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2. Safety and efficacy of non-steroidal anti-inflammatory drugs to reduce ileus after colorectal surgery
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Chapman, Sj, Clerc, D, Blanco‐colino, R, Otto, A, Nepogodiev, D, Pagano, G, Schaeff, V, Soares, A, Zaffaroni, G, Žebrák, R, Hodson, J, Glasbey, Jc, Pata, P, Pellino, G, Sgrò, A, Elst, T, Van Straten, S, Knowles, Ch, Borakati, A, Bath, Mf, Yasin, Ih, Mclean, K, Arthur, T, Kovacevic, M, Delibegovic, S, Karamanliev, M, Swamad, M, Paramasivam, R, Martensen, A, Larsen, Hm, Rädeker, L, Frey, Pe, Kechagias, A, Venara, A, Duchalais, E, Ioannidis, A, Pata, F, Pasquali, S, Simioni, A, Farina, V, Podda, M, Lorenzon, L, Jakubauskas, M, Elst, Tr, Chu, M, Fagan, Pvb, Wells, Ci, Alagoa João, A, Juloski, J, Ciubotaru, C, Popescu, S, Yanishev, A, Lee, S, Ozkan, Bb, Yagız Sen, A, Aktas, Mk, Baki, Be, Yüksek, B, Kamarajah, S, Khaw, Ra, Mills, E, Goodson, R, Thakral, N, Ablett, Ad, Adra, M, Kwek, I, Khan, Sm, Quinn, P, Manley, Lr, Badran, A, Ramjeeawon, A, Campbell, A, Tan, Hl, Rye, Ds, Rajaraman, N, Norman, Jg, Vutipongsatorn, K, Solomou, G, Akhbari, M, Ali, A, Murray, V, Baker, Dm, Brandao, Bd, Stainer, B, Thavayogan, R, Jones, D, Onafowokan, Oo, Gharooni, A, Dabab, N, Carlton‐carew, S, Kungwengwe, G, Gabriel, M, Sewart, E, Shortland, Tc, Lawday, S, Pockney, P, Dawson, A, Brumfitt, Cd, Stewart, P, Ng, B, Luong, Jk, Ivanov, V, Borisova, A, Neykov, V, Kunčarová, K, Kološová, B, Antonova, T, Farkašová, M, Harbjerg, Jl, Brandsborg, S, Brinck, S, Kjaer, Md, Mark‐christensen, A, Unbehaun, Kp, Dalsgaard, P, Lycke, Kd, Lenaoures, P, Brigand, C, Dumange, E, Gout, M, Moehwald, C, Prem, M, Alhalabi, O, Sliwinski, S, Krupp, J, Gablenz, E, Schmitzer, L, Kopp, A, Steinle, J, Gsenger, J, Pohl, Lj, Riccardi, M, Christodoulou, Im, Konstantinidis, M, Machairas, N, Zoikas, A, Balalis, D, Manatakis, Dk, Aguilera, Ml, Marano, L, Fleres, F, Lovisetto, F, Sasia, D, Segalini, E, Pata, G, Lucchi, A, Sagnotta, A, Campagnaro, T, Petrelli, F, Gallo, G, Papandrea, M, Testa, V, Sinibaldi, G, Di Candido, F, Colombo, F, Perrone, G, Aresu, S, Biancafarina, A, Canonico, G, Pagnanelli, M, Curletti, G, Bini, R, Manzoni Garberini, A, Impellizzeri, H, Cillara, N, Tutino, R, Picciariello, A, Coletta, D, Savino, G, Ferrara, F, Tamini, N, Talamo, G, Parini, D, Giamundo, P, lo Conte, A, Ripetti, V, Pesce, A, Menduni, N, Giudicissi, R, Goldin, E, Rega, D, Belli, A, Andriola, V, Gordini, L, Foppa, C, Piccolo, G, Birindelli, A, Ferrari, C, Ballarini, Z, Tirelli, F, Milone, M, De Rosa, M, Pipitone Federico, Ns, Molteni, B, Tilocca, Pl, Sancini, G, Piozzi, Gn, Lauretta, A, Poillucci, G, Mulas, S, Simcikas, D, Portelli, L, Wijnbergen, Jwm, Dinger, Tl, Doesschate, Sfh, Dalen, Ashm, Bos, Dd, Hansmann, M, Medina Feliz, J, Kuiper, Sz, Abdulrahman, Z, Pruijssers, Sr, Farik, S, Elliott, Bm, Geneta, Vp, Wilton, S, Kandelaki, H, Peng, Sl, Campbell, S, Lim, Yk, Yassaie, Ss, Murray, M, Haran, C, Tan, J, Castro, J, Laranjeira, A, Catarino, S, Neves‐marques, C, Correia, Jg, Vieira, Bn, Quintela, Ac, Serra, Ml, Maciel, J, Cunha, M, Aparício, Dj, Neves, J, Azevedo, J, Romano, M, Eiró, F, Romano, J, Monteiro, C, Claro, M, Almeida, Mr, Peyroteo, M, Machado, Nd, Capote, H, Ferreira, M, Sousa, X, Devesa, H, Cavadas, D, Guerreiro, I, Costa, M, Salman, M, English, C, Mohammed, N, Litvin, A, Ćuk, Vv, Mészárosová, K, Jaich, R, De Lima, H, Brooks, S, Marx, M, Nshalati Salvation, M, Blaser, B, Piazza, G, Gagliardi, B, Serin, H, Yurdaor, Ss, Arslan, E, Kopac, O, Uyanik, A, Ozmen, Bb, Tiftik, E, Aksoy, B, Yalcinkaya, A, Ozoglu, F, Kocer, Md, Bilicen, G, Cinar, En, Uslu, Ö, Kaya, Y, Wong, J, Farhan‐alanie, Mmh, Suresh, G, Asif, A, Finch, Bj, Bhahirathan, Y, Herron, J, Yi Tew, Z, Obukofe, R, Russell, C, Suchett‐kay, I, Netke, T, Williams, L, Kisiel, A, Liu, Fy, Claireaux, H, James, P, Mondal, A, Kalderon, R, Nadama, Hh, Al‐saraff, Z, Tam, Jph, Powell‐chandler, A, Wood, F, Gorgievska, Rebecca, Ragavoodoo, A, Thakrar, C, Rojoa, D, Palmer, C, Davidson, K, Giacci, L, Hale, J, Gan, Fw, Makin‐taylor, R, Hey, Cy, Toh, C, Findlay, Jm, Griffiths, N, Ganesananthan, S, Jasionowska, S, Poustie, M, Wong, C, Turner, T, Pyc, W, Sloper, W, Warner, C, Coey, J, Mason, D, Sait, S, Kowal, M, Owen, M, Saiyed, A, Ashworth, I, Akbari, K, Curran, M, Martin, P, Parker, D, Kwok, K, Lye, C, Ghaly, M, Sammour, T, Lewis, D, Mundasad, R, Wilkes, A, Ctercteko, G, Maslyankov, S, Dimov, R, Iliev, S, Dimitrov, D, Marek, F, Örhalmi, J, Skalický, P, Skalický, T, Chrz, K, Christensen, P, Worsøe, J, Kristensen, Es, Emmertsen, Kj, Loeve, Us, Mihaljevic, Al, Herrle, F, Konstantinidis, Km, Korkolis, D, Karanikas, I, Vincenti, L, Anania, G, Borghi, F, Agresta, F, Maretto, I, Parisi, A, Bucci, L, De Palma, G, Guglielmi, A, Cucinotta, E, La Torre, F, Cianchi, F, Guerrieri, M, Trompetto, M, Persiani, R, Micheletto, G, Cantafio, S, Ronconi, M, Bisagni, Pag, De Prizio, M, Franceschi, A, Galleano, R, Cavallini, M, Brescia, A, D'Ambra, L, Benevento, A, Niolu, P, Calgaro, M, Colangelo, E, Grottola, T, Altomare, Df, Puleo, S, Salamone, G, Pietrabissa, A, Poggioli, G, Erdas, E, Ottonello, R, Tonini, V, Selvaggi, F, Sammarco, G, Ceccarelli, G., De Nisco, C, Surgo, D, Taglietti, L., Ozolins, A, Sivinš, A, Poskus, T, Psaila, J, Bemelman, Wa, Graat, Lj, Langenhoff, B, Wijnhoven, Bpl, Ven, Ahw, Poelman, M, Stassen, Lps, Slooter, G, Acherman, Yiz, Hoff, C, Gerhards, Mf, Stommel, Mwj, Hazebroek, Ej, Geloven, Aaw, Schasfoort, Ra, Leeuwen, Bl, Tuynman, Jb, Tilburg, Mwa, Boerma, Eg, Sharma, P, Jenkins, B, Bissett, Ip, Herd, A, Gordon, A, Vernon, D, Omundsen, M, Ly, J, Reddy, A, Bonnet, G, Harmston, C, Morales, M, Francisco, V, Costa, S, Manso, A, Amorim, E, Pereira, J, Cardoso, J, Ourô, S, Caratão, M, Nascimento, C, Ribeiro da Silva, B, Taranu, V, Dias, R, Mendes, J, Allen, M, Silva, A, Carlos, S, Barbosa, E, Carneiro, C, Ramos, L, Lencastre, L, Martins, R, Silva‐vaz, P, Ridgway, Pf, Mcnamara, Da, Cahill, R, Hogan, A, Larkin, J, O'Connell, Pr, Negoi, I, Abelevich, A, Ćuk, Vm, Vician, M, Ede, C, Sardiwalla, I, Mulira, S, Montwedi, D, Oyomno, M, Hübner, M, Petermann, D, Sauvain, Mo, Ozben, V, Geçim, Ie, Disçi, E, Rencuzogullari, A, Kurt, A, Bisgin, T, Pehlivan, M, Isik, A, Onur, E, Leventoglu, S, Haksal, Mc, Erturk, Ms, Keskin, M, Guner, A, Tutcu Sahin, S, Ozbalci, Gs, Pergel, A, Albayrak, D, Bruce, D, Fearnhead, N, Arthur, J, Harron, M, Beattie, G, Titu, L, Saunders, M, Phillips, J, Dindyal, S, Cresswell, B, Gercek, Y, Lee, J, Linn, T, Faulkner, G, Lockwood, S, Rees, J, Charalabopoulos, A, Campbell, B, Kontovounisios, C, Amarnath, T, Johnson, M, Epanomeritakis, E, Vigs, S, Nastro, P, Gilliam, A, Smolarek, S, Wilson, T, Orbell, J, Mcintyre, R, Agarwal, T, Hainsworth, P, Patel, P, Vijay, J, Liu, B, Dhruva Rao, P, Roxburgh, C, Vipond, M, Youssef, H, Thorn, C, Schizas, A, Denley, S, Bowley, D, Das, K, Cuming, T, Saha, A, Chung, L, Pitt, J, Davis, P, Jones, O, Taylor, M, Bhargava, A, Haji, A, Watson, N, Bloom, I, Singh, B, Norwood, M, Gurjar, S, Stylianides, N, Mirza, S, Evans, M, Williams, G, Patil, P, Hernon, J, Finch, G, Green, S, Chapple, K, Fafemi, O, Warusavitarne, J, Samee, A, Carden, C, Ong, L, Verma, K, Joseph, A, Rawat, N, Pinkney, T, Oke, O, Glen, P, Maxwell‐armstrong, C, Oliphant, R, Garner, J, Moug, Sj, Middleton, S, Lund, Jn, Smart, Nj, Osborn, G, Moore, T, Raymond, T, Hany, Ts, Clarke, R, Khera, G, Brady, R, Sellahewa, C, Mason, C, Torrance, A, Lasithiotakis, K, Knight, J, Pullybank, A, Ainsworth, P, Reid, F, Ramwell, A, Maslekar, S, George, R, Skull, A, Holtham, S, Muhammad, K, Lal, R, Varcada, M, Smith, Fm, Howlader, M, Defriend, D, Kirk, S, Richards, T, Evans, C, Borg, C, Telford, K, Sarfraz, N, Busby, K, Hollingshead, J, Speake, D, Pawa, N, West, D, Chadwick, M, Komolafe, O, Richardson, S, Thornton, M, Goede, A, Osborne, C, Bandyopadhyay, D, Foong, J, Lee, Yj, Liebenberg, P, Mijalkov, D, Wells, A, Bull, N, Ajmera, A, Warburton, T, Morgan, S, Mahmoud, A, Schachtel, M, Mikhail, B, Fomin, I, Mekaeil, B, Taylor, N, Stevenson, C, Drane, A, Pahalawatta, U, Lai, Lt, Debiasio, A, Jun, Hjs, Hengpoonthana, R, Mendis, Dm, Robb, Pm, Lee, Hj, Wyche, Aab, Davis, Lt, Chrimes, A, Agarwal, A, Zhao, J, Williams, S, Jayalath, Jmsn, Khor, S, Muddasani, T, Childs, S, Ridgway, S, Blefari, Nda, Tam, H, Puchalski, N, Ngai, C, Mackenzie, J, Johnson, N, Holmes, M, Zuzek, R, Saluja, T, Gould, T, Goh, Yk, Selvaraj, T, Beh, Yz, Dudi‐venkata, Nn, Horne, D, Borrow, Jl, Campbell, C, Cousins, G, Jackson, L, Maheepala, K, Zhao, S, Holden, E, Tutt, L, Thompson, B, Collins, H, Louie, F, Buckland, B, Smith, D, Chong, C, Chua, Th, Nayak, C, Redmond, J, Tan, Rr, Gramlick, M, Teh, Js, Sy, Ng, Britten‐jones, P, Mohd Rosli, R, Pham, Hdv, Jegathees, T, Coulter‐nile, Smcj, Gosselink, Mp, Wang, Yl, Maciaszek, M, Chrapko, Ps, Nair, A, Thirugnanasundralingam, V, Muir, K, Salibasic, M, Pavlov, V, Paycheva, T, Lyulenina, E, Kolev, N, Nguen, D, Mitkov, Y, Mitkov, E, Vladova, P, Dimitrov, V, Hussain, M, Gabarski, A, Ivanov, T, Yotsov, T, Ilieva, I, Akisheva, A, Shoshkova, M, Nawaz, E, Feradova, H, Mladenov, T, Jozaf, V, Klail, T, Pös, M, Adel, A, Sotona, O, Bartoš, M, Amjad, T, Malý, O, Berec, S, Hanušová, M, Hurný, M, Riško, J, Ludvik, M, Stercz, M, Treskoň, R, Pospíšil, M, Hlaváčová, L, Tomanová, D, Chodora, S, Houdek, O, Novický, R, Sobotková, K, Cha, S, šuta Kimle, K, Jirankova, K, Bujda, M, Paclík, A, Trap, A, Jürgens‐lahnstein, J, Storm, M, Damgaard, I, Olawi, F, Ehlem, F, Raos, M, Kristensen, Fp, Bønnerup, K, Amiri, S, Enevoldsen, M, Højgaard Pedersen, J, Jepsen, Bn, Hillgaard, Tk, Erichsen, Sb, Nielsen, Cv, Madsen, Cp, Bjerke, J, Skejø, Cd, Aabling, Rr, Sørensen, Js, Turunen, A, Katunin, J, Niskakangas, M, Vignaud, T, Frey, S, Ricolleau, C, Chanut, F, Magnin, J, Seiboldt, T, Beck, L, Zamzow, K, Betge, F, Poncelet, A, Truant, M, Hauschild, H, Neugebauer, N, Schöning, L, Simon, S CS, Galata, C, Karampinis, I, Thäwel, T, Seckler, Am, Kerem, C, Durdevic, S, Antonakopoulos, F, Mathioulaki, A, Chrysoheris, P, Athanasopoulos, Pg, Kalles, V, Spyrou, I, Barkolias, C, Paspala, A, Papaconstantinou, D, Spartalis, E, Arkadopoulos, N, Prodromidou, A, Garoufalia, Z, Mendez, D, Rosales, J, Flores, M, Garcia, M, Garcia, A, Noriega, Z, Torselli, D, Rodriguez, J, Lafranceschina, S, Artioli, E, Giaccari, S, Nevoso, V, Schimera, A, Marino, S, Geretto, P, Pellegrino, L, Borghi, B, Marano, A, Corino, C, Cannata, G, Giuffrida, Mc, Landra, F, Ongaro, D, Baronio, G, Raimondo, S, Casiraghi, S, Salvadori, R, Finotti, E, Ciccioli, E, Galgano, A, Zuin, M, Bettella, A, Barina, A, Vendramin, E, Palano, G, Schiavone, D, Di Cintio, A, Gemini, A, Trastulli, S, De Luca, M, Desiderio, J, Gubbiotti, F, Cigognini, M, Maffioli, A, Colombo, S, Bondurri, A, Sampietro, G, Foschi, D, Manigrasso, M, Danzi, M, Amato, R, Anastasio, L, Mastella, F, Basile, R, Peltrini, R, Marra, E, Luglio, G, Giglio, M, Anoldo, P, Vertaldi, S, Grimaldi, L, Tammaro, N, Pedrazzani, C, Turri, G, Lazzarini, E, Conti, C, Vulcano, I, Bertilone, E, Pintabona, G, Viscosi, F, Cerasari, S, Galiffa, G, Lapolla, P, Del Basso, C, Cirillo, B, De Toma, G, Fazzi, K, Bini, S, Coratti, F, Montanelli, P, Grandi, S, Nelli, T, Ben Khaled, N, Cammelli, F, Ferrini, E, Billo, Me, Marrosu, Ag, Scognamillo, F, Pala, C, Attene, F, Carboni, L, Ruggiu, Mw, Gabbas, G, Marziali, I, Mazzocato, S, Vergari, R, Piazzai, F, Kubolli, I, Aggiusti, A, Paolucci, A, Ortenzi, M, Olivieri, M, Belluco, C, Antona, Ad, Basso, S, Morino, M, Mistrangelo, M, Clerico, G, De Santi, G, Bitonti, Mf, Frattalone, M, Fico, V, Santullo, F, Belia, F, Spinelli, A, Marco, M, Bevilacqua, M, Tringali, D, Bevilacqua, E, Panizzo, V, La Manna, V, Migliore, G, Aversano, A, Fares Bucci, A, Marino, F, Carbone, F, Incollingo, P, Romano, Fm, Zalla, T, Baraghini, M, Romoli, L, Calussi, M, Vellei, S, Genzano, C, Feroci, F, Vita, M, Barberis, A, Serra, D, Grassia, M, Romelli, M, Ruggiero, S, Percassi, A, Magri Piccinini, A, Monti, M, Magnoli, M, Romano, S, Gaetano, P, Pilotta, F, Baldassarre, L, Bonati, E, Saba, A, Moretto, G, Bacchion, M, Casaril, A, Inama, M, Creciun, M, Stella, M, Gobatti, D, Angelini, M, Andolfi, E, Miranda, E, Scricciolo, M, Provenza, G, Cavallina, G, Frezza, B, Fontani, A, Malatesti, R, Pellicanò, Ga, Anania, M, Pulighe, F, Cruccu, A, Murru, Ml, Massaiu, C, Balestra, F, Pazzona, M, Giannella, A, Santangelo, M, Frangella, F, Magagnano, D, Liberatore, P, Brenna, R, Giani, A, Tirotta, F, Famularo, S, Angrisani, M, Ceresoli, M, Rondelli, F, Ceccarelli, G, Angelucci, Gp, Scaramuzzo, R, Larcinese, A, Fioriti, C, Picone, E, Nardi, M, Castagnoli, G, Bartoli, A, Bellochi, R, Spaziani, A, Conti, D, Poponesi, V, Trippetti, M, Amicucci, S, Tazza, G, Procacci, P, Giovannini, F, Basile, E, Caristo, G, De Nardi, P, Rosati, R, Marcocci, G, Vignali, A, Malerba, M, Percivale, A, Ghazouani, O, Reggiani, L, Spirito, C, Moschetta, G, Cosmi, F, Romeo, G, Gasparrini, M, Sucameli, F, Gennai, A, Moggia, E, Bianchi, C, Bonfante, P, Macina, S, Feleppa, C, Imperatore, M, Tenconi, Sm, Rausei, S, Maioli, D, Marchionini, V, Sparta, C, Mura, Fa, Barmina, M, Lorettu, A, Rettaroli, C, Mastino, G, Ruggiu, Gv, Mura, Ga, Perrone, Ba, De Angelis, M, Mereu, A, Adamo, V, Bianco, C, Ricciardiello, M, Campanaro, C, Panaccio, P, Esposito, Lm, D'Ascanio, F, Pietroletti, R, Chetta, N, Aquilino, F, Di Marco, F, Amico, A, Schembari, E, Puglisi, S, Licari, L, Campanella, S, Profita, G, Falco, N, Rotolo, G, Venturelli, P, De