.18 to 2.55, p=0.005) and congestive heart failure (OR 1.62, 95% CI 1.06 to 2.48, p=0.025). Mortality at 30 days was lower in patients with a preoperative diagnosis of SARS-CoV-2 (OR 0.6, 95% CI 0.6 (0.42 to 0.85), p=0.004). There was no difference in mortality in patients with an increase to delay in surgery (p=0.220) or type of anaesthetic given (p=0.787).ConclusionsPatients undergoing surgery for a proximal femoral fracture with a perioperative infection of SARS-CoV-2 have a high rate of mortality. This study would support the need for providing these patients with individualised medical and anaesthetic care, including medical optimisation before theatre. Careful preoperative counselling is needed for those with a proximal femoral fracture and SARS-CoV-2, especially those in the highest risk groups.Trial registration numberNCT04323644
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- 2021
3. Recombination-aware phylogenetic analysis sheds light on the evolutionary origin of SARS-CoV-2.
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Esquivel Gomez LR, Weber A, Kocher A, and Kühnert D
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- Animals, Humans, SARS-CoV-2 genetics, Phylogeny, Pangolins, Bayes Theorem, Recombination, Genetic, Amino Acids genetics, COVID-19, Chiroptera
- Abstract
SARS-CoV-2 can infect human cells through the recognition of the human angiotensin-converting enzyme 2 receptor. This affinity is given by six amino acid residues located in the variable loop of the receptor binding domain (RBD) within the Spike protein. Genetic recombination involving bat and pangolin Sarbecoviruses, and natural selection have been proposed as possible explanations for the acquisition of the variable loop and these amino acid residues. In this study we employed Bayesian phylogenetics to jointly reconstruct the phylogeny of the RBD among human, bat and pangolin Sarbecoviruses and detect recombination events affecting this region of the genome. A recombination event involving RaTG13, the closest relative of SARS-CoV-2 that lacks five of the six residues, and an unsampled Sarbecovirus lineage was detected. This result suggests that the variable loop of the RBD didn't have a recombinant origin and the key amino acid residues were likely present in the common ancestor of SARS-CoV-2 and RaTG13, with the latter losing five of them probably as the result of recombination., (© 2024. The Author(s).)
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- 2024
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4. Phylogenetic analysis of the origin and spread of plague in Madagascar.
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Esquivel Gomez LR, Savin C, Andrianaivoarimanana V, Rahajandraibe S, Randriantseheno LN, Zhou Z, Kocher A, Didelot X, Rajerison M, and Kühnert D
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- Animals, Humans, Phylogeny, Madagascar epidemiology, Bayes Theorem, Phylogeography, Zoonoses, Yersinia pestis genetics
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Background: Plague is a zoonotic disease caused by the bacterium Yersinia pestis, highly prevalent in the Central Highlands, a mountainous region in the center of Madagascar. After a plague-free period of over 60 years in the northwestern coast city of Mahajanga, the disease reappeared in 1991 and caused several outbreaks until 1999. Previous research indicates that the disease was reintroduced to the city of Mahajanga from the Central Highlands instead of reemerging from a local reservoir. However, it is not clear how many reintroductions occurred and when they took place., Methodology/principal Findings: In this study we applied a Bayesian phylogeographic model to detect and date migrations of Y. pestis between the two locations that could be linked to the re-emergence of plague in Mahajanga. Genome sequences of 300 Y. pestis strains sampled between 1964 and 2012 were analyzed. Four migrations from the Central Highlands to Mahajanga were detected. Two resulted in persistent transmission in humans, one was responsible for most of the human cases recorded between 1995 and 1999, while the other produced plague cases in 1991 and 1992. We dated the emergence of the Y. pestis sub-branch 1.ORI3, which is only present in Madagascar and Turkey, to the beginning of the 20th century, using a Bayesian molecular dating analysis. The split between 1.ORI3 and its ancestor lineage 1.ORI2 was dated to the second half of the 19th century., Conclusions/significance: Our results indicate that two independent migrations from the Central Highlands caused the plague outbreaks in Mahajanga during the 1990s, with both introductions occurring during the early 1980s. They happened over a decade before the detection of human cases, thus the pathogen likely survived in wild reservoirs until the spillover to humans was possible. This study demonstrates the value of Bayesian phylogenetics in elucidating the re-emergence of infectious diseases., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Esquivel Gomez et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
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- 2023
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5. Genome Structure, Life Cycle, and Taxonomy of Coronaviruses and the Evolution of SARS-CoV-2.