Marco, P, Marcianò, M, Argenti, F, Milani, Ms, Malabarba, S, Giambartolomei, G, Vella, I, Gronchi, F, Ruggieri, A, Roggiani, A, Balsamo, F, Gori, A, Cuicchi, D, D'Alessio, R, Benvenuto, D, Podda, F, Cappellacci, F, Salaris, C, Sanna, S, Marcialis, J, Mosino, L, Peddis, M, Melis, S, De Donno, G, Aru, Ac, Falsetti, E, Lanari, J, D'Errico, U, Bianchini, S, Figà, F, Caiazzo, A, Selvaggi, L, Capozzolo, A, Cerra, C, Pirillo, M, Cravano, S, Libri, I, Laquatra, N, Isabello, A, Truškovs, A, Bartnick, A, Malcevs, E, Machatschek, Mj, Alm, J, Lapsa, S, Delorme, M, Zeynalov, F, Larnovskis, J, Sauka, J, Bodrov, D, Gailumsis, R, Wiemann, Am, Müller, Nl, Jelovskis, I, Deksnis, D, Bauermeister Potts, O, Slimbajevs, T, Samalavicius, Ne, 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Staden N., McDuling C.R., Claassen L., Kruger C., Weyers J., Lecler J., Mignon G., Vanoni A., Henkens A., Jarrar G., Odovic M., Willemin M., Milliet O., Hahnloser D., Demartines N., Teixeira H., Pittet O., Haller M.L., Huot A., Kefleyesus A., Bugmann A., Piotet L.M., Meijers L., Kurtoglu G.K., Sel E.K., Isler V.C., Yilmaz B.S., Adiyaman C., Kara M., Demirkaya H.C., Korkmaz H.K., Pektas A.M., Guner B., Islek E.C., Tombul H.B., Boztug C.Y., Tinaz A., Yilmaz M., Karaman Y., Akin F.A., Dansuk S., Bascavus M., Kaya M., Kutlu B., Seker M.C., Erten V., Memis U., Kocak Z.B., Karapinar Y.E., Fakirullahoglu M., Koseoglu E., Yeni M., Aykun N., Agca M.H., Bilen C., Kilinc I., Atar C., Kilic V., Aktuna C., Aba M., Alim Y.E., Binbuga M., Kurklu O., Ceylan C., Yilmaz S., Calar S.N., Yildirim N., Yavuz G., Can B., Cesmeli E., Kus D., Kavar R.C., Cevlik A.D., Cengiz U., Turk E.G., Yilmaz I., Erdonmez H., Gursoy F., Kara H., Onsal U., Ozbek M., Kasar P.A., Ipor A., Ozen D., Olmez M., Altintas E., Toklu 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S., Alshakhs A., Ahmeidat A., Goergen N., Ali Z., Mullarkey L., Walshe R., Lewis E., Berry B., Moneim J., Mookerjee S., Christy S., Ojofeitimi O., Carroll L., Hylands A., Delaugere L.P., Reveendran D., Coulter C., Ralston C., Laverty L., Gallagher P., Ahmed A., Yeo Y.Q., Elliott D., Bennett J., Mcnamara M., Sivarajah S., Dunmore C., Aitken G., Nair M., Aly M.H., Buari M., Ahmed K., Sheikh Z., Monks M., Lehmann J., Rotimi O., Bell T., Limnatitou D., Gormley S., Taleongpong P., Patel V., Macgregor L., Amini S., Turner C., Dwyer-Hemmings L., Busuttil A., Powell J., Hensher C., Vivian F., Wcislo K., Millar Z., Hirosue S., Ogunmwonyi I., Nakakande D., Gaze H., Nirmalanantha A., Bin Amran A.M., Foulkes A., Jones N., Pillai S., Khoury G., Powell T., Maleyko I., Sangheli A., Ransome M., Isse M., Aromolaran O., Bholah H., Anbarasan J., Rehman S., Hu E., Timms S., Reynolds W., Hotchkies A., Misra V., Theocharidou L., Malik T., Janmohamed I., Carhart B., Khan A., Hullait R., Rylance A., Butt S., Leathes J., Philip Rajathasan T., Jeddy H., Kyaw H.A., Wong N., Karelia S., Clements J.M., Rainey M., Joshi N., Rahman A., Gallagher M., Rebuffa N., Abdelgalil R., Siaw Yen Lai R., Laurence N., Thomas S., Green C., Frostick R., Khera R., Povey M., Wong H.L., McCusker C., Hlukha L., Pike G., Kamel F., Thakkar R., Donaldson C., Sequeira Campos M., Armitage M.N., Hussain A.S., Hardy B., Hassan Serry M.Y., Bradbury M., Osunronbi T., Tam L.Y.C., Khanan Kaabneh A., Lawther J., Fisher P., Tribedi T., Moosa A., Ramdin A., Goble M., Downs E., Wheldon L., Baggus E., Mandal A., Nayeem A., Ahmed S., Fradley W., Wilson C., Gallagher S., Criswell T., Ward J., Mukkavilli A., Stubbs B., Fordyce W., Suchdev N., Wei Lim S., Sookramanien S.R., Chan A., Bointas G., Paul M., Ward K.L., Bagnall M., Pherwani S.A., Wang K., Mitchell L., Heyworth J., Ayyar S., Polson R., Mackenzie E., Doyle N., Habib Z., Zardab M., Sartaj F., Farooq H., Tabibi M., Drury D.J., James S.J., Barnett R., Teasdale A.B., Richardson E.T.J., Thomas D.A., Williams R.L., Najabat-Lattif H.F., Cahya E., Lou G., Coyle M., Homyer K., Zhu L.Y., Woods M., Chang J., O'Callaghan H., Suchett-Kaye I., Mihailidis T.H., Alawattegama H., Seite E., Barrett A., Riordan E., Lam W., Dowdeswell M., Mulvenna C., Awokoya O., Gurowich L., Dhera K., Hayat S., Tincknell L., Spazzapan M., Teeling F., Sysum K., Latter J., Latter M., Khan S., Guruswamy M., Beedham W., Brazier E., Elghobashy M., Bajaj M., Mann H., Etel E., Woodmass M., Hayden H., Ali Y., Husain S., Arnold A., Pedersen A.C., Cunha P., Ahmed M., Al Zawawi S., Kudva V., Theodoropoulou K., Miscampbell M., Robinson A.V., Johnston J., Dharni A., Lamb S., Westerman T., Evans E., Campbell L., Gillespie M., Cheong C.M., Kulathevanayagam K., Varghese A., Ike S.I., Chu T.S.M., Baljer B., Mogg J.A.W., Rai P., Claireaux H.A., Williams M., Smillie R., Goetz J., Appleby E., Fadipe T., Vaughan-Burleigh S., Puri G., Hussain P., Flather R., Cutler A., Pathak S., Sheldon J., Collicott T., al-Ausi M., Jovaisaite A., Shah S.M., Khalid N., Gutmann D., Davison S., Alame Y.J., Syed L., Owen W.J., Ahsan S.D., Anthony-Uzoeto U., Macleod Hall C., Zheng S., Wynter K., James C., Sapre D., Ghosh R., Baird J., Cockburn L., Blackwood O., Simpson W., Jeong S., Bishop S., Bate R., Hobson C., Adam A.H., Redclift C., Do J., Adeleye O., Poli F., Batterham A., Brown S., Parekh J.N., Clay W., Pieri K., Jackson A., Saxena A., Gurung B., Oyebola T., O'Brien F., Djeugam B., Gardezi S., Ul-Hasan S., Martin-Hernandez M.P., Sisley M., Modi S., Antakia R., Elbayouk A., Soh Y.J., Mather J., Yusuf Z., Al-Sarraf Z., Naja M., Rassool S.B., Convill J., Nikookam Y., Warsame A., Pace C., Kiandee M., Ridwan R., Carey C., Hirri F., McMillan M.J.A., Ling J.J., Pendelbury L., Kerimzade K., Tang A., Howard E.O., Humayun S., Wadsworth O.J., Tan K., Abdelhameed F., Haglund C., Radnaeva I., Hu N., Rambhatla S., Waldron D., Madahar P., Malik S., Meney L.C., Ibrahim I., Kang C.K., Chiu J.Z.J., Livie V., Ibrahim 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Gadhvi A., Grant R., Lewsey J., Morris A., Martin H., McClarty C., Sanyal S., Alsaif A., Palkhi A., Bhopal S., Vishnu K S., Papanikolaou A., Mitra A., Nur A., Ali F., Burford C., Huq T., Irwin E., Matthews L., Ngu W.S., Hosfield T., Muneeb F., Page O., Zeb E., Al-Azzawi A., McIntosh J., Vucicevic A., Hughes M., Brooks L., Fanibi B., Dixon M., Njoku P., Morris D., Jobson J., Chowdhury H., Alawode D.O.T., Wynell-Mayow W., Udayachandran V., Alsoof D., Ekert J., Joseph N., Zulkefley N., Hunt G., Christodoulou T., Wright O., Soman S., Jamal M., Beqiri S., Borgas P., Christie S., Pereira F., Browne S., Yiu J., Dworkin A., Brayley J., Palmer A., Charalambos M., Jones C.J., Toner S., Cowden R., Lee L., Nicol P., Holman O., Imtiaz M., Albert V., Leung S.P., Erotocritou M., Stroud R., Wilkin R., Thomson W., Mackee L., G N., Bei Y., Mckenna Favier S., Ibrahim A., Kler A., Reynolds L., Mohamed S.H., Majeed Y., Fakim B., Jones A., Liversedge G., Carrington Z., Windebank J., Izzarina A., Akbani U., Craven J., Aldarragi A., Harding S., Millward A., Bedford M., Gopalan V., Midgen A., Khadka P., Cheng O., Taneja S., Manobharath N., Kok J.Y., Lim D.W.E., Buick T., Boland M., Piya S., Devlin R., Fairfield C.J., George R.J., Rahi M., Zaman S., Hajiev S., Ross T., Crisp E., Thompson C., Charalambous A., Hollywood J.L., Hammond R.F.L., Matthews J., Mendonca V., Spinty J., Khan K., Cheng J., Glynn N., Muhammad U., Khan M., Anderson L., Mccormack K., Mak J., Patrawala S., Milinkovic N., Schofield R., Chauhan M., Hartley L., Hind J., Nelson L., Ratnasingham D., Whitehead T., Dimitriadis S., Marshall K., Flint E.J., Horner C., Heybourne A., Morgan H., Wickstone C., Panagiotou D., O'Connell E., Dean K., Iqbal R., Walsh L., Yu N., Rana N., Massie E., Ng J., Jung M., Lee Y.D., Harris M., White S., Boev B., Tonchev P., Prochazka V., Skalicky A., Ravn S., Ojakaar A., Dorr-Harim C., Koutserimpas C., Giraudo G., Armellini A., Ruzzenente A., Mazzeo C., De Padua C., Realis Luc A., Maroli A., Giani I., Cufari M.E., Vitali M., Gusai G.P., Quattromani R., Virgilio E., Berti S., Di Mola F.F., Papagni V., Tuminello F., Vittori L., Longheu A., Loche G.A., Braccio B., De Luca E., Resta G., Ancans G., Tamosiunas A., Petrulionis M., Andrejevic P., Stellingwerf M.E., Abdulrahman N., van de Pas K.G.H., Thomas G., Brandsma A.M., Davids J., Rottier S.J., de Roy van Zuidewijn D., Hawkins R., Ong H.I., Li Y., Desmond B., Winstanley J., Martins M., Americano M., Frade S., Senhorinho R., Peixoto R., Alves-Vale C., Lamas M., O'Connor D.B., Hoo M., Gopaul A., Scanlon K., O'Dwyer N., Jovanovic M., Panyko A., Van Vuuren S., Curchod P., Gaspar S., Imadalou L., Mutlu D., Akyol C., Uygur F.A., Eray I.C., Biyiklioglu O., Cetin M.F., Isik A.E., Karip B., Dogan H., Sarigul L., Tunc E., Aydin T., Bodur S., Karabulut K., Francis A.A., Al-hadithi A., To N., Lau I.S.F., Smith E., Mahapatra S., McAuliffe O., Imam L., Akram B., Hossaini S., Davies R., Ko M., Collins J., Pandya A., Reilly S., Archer J., Auty C., Roche C.D., Livie J., Chaudhry F.A., Ntakomyti E., Diallo R., Bylinski T., Wright J., Masiha E., Tung J., Shirazi B., Neilson A., Epton S., Patel N., Trussell S., Couldrey A., Donnelly C., Eftychiou S., Chapman, S. 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Geçim, Ie, Disçi, E, Haksal, Mc, Agarwal, T, Maxwell‐armstrong, C, Moug, Sj, Lund, Jn, Smart, Nj, Smith, Fm, Lee, Yj, Lai, Lt, Jun, Hj, Mendis, Dm, Robb, Pm, Lee, Hj, Wyche, Aab, Davis, Lt, Jayalath, Jmsn, Blefari, Nda, Goh, Yk, Beh, Yz, Dudi‐venkata, Nn, Borrow, Jl, Chua, Th, Tan, Rr, Ng, Sy, Britten‐jones, P, Pham, Hdv, Coulter‐nile, Smcj, Gosselink, Mp, Wang, Yl, Pös, M, Bartoš, M, Malý, O, Hanušová, M, Hurný, M, Riško, J, Treskoň, R, Pospíšil, M, Hlaváčová, L, Tomanová, D, Novický, R, Sobotková, K, šuta Kimle, K, Paclík, A, Jürgens‐lahnstein, J, Kristensen, Fp, Bønnerup, K, Højgaard Pedersen, J, Jepsen, Bn, Hillgaard, Tk, Erichsen, Sb, Nielsen, Cv, Madsen, Cp, Skejø, Cd, Aabling, Rr, Sørensen, J, Schöning, L, Simon, S CS, Thäwel, T, Seckler, Am, Athanasopoulos, Pg, Giuffrida, Mc, Billo, Me, Marrosu, Ag, Ruggiu, Mw, Antona, Ad, Bitonti, Mf, Romano, Fm, Pellicanò, Ga, Murru, Ml, Angelucci, Gp, Tenconi, Sm, Mura, Fa, Ruggiu, Gv, Mura, Ga, Perrone, Ba, Esposito, Lm, Marcianò, M, Aru, Ac, Figà, F, Truškovs, A, Machatschek, Mj, Wiemann, Am, Müller, Nl, Samalavicius, Ne, Poškus, E, Kryžauskas, M, Poškus, T, Looyen, R, Becker, Maj, Molder, L, Tissen, Ym, Vries, H, Smaalen, Tc, Veen, Oc, Dingemans, Sa, Brink, Lc, Vijgen, Ghej, Voort, Emf, Pool, A, Rest, Klc, Sluijpers, Nrf, Molenaar, Cjl, Gordinou de Gouberville, Mc, Mens, Ma, Hoeks, Em, Praag, Em, Smit, Mpcm, Lely, Sj, Stijns, Rch, Leow, Ty, Ruiter, A, Aarts, Cam, Jonge, J, Alqethami, Hj, Elst, Pc, Tissink, Mw, Grüter, A, Voeten, Dm, Boon, Cl, Franssen, Rjm, Jense, Mtf, Lau, Wk, Adams, Sib, Chen, Sy, Kim, Dh, Mclaughlin, Sjp, Chapman, Da, Mcintosh, Nd, Tewhaiti‐smith, J, Yam, St, Tomé, M, Santos, Tc, Lages, Rr, Sá, Tc, Bernardes, Fm, Cunha, Mf, Veiga, Dn, Loureiro, Ar, Torre, Ap, Paixão, I, Rocha, Af, Jervis, Mj, Paixão, V, Silva, Ag, Galvão, D, Mónica, I, Guimarães, N, Martins, Sf, Rocha‐melo, M, Patrício, J, Cinza, Am, Simões, J, Gonçalves, Jp, Guimarães, J, Martins, Ar, Lérias, R, Bártolo, J, Correia, Am, Martins, Pc, Jardim, Jam, Domingos, Sp, Baião, Jm, Lopes, Nmro, Jordão, Dm, Ângelo, Md, Caroço, T, Gomes, Jr, Monteiro, Rg, Colon, Lf, Dockry, É, Aly, Ak, Kang, Sj, Pentony, Ar, Piong, Cl, Eow, Sy, Kamath, Pj, Soh, Tbw, Dyer, Ah, Chee, Sy, Tan, Ixh, Jones, Mr, Al‐salihi, A, Ciubotaru, Ci, Radulović, R, Miloševic, K, Bojičić, J, Genčić, M, Janković, U, Sucháň, Pk, Dubovský, M, Sautter, Sc, Mcduling, Cr, Haller, Ml, Piotet, Lm, Kurtoglu, Gk, Sel, Ek, Isler, Vc, Demirkaya, Hc, Korkmaz, Hk, Pektas, Am, Güner, B, İşlek, Ec, Tombul, Hb, Boztuğ, Cy, Tınaz, A, Yılmaz, M, Akın, Fa, Başçavuş, M, Seker, Mc, Koçak, Zb, Karapinar, Ye, Köseoglu, E, Agca, Mh, Alim, Ye, Kürklü, Ö, Çalar, Sn, Kavar, Rc, Cevlik, Ad, Turk, Eg, Erdönmez, H, Gürsoy, F, Önsal, U, Özbek, M, Kasar, Pa, Özen, D, Ölmez, M, Sariçiçek, T, Tipi, Ou, Benli, Ge, Bilgili, Ac, Kiraz, In, Aksoy, Ab, Karagöz, E, Tümer, S, Abdulrahman, Smf, Kuyumcu, Of, Afsar, Hb, Guler, Se, Gul, Eb, Dossa, Saa, Mizan, Sr, Sahin, Az, Kilinç, A, Yumurtaci, Ö, Girit, Çagri, Yildirak, Mk, Güldag, A, Söyleyici, B, Aytin, Ye, Akay, Fe, Iskan, Ng, Sunay, Ao, Tie‐gill, T, Delaugere, Lp, Yeo, Yq, Aly, Mh, Dwyer‐hemmings, L, Bin Amran, Am, Kyaw, Ha, Clements, Jm, Wong, Hl, Armitage, Mn, Hassan Serry, My, Tam, Lyc, Sookramanien, Sr, Ward, Kl, Pherwani, Sa, Drury, Dj, James, Sj, Teasdale, Ab, Richardson, Etj, Thomas, Da, Williams, Rl, Najabat‐lattif, Hf, Zhu, Ly, Suchett‐kaye, I, Mihailidis, Th, Pedersen, Ac, Robinson, Av, Cheong, Cm, Ike, Si, Chu, Tsm, Mogg, Jaw, Claireaux, Ha, Vaughan‐burleigh, S, Al‐ausi, M, Shah, Sm, Alame, Yj, Owen, Wj, Ahsan, Sd, Anthony‐uzoeto, U, Adam, Ah, Parekh, Jn, Ul‐hasan, S, Martin‐hernandez, Mp, Soh, Yj, Al‐sarraf, Z, Rassool, Sb, Mcmillan, Mja, Ling, Jj, Howard, Eo, Wadsworth, Oj, Meney, Lc, Kang, Ck, Chiu, Jzj, Tan, Qj, Cross, Gwv, Shah, Dr, Ng, Mpe, Wong, Rtw, Rojoa, Dm, Ruddy, Cm, Hall, Jd, Hassane, Asi, Azhar, Aw, Tan, Tk, Kwak, Sy, Ong, Eh, Goolam‐mahomed, Z, Kirnon‐jackman, O, Lim, Qx, Yong, Sq, Chen, Jy, Sam, Zh, Goh, Yn, Muthukumar, Mg, Johnson, Ta, Williams, Ri, Honeyman, Si, Malcolm, Fl, Wilkerson, Ht, Chatterjee‐woolman, S, Ahmed, Wur, Kwan, Kwl, Sanders‐crook, L, Boh, Zy, English, Wj, Novotny, Sa, Chong, Jt, Lee, De, Embury‐young, Y, Clavé Llavall, A, Pang, Yl, Dellen, J, Al‐azzawi, A, Alawode, Dot, Wynell‐mayow, W, Christodoulou, T, Jones, Cj, Leung, Sp, Mohamed, Sh, Kok, Jy, Lim, Dwe, Fairfield, Cj, George, Rj, Hollywood, Jl, Hammond, Rfl, Flint, Ej, Lee, Yd, Skalický, A, Ojakäär, A, Dörr‐harim, C, Cufari, Me, Gusai, Gp, Di Mola, Ff, Loche, Ga, Stellingwerf, Me, Pas, Kgh, Brandsma, Am, Rottier, Sj, Roy van Zuidewijn, D, Ong, Hi, Alves‐vale, C, O'Connor, Db, Jovanović, M, Uygur, Fa, Eray, Ic, Çetin, Mf, Isik, Ae, Sarıgül, L, Francis, Aa, Al‐hadithi, A, Lau, Isf, Roche, Cd, and Chaudhry, Fa
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Male ,renal failure ,Time Factors ,medicine.medical_treatment ,Adult ,Aged ,Anti-Inflammatory Agents, Non-Steroidal ,Elective Surgical Procedures ,Female ,Humans ,Ileus ,Kaplan-Meier Estimate ,Middle Aged ,Patient Safety ,Postoperative Care ,Postoperative Complications ,Proportional Hazards Models ,Prospective Studies ,Recovery of Function ,Treatment Outcome ,Colectomy ,Proctectomy ,Anti-Inflammatory Agents ,colorectal surgery ,ileus ,non-steroidal anti-inflammatory drugs ,NSAIDS ,030230 surgery ,Tumours of the digestive tract Radboud Institute for Health Sciences [Radboudumc 14] ,0302 clinical medicine ,Prospective cohort study ,Colorectal ,RISK ,Hazard ratio ,Acute kidney injury ,Colorectal surgery ,NSAID ,030220 oncology & carcinogenesis ,Non-Steroidal ,Cohort study ,colorectal Surgery, ileus, non-steroidal anti-inflammatory drugs ,medicine.medical_specialty ,Non‐steroidal anti‐inflammatory drugs. NSAIDs. Postoperative ileus. Colorectal surgery ,ACUTE KIDNEY INJURY ,anti-inflammatory agents ,03 medical and health sciences ,Internal medicine ,medicine ,Adverse effect ,non-steroidal anti-inflammatory drugs - ileus - colorectal surgery ,business.industry ,medicine.disease ,Settore MED/18 - Chirurgia Generale ,colorectal cancer ,Surgery ,business - Abstract
Ileus is common after elective colorectal surgery, and is associated with increased adverse events and prolonged hospital stay. The aim was to assess the role of non-steroidal anti-inflammatory drugs (NSAIDs) for reducing ileus after surgery.A prospective multicentre cohort study was delivered by an international, student- and trainee-led collaborative group. Adult patients undergoing elective colorectal resection between January and April 2018 were included. The primary outcome was time to gastrointestinal recovery, measured using a composite measure of bowel function and tolerance to oral intake. The impact of NSAIDs was explored using Cox regression analyses, including the results of a centre-specific survey of compliance to enhanced recovery principles. Secondary safety outcomes included anastomotic leak rate and acute kidney injury.A total of 4164 patients were included, with a median age of 68 (i.q.r. 57-75) years (54·9 per cent men). Some 1153 (27·7 per cent) received NSAIDs on postoperative days 1-3, of whom 1061 (92·0 per cent) received non-selective cyclo-oxygenase inhibitors. After adjustment for baseline differences, the mean time to gastrointestinal recovery did not differ significantly between patients who received NSAIDs and those who did not (4·6 versus 4·8 days; hazard ratio 1·04, 95 per cent c.i. 0·96 to 1·12; P = 0·360). There were no significant differences in anastomotic leak rate (5·4 versus 4·6 per cent; P = 0·349) or acute kidney injury (14·3 versus 13·8 per cent; P = 0·666) between the groups. Significantly fewer patients receiving NSAIDs required strong opioid analgesia (35·3 versus 56·7 per cent; P 0·001).NSAIDs did not reduce the time for gastrointestinal recovery after colorectal surgery, but they were safe and associated with reduced postoperative opioid requirement.El ileo es frecuente tras cirugía colorrectal electiva y se asocia con un incremento de los eventos adversos y de la duración de la estancia hospitalaria. El objetivo fue evaluar el papel de los fármacos antiinflamatorios no esteroideos (non-steroidal anti-inflammatory drugs, NSAIDs) para reducir el ileo tras la cirugía. MÉTODOS: Estudio de cohortes prospectivo y multicéntrico efecuado por un grupo colaborativo dirigido por estudiantes y cirujanos en formación. Se incluyeron pacientes adultos sometidos a cirugía colorectal electiva entre enero y abril 2018. El resultado primario fue el tiempo hasta la recuperaciòn gastrointestinal, medido por una variable compuesta de función intestinal y tolerancia a la alimentación oral. El impacto de los NSAIDs se exploró utilizando un análisis de regresión de Cox, que incluía los resultados de una encuesta específica dirigida a los centros sobre la adherencia a los principios de la recuperación intensificada. Los resultados secundarios de seguridad incluyeron la dehiscencia anastomótica y la insuficiencia renal aguda.Se incluyeron 4.164 pacientes con una mediana de edad de 68 años (rango intercuartílico: 57-75; 54,9% varones). Un total de 1.153 (27,7%) pacientes fueron tratados con NSAIDs en los días postoperarorios 1-3, de los cuales 1.061 (92,0%) recibieron inhibidores no selectivos de la ciclooxigenasa. Tras los ajustes por las diferencias basales, el tiempo medio hasta la recuperación gastrointestinal no difería significativamente entre pacientes que recibieron o no recibieron NSAIDs (4,6 versus 4,8 días; cociente de riesgos instantáneos, hazard ratio, HR 1,04, i.c. del 95%: 0,96-1,12, P = 0,360). No hubo diferencias significativas en la tasa de dehiscencias anastomóticas (5,4% versus 4,6%; P = 0,349) o insuficiencia renal aguda (14,3% versus 13,8%; P = 0,666) entre los grupos. Sin embargo, significativamente menos pacientes de los que recibieron NSAIDs precisaron una analgesia intensa con opioides (35,3% versus 56,7%; P 0,001). CONCLUSIÓN: La administración de NSAIDs no redujo el tiempo hasta la recuperación gastrointestinal tras cirugía colorrectal, pero fueron seguros y se asociaron con una reducción en la necesidad de opioides postoperarorios.
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- 2019
3. LEAVING A Legacy.
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Davis, Lt. Colonel Margaret
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CHRISTIAN women - Published
- 2022
4. No LIMITS.
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DAVIS, LT. COLONEL LESA
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KINGDOM of God ,MARCHING bands ,ZIP codes - Published
- 2023
5. The comparative effects of 0.5 and 1.0 minimum alveolar concentration concentrations of sevoflurane and desflurane on middle cerebral artery flow parameters using transcranial Doppler in patients undergoing surgery for supratentorial tumours
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Davis, Lt., additional and S., Manikandan, additional
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- 2016
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6. How We Do It
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Keith Cr and Davis Lt
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Philosophy ,medicine.medical_specialty ,Intermediary ,Public Health, Environmental and Occupational Health ,medicine ,Anxiety ,medicine.symptom ,Psychology ,Psychiatry ,Mental health ,Education - Published
- 1976
7. The Midwest Pioneer: His Ills, Cures, & Doctors
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Davis, Lt. Paul M., primary, Pickard, Madge E., additional, and Buley, R. Carlyle, additional
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- 1945
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8. The Effect of Intravenous Paraldehyde as Recorded by the Chest X-Ray Film
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GOLD, LT. JEROME A., primary, GARCIA, LT. ROBERT C., additional, and DAVIS, LT. JOHN W., additional
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- 1960
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9. The comparative effects of 0.5 and 1.0 minimum alveolar concentration concentrations of sevoflurane and desflurane on middle cerebral artery flow parameters using transcranial Doppler in patients undergoing surgery for supratentorial tumours
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Davis, Lt. Col. Josemine and S., Manikandan
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- 2016
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10. Direct-Acting Oral Anticoagulants and Potential Inconsistencies with FDA-Approved Dosing for Non-Valvular Atrial Fibrillation: A Retrospective Real-World Analysis Across Nine US Healthcare Systems.
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DeLor B, Glover JJ, Hartman TJ, Manzey LL, Ateya M, Kelsh S, Taylor K, Zemrak WR, Gowen JR, Parks A, Gust C, Medico C, Akpoji UC, Naylor S, Chou CW, Fakelmann G, Hart S, Wiethorn EE, Trinh T, Wilson WW, Bowen R, Stanton J, Duvall L, and Davis LT
- Abstract
Background: Direct-acting oral anticoagulants (DOACs) are recommended to reduce risk of stroke and systemic embolism in patients with non-valvular atrial fibrillation (NVAF). However, DOAC dosing inconsistent with FDA-approved product labels is common and associated with poor clinical outcomes., Objectives: Identify DOAC dosing inconsistent with FDA-approved product labels in ambulatory care patients with NVAF; identify variables associated with dosing lower and higher than label., Design: Retrospective analysis using electronic health records from nine US healthcare systems., Patients: Adults with NVAF receiving DOAC therapy in 2022., Main Measures: Rates of label-inconsistent dosing; multivariable regression analysis to identify demographic and clinical variables associated with dosing lower and higher than label., Key Results: Among 51,128 NVAF patients (56.1% male, 94.3% White, mean [SD] age 73.5 [10.5] years), 5008 (9.8%) were prescribed label-inconsistent doses of DOACs (6.8% lower and 3.0% higher than label). Age ≥ 75 years, renal impairment, and hypertension were significantly associated with inconsistent dosing both higher and lower than label. Female sex and higher weight were significantly associated with dosing lower than label, as were heart failure, vascular or liver disease, and bleeding history. Dosing higher than label was significantly associated with male sex, race (African American/Black), weight < 60 kg, and use of drugs with potential drug-drug interactions. When prescribed by primary care physicians, DOAC doses were 37% (95% CI, 27-49%) more likely to be lower than label and 30% (95% CI, 16-46%) more likely to be higher than label than when prescribed by cardiologists or electrophysiologists. Label-inconsistent dosing varied (6.7 to 15.8%) across participating systems., Conclusions: DOAC dosing inconsistent with label varied by demographics, clinical characteristics, prescriber specialty, and healthcare system, suggesting a need to monitor and assess dosing decisions in NVAF. Identification of variables associated with dosing inconsistencies may enable targeted interventions to ensure label-consistent dosing in vulnerable populations., (© 2024. The Author(s).)
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- 2024
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11. Cross-site reproducibility of human cortical organoids reveals consistent cell type composition and architecture.
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Glass MR, Waxman EA, Yamashita S, Lafferty M, Beltran AA, Farah T, Patel NK, Singla R, Matoba N, Ahmed S, Srivastava M, Drake E, Davis LT, Yeturi M, Sun K, Love MI, Hashimoto-Torii K, French DL, and Stein JL
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- Humans, Reproducibility of Results, Neurons metabolism, Neurons cytology, Cell Culture Techniques methods, Phenotype, Organoids cytology, Organoids metabolism, Induced Pluripotent Stem Cells cytology, Induced Pluripotent Stem Cells metabolism, Cell Differentiation, Cerebral Cortex cytology, Cerebral Cortex metabolism
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While guided human cortical organoid (hCO) protocols reproducibly generate cortical cell types at one site, variability in hCO phenotypes across sites using a harmonized protocol has not yet been evaluated. To determine the cross-site reproducibility of hCO differentiation, three independent research groups assayed hCOs in multiple differentiation replicates from one induced pluripotent stem cell (iPSC) line using a harmonized miniaturized spinning bioreactor protocol across 3 months. hCOs were mostly cortical progenitor and neuronal cell types in reproducible proportions that were consistently organized in cortical wall-like buds. Cross-site differences were detected in hCO size and expression of metabolism and cellular stress genes. Variability in hCO phenotypes correlated with stem cell gene expression prior to differentiation and technical factors associated with seeding, suggesting iPSC quality and treatment are important for differentiation outcomes. Cross-site reproducibility of hCO cell type proportions and organization encourages future prospective meta-analytic studies modeling neurodevelopmental disorders in hCOs., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)
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- 2024
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12. Distribution of Silent Cerebral Infarcts in Adults With Sickle Cell Disease.