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Lamkiewicz K, Esquivel Gomez LR, Kühnert D, and Marz M
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- Animals, Genome, Viral, Genomics, Life Cycle Stages, SARS-CoV-2 genetics, COVID-19 genetics
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Coronaviruses have a broad host range and exhibit high zoonotic potential. In this chapter, we describe their genomic organization in terms of encoded proteins and provide an introduction to the peculiar discontinuous transcription mechanism. Further, we present evolutionary conserved genomic RNA secondary structure features, which are involved in the complex replication mechanism. With a focus on computational methods, we review the emergence of SARS-CoV-2 starting with the 2019 strains. In that context, we also discuss the debated hypothesis of whether SARS-CoV-2 was created in a laboratory. We focus on the molecular evolution and the epidemiological dynamics of this recently emerged pathogen and we explain how variants of concern are detected and characterised. COVID-19, the disease caused by SARS-CoV-2, can spread through different transmission routes and also depends on a number of risk factors. We describe how current computational models of viral epidemiology, or more specifically, phylodynamics, have facilitated and will continue to enable a better understanding of the epidemic dynamics of SARS-CoV-2., (© 2023. The Author(s), under exclusive license to Springer Nature Switzerland AG.)
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- 2023
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6. Innate immune signaling in the olfactory epithelium reduces odorant receptor levels: modeling transient smell loss in COVID-19 patients.
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Rodriguez S, Cao L, Rickenbacher GT, Benz EG, Magdamo C, Gomez LR, Holbrook EH, Albers AD, Gallagher R, Westover MB, Evans KE, Tatar DJ, Mukerji S, Zafonte R, Boyer EW, Yu CR, and Albers MW
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Post-infectious anosmias typically follow death of olfactory sensory neurons (OSNs) with a months-long recovery phase associated with parosmias. While profound anosmia is the leading symptom associated with COVID-19 infection, many patients regain olfactory function within days to weeks without distortions. Here, we demonstrate that sterile induction of anti-viral type I interferon signaling in the mouse olfactory epithelium is associated with diminished odor discrimination and reduced odor-evoked local field potentials. RNA levels of all class I, class II, and TAAR odorant receptors are markedly reduced in OSNs in a non-cell autonomous manner. We find that people infected with COVID-19 rate odors with lower intensities and have odor discrimination deficits relative to people that tested negative for COVID-19. Taken together, we propose that inflammatory-mediated loss of odorant receptor expression with preserved circuit integrity accounts for the profound anosmia and rapid recovery of olfactory function without parosmias caused by COVID-19.
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- 2020
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7. Emergence of human-adapted Salmonella enterica is linked to the Neolithization process.
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Key FM, Posth C, Esquivel-Gomez LR, Hübler R, Spyrou MA, Neumann GU, Furtwängler A, Sabin S, Burri M, Wissgott A, Lankapalli AK, Vågene ÅJ, Meyer M, Nagel S, Tukhbatova R, Khokhlov A, Chizhevsky A, Hansen S, Belinsky AB, Kalmykov A, Kantorovich AR, Maslov VE, Stockhammer PW, Vai S, Zavattaro M, Riga A, Caramelli D, Skeates R, Beckett J, Gradoli MG, Steuri N, Hafner A, Ramstein M, Siebke I, Lösch S, Erdal YS, Alikhan NF, Zhou Z, Achtman M, Bos K, Reinhold S, Haak W, Kühnert D, Herbig A, and Krause J
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- Animals, Genome, Bacterial, Humans, Salmonella enterica
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It has been hypothesized that the Neolithic transition towards an agricultural and pastoralist economy facilitated the emergence of human-adapted pathogens. Here, we recovered eight Salmonella enterica subsp. enterica genomes from human skeletons of transitional foragers, pastoralists and agropastoralists in western Eurasia that were up to 6,500 yr old. Despite the high genetic diversity of S. enterica, all ancient bacterial genomes clustered in a single previously uncharacterized branch that contains S. enterica adapted to multiple mammalian species. All ancient bacterial genomes from prehistoric (agro-)pastoralists fall within a part of this branch that also includes the human-specific S. enterica Paratyphi C, illustrating the evolution of a human pathogen over a period of 5,000 yr. Bacterial genomic comparisons suggest that the earlier ancient strains were not host specific, differed in pathogenic potential and experienced convergent pseudogenization that accompanied their downstream host adaptation. These observations support the concept that the emergence of human-adapted S. enterica is linked to human cultural transformations.
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- 2020
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8. Pervasive and non-random recombination in near full-length HIV genomes from Uganda.