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Jones RS, Ford AL, Donahue MJ, Fellah S, Davis LT, Pruthi S, Balamurugan C, Cohen R, Davis S, Debaun MR, Kassim AA, Rodeghier M, and Jordan LC
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- Humans, Male, Female, Adult, Young Adult, Cross-Sectional Studies, Middle Aged, Adolescent, Risk Factors, Brain diagnostic imaging, Brain pathology, Cerebrovascular Circulation physiology, Anemia, Sickle Cell complications, Anemia, Sickle Cell diagnostic imaging, Anemia, Sickle Cell epidemiology, Cerebral Infarction diagnostic imaging, Cerebral Infarction epidemiology, Cerebral Infarction etiology, Magnetic Resonance Imaging
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Background and Objectives: Previously we demonstrated that 90% of infarcts in children with sickle cell anemia occur in the border zone regions of cerebral blood flow (CBF). We tested the hypothesis that adults with sickle cell disease (SCD) have silent cerebral infarcts (SCIs) in the border zone regions, with a secondary hypothesis that older age and traditional stroke risk factors would be associated with infarct occurrence in regions outside the border zones., Methods: Adults with SCD 18-50 years of age were enrolled in a cross-sectional study at 2 centers and completed a 3T brain MRI. Participants with a history of overt stroke were excluded. Infarct masks were manually delineated on T2-fluid-attenuated inversion-recovery MRI and registered to the Montreal Neurological Institute 152 brain atlas to generate an infarct heatmap. Border zone regions between anterior, middle, and posterior cerebral arteries (ACA, MCA, and PCA) were quantified using the Digital 3D Brain MRI Arterial Territories Atlas, and logistic regression was applied to identify relationships between infarct distribution, demographics, and stroke risk factors., Results: Of 113 participants with SCD (median age 26.1 years, interquartile range [IQR] 21.6-31.4 years, 51% male), 56 (49.6%) had SCIs. Participants had a median of 5.5 infarcts (IQR 3.2-13.8). Analysis of infarct distribution showed that 350 of 644 infarcts (54.3%) were in 4 border zones of CBF and 294 (45.6%) were in non-border zone territories. More than 90% of infarcts were in 3 regions: the non-border zone ACA and MCA territories and the ACA-MCA border zone. Logistic regression showed that older participants have an increased chance of infarcts in the MCA territory (odds ratio [OR] 1.08; 95% CI 1.03-1.13; p = 0.001) and a decreased chance of infarcts in the ACA-MCA border zone (OR 0.94; 95% CI 0.90-0.97; p < 0.001). The presence of at least 1 stroke risk factor did not predict SCI location in any model., Discussion: When compared with children with SCD, in adults with SCD, older age is associated with expanded zones of tissue infarction that stretch beyond the traditional border zones of CBF, with more than 45% of infarcts in non-border zone regions.
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- 2024
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13. Cerebrovascular reactivity dispersion as a new biomarker of recent stroke symptomatology in moyamoya.
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Han C, Richerson WT, Garza M, Rodeghier M, Mishra M, Davis LT, Fusco M, Chitale R, Shiino S, Jordan LC, and Donahue MJ
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Background: Moyamoya disease (MMD) is a non-atherosclerotic intracranial steno-occlusive condition placing patients at high risk for ischemic stroke. Direct and indirect surgical revascularization can improve blood flow in MMD; however, randomized trials demonstrating efficacy have not been performed and biomarkers of parenchymal hemodynamic impairment are needed to triage patients for interventions and evaluate post-surgical efficacy. We test the hypothesis that hypercapnia-induced maximum cerebrovascular reactivity (CVR
MAX ) and the more novel indicator cerebrovascular reactivity (CVR) response time (CVRDELAY ), both assessed from time-regression analyses of non-invasive hypercapnic imaging, correlate with recent focal ischemic symptoms., Methods: Hypercapnic reactivity medical resonance imaging (blood oxygenation level-dependent; echo time=35ms; spatial resolution=3.5×3.5×3.5mm) and catheter angiography assessments of cortical reserve capacity and vascular patency, respectively, in MMD participants (n=73) were performed in sequence. Time regression analyses were applied to quantify CVRMAX and CVRDELAY . Symptomatology information for each hemisphere (n=109) was categorized into symptomatic (ischemic symptoms within six months) or asymptomatic (no history of ischemic symptoms) and logistic regression analysis assessed the association of CVR metrics with ischemic symptoms after controlling for age and sex., Results: Symptomatic hemispheres displayed lengthened CVRDELAY (p<0.001), which was more discriminatory between hemispheres than CVRMAX (p=0.037). CVRDELAY (p<0.001), but not CVRMAX (p=0.127), was found to be sensitively related to age in asymptomatic tissue (0.33-unit increase/year); age-dependent normative ranges are presented to enable quantitative assessment of patient-specific impairment. Furthermore, the area under the receiver operating characteristic curves shows that CVRDELAY predicts ischemic symptoms (p<0.001), whereas CVRMAX does not (p=0.056)., Conclusion: Findings support that CVR metrics are uniquely altered in hemispheres with recent ischemic symptoms, motivating the investigation of CVR as a surrogate of ischemic symptomatology and treatment efficacy.- Published
- 2024
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14. Cerebral hemodynamic changes after haploidentical hematopoietic stem cell transplant in adults with sickle cell disease.
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Aumann MA, Richerson W, Song AK, Davis LT, Pruthi S, Davis S, Patel NJ, Custer C, Kassim AA, DeBaun MR, Donahue MJ, and Jordan LC
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- Adult, Child, Humans, Young Adult, Bone Marrow Transplantation, Hemodynamics, Oxygen metabolism, Anemia, Sickle Cell therapy, Hematopoietic Stem Cell Transplantation adverse effects, Hematopoietic Stem Cell Transplantation methods
- Abstract
Abstract: Preliminary evidence from a series of 4 adults with sickle cell disease (SCD) suggests that hematopoietic stem cell transplant (HSCT) improves cerebral hemodynamics. HSCT largely normalizes cerebral hemodynamics in children with SCD. We tested the hypothesis in adults with SCD that cerebral blood flow (CBF), oxygen extraction fraction (OEF), and cerebral metabolic rate of oxygen (CMRO2) measured using magnetic resonance imaging, normalized to healthy values, comparing measurements from ∼1 month before to 12 to 24 months after HSCT (n = 11; age, 33.3 ± 8.9 years; 389 ± 150 days after HSCT) with age-, race- and sex-matched values from healthy adults without sickle trait (n = 28; age, 30.2 ± 5.6 years). Before transplant, 7 patients had neurological indications for transplant (eg, overt stroke) and 4 had nonneurological reasons for haploidentical bone marrow transplant (haplo-BMT). All received haplo-BMT from first-degree relatives (parent, sibling, or child donor) with reduced-intensity preparation and maintained engraftment. Before transplant, CBF was elevated (CBF, 69.11 ± 24.7 mL/100 g/min) compared with that of controls (P = .004). Mean CBF declined significantly after haplo-BMT (posttransplant CBF, 48.2 ± 13.9 mL/100 g/min; P = .003). OEF was not different from that of controls at baseline and did not change significantly after haplo-BMT (pretransplant, 43.1 ± 6.7%; posttransplant, 39.6 ± 7.0%; P = .34). After transplant, CBF and OEF were not significantly different from controls (CBF, 48.2 ± 13.4 mL/100 g/min; P = .78; and OEF, 39.6 ± 7.0%; P > .99). CMRO2 did not change significantly after haplo-BMT (pretransplant, 3.18 ± 0.87 mL O2/100 g/min; posttransplant, 2.95 ± 0.83; P = .56). Major complications of haplo-BMT included 1 infection-related death and 1 severe chronic graft-versus-host disease. Haplo-BMT in adults with SCD reduces CBF to that of control values and maintains OEF and CMRO2 on average at levels observed in healthy adult controls. The trial was registered at www.clinicaltrials.gov as #NCT01850108., (© 2024 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)
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- 2024
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15. Multivariate lesion symptom mapping for predicting trajectories of recovery from aphasia.
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Levy DF, Entrup JL, Schneck SM, Onuscheck CF, Rahman M, Kasdan A, Casilio M, Willey E, Davis LT, de Riesthal M, Kirshner HS, and Wilson SM
- Abstract
Individuals with post-stroke aphasia tend to recover their language to some extent; however, it remains challenging to reliably predict the nature and extent of recovery that will occur in the long term. The aim of this study was to quantitatively predict language outcomes in the first year of recovery from aphasia across multiple domains of language and at multiple timepoints post-stroke. We recruited 217 patients with aphasia following acute left hemisphere ischaemic or haemorrhagic stroke and evaluated their speech and language function using the Quick Aphasia Battery acutely and then acquired longitudinal follow-up data at up to three timepoints post-stroke: 1 month ( n = 102), 3 months ( n = 98) and 1 year ( n = 74). We used support vector regression to predict language outcomes at each timepoint using acute clinical imaging data, demographic variables and initial aphasia severity as input. We found that ∼60% of the variance in long-term (1 year) aphasia severity could be predicted using these models, with detailed information about lesion location importantly contributing to these predictions. Predictions at the 1- and 3-month timepoints were somewhat less accurate based on lesion location alone, but reached comparable accuracy to predictions at the 1-year timepoint when initial aphasia severity was included in the models. Specific subdomains of language besides overall severity were predicted with varying but often similar degrees of accuracy. Our findings demonstrate the feasibility of using support vector regression models with leave-one-out cross-validation to make personalized predictions about long-term recovery from aphasia and provide a valuable neuroanatomical baseline upon which to build future models incorporating information beyond neuroanatomical and demographic predictors., Competing Interests: The authors report no competing interests., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain.)
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- 2024
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16. Choroid plexus vascular reactivity in moyamoya: Implications for choroid plexus regulation in ischemic stress.
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Han C, Waddle S, Garza M, Davis LT, Eisma JJ, Richerson WT, Fusco M, Chitale R, Custer C, McKnight CD, Jordan LC, and Donahue MJ
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- Humans, Choroid Plexus diagnostic imaging, Constriction, Pathologic, Ischemia, Hyperemia, Moyamoya Disease diagnostic imaging, Cerebrovascular Disorders
- Abstract
Background and Purpose: Choroid plexus (ChP) hyperemia has been observed in patients with intracranial vasculopathy and to reduce following successful surgical revascularization. This observation may be attributable to impaired vascular reserve of the ChP or other factors, such as the ChP responding to circulating markers of stress. We extend this work to test the hypothesis that vascular reserve of the ChP is unrelated to intracranial vasculopathy., Methods: We performed hypercapnic reactivity (blood oxygenation level-dependent; echo time = 35 ms; spatial resolution = 3.5 × 3.5 × 3.5 mm, repetition time = 2000 ms) and catheter angiography assessments of ChP reserve capacity and vascular patency in moyamoya patients (n = 53) with and without prior surgical revascularization. Time regression analyses quantified maximum cerebrovascular reactivity and reactivity delay time in ChP and cortical flow territories of major intracranial vessels with steno-occlusion graded as <70%, 70%-99%, and occlusion using Warfarin-Aspirin-Symptomatic-Intracranial-Disease stenosis grading criteria. Analysis of variance (significance: two-sided Bonferroni-corrected p < .05) was applied to evaluate cortical and ChP reactivity, after accounting for end-tidal carbon dioxide change, for differing vasculopathy categories., Results: In patients without prior revascularization, arterial vasculopathy was associated with reduced cortical reactivity and lengthened reactivity delay (p ≤ .01), as expected. Regardless of surgical history, the ChP reactivity metrics were not significantly related to the degree of proximal stenosis, consistent with ChP reactivity being largely preserved in this population., Conclusions: Findings are consistent with ChP reactivity in moyamoya not being dependent on observed vasculopathy. Future work may investigate the extent to which ChP hyperemia in chronic ischemia reflects circulating markers of glial or ischemic stress., (© 2023 American Society of Neuroimaging.)
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- 2024
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17. Leukoaraiosis Is Not Associated With Recovery From Aphasia in the First Year After Stroke.
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Brito AC, Levy DF, Schneck SM, Entrup JL, Onuscheck CF, Casilio M, de Riesthal M, Davis LT, and Wilson SM
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After a stroke, individuals with aphasia often recover to a certain extent over time. This recovery process may be dependent on the health of surviving brain regions. Leukoaraiosis (white matter hyperintensities on MRI reflecting cerebral small vessel disease) is one indication of compromised brain health and is associated with cognitive and motor impairment. Previous studies have suggested that leukoaraiosis may be a clinically relevant predictor of aphasia outcomes and recovery, although findings have been inconsistent. We investigated the relationship between leukoaraiosis and aphasia in the first year after stroke. We recruited 267 patients with acute left hemispheric stroke and coincident fluid attenuated inversion recovery MRI. Patients were evaluated for aphasia within 5 days of stroke, and 174 patients presented with aphasia acutely. Of these, 84 patients were evaluated at ∼3 months post-stroke or later to assess longer-term speech and language outcomes. Multivariable regression models were fit to the data to identify any relationships between leukoaraiosis and initial aphasia severity, extent of recovery, or longer-term aphasia severity. We found that leukoaraiosis was present to varying degrees in 90% of patients. However, leukoaraiosis did not predict initial aphasia severity, aphasia recovery, or longer-term aphasia severity. The lack of any relationship between leukoaraiosis severity and aphasia recovery may reflect the anatomical distribution of cerebral small vessel disease, which is largely medial to the white matter pathways that are critical for speech and language function., (© 2023 Massachusetts Institute of Technology.)
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- 2023
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18. Blood Pressure Management After Endovascular Therapy for Acute Ischemic Stroke: The BEST-II Randomized Clinical Trial.
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Mistry EA, Hart KW, Davis LT, Gao Y, Prestigiacomo CJ, Mittal S, Mehta T, LaFever H, Harker P, Wilson-Perez HE, Beasley KA, Krothapalli N, Lippincott E, Stefek H, Froehler M, Chitale R, Fusco M, Grossman A, Shirani P, Smith M, Jaffa MN, Yeatts SD, Albers GW, Wanderer JP, Tolles J, Lindsell CJ, Lewis RJ, Bernard GR, and Khatri P
- Subjects
- Aged, Female, Humans, Hypotension, Infarction, Stroke surgery, Acute Disease, Male, Middle Aged, Aged, 80 and over, Systole, Blood Pressure drug effects, Endovascular Procedures, Ischemic Stroke drug therapy, Ischemic Stroke surgery, Hypertension drug therapy, Antihypertensive Agents administration & dosage, Antihypertensive Agents pharmacology, Antihypertensive Agents therapeutic use, Brain Infarction diagnostic imaging, Brain Infarction drug therapy, Brain Infarction surgery
- Abstract
Importance: The effects of moderate systolic blood pressure (SBP) lowering after successful recanalization with endovascular therapy for acute ischemic stroke are uncertain., Objective: To determine the futility of lower SBP targets after endovascular therapy (<140 mm Hg or 160 mm Hg) compared with a higher target (≤180 mm Hg)., Design, Setting, and Participants: Randomized, open-label, blinded end point, phase 2, futility clinical trial that enrolled 120 patients with acute ischemic stroke who had undergone successful endovascular therapy at 3 US comprehensive stroke centers from January 2020 to March 2022 (final follow-up, June 2022)., Intervention: After undergoing endovascular therapy, participants were randomized to 1 of 3 SBP targets: 40 to less than 140 mm Hg, 40 to less than 160 mm Hg, and 40 to 180 mm Hg or less (guideline recommended) group, initiated within 60 minutes of recanalization and maintained for 24 hours., Main Outcomes and Measures: Prespecified multiple primary outcomes for the primary futility analysis were follow-up infarct volume measured at 36 (±12) hours and utility-weighted modified Rankin Scale (mRS) score (range, 0 [worst] to 1 [best]) at 90 (±14) days. Linear regression models were used to test the harm-futility boundaries of a 10-mL increase (slope of 0.5) in the follow-up infarct volume or a 0.10 decrease (slope of -0.005) in the utility-weighted mRS score with each 20-mm Hg SBP target reduction after endovascular therapy (1-sided α = .05). Additional prespecified futility criterion was a less than 25% predicted probability of success for a future 2-group, superiority trial comparing SBP targets of the low- and mid-thresholds with the high-threshold (maximum sample size, 1500 with respect to the utility-weighted mRS score outcome)., Results: Among 120 patients randomized (mean [SD] age, 69.6 [14.5] years; 69 females [58%]), 113 (94.2%) completed the trial. The mean follow-up infarct volume was 32.4 mL (95% CI, 18.0 to 46.7 mL) for the less than 140-mm Hg group, 50.7 mL (95% CI, 33.7 to 67.7 mL), for the less than 160-mm Hg group, and 46.4 mL (95% CI, 24.5 to 68.2 mL) for the 180-mm Hg or less group. The mean utility-weighted mRS score was 0.51 (95% CI, 0.38 to 0.63) for the less than 140-mm Hg group, 0.47 (95% CI, 0.35 to 0.60) for the less than 160-mm Hg group, and 0.58 (95% CI, 0.46 to 0.71) for the high-target group. The slope of the follow-up infarct volume for each mm Hg decrease in the SBP target, adjusted for the baseline Alberta Stroke Program Early CT score, was -0.29 (95% CI, -0.81 to ∞; futility P = .99). The slope of the utility-weighted mRS score for each mm Hg decrease in the SBP target after endovascular therapy, adjusted for baseline utility-weighted mRS score, was -0.0019 (95% CI, -∞ to 0.0017; futility P = .93). Comparing the high-target SBP group with the lower-target groups, the predicted probability of success for a future trial was 25% for the less than 140-mm Hg group and 14% for the 160-mm Hg group., Conclusions and Relevance: Among patients with acute ischemic stroke, lower SBP targets less than either 140 mm Hg or 160 mm Hg after successful endovascular therapy did not meet prespecified criteria for futility compared with an SBP target of 180 mm Hg or less. However, the findings suggested a low probability of benefit from lower SBP targets after endovascular therapy if tested in a future larger trial., Trial Registration: ClinicalTrials.gov Identifier: NCT04116112.
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- 2023
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19. Cross-site reproducibility of human cortical organoids reveals consistent cell type composition and architecture.
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Glass MR, Waxman EA, Yamashita S, Lafferty M, Beltran A, Farah T, Patel NK, Matoba N, Ahmed S, Srivastava M, Drake E, Davis LT, Yeturi M, Sun K, Love MI, Hashimoto-Torii K, French DL, and Stein JL
- Abstract
Background: Reproducibility of human cortical organoid (hCO) phenotypes remains a concern for modeling neurodevelopmental disorders. While guided hCO protocols reproducibly generate cortical cell types in multiple cell lines at one site, variability across sites using a harmonized protocol has not yet been evaluated. We present an hCO cross-site reproducibility study examining multiple phenotypes., Methods: Three independent research groups generated hCOs from one induced pluripotent stem cell (iPSC) line using a harmonized miniaturized spinning bioreactor protocol. scRNA-seq, 3D fluorescent imaging, phase contrast imaging, qPCR, and flow cytometry were used to characterize the 3 month differentiations across sites., Results: In all sites, hCOs were mostly cortical progenitor and neuronal cell types in reproducible proportions with moderate to high fidelity to the in vivo brain that were consistently organized in cortical wall-like buds. Cross-site differences were detected in hCO size and morphology. Differential gene expression showed differences in metabolism and cellular stress across sites. Although iPSC culture conditions were consistent and iPSCs remained undifferentiated, primed stem cell marker expression prior to differentiation correlated with cell type proportions in hCOs., Conclusions: We identified hCO phenotypes that are reproducible across sites using a harmonized differentiation protocol. Previously described limitations of hCO models were also reproduced including off-target differentiations, necrotic cores, and cellular stress. Improving our understanding of how stem cell states influence early hCO cell types may increase reliability of hCO differentiations. Cross-site reproducibility of hCO cell type proportions and organization lays the foundation for future collaborative prospective meta-analytic studies modeling neurodevelopmental disorders in hCOs.
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- 2023
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20. Vascular space occupancy asymmetric spin echo (VASO-ASE) for non-invasive quantification of cerebral oxygen extraction fraction.
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Waddle SL, Garza M, Ying C, Davis LT, Jordan LC, An H, and Donahue MJ
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- Adult, Humans, Male, Female, Animals, Cattle, Young Adult, Heart Rate, Brain diagnostic imaging, Brain blood supply, Cerebrovascular Circulation, Oxygen Consumption, Oxygen, Magnetic Resonance Imaging methods
- Abstract
Purpose: Asymmetric spin echo (ASE) MRI is a method for measuring regional oxygen extraction fraction (OEF); however, extravascular tissue models have been shown to under-estimate OEF. The hypothesis investigated here is that the addition of a vascular-space-occupancy (VASO) pre-pulse will more fully suppress blood water signal and provide global OEF values more consistent with physiological expectation and
15 O positron emission tomography (PET)-validated T2 -relaxation-under-spin-tagging (TRUST) OEF measures., Methods: Healthy adults (n = 14; age = 27.7 ± 5.2 y; sex = 7/7 male/female) were scanned at 3.0T. Multi-echo ASE without inter-readout refocusing (ASERF- ), multi-echo ASE with inter-readout refocusing (ASERF+ ), and single-echo VASO-ASE were acquired twice each with common spatial resolution = 3.44 × 3.44 × 3.0 mm and τ = 0-20 ms (interval = 0.5 ms). TRUST was acquired twice sequentially for independent global OEF assessment (τCPMG = 10 ms; effective TEs = 0, 40, 80, and 160 ms; spatial resolution = 3.4 × 3.4 × 5 mm). OEF intraclass-correlation-coefficients (ICC), summary statistics, and group-wise differences were assessed (Wilcoxon rank-sum; significance: two-sided p < 0.05)., Results: ASERF+ (OEF = 36.8 ± 1.9%) and VASO-ASE (OEF = 34.4 ± 2.3%) produced OEF values similar to TRUST (OEF = 36.5 ± 4.6%, human calibration model; OEF = 32.7 ± 4.9%, bovine calibration model); however, ASERF- yielded lower OEF (OEF = 26.1 ± 1.0%; p < 0.01) relative to TRUST. VASO-ASE (ICC = 0.61) yielded lower ICC compared to other ASE variants (ICC >0.89)., Conclusion: VASO-ASE and TRUST provide similar OEF values; however, VASO-ASE spatial coverage and repeatability improvements are required., (© 2023 International Society for Magnetic Resonance in Medicine.)- Published
- 2023
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21. Enlarged perivascular space burden associations with arterial stiffness and cognition.
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Bown CW, Khan OA, Liu D, Remedios SW, Pechman KR, Terry JG, Nair S, Davis LT, Landman BA, Gifford KA, Hohman TJ, Carr JJ, and Jefferson AL
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- Humans, Cross-Sectional Studies, Cognition, Brain diagnostic imaging, Magnetic Resonance Imaging, Vascular Stiffness, Glymphatic System
- Abstract
Enlarged perivascular spaces (ePVS) are difficult to quantify, and their etiologies and consequences are poorly understood. Vanderbilt Memory and Aging Project participants (n = 327, 73 ± 7 years) completed 3T brain MRI to quantify ePVS volume and count, longitudinal neuropsychological assessment, and cardiac MRI to quantify aortic stiffness. Linear regressions related (1) PWV to ePVS burden and (2) ePVS burden to cross-sectional and longitudinal neuropsychological performance adjusting for key demographic and medical factors. Higher aortic stiffness related to greater basal ganglia ePVS volume (β = 7.0×10
-5 , p = 0.04). Higher baseline ePVS volume was associated with worse baseline information processing (β = -974, p = 0.003), executive function (β = -81.9, p < 0.001), and visuospatial performances (β = -192, p = 0.02) and worse longitudinal language (β = -54.9, p = 0.05), information processing (β = -147, p = 0.03), executive function (β = -10.9, p = 0.03), and episodic memory performances (β = -10.6, p = 0.02). Results were similar for ePVS count. Greater arterial stiffness relates to worse basal ganglia ePVS burden, suggesting cardiovascular aging as an etiology. ePVS burden is associated with adverse cognitive trajectory, emphasizing the clinical relevance of ePVS., (Copyright © 2022 Elsevier Inc. All rights reserved.)- Published
- 2023
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22. Silent infarction in sickle cell disease is associated with brain volume loss in excess of infarct volume.
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Jones RS, Donahue MJ, Davis LT, Pruthi S, Waddle SL, Custer C, Patel NJ, DeBaun MR, Kassim AA, Rodeghier M, and Jordan LC
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Introduction: Sickle cell disease (SCD) increases cerebral infarct risk, but reported effects on brain volume have varied. More detailed information using larger cohorts and contemporary methods could motivate the use of longitudinal brain volume assessment in SCD as an automated marker of disease stability or future progression. The purpose of this study was to rigorously evaluate whether children and young adults with SCD have reduced gray matter volume (GMV) and white matter volume (WMV) compared to healthy controls using high-resolution MRI. We tested the hypotheses that (i) elevated CBF, a marker of cerebral hemodynamic compensation in SCD, is associated with global and regional brain atrophy, and (ii) silent cerebral infarct burden is associated with brain atrophy in excess of infarct volume., Methods: Healthy controls ( n = 49) and SCD participants without overt stroke ( n = 88) aged 7-32 years completed 3 T brain MRI; pseudocontinuous arterial spin labeling measured CBF. Multivariable linear regressions assessed associations of independent variables with GMV, WMV, and volumes of cortical/subcortical regions., Results: Reduced hemoglobin was associated with reductions in both GMV ( p = 0.032) and WMV ( p = 0.005); reduced arterial oxygen content (CaO
2 ) was also associated with reductions in GMV ( p = 0.035) and WMV ( p = 0.006). Elevated gray matter CBF was associated with reduced WMV ( p = 0.018). Infarct burden was associated with reductions in WMV 30-fold greater than the infarct volume itself ( p = 0.005). Increased GM CBF correlated with volumetric reductions of the insula and left and right caudate nuclei ( p = 0.017, 0.017, 0.036, respectively). Infarct burden was associated with reduced left and right nucleus accumbens, right thalamus, and anterior corpus callosum volumes ( p = 0.002, 0.002, 0.009, 0.002, respectively)., Discussion: We demonstrate that anemia and decreased CaO2 are associated with reductions in GMV and WMV in SCD. Increased CBF and infarct burden were also associated with reduced volume in subcortical structures. Global WMV deficits associated with infarct burden far exceed infarct volume itself. Hemodynamic compensation via increased cerebral blood flow in SCD seems inadequate to prevent brain volume loss. Our work highlights that silent cerebral infarcts are just a portion of the brain injury that occurs in SCD; brain volume is another potential biomarker of brain injury in SCD., Competing Interests: MJD is a paid consultant for Global Blood Therapeutics, receives advisory board receives research-related support from Philips North America, and is the CEO of Biosight LLC, which provides healthcare technology consulting services. These agreements have been approved by Vanderbilt University Medical Center in accordance with its conflict-of-interest policy. MR is an independent statistical consultant. He owns Rodeghier Consulting, Chicago, IL, United States. He was paid for his work on this manuscript via NIH grant funding. MRD and his institution are the sponsor of two externally funded research investigator-initiated projects. Global Blood Therapeutics will provide funding for the cost of these clinical studies but will not be a cosponsor of either study. MRD is not receiving any compensation for the conduct of these two-investigator initiated observational studies. MRD is a member of the Global Blood Therapeutics advisory board for a proposed randomized controlled trial for which he receives compensation. MRD is the steering committee for a Novartis-sponsored phase 2 trial to prevent priapism in men. MRD was a medical advisor for the development of the CTX001 Early Economic Model. MRD provided medical input on the economic model as part of an expert reference group for Vertex/CRISPR CTX001 Early Economic Model in 2020. MRD provided a onetime consultation to the Forma Pharmaceutical company about sickle cell disease in 2021. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Jones, Donahue, Davis, Pruthi, Waddle, Custer, Patel, DeBaun, Kassim, Rodeghier and Jordan.)- Published
- 2023
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23. Recovery from aphasia in the first year after stroke.
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Wilson SM, Entrup JL, Schneck SM, Onuscheck CF, Levy DF, Rahman M, Willey E, Casilio M, Yen M, Brito AC, Kam W, Davis LT, de Riesthal M, and Kirshner HS
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- Humans, Temporal Lobe pathology, Speech, Language, Magnetic Resonance Imaging, Aphasia pathology, Stroke
- Abstract
Most individuals who experience aphasia after a stroke recover to some extent, with the majority of gains taking place in the first year. The nature and time course of this recovery process is only partially understood, especially its dependence on lesion location and extent, which are the most important determinants of outcome. The aim of this study was to provide a comprehensive description of patterns of recovery from aphasia in the first year after stroke. We recruited 334 patients with acute left hemisphere supratentorial ischaemic or haemorrhagic stroke and evaluated their speech and language function within 5 days using the Quick Aphasia Battery (QAB). At this initial time point, 218 patients presented with aphasia. Individuals with aphasia were followed longitudinally, with follow-up evaluations of speech and language at 1 month, 3 months, and 1 year post-stroke, wherever possible. Lesions were manually delineated based on acute clinical MRI or CT imaging. Patients with and without aphasia were divided into 13 groups of individuals with similar, commonly occurring patterns of brain damage. Trajectories of recovery were then investigated as a function of group (i.e. lesion location and extent) and speech/language domain (overall language function, word comprehension, sentence comprehension, word finding, grammatical construction, phonological encoding, speech motor programming, speech motor execution, and reading). We found that aphasia is dynamic, multidimensional, and gradated, with little explanatory role for aphasia subtypes or binary concepts such as fluency. Patients with circumscribed frontal lesions recovered well, consistent with some previous observations. More surprisingly, most patients with larger frontal lesions extending into the parietal or temporal lobes also recovered well, as did patients with relatively circumscribed temporal, temporoparietal, or parietal lesions. Persistent moderate or severe deficits were common only in patients with extensive damage throughout the middle cerebral artery distribution or extensive temporoparietal damage. There were striking differences between speech/language domains in their rates of recovery and relationships to overall language function, suggesting that specific domains differ in the extent to which they are redundantly represented throughout the language network, as opposed to depending on specialized cortical substrates. Our findings have an immediate clinical application in that they will enable clinicians to estimate the likely course of recovery for individual patients, as well as the uncertainty of these predictions, based on acutely observable neurological factors., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
- Published
- 2023
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24. R 1ρ dispersion in white matter correlates with quantitative metrics of cognitive impairment.
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Adelnia F, Davis LT, Acosta LM, Puckett A, Wang F, Zu Z, Harkins KD, and Gore JC
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- Aged, Humans, Cross-Sectional Studies, Magnetic Resonance Imaging, Middle Aged, Aged, 80 and over, Alzheimer Disease pathology, Cognitive Dysfunction, White Matter pathology
- Abstract
Much previous neuroimaging research in Alzheimer
' s disease has focused on the roles of amyloid and tau proteins, but recent studies have implicated microvascular changes in white matter as early indicators of damage related to later dementia. We used MRI to derive novel, non-invasive measurements of R1ρ dispersion using different locking fields to characterize variations of microvascular structure and integrity in brain tissues. We developed a non-invasive 3D R1ρ dispersion imaging technique using different locking fields at 3T. We acquired MR images and cognitive assessments of participants with mild cognitive impairment (MCI) and compared them to age-matched healthy controls in a cross-sectional study. After providing informed consent, 40 adults aged 62 to 82 years (n = 17 MCI) were included in this study. White matter ΔR1ρ -fraction measured by R1ρ dispersion imaging showed a strong correlation with the cognitive status of older adults (βstd = -0.4, p-value < 0.01) independent of age, in contrast to other conventional MRI markers such as T2 , R1ρ , and white matter hyperintense lesion volume (WMHs) measured with T2 -FLAIR. The correlation of WMHs with cognitive status was no longer significant after adjusting for age and sex in linear regression analysis, and the size of the regression coefficient was substantially decreased (53% lower). This work establishes a new non-invasive method that potentially characterizes impairment of the microvascular structure of white matter in MCI patients compared to healthy controls. The application of this method in longitudinal studies would improve our fundamental understanding of the pathophysiologic changes that accompany abnormal cognitive decline with aging and help identify potential targets for treatment of Alzheimer's disease., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)- Published
- 2023
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25. Presurgical Magnetic Resonance Imaging Indicators of Revascularization Response in Adults With Moyamoya Vasculopathy.
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L Waddle S, Garza M, Davis LT, V Chitale R, R Fusco M, A Lee C, Patel NJ, Kang H, Jordan LC, and Donahue MJ
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- Adult, Angiography, Digital Subtraction, Cerebrovascular Circulation physiology, Female, Humans, Magnetic Resonance Imaging methods, Middle Aged, Middle Cerebral Artery diagnostic imaging, Middle Cerebral Artery surgery, Prospective Studies, Cerebral Revascularization methods, Moyamoya Disease diagnostic imaging, Moyamoya Disease surgery
- Abstract
Background: Moyamoya is a progressive intracranial vasculopathy, primarily affecting distal segments of the internal carotid and middle cerebral arteries. Treatment may comprise angiogenesis-inducing surgical revascularization; however, lack of randomized trials often results in subjective treatment decisions., Hypothesis: Compensatory presurgical posterior vertebrobasilar artery (VBA) flow-territory reactivity, including greater cerebrovascular reactivity (CVR) and reduced vascular delay time, portends greater neoangiogenic response verified on digital subtraction angiography (DSA) at 1-year follow-up., Study Type: Prospective intervention cohort., Subjects: Thirty-one patients with moyamoya (26 females; age = 45 ± 13 years; 41 revascularized hemispheres)., Methods: Anatomical MRI, hypercapnic CVR MRI, and DSA acquired presurgically in adult moyamoya participants scheduled for clinically indicated surgical revascularization. One-year postsurgery, DSA was repeated to evaluate collateralization., Field Strength: 3 T., Sequence: Hypercapnic T 2 * -weighted gradient-echo blood-oxygenation-level-dependent, T
2 -weighted turbo-spin-echo fluid-attenuated-inversion-recovery, T1 -weighted magnetization-prepared-rapid-gradient-echo, and T2 -weighted diffusion-weighted-imaging., Assessment: Presurgical maximum CVR and response times were evaluated in VBA flow-territories. Revascularization success was determined using an ordinal scoring system of neoangiogenic collateralization from postsurgical DSA by two cerebrovascular neurosurgeons (R.V.C. with 8 years of experience; M.R.F. with 9 years of experience) and one neuroradiologist (L.T.D. with 8 years of experience). Stroke risk factors (age, sex, race, vasculopathy, and diabetes) were recorded., Statistical Tests: Fisher's exact and Wilcoxon rank-sum tests were applied to compare presurgical variables between cohorts with angiographically confirmed good (>1/3 middle cerebral artery [MCA] territory revascularized) vs. poor (<1/3 MCA territory revascularized) outcomes., Significance: two-sided P < 0.05. Normalized odds ratios (ORs) were calculated., Results: Criteria for good collateralization were met in 25 of the 41 revascularized hemispheres. Presurgical normalized VBA flow-territory CVR was significantly higher in those with good (1.12 ± 0.13 unitless) vs. poor (1.04 ± 0.05 unitless) outcomes. Younger (OR = -0.60 ± 0.67) and White (OR = -1.81 ± 1.40) participants had highest revascularization success (good outcomes: age = 42 ± 14 years, race = 84% White; poor outcomes: age = 49 ± 11 years, race = 44% White)., Data Conclusion: Presurgical MRI-measures of VBA flow-territory CVR are highest in moyamoya participants with better angiographic responses to surgical revascularization., Level of Evidence: 1 TECHNICAL EFFICACY STAGE: 4., (© 2022 International Society for Magnetic Resonance in Medicine.)- Published
- 2022
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26. Rapid Response to the Acute Iodinated Contrast Shortage During the COVID-19 Pandemic: Single-Institution Experience.