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Grant HE, Hodcroft EB, Ssemwanga D, Kitayimbwa JM, Yebra G, Esquivel Gomez LR, Frampton D, Gall A, Kellam P, de Oliveira T, Bbosa N, Nsubuga RN, Kibengo F, Kwan TH, Lycett S, Kao R, Robertson DL, Ratmann O, Fraser C, Pillay D, Kaleebu P, and Leigh Brown AJ
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Recombination is an important feature of HIV evolution, occurring both within and between the major branches of diversity (subtypes). The Ugandan epidemic is primarily composed of two subtypes, A1 and D, that have been co-circulating for 50 years, frequently recombining in dually infected patients. Here, we investigate the frequency of recombinants in this population and the location of breakpoints along the genome. As part of the PANGEA-HIV consortium, 1,472 consensus genome sequences over 5 kb have been obtained from 1,857 samples collected by the MRC/UVRI & LSHTM Research unit in Uganda, 465 (31.6 per cent) of which were near full-length sequences (>8 kb). Using the subtyping tool SCUEAL, we find that of the near full-length dataset, 233 (50.1 per cent) genomes contained only one subtype, 30.8 per cent A1 ( n = 143), 17.6 per cent D ( n = 82), and 1.7 per cent C ( n = 8), while 49.9 per cent ( n = 232) contained more than one subtype (including A1/D ( n = 164), A1/C ( n = 13), C/D ( n = 9); A1/C/D ( n = 13), and 33 complex types). K -means clustering of the recombinant A1/D genomes revealed a section of envelope (C2gp120-TMgp41) is often inherited intact, whilst a generalized linear model was used to demonstrate significantly fewer breakpoints in the gag-pol and envelope C2-TM regions compared with accessory gene regions. Despite similar recombination patterns in many recombinants, no clearly supported circulating recombinant form (CRF) was found, there was limited evidence of the transmission of breakpoints, and the vast majority (153/164; 93 per cent) of the A1/D recombinants appear to be unique recombinant forms. Thus, recombination is pervasive with clear biases in breakpoint location, but CRFs are not a significant feature, characteristic of a complex, and diverse epidemic., (© The Author(s) 2020. Published by Oxford University Press.)
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- 2020
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9. Paleomicrobiology: Diagnosis and Evolution of Ancient Pathogens.
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Bos KI, Kühnert D, Herbig A, Esquivel-Gomez LR, Andrades Valtueña A, Barquera R, Giffin K, Kumar Lankapalli A, Nelson EA, Sabin S, Spyrou MA, and Krause J
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- Biological Evolution, DNA, Bacterial, Fossils parasitology, Genome, Bacterial, Genomics methods, Helicobacter pylori genetics, High-Throughput Nucleotide Sequencing methods, History, Ancient, Humans, Mycobacterium leprae genetics, Mycobacterium tuberculosis genetics, Paleontology methods, Phylogeny, Yersinia pestis genetics, Communicable Diseases history, DNA, Ancient analysis, Fossils microbiology, Paleopathology methods
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The last century has witnessed progress in the study of ancient infectious disease from purely medical descriptions of past ailments to dynamic interpretations of past population health that draw upon multiple perspectives. The recent adoption of high-throughput DNA sequencing has led to an expanded understanding of pathogen presence, evolution, and ecology across the globe. This genomic revolution has led to the identification of disease-causing microbes in both expected and unexpected contexts, while also providing for the genomic characterization of ancient pathogens previously believed to be unattainable by available methods. In this review we explore the development of DNA-based ancient pathogen research, the specialized methods and tools that have emerged to authenticate and explore infectious disease of the past, and the unique challenges that persist in molecular paleopathology. We offer guidelines to mitigate the impact of these challenges, which will allow for more reliable interpretations of data in this rapidly evolving field of investigation.
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- 2019
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10. A multi-gene panel study in hereditary breast and ovarian cancer in Colombia.