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Allen LM, Shechtel J, Frederick-Dyer K, Davis LT, Stokes LS, Savoie B, Pruthi S, Henry C, Allen S, Frazier SR, and Omary RA
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- Contrast Media, Humans, Pandemics, SARS-CoV-2, COVID-19
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- 2022
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27. Elevated Aortic Pulse Wave Velocity Relates to Longitudinal Gray and White Matter Changes.
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Bown CW, Khan OA, Moore EE, Liu D, Pechman KR, Cambronero FE, Terry JG, Nair S, Davis LT, Gifford KA, Landman BA, Hohman TJ, Carr JJ, and Jefferson AL
- Subjects
- Aged, Aging physiology, Alzheimer Disease diagnosis, Aorta, Thoracic diagnostic imaging, Female, Follow-Up Studies, Gray Matter physiopathology, Humans, Male, Pulse Wave Analysis, Retrospective Studies, Time Factors, Vascular Stiffness, White Matter physiopathology, Alzheimer Disease physiopathology, Aorta, Thoracic physiopathology, Blood Flow Velocity physiology, Cognition physiology, Gray Matter diagnostic imaging, Magnetic Resonance Imaging methods, White Matter diagnostic imaging
- Abstract
Objective: To determine whether baseline aortic stiffness, measured by aortic pulse wave velocity (PWV), relates to longitudinal cerebral gray or white matter changes among older adults. Baseline cardiac magnetic resonance imaging will be used to assess aortic PWV while brain magnetic resonance imaging will be used to assess gray matter and white matter hyperintensity (WMH) volumes at baseline, 18 months, 3 years, 5 years, and 7 years. Approach and Results: Aortic PWV (m/s) was quantified from cardiac magnetic resonance. Multimodal 3T brain magnetic resonance imaging included T
1 -weighted imaging for quantifying gray matter volumes and T2 -weighted fluid-attenuated inversion recovery imaging for quantifying WMHs. Mixed-effects regression models related baseline aortic PWV to longitudinal gray matter volumes (total, frontal, parietal, temporal, occipital, hippocampal, and inferior lateral ventricle) and WMH volumes (total, frontal, parietal, temporal, and occipital) adjusting for age, sex, race/ethnicity, education, cognitive diagnosis, Framingham stroke risk profile, APOE (apolipoprotein E)-ε4 carrier status, and intracranial volume. Two hundred seventy-eight participants (73±7 years, 58% male, 87% self-identified as non-Hispanic White, 159 with normal cognition, and 119 with mild cognitive impairment) from the Vanderbilt Memory & Aging Project (n=335) were followed on average for 4.9±1.6 years with PWV measurements occurring from September 2012 to November 2014 and longitudinal brain magnetic resonance imaging measurements occurring from September 2012 to June 2021. Higher baseline aortic PWV was related to greater decrease in hippocampal (β=-3.6 [mm3 /y]/[m/s]; [95% CI, -7.2 to -0.02] P =0.049) and occipital lobe (β=-34.2 [mm3 /y]/[m/s]; [95% CI, -67.8 to -0.55] P =0.046) gray matter volume over time. Higher baseline aortic PWV was related to greater increase in WMH volume over time in the temporal lobe (β=17.0 [mm3 /y]/[m/s]; [95% CI, 7.2-26.9] P <0.001). All associations may be driven by outliers., Conclusions: In older adults, higher baseline aortic PWV related to greater decrease in gray matter volume and greater increase in WMHs over time. Because of unmet cerebral metabolic demands and microvascular remodeling, arterial stiffening may preferentially affect certain highly active brain regions like the temporal lobes. These same regions are affected early in the course of Alzheimer disease.- Published
- 2021
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28. Choroid plexus perfusion in sickle cell disease and moyamoya vasculopathy: Implications for glymphatic flow.
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Johnson SE, McKnight CD, Jordan LC, Claassen DO, Waddle S, Lee C, Garza M, Patel NJ, Davis LT, Pruthi S, Trujillo P, Chitale R, Fusco M, and Donahue MJ
- Subjects
- Adult, Female, Humans, Male, Anemia, Sickle Cell physiopathology, Choroid Plexus physiopathology, Glymphatic System physiopathology, Moyamoya Disease physiopathology, Vascular Diseases physiopathology
- Abstract
Cerebrospinal fluid (CSF) and interstitial fluid exchange have been shown to increase following pharmacologically-manipulated increases in cerebral arterial pulsatility, consistent with arterial pulsatility improving CSF circulation along perivascular glymphatic pathways. The choroid plexus (CP) complexes produce CSF, and CP activity may provide a centralized indicator of perivascular flow. We tested the primary hypothesis that elevated cortical cerebral blood volume and flow, present in sickle cell disease (SCD), is associated with fractionally-reduced CP perfusion relative to healthy adults, and the supplementary hypothesis that reduced arterial patency, present in moyamoya vasculopathy, is associated with elevated fractional CP perfusion relative to healthy adults. Participants (n = 75) provided informed consent and were scanned using a 3-Tesla arterial-spin-labeling MRI sequence for CP and cerebral gray matter (GM) perfusion quantification. ANOVA was used to calculate differences in CP-to-GM perfusion ratios between groups, and regression analyses applied to evaluate the dependence of the CP-to-GM perfusion ratio on group after co-varying for age and sex. ANOVA yielded significant (p < 0.001) group differences, with CP-to-GM perfusion ratios increasing between SCD (ratio = 0.93 ± 0.28), healthy (ratio = 1.04 ± 0.32), and moyamoya (ratio = 1.29 ± 0.32) participants, which was also consistent with regression analyses. Findings are consistent with CP perfusion being inversely associated with cortical perfusion.
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- 2021
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29. Comparison of convolutional neural networks for detecting large vessel occlusion on computed tomography angiography.
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Remedios LW, Lingam S, Remedios SW, Gao R, Clark SW, Davis LT, and Landman BA
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- Artificial Intelligence, Computed Tomography Angiography, Humans, Neural Networks, Computer, Brain Ischemia, Stroke diagnostic imaging
- Abstract
Purpose: Artificial intelligence diagnosis and triage of large vessel occlusion may quicken clinical response for a subset of time-sensitive acute ischemic stroke patients, improving outcomes. Differences in architectural elements within data-driven convolutional neural network (CNN) models impact performance. Foreknowledge of effective model architectural elements for domain-specific problems can narrow the search for candidate models and inform strategic model design and adaptation to optimize performance on available data. Here, we study CNN architectures with a range of learnable parameters and which span the inclusion of architectural elements, such as parallel processing branches and residual connections with varying methods of recombining residual information., Methods: We compare five CNNs: ResNet-50, DenseNet-121, EfficientNet-B0, PhiNet, and an Inception module-based network, on a computed tomography angiography large vessel occlusion detection task. The models were trained and preliminarily evaluated with 10-fold cross-validation on preprocessed scans (n = 240). An ablation study was performed on PhiNet due to superior cross-validated test performance across accuracy, precision, recall, specificity, and F1 score. The final evaluation of all models was performed on a withheld external validation set (n = 60) and these predictions were subsequently calibrated with sigmoid curves., Results: Uncalibrated results on the withheld external validation set show that DenseNet-121 had the best average performance on accuracy, precision, recall, specificity, and F1 score. After calibration DenseNet-121 maintained superior performance on all metrics except recall., Conclusions: The number of learnable parameters in our five models and best-ablated PhiNet directly related to cross-validated test performance-the smaller the model the better. However, this pattern did not hold when looking at generalization on the withheld external validation set. DenseNet-121 generalized the best; we posit this was due to its heavy use of residual connections utilizing concatenation, which causes feature maps from earlier layers to be used deeper in the network, while aiding in gradient flow and regularization., (© 2021 American Association of Physicists in Medicine.)
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- 2021
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30. A Prospective, Longitudinal Magnetic Resonance Imaging Evaluation of Cerebrovascular Reactivity and Infarct Development in Patients With Intracranial Stenosis.
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Juttukonda MR, Davis LT, Lants SK, Waddle SL, Lee CA, Patel NJ, Jordan LC, and Donahue MJ
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- Adolescent, Adult, Aged, Aged, 80 and over, Constriction, Pathologic diagnostic imaging, Humans, Infarction, Longitudinal Studies, Middle Aged, Prospective Studies, Young Adult, Cerebrovascular Circulation, Magnetic Resonance Imaging
- Abstract
Background: Patients with symptomatic atherosclerotic and non-atherosclerotic (i.e., moyamoya) intracranial steno-occlusive disease experience high 2-year infarct rates., Purpose: To investigate whether cerebral blood flow (CBF) and cerebrovascular reactivity (CVR) measures may provide biomarkers of 1-to-2-year infarct risk., Study Type: Prospective, longitudinal study., Subjects: Adult participants (age = 18-85 years) with symptomatic intracranial atherosclerotic disease (N = 26) or non-atherosclerotic (i.e., moyamoya; N = 43) and stenosis ≥50% of a major intracranial artery were initially scanned within 45 days of stroke. Follow-up imaging (target = 1.5 years) was acquired for new infarct assessment., Field Strength/sequence: 3.0 Tesla with normocapnic arterial spin labeling (ASL) and blood oxygenation level-dependent (BOLD) imaging acquired during an interleaved hypercapnic (3 minutes) and normocapnic (3 minutes) respiratory stimulus., Assessment: CBF, maximum CVR, and time-to-maximum CVR (i.e., CVR
DELAY ) were calculated. Laterality indices (difference between infarcted and contralesional hemispheres divided by sum of absolute values) of metrics at enrollment were contrasted between participants with vs. without new infarcts on follow-up., Statistical Tests: Laterality indices were compared using non-parametric Wilcoxon tests (significance: two-sided P < 0.05) and effect sizes as Cohen's d. Continuous variables are presented as mean ± SD., Results: New infarcts were observed on follow-up in 15.0% of participants. The laterality index of the CVRDELAY was elevated (P = 0.01) in participants with atherosclerosis with new infarcts (index = 0.13) compared to participants without new infarcts (index = 0.05)., Data Conclusion: Elevated CVRDELAY may indicate brain parenchyma at increased risk for new infarcts in patients with symptomatic intracranial atherosclerotic disease treated with standard-of-care medical management., Level of Evidence: 2 TECHNICAL EFFICACY STAGE: 3., (© 2021 International Society for Magnetic Resonance in Medicine.)- Published
- 2021
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31. Lower cardiac output is associated with neurodegeneration among older adults with normal cognition but not mild cognitive impairment.
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Moore EE, Liu D, Bown CW, Kresge HA, Gupta DK, Pechman KR, Mendes LA, Davis LT, Gifford KA, Anderson AW, Wang TJ, Landman BA, Hohman TJ, and Jefferson AL
- Subjects
- Aged, Brain diagnostic imaging, Cardiac Output, Cognition, Diffusion Tensor Imaging, Humans, Magnetic Resonance Imaging, Cognitive Dysfunction diagnostic imaging, White Matter
- Abstract
Subclinical cardiac dysfunction is associated with smaller total brain volume on magnetic resonance imaging (MRI). To study whether cardiac output relates to regional measurements of grey and white matter structure, older adults (n = 326) underwent echocardiogram to quantify cardiac output (L/min) and brain MRI. Linear regressions related cardiac output to grey matter volumes measured on T
1 and white matter hyperintensities assessed on T2 -FLAIR. Voxelwise analyses related cardiac output to diffusion tensor imaging adjusting for demographic, genetic, and vascular risk factors. Follow-up models assessed a cardiac output x diagnosis interaction with stratification (normal cognition, mild cognitive impairment). Cardiac output interacted with diagnosis, such that lower cardiac output related to smaller total grey matter (p = 0.01), frontal lobe (p = 0.01), and occipital lobe volumes (p = 0.01) among participants with normal cognition. When excluding participants with cardiovascular disease and atrial fibrillation, associations emerged with smaller parietal lobe (p = 0.005) and hippocampal volume (p = 0.05). Subtle age-related cardiac changes may disrupt neuronal homeostasis and impact grey matter integrity prior to cognitive impairment., (© 2020. Springer Science+Business Media, LLC, part of Springer Nature.)- Published
- 2021
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32. Safety of 3 Tesla Magnetic Resonance Imaging in Patients with Sickle Cell Disease.
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Justice O, Jordan LC, Lee CA, Patel NJ, Waddle S, Pruthi S, Davis LT, Kassim AA, and Donahue MJ
- Abstract
Sickle cell disease (SCD) is a well-characterized hemoglobinopathy affecting more than 20 million individuals worldwide and carries an increased risk of cerebral vasculopathy, cerebral infarct, and stroke. As mechanisms of cerebral infarction in SCD are partly attributable to microvascular vaso-occlusive crises, manifesting as altered cerebral blood flow and associated impaired oxygen delivery, magnetic resonance imaging (MRI) methods that can quickly provide a comprehensive perspective on structural and functional disease status, without exogenous contrast administration or ionizing radiation, have emerged as crucial clinical tools for surveillance. However, early ex vivo MRI work in suspended erythrocytes containing hemoglobin S at 0.35 Tesla (T) suggested that sickled erythrocytes can orient preferentially in the presence of an external magnetic field, and as such, it was suggested that MRI exams in sickle cell hemoglobinopathy could induce vaso-occlusion. While this observation has generally not impacted clinical imaging in individuals with SCD, it has led to resistance for some sickle cell studies within the engineering community among some imaging scientists as this early observation has never been rigorously shown to be unconcerning. Here, we performed MRI at the clinical field strength of 3 T in 172 patients with SCD, which included standard anatomical and angiographic assessments together with gold standard diffusion-weighted imaging (DWI; spatial resolution = 1.8 × 1.8 × 4 mm; b -value = 1000 s/mm
2 ) for acute infarct assessment (performed approximately 20 min after patient introduction to the field isocenter). The presence of vasculopathy, as well as chronic and acute infarcts, was evaluated by two independent board-certified radiologists using standard clinical criteria. In these patients (52.3% female; mean age = 19.6 years; age range = 6-44 years), hematocrit (mean = 25.8%; range = 15-36%), hemoglobin phenotype (87.8% HbSS variant), presence of silent infarct (44.2%), and overt chronic infarct (13.4%) were consistent with a typical SCD population; however, no participants exhibited evidence of acute infarction. These findings are consistent with 3 T MRI not inducing acute infarction or vaso-occlusion in individuals with SCD and suggest that earlier low-field ex vivo work of erythrocytes in suspension is not a sufficient cause to discourage MRI scans in patients with SCD., Competing Interests: Manus J. Donahue received research-related support from Philips Healthcare, is a paid consultant for Global Blood Therapeutics and bluebird bio, and provides consultancy services to Pfizer Inc., LymphaTouch, and PureTech. He is also the CEO of Biosight, LLC, which provides healthcare technology consulting services., (Copyright © 2021 Olivia Justice et al.)- Published
- 2021
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33. Reduced oxygen extraction efficiency in sickle cell anemia patients with evidence of cerebral capillary shunting.
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Juttukonda MR, Donahue MJ, Waddle SL, Davis LT, Lee CA, Patel NJ, Pruthi S, Kassim AA, and Jordan LC
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- Adolescent, Adult, Brain diagnostic imaging, Brain physiology, Cerebral Infarction etiology, Contrast Media chemistry, Coronary Angiography, Female, Humans, Magnetic Resonance Imaging, Male, Spin Labels, White Matter physiopathology, Young Adult, Anemia, Sickle Cell physiopathology, Capillaries physiopathology, Cerebrovascular Circulation physiology, Oxygen metabolism
- Abstract
Arterial spin labeling (ASL) magnetic resonance imaging (MRI) utilizes arterial blood water as an endogenous contrast agent to provide a quantitative measure of cerebral blood flow (CBF). Recently, hyperintense signal within dural venous sinuses in ASL images of sickle cell anemia (SCA) patients has been shown to be consistent with elevated flow velocities and may indicate capillary shunting and reduced oxygen extraction. Here, we performed oxygen extraction fraction (OEF) and CBF measurements in adults (cumulative n = 114) with ( n = 69) and without ( n = 45) SCA to test the hypothesis that hyperintense venous ASL signal is associated with reduced OEF. Higher categorical scores of shunting on ASL MRI were associated with lower OEF in participants with silent cerebral infarcts or white matter hyperintensities ( p = 0.003), but not in those without lesions ( p = 0.551). These findings indicate that venous hyperintense signal in ASL images in SCA patients may represent a marker of capillary-level disturbances in oxygen exchange efficiency and small vessel pathology.
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- 2021
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34. A cross-sectional, case-control study of intracranial arterial wall thickness and complete blood count measures in sickle cell disease.
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Yuan S, Jordan LC, Davis LT, Cogswell PM, Lee CA, Patel NJ, Waddle SL, Juttukonda M, Sky Jones R, Griffin A, and Donahue MJ
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- Adolescent, Adult, Anemia, Sickle Cell complications, Anemia, Sickle Cell diagnostic imaging, Anemia, Sickle Cell pathology, Arteries pathology, Case-Control Studies, Cerebrovascular Circulation, Child, Cross-Sectional Studies, Female, Humans, Intracranial Arterial Diseases blood, Intracranial Arterial Diseases etiology, Intracranial Arterial Diseases pathology, Magnetic Resonance Imaging, Male, Young Adult, Anemia, Sickle Cell blood, Arteries diagnostic imaging, Blood Cell Count, Intracranial Arterial Diseases diagnostic imaging
- Abstract
In sickle cell disease (SCD), cerebral oxygen delivery is dependent on the cerebral vasculature's ability to increase blood flow and volume through relaxation of the smooth muscle that lines intracranial arteries. We hypothesised that anaemia extent and/or circulating markers of inflammation lead to concentric macrovascular arterial wall thickening, visible on intracranial vessel wall magnetic resonance imaging (VW-MRI). Adult and pediatric SCD (n = 69; age = 19.9 ± 8.6 years) participants and age- and sex-matched control participants (n = 38; age = 22.2 ± 8.9 years) underwent 3-Tesla VW-MRI; two raters measured basilar and bilateral supraclinoid internal carotid artery (ICA) wall thickness independently. Mean wall thickness was compared with demographic, cerebrovascular and haematological variables. Mean vessel wall thickness was elevated (P < 0·001) in SCD (1·07 ± 0·19 mm) compared to controls (0·97 ± 0·07 mm) after controlling for age and sex. Vessel wall thickness was higher in participants on chronic transfusions (P = 0·013). No significant relationship between vessel wall thickness and flow velocity, haematocrit, white blood cell count or platelet count was observed; however, trends (P < 0·10) for wall thickness increasing with decreasing haematocrit and increasing white blood cell count were noted. Findings are discussed in the context of how anaemia and circulating inflammatory markers may impact arterial wall morphology., (© 2020 British Society for Haematology and John Wiley & Sons Ltd.)
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- 2021
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35. Intracranial and Extracranial Vascular Stenosis as Risk Factors for Stroke in Sickle Cell Disease.
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Schlotman AA, Donahue MJ, Kassim AA, Lee CA, Waddle SL, Pruthi S, Davis LT, Rodeghier M, DeBaun MR, and Jordan LC
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- Adolescent, Adult, Anemia, Sickle Cell epidemiology, Arterial Occlusive Diseases diagnostic imaging, Arterial Occlusive Diseases epidemiology, Cerebral Infarction diagnostic imaging, Cerebral Infarction epidemiology, Cerebral Infarction etiology, Child, Constriction, Pathologic complications, Constriction, Pathologic diagnostic imaging, Constriction, Pathologic epidemiology, Cross-Sectional Studies, Female, Humans, Intracranial Arterial Diseases diagnostic imaging, Intracranial Arterial Diseases epidemiology, Magnetic Resonance Angiography, Magnetic Resonance Imaging, Male, Neck blood supply, Neck diagnostic imaging, Prevalence, Risk Factors, Stroke diagnostic imaging, Stroke epidemiology, Young Adult, Anemia, Sickle Cell complications, Arterial Occlusive Diseases complications, Intracranial Arterial Diseases complications, Stroke etiology
- Abstract
Background: Prevalence and contribution of intracranial and extracranial arterial stenosis to stroke risk were assessed prospectively in children and young adults with sickle cell disease., Methods: In this cross-sectional study, children and young adults (mean = 19.4 years) with sickle cell disease underwent neurological examination, brain MRI, and magnetic resonance angiography of the head and neck. Two neuroradiologists independently recorded infarcts and arterial stenosis. Clinical features and stroke outcomes were compared between participants with and without stenosis and between children and young adults. Logistic regression analysis assessed the association of variables of interest with overt stroke and silent cerebral infarct., Results: Of 167 participants (79 children and 88 young adults), 20 (12.0%) had intracranial stenosis, all in the anterior circulation, and nine had concurrent extracranial stenosis. No participants had isolated extracranial stenosis. Participants with intracranial stenosis were more likely than those without stenosis to have an overt stroke (70% vs 5%, P < 0.001) or silent cerebral infarct (95% vs 35%, P < 0.001). Logistic regression analysis indicated that intracranial stenosis was strongly associated with overt stroke when compared with participants with silent cerebral infarct alone and strongly associated with silent cerebral infarct when compared with participants with normal brain MRI; male sex and age were also significant predictors of silent cerebral infarct., Conclusions: Intracranial stenosis was strongly associated with both overt stroke and silent cerebral infarct; prevalence of intracranial stenosis was similar to prior estimates in sickle cell disease. Extracranial stenosis without concurrent intracranial stenosis did not occur and thus could not be evaluated as an independent risk factor for stroke., (Copyright © 2020 Elsevier Inc. All rights reserved.)
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- 2021
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36. Glioblastoma Distance From the Subventricular Neural Stem Cell Niche Does Not Correlate With Survival.
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Mistry AM, Mummareddy N, Salwi S, Davis LT, and Ihrie RA
- Abstract
Objective: To determine the relationship between survival and glioblastoma distance from the ventricular-subventricular neural stem cell niche (VSVZ)., Methods: 502 pre-operative gadolinium-enhanced, T1-weighted MRIs with glioblastoma retrieved from an institutional dataset (n = 252) and The Cancer Imaging Atlas (n=250) were independently reviewed. The shortest distance from the tumor contrast enhancement to the nearest lateral ventricular wall, the location of the VSVZ, was measured (GBM-VSVZ
Dist ). The relationship of GBM-VSVZDist with the proportion of glioblastomas at each distance point and overall survival was explored with a Pearson's correlation and Cox regression model, respectively, adjusting for the well-established glioblastoma prognosticators., Results: 244/502 glioblastomas had VSVZ contact. The proportion of non-VSVZ-contacting glioblastomas correlated inversely with GBM-VSVZDist (partial Pearson's correlation adjusted for tumor volume R=-0.79, p=7.11x10-7 ). A fit of the Cox regression model adjusted for age at diagnosis, Karnofsky performance status score, post-operative treatment with temozolomide and/or radiotherapy, IDH1/2 mutation status, MGMT promoter methylation status, tumor volume, and extent of resection demonstrated a significantly decreased overall survival only when glioblastoma contacted the VSVZ. Overall survival did not correlate with GBM-VSVZDist ., Conclusions: In the two independent cohorts analyzed, glioblastomas at diagnosis were found in close proximity or in contact with the VSVZ with a proportion that decreased linearly with GBM-VSVZDist . Patient survival was only influenced by the presence or absence of a gadolinium-enhanced glioblastoma contact with the VSVZ. These results may guide analyses to test differential effectiveness of VSVZ radiation in VSVZ-contacting and non-contacting glioblastomas and/or inform patient selection criteria in clinical trials of glioblastoma radiation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2020 Mistry, Mummareddy, Salwi, Davis and Ihrie.)- Published
- 2020
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37. Vessel Wall and Lumen Features in North American Moyamoya Patients.
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Cogswell PM, Lants SK, Davis LT, Juttukonda MR, Fusco MR, and Donahue MJ
- Subjects
- Adult, Aged, Angiography, Digital Subtraction, Case-Control Studies, Cerebral Angiography, Female, Humans, Image Interpretation, Computer-Assisted, Magnetic Resonance Angiography, Male, Middle Aged, Severity of Illness Index, United States, Basilar Artery diagnostic imaging, Carotid Artery, Internal diagnostic imaging, Moyamoya Disease diagnostic imaging
- Abstract
Purpose: To apply intracranial vessel wall imaging (VWI) to determine changes in vessel wall characteristics between North American moyamoya patients and controls, as well as with standard clinical measures of moyamoya disease severity., Methods: North American moyamoya patients and controls underwent intracranial 3.0 T VWI. Moyamoya patients also underwent digital subtraction angiography (DSA), from which modified Suzuki scores (mSS) were calculated. Lumen and outer vessel wall diameters of the supraclinoid internal carotid arteries (ICAs) and basilar artery on VWI were measured by two readers from which wall thickness was calculated. Controls and moyamoya patients were compared in logistic regression using disease category (moyamoya or none) as the dependent variable and wall thickness, age, gender, and side as the explanatory variables (significance: two-sided p < 0.05). In moyamoya patients, regression was performed with mSS as the dependent variable and wall thickness, age, gender, and side as the explanatory variables. Analyses were repeated for each lumen diameter and outer vessel wall diameter in place of wall thickness., Results: Patients with moyamoya (n = 23, gender = 3/20 male/female; age = 43 ± 12 years) and controls (n = 23, gender = 3/20 male/female, age = 43 ± 13 years) were included. Moyamoya patients showed a significantly smaller ICA lumen and outer vessel wall diameter compared to controls (p < 0.05) but no significant change in vessel wall thickness. Similarly, ICA lumen and outer vessel wall diameters decreased with increasing mSS (p < 0.05)., Conclusion: Findings suggest decreased ICA lumen and outer vessel wall diameters, but no significant difference in wall thickness, between patients and controls. Lumen and outer vessel wall diameters also decreased with disease severity.
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- 2020
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38. Mild Cognitive Impairment Staging Yields Genetic Susceptibility, Biomarker, and Neuroimaging Differences.
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Moore EE, Liu D, Pechman KR, Acosta LMY, Bell SP, Davis LT, Blennow K, Zetterberg H, Landman BA, Schrag MS, Hohman TJ, Gifford KA, and Jefferson AL
- Abstract
Introduction: While Alzheimer's disease (AD) is divided into severity stages, mild cognitive impairment (MCI) remains a solitary construct despite clinical and prognostic heterogeneity. This study aimed to characterize differences in genetic, cerebrospinal fluid (CSF), neuroimaging, and neuropsychological markers across clinician-derived MCI stages., Methods: Vanderbilt Memory & Aging Project participants with MCI were categorized into 3 severity subtypes at screening based on neuropsychological assessment, functional assessment, and Clinical Dementia Rating interview, including mild ( n = 18, 75 ± 8 years), moderate ( n = 89 72 ± 7 years), and severe subtypes ( n = 18, 78 ± 8 years). At enrollment, participants underwent neuropsychological testing, 3T brain magnetic resonance imaging (MRI), and optional fasting lumbar puncture to obtain CSF. Neuropsychological testing and MRI were repeated at 18-months, 3-years, and 5-years with a mean follow-up time of 3.3 years. Ordinary least square regressions examined cross-sectional associations between MCI severity and apolipoprotein E ( APOE )-ε4 status, CSF biomarkers of amyloid beta (Aβ), phosphorylated tau, total tau, and synaptic dysfunction (neurogranin), baseline neuroimaging biomarkers, and baseline neuropsychological performance. Longitudinal associations between baseline MCI severity and neuroimaging and neuropsychological trajectory were assessed using linear mixed effects models with random intercepts and slopes and a follow-up time interaction. Analyses adjusted for baseline age, sex, race/ethnicity, education, and intracranial volume for MRI models., Results: Stages differed at baseline on APOE -ε4 status (early < middle = late; p -values < 0.03) and CSF Aβ (early > middle = late), phosphorylated and total tau (early = middle < late; p -values < 0.05), and neurogranin concentrations (early = middle < late; p -values < 0.05). MCI stage related to greater longitudinal cognitive decline, hippocampal atrophy, and inferior lateral ventricle dilation (early < late; p -values < 0.03)., Discussion: Clinician staging of MCI severity yielded longitudinal cognitive trajectory and structural neuroimaging differences in regions susceptible to AD neuropathology and neurodegeneration. As expected, participants with more severe MCI symptoms at study entry had greater cognitive decline and gray matter atrophy over time. Differences are likely attributable to baseline differences in amyloidosis, tau, and synaptic dysfunction. MCI staging may provide insight into underlying pathology, prognosis, and therapeutic targets., (Copyright © 2020 Moore, Liu, Pechman, Acosta, Bell, Davis, Blennow, Zetterberg, Landman, Schrag, Hohman, Gifford and Jefferson.)
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- 2020
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39. Longitudinal Radiographic Outcomes of Vestibular Schwannoma in Single and Fractionated Stereotactic Radiosurgery: A Retrospective Cohort Study.
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Khattab MH, Newman NB, Wharton DM, Sherry AD, Luo G, Manzoor NF, Rivas A, Davis LT, Chambless LB, Attia A, and Cmelak AJ
- Abstract
Management of vestibular schwannoma (VS) includes stereotactic radiosurgery (SRS) in single or fractionated treatments. There is a paucity of literature on the three-dimensional (3D) volumetric kinetics and radiological changes following SRS and no consensus on appropriate post-SRS surveillance imaging timeline. This is a retrospective cohort study with institutional review board approval. A total of 55 patients met study criteria. We collected volumetric kinetic data in VS treated with SRS over time using a target volume contouring software. We also tracked radiographic phenomena such as pseudoprogression and necrosis. A secondary objective was to describe our overall treatment success rate and any failures. For all treatments groups, pseudoprogression most typically occurred within 12 months post-SRS, after which tumor volumes on average normalized and then decreased from pretreatment size at the last follow-up. Only two patients required salvage therapy post-SRS and were considered SRS treatment failures. Both patients were in the five-fraction cohort but with a lower biologically equivalent dose. Our study is first to collect 3D volumetric kinetics of VS following single and fractionated SRS in contrast to extrapolations from single and two-dimensional measurements. Our longitudinal data also show initial increases in volume in the first 12 months post-SRS followed by later declines, setting up interesting questions regarding the utility of early posttreatment surveillance imaging in the asymptomatic patient. Finally, we show low rates of treatment failure (3.6%) and show in our cohort that SRS dose de-escalation posed a risk of treatment failure., Competing Interests: Conflict of Interest None., (© Thieme Medical Publishers.)
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- 2020
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40. Classifying intracranial stenosis disease severity from functional MRI data using machine learning.
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Waddle SL, Juttukonda MR, Lants SK, Davis LT, Chitale R, Fusco MR, Jordan LC, and Donahue MJ
- Subjects
- Brain blood supply, Case-Control Studies, Female, Humans, Middle Aged, Moyamoya Disease physiopathology, Sensitivity and Specificity, Severity of Illness Index, Young Adult, Brain diagnostic imaging, Cerebral Angiography methods, Cerebrovascular Circulation physiology, Image Processing, Computer-Assisted, Machine Learning, Magnetic Resonance Angiography methods, Moyamoya Disease diagnostic imaging
- Abstract
Translation of many non-invasive hemodynamic MRI methods to cerebrovascular disease patients has been hampered by well-known artifacts associated with delayed blood arrival times and reduced microvascular compliance. Using machine learning and support vector machine (SVM) algorithms, we investigated whether arrival time-related artifacts in these methods could be exploited as novel contrast sources to discriminate angiographically confirmed stenotic flow territories. Intracranial steno-occlusive moyamoya patients ( n = 53; age = 45 ± 14.2 years; sex = 43 F) underwent (i) catheter angiography, (ii) anatomical MRI, (iii) cerebral blood flow (CBF)-weighted arterial spin labeling, and (iv) cerebrovascular reactivity (CVR)-weighted hypercapnic blood-oxygenation-level-dependent MRI. Mean, standard deviation (std), and 99th percentile of CBF, CVR, CVR
Delay , and CVRMax were calculated in major anterior and posterior flow territories perfused by vessels with vs. without stenosis (≥70%) confirmed by catheter angiography. These and demographic variables were input into SVMs to evaluate discriminatory capacity for stenotic flow territories using k-fold cross-validation and receiver-operating-characteristic-area-under-the-curve to quantify variable combination relevance. Anterior circulation CBF-std, attributable to heterogeneous endovascular signal and prolonged arterial transit times, was the best performing single variable and CVRDelay -mean and CBF-std, both reflective of delayed vascular compliance, were a high-performing two-variable combination (specificity = 0.67; sensitivity = 0.75). Findings highlight the relevance of hemodynamic imaging and machine learning for identifying cerebrovascular impairment.- Published
- 2020
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41. Cerebral hemodynamics and metabolism are similar in sickle cell disease patients with hemoglobin SS and Sβ 0 thalassemia phenotypes.
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Ikwuanusi I, Jordan LC, Lee CA, Patel NJ, Waddle S, Pruthi S, Davis LT, Griffin A, DeBaun MR, Kassim AA, and Donahue MJ
- Subjects
- Adolescent, Adult, Child, Female, Humans, Male, Anemia, Sickle Cell blood, Anemia, Sickle Cell genetics, Anemia, Sickle Cell pathology, Anemia, Sickle Cell physiopathology, Cerebrovascular Circulation, Hemodynamics, Hemoglobin, Sickle genetics, Hemoglobin, Sickle metabolism, Thalassemia genetics, Thalassemia pathology, Thalassemia physiopathology
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- 2020
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42. Current Volumetric Models Overestimate Vestibular Schwannoma Size Following Stereotactic Radiosurgery.
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Sherry AD, Khattab MH, Totten DJ, Wharton DM, Luo G, Manzoor NF, Rivas A, Chambless LB, Davis LT, Attia A, and Cmelak AJ
- Subjects
- Humans, Reproducibility of Results, Retrospective Studies, Treatment Outcome, Tumor Burden, Neuroma, Acoustic diagnostic imaging, Neuroma, Acoustic radiotherapy, Neuroma, Acoustic surgery, Radiosurgery
- Abstract
Objective: Accurate volume assessment is essential for the management of vestibular schwannoma after stereotactic radiosurgery (SRS). A cuboidal approximation for volume is the standard surveillance method; however, this may overestimate tumor volume. We sought to evaluate several volumetric models and their suitability for post-SRS surveillance., Study Design: Retrospective cohort study., Setting: Tertiary referral center., Patients: We evaluated 54 patients with vestibular schwannoma before and after SRS., Intervention(s): Gold-standard volumes were obtained by a radiation oncologist using contouring software. Volume was also calculated by cuboidal, ellipsoidal, and spherical formulae using tumor diameters obtained by a neuroradiologist., Main Outcome Measure(s): Percent error (PE) and absolute percent error (APE) were calculated. Paired t test evaluated bias, and the Bland-Altman method evaluated reproducibility. Linear regression evaluated predictors of model error., Results: All models overestimated volume compared with the gold standard. The cuboidal model was not reproducible before SRS (p < 0.001), and no model was reproducible after SRS (cuboidal p < 0.001; ellipsoidal p = 0.02; spherical p = 0.02). Significant bias was present before SRS for the cuboidal model (p < 0.001), and post-SRS for all models [cuboidal (p < 0.001), ellipsoidal (p < 0.02), and spherical (p = 0.005)]. Model error was negatively associated with pretreatment volume for the cuboidal (PE p = 0.03; APE p = 0.03), ellipsoidal (PE p = 0.03; APE p = 0.04), and spherical (PE p = 0.02; APE p = 0.03) methods and lost linearity post-SRS., Conclusions: The standard cuboidal practice for following vestibular schwannoma tumor volume after SRS overestimates size. Ellipsoidal and spherical estimations have improved performance but also overestimate volume and lack reliability post-SRS. The development of other volumetric models or application of contouring software should be investigated.