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Cock-Rada AM, Ossa CA, Garcia HI, and Gomez LR
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- Adult, Colombia, DNA Mutational Analysis, Female, Germ-Line Mutation genetics, Hereditary Breast and Ovarian Cancer Syndrome diagnosis, Humans, Middle Aged, Retrospective Studies, Triple Negative Breast Neoplasms diagnosis, Genetic Predisposition to Disease, Genetic Testing methods, Hereditary Breast and Ovarian Cancer Syndrome genetics, Triple Negative Breast Neoplasms genetics
- Abstract
Germline mutations in BRCA1 and BRCA2 account for approximately 50% of inherited breast and ovarian cancers. Three founder mutations in BRCA1/2 have been reported in Colombia, but the pattern of mutations in other cancer susceptibility genes is unknown. This study describes the frequency and type of germline mutations in hereditary breast and/or ovarian cancer genes in a referral cancer center in Colombia. Eighty-five women referred to the oncogenetics unit of the Instituto de Cancerologia Las Americas in Medellin (Colombia), meeting testing criteria for hereditary breast and ovarian cancer syndrome (NCCN 2015), who had germline testing with a commercial 25-gene hereditary cancer panel, were included in the analysis. Nineteen patients (22.4%) carried a deleterious germline mutation in a cancer susceptibility gene: BRCA1 (7), BRCA2 (8), PALB2 (1), ATM (1), MSH2 (1) and PMS2 (1). The frequency of mutations in BRCA1/2 was 17.6%. One BRCA2 mutation (c.9246dupG) was recurrent in five non-related individuals and is not previously reported in the country. Seventeen mutation-carriers had a diagnosis of breast cancer (median age of diagnosis of 36 years) and two of ovarian cancer. All BRCA1 mutation-carriers with breast cancer had triple negative tumors (median age of diagnosis of 31 years). Variants of unknown significance were reported in 35% of test results. This is the first report of a multi-gene study for hereditary breast and/or ovarian cancer in a Latin American country. We found a high frequency and a wide spectrum of germline mutations in cancer susceptibility genes in Colombian patients, some of which were not previously reported in the country. We observed a very low frequency of known Colombian founder BRCA1/2 mutations (1.2%) and we found mutations in other genes such as PALB2, ATM, MSH2 and PMS2. Our results highlight the importance of performing multi-gene panel testing, including comprehensive BRCA1/2 analysis (full gene sequencing and large rearrangement analysis), in high-risk breast and/or ovarian cancer patients in Colombia.
- Published
- 2018
- Full Text
- View/download PDF
11. Late presentation of familial mediterranean fever: a case report.
- Author
-
Gomez LR and Mellado RH
- Subjects
- Aged, Female, Humans, Time Factors, Familial Mediterranean Fever diagnosis
- Abstract
Familial Mediterranean Fever (FMF) is an autosomal recessive disorder predominantly affecting people of Mediterranean origin. It is characterized by recurrent episodes of fever and polyserositis of unexplained origin. Most patients with FMF experience their first attack in early childhood with 90% suffering their first bout of pain by the age of 20. We present a case of a 68 years old woman who presented with fevers of 9 months of evolution which culminated with a diagnosis of Familial Mediterranean Fever after successful treatment with Colchicine.
- Published
- 2010
12. AMD473 (ZD0473) exhibits marked in vitro anticancer activity in human tumor specimens taken directly from patients.
- Author
-
Medina-Gundrum L, Cerna C, Gomez LR, Yochmowitz M, and Weitman S
- Subjects
- Antineoplastic Agents administration & dosage, Breast Neoplasms pathology, Carcinoma, Non-Small-Cell Lung pathology, Dose-Response Relationship, Drug, Female, Humans, Lung Neoplasms pathology, Neoplasms drug therapy, Neoplasms pathology, Organoplatinum Compounds administration & dosage, Ovarian Neoplasms pathology, Tumor Cells, Cultured, Antineoplastic Agents pharmacology, Organoplatinum Compounds pharmacology
- Abstract
AMD473 (ZD0473; cis-amminedichloro[2-methylpyridine]platinum [II]) is a new generation anticancer agent that, in preclinical studies, shows evidence of an extended spectrum of antitumor activity and overcomes platinum resistance mechanisms. Here we evaluate the activity of AMD473 (ZD0473) in a panel of 120 human tumor specimens using a soft agar cloning assay (human tumor colony-forming assay). When tumor cells were treated with 1.0, 4.0 or 16.0 microg/ml AMD473 (ZD0473) for 2 h, in vitro responses were observed in 18% (9/51), 33% (17/51) and 44% (19/43) of assessable specimens. Treatment of tumor cells with the same concentrations of AMD473 (ZD0473) for 24 h resulted in responses of 33% (16/48), 63% (30/48) and 85% (35/41). AMD473 (ZD0473) (16 microg/ml; 24 h) demonstrated activity towards 100% of the non-small cell lung (5/5) and ovarian (8/8) cancer specimens and 73% (8/11) of the breast cancer specimens treated. Low levels of cross-resistance to cisplatin cyclophosphamide, 5-flurouracil, etoposide and gemcitabine were observed. There was a positive relationship between AMD473 (ZD0473) concentration and effect, and a significant difference between response to 2- versus 24-h exposure to 4 or 16 microg/ml (p=0.003 and p=0.001, respectively). These responses demonstrate efficacy at pharmacologically relevant concentrations, suggesting AMD473 (ZD0473) deserves further evaluation.
- Published
- 2003
- Full Text
- View/download PDF
13. Day care and selected employee work behaviors.
- Author
-
Milkovich GT and Gomez LR
- Subjects
- Absenteeism, Child, Preschool, Employee Performance Appraisal, Female, Humans, Industry, Minnesota, Mothers, Child Day Care Centers, Employee Incentive Plans, Personnel Management, Personnel Staffing and Scheduling
- Published
- 1976
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