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- 2020
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43. Vessel wall and lumen characteristics with age in healthy participants using 3T intracranial vessel wall magnetic resonance imaging.
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Cogswell PM, Lants SK, Davis LT, and Donahue MJ
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- Adolescent, Adult, Age Factors, Aged, Carotid Artery, Internal physiopathology, Cerebrovascular Circulation, Cerebrovascular Disorders physiopathology, Child, Female, Healthy Volunteers, Humans, Linear Models, Male, Middle Aged, Reproducibility of Results, Sex Factors, Young Adult, Brain diagnostic imaging, Carotid Artery, Internal diagnostic imaging, Cerebrovascular Disorders diagnostic imaging, Magnetic Resonance Imaging
- Abstract
Background: Intracranial vessel wall imaging (VWI) at a clinical field strength of 3T has become more widely available. However, how vessel measurements change with age and sex, over an age range spanning a typical lifespan, are needed., Purpose/hypothesis: To assess for identifiable changes in arterial wall thickness, outer vessel wall diameter, and lumen diameter with age cross-sectionally in healthy controls without cerebrovascular disease risk factors at the spatial resolution afforded by currently recommended 3T VWI approaches., Study Type: Prospective., Population/subjects: Healthy subjects (n = 82; age = 8-79 years)., Field Strength/sequence: 3T intracranial VWI, angiography, and T
1 -weighted anatomical imaging., Assessment: Two readers measured lumen and outer wall diameters of the supraclinoid internal carotid artery (ICA) and distal basilar artery. Wall thickness and intraclass correlation coefficients (ICCs) were calculated., Statistical Tests: Separate linear regressions were performed to understand the relationship between wall measurements (lumen diameter, outer vessel wall diameter, and wall thickness) and age, gender, side (left or right); significance: two-sided P < 0.05., Results: Readers showed excellent agreement for lumen and outer wall diameters (ICC 0.83-094). Linear regression of supraclinoid ICA wall measurements showed a statistically significant increase in wall thickness (P = 0.00051) and outer vessel wall diameter (P = 0.030) with age. ICA lumen and outer vessel wall diameters were statistically greater in males vs. females (lumen diameter 3.69 ± 0.41 vs. 3.54 ± 0.35 mm, P = 0.026; outer wall diameter 5.78 ± 0.52 vs. 5.56 ± 0.44 mm, P = 0.0089) with a trend toward increase in wall thickness (1.05 ± 0.12 vs. 1.01 ± 0.10 mm, P = 0.055). No significant difference was found in basilar artery wall thickness (P = 0.45, P = 0.72), lumen diameter (P = 0.15, P = 0.42), or outer vessel wall diameter (P = 0.34, P = 0.41) with age or gender, respectively., Data Conclusion: Intracranial vessel wall measurements were shown to be consistent between readers. At the available spatial resolution of 3T intracranial VWI sequences, supraclinoid ICA vessel wall thickness and outer vessel wall diameter appear to mildly increase with age. There was no detectable change in basilar artery vessel wall characteristics with age., Level of Evidence: 2 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2019;50:1452-1460., (© 2019 International Society for Magnetic Resonance in Medicine.)- Published
- 2019
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44. Cerebral blood flow territory instability in patients with atherosclerotic intracranial stenosis.
- Author
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Arteaga DF, Strother MK, Faraco CC, Davis LT, Scott AO, and Donahue MJ
- Subjects
- Aged, Aged, 80 and over, Atherosclerosis physiopathology, Constriction, Pathologic physiopathology, Female, Hemodynamics, Humans, Ischemic Attack, Transient, Magnetic Resonance Angiography, Male, Middle Aged, Pressure, Prospective Studies, ROC Curve, Risk Factors, Atherosclerosis diagnostic imaging, Cerebrovascular Circulation, Constriction, Pathologic diagnostic imaging, Intracranial Arteriosclerosis physiopathology, Spin Labels
- Abstract
Background: Stroke risk stratification in patients with symptomatic intracranial atherosclerotic arterial disease (ICAD) remains an important clinical objective owing to the high 14-19% recurrent stroke rate in these patients on standard-of-care medical management. There thus remains a need for hemodynamic markers that may allow for the selection of personalized therapies for high-risk symptomatic patients., Purpose: To determine if shifting of cerebral blood flow (CBF) territories in response to changes in cerebral perfusion pressure (CPP) may provide a marker for stroke risk in ICAD patients., Study Type: Prospective., Population: Twenty ICAD patients who experienced a stroke within 45 days of study enrollment and 10 healthy controls., Sequence: 3.0T MRI including anatomical imaging (T
1 -weighted, T2 -weighted/FLAIR), 3D MR angiography, and normocapnic and hypercapnic vessel-encoded CBF-weighted arterial spin labeling., Assessment: Patients were scanned within 45 days of overt stroke and monitored (duration = 13.2 ± 4.4 months) for the endpoint of non-cardioembolic stroke or transient ischemic attack. Flow territory shifting (shifting index) was calculated from the first scan by determining whether a voxel shifted from its primary arterial source from normocapnia to hypercapnia., Statistical Tests: A Mann-Whitney U-test (significance: P < 0.05) was performed to determine whether patients meeting the endpoint had greater shifting indices relative to controls or patients not meeting the endpoint., Results: Shifting indices (mean ± standard error) were significantly higher in patients meeting endpoint criteria relative to controls (P = 0.0057; adjusted P = 0.036) and patients not meeting endpoint criteria (P = 0.0047; adjusted P = 0.036)., Data Conclusion: Flow territory shifting may provide a marker of recurrent stroke risk in symptomatic ICAD patients on standard-of-care medical management therapies., Level of Evidence: 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;50:1441-1451., (© 2019 International Society for Magnetic Resonance in Medicine.)- Published
- 2019
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45. Haploidentical bone marrow transplantation improves cerebral hemodynamics in adults with sickle cell disease.
- Author
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Jordan LC, Juttukonda MR, Kassim AA, DeBaun MR, Davis LT, Pruthi S, Patel NJ, Lee CA, Waddle SL, and Donahue MJ
- Subjects
- Adolescent, Adult, Allografts, Female, Humans, Male, Anemia, Sickle Cell physiopathology, Anemia, Sickle Cell therapy, Bone Marrow Transplantation, Cerebrovascular Circulation, Hemodynamics
- Published
- 2019
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46. Preliminary evidence for cerebral capillary shunting in adults with sickle cell anemia.
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Juttukonda MR, Donahue MJ, Davis LT, Gindville MC, Lee CA, Patel NJ, Kassim AA, Pruthi S, Hendrikse J, and Jordan LC
- Subjects
- Adult, Anemia, Sickle Cell blood, Capillaries diagnostic imaging, Case-Control Studies, Female, Humans, Magnetic Resonance Angiography, Magnetic Resonance Imaging, Male, Middle Aged, Oxygen blood, Spin Labels, Anemia, Sickle Cell physiopathology, Capillaries physiopathology, Cerebrovascular Circulation
- Abstract
Elevated flow velocities in adults with sickle cell anemia (SCA) may cause rapid erythrocyte transit through capillaries. This phenomenon could present as dural venous sinus hyperintensity on arterial spin labeling (ASL)-MRI and could be indicative of capillary shunting. Here, the prevalence of ASL venous hyperintensities and association with relevant physiology in adults with SCA was investigated. SCA ( n = 46) and age-matched control ( n = 16) volunteers were recruited for 3.0 T MRI. Pseudo-continuous ASL-MRI was acquired for cerebral blood flow (CBF) calculation and venous hyperintensity determination; venous signal intensity and a categorical venous score (three raters; 0 = no hyperintensity, 1 = focal hyperintensity, and 2 = diffuse hyperintensity) were recorded. Flow velocity in cervical internal carotid artery segments was determined from phase contrast data (v
enc = 40 cm/s) and whole-brain oxygen extraction fraction (OEF) was determined from T2 -relaxation-under-spin-tagging MRI. Cerebral metabolic rate of oxygen was calculated as the product of OEF, CBF, and blood oxygen content. ASL venous hyperintensities were significantly ( p < 0.001) more prevalent in SCA (65%) relative to control (6%) participants and were associated with elevated flow velocities ( p = 0.03). CBF ( p < 0.001), but not OEF, increased with increasing hyperintensity score. Prospective trials that evaluate this construct as a possible marker of impaired oxygen delivery and stroke risk may be warranted.- Published
- 2019
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47. Angiocentric glioma mimicking encephalomalacia.
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Harmsen H, Mobley BC, and Davis LT
- Abstract
Angiocentric glioma is a rare low-grade neoplasm of the central nervous system which typically presents with medication-refractory seizures in children and young adults. On magnetic resonance imaging, angiocentric glioma is classically T1 hypointense and T2/FLAIR hyperintense. We present the case of a 40-year-old male who had been followed by our institution for 17 years for management of epilepsy. Initial and repeat brain imaging showed an apparent region of cystic encephalomalacia in the right frontal lobe. In an attempt to control his seizures, the lesion was resected. Grossly, the cut surface of the specimen was characterized by multiple small cystic spaces. Microscopically, the lesion was composed of an infiltrative population of glial cells variably arranged in perivascular "pseudorosettes," nodules, and subpial "palisades." The final diagnosis was angiocentric glioma. This is the second reported case of an angiocentric glioma mistaken for encephalomalacia.
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- 2019
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48. Perivascular spaces contribute to cognition beyond other small vessel disease markers.
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Passiak BS, Liu D, Kresge HA, Cambronero FE, Pechman KR, Osborn KE, Gifford KA, Hohman TJ, Schrag MS, Davis LT, and Jefferson AL
- Subjects
- Aged, Aged, 80 and over, Brain blood supply, Cross-Sectional Studies, Female, Humans, Longitudinal Studies, Magnetic Resonance Imaging, Male, Middle Aged, Neuropsychological Tests, Brain diagnostic imaging, Cerebrovascular Disorders diagnostic imaging, Cerebrovascular Disorders psychology, Cognition
- Abstract
Objective: To cross-sectionally relate multiple small vessel disease (SVD) neuroimaging markers to cognition among older adults., Methods: Vanderbilt Memory & Aging Project participants free of clinical dementia and stroke (n = 327, age 73 ± 7 years, 59% male, 40% with mild cognitive impairment) completed neuropsychological assessment and 3T MRI to measure white matter hyperintensities (WMH), perivascular spaces (PVS), cerebral microbleeds (CMBs), and lacunes. Linear regressions related each SVD marker to neuropsychological performances and adjusted for age, sex, race/ethnicity, education, cognitive diagnosis, APOE ε4 presence, Framingham Stroke Risk Profile, and intracranial volume., Results: WMH related to the most neuropsychological measures, including the Boston Naming Test, Animal Naming, Coding, Number Sequencing, Executive Function Composite, and Hooper Visual Organization Test performances ( p ≤ 0.01). PVS related to multiple information processing and executive function performances ( p ≤ 0.02). Lacunes and CMBs related to fewer measures than expected. Combined models simultaneously testing multiple statistically significant SVD predictors suggested that WMH, PVS, and CMBs each independently related to information processing and executive function performances; however, compared to other SVD markers, PVS remained statistically significant in models related to information processing and executive functioning performances., Conclusions: As expected, increased WMH corresponded to poorer performances across multiple cognitive domains. PVS, previously considered a benign neuroimaging feature in older adults, may have important clinical implications because PVS was related to information processing and executive function performances even in combined models. On the basis of models with multiple SVD predictors, WMH, PVS, and CMBs may each reflect a separate pathway of small vessel injury., (© 2019 American Academy of Neurology.)
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- 2019
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49. Ventricular-Subventricular Zone Contact by Glioblastoma is Not Associated with Molecular Signatures in Bulk Tumor Data.
- Author
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Mistry AM, Wooten DJ, Davis LT, Mobley BC, Quaranta V, and Ihrie RA
- Subjects
- Adult, Brain Neoplasms mortality, Brain Neoplasms pathology, Cell Line, Tumor, DNA Methylation, Datasets as Topic, Female, Gene Expression Profiling, Gene Expression Regulation, Neoplastic, Glioblastoma mortality, Glioblastoma pathology, Humans, Male, Survival Analysis, Tumor Microenvironment, Brain Neoplasms genetics, Glioblastoma genetics, Lateral Ventricles pathology, Stem Cell Niche physiology
- Abstract
Whether patients with glioblastoma that contacts the ventricular-subventricular zone stem cell niche (VSVZ + GBM) have a distinct survival profile from VSVZ - GBM patients independent of other known predictors or molecular profiles is unclear. Using multivariate Cox analysis to adjust survival for widely-accepted predictors, hazard ratios (HRs) for overall (OS) and progression free (PFS) survival between VSVZ + GBM and VSVZ - GBM patients were calculated in 170 single-institution patients and 254 patients included in both The Cancer Genome (TCGA) and Imaging (TCIA) atlases. An adjusted, multivariable analysis revealed that VSVZ contact was independently associated with decreased survival in both datasets. TCGA molecular data analyses revealed that VSVZ contact by GBM was independent of mutational, DNA methylation, gene expression, and protein expression signatures in the bulk tumor. Therefore, while survival of GBM patients is independently stratified by VSVZ contact, with VSVZ + GBM patients displaying a poor prognosis, the VSVZ + GBMs do not possess a distinct molecular signature at the bulk sample level. Focused examination of the interplay between the VSVZ microenvironment and subsets of GBM cells proximal to this region is warranted.
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- 2019
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50. Differential cerebral hemometabolic responses to blood transfusions in adults and children with sickle cell anemia.
- Author
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Juttukonda MR, Lee CA, Patel NJ, Davis LT, Waddle SL, Gindville MC, Pruthi S, Kassim AA, DeBaun MR, Donahue MJ, and Jordan LC
- Subjects
- Adolescent, Adult, Age Factors, Brain metabolism, Child, Female, Hematocrit, Hemodynamics, Humans, Longitudinal Studies, Magnetic Resonance Imaging, Male, Oximetry, Oxygen metabolism, Oxygen Consumption, Pain Management, Prospective Studies, Recurrence, Stroke, Young Adult, Anemia, Sickle Cell diagnostic imaging, Blood Transfusion, Cerebrovascular Circulation
- Abstract
Background: Blood transfusions are administered to children and adults with sickle cell anemia (SCA) for secondary stroke prevention, or as treatment for recurrent pain crises or acute anemia, but transfusion effects on cerebral hemodynamics and metabolism are not well-characterized., Purpose: To compare blood transfusion-induced changes in hemometabolic parameters, including oxygen extraction fraction (OEF) and cerebral blood flow (CBF), within and between adults and children with SCA., Study Type: Prospective, longitudinal study., Subjects: Adults with SCA (n = 16) receiving simple (n = 7) or exchange (n = 9) transfusions and children with SCA (n = 11) receiving exchange transfusions were scanned once when hematocrit was near nadir and again within 7 days of transfusion. Adult controls without SCA or sickle trait (n = 7) were scanned twice on separate days., Field Strength/sequence: 3.0T T
1 -weighted, T2 -weighted, and T2 -relaxation-under-spin-tagging (TRUST) imaging, and phase contrast angiography., Assessment: Global OEF was computed as the relative difference between venous oxygenation (from TRUST) and arterial oxygenation (from pulse oximetry). Global CBF was computed as total blood flow to the brain normalized by intracranial tissue volume., Statistical Tests: Hemometabolic variables were compared using two-sided Wilcoxon signed-rank tests; associations were analyzed using two-sided Spearman's correlation testing., Results: In adults with SCA, posttransfusion OEF = 0.38 ± 0.05 was lower (P = 0.001) than pretransfusion OEF = 0.45 ± 0.09. A change in OEF was correlated with increases in hematocrit (P = 0.02; rho = -0.62) and with pretransfusion hematocrit (P = 0.02; rho = 0.65). OEF changes after transfusion were greater (P = 0.002) in adults receiving simple versus exchange transfusions. Posttransfusion CBF = 77.7 ± 26.4 ml/100g/min was not different (P = 0.27) from pretransfusion CBF = 82.3 ± 30.2 ml/100g/min. In children with SCA, both posttransfusion OEF = 0.28 ± 0.04 and CBF = 76.4 ± 26.4 were lower than pretransfusion OEF = 0.36 ± 0.06 (P = 0.004) and CBF = 96.4 ± 16.5 (P = 0.004)., Data Conclusion: Cerebral OEF reduces following transfusions in adults and children with SCA. CBF reduces following transfusions more often in children compared to adults, indicating that vascular reserve capacity may remain near exhaustion posttransfusion in many adults., Level of Evidence: 2 Technical Efficacy Stage 5 J. Magn. Reson. Imaging 2019;49:466-477., (© 2018 International Society for Magnetic Resonance in Medicine.)- Published
- 2019
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