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1. Lupus anticoagulant associates with thrombosis in patients with COVID‐19 admitted to intensive care units: A retrospective cohort study

Author

Noordermeer, Tessa, Schutgens, Roger E.G., Visser, Chantal, Rademaker, Emma, de Maat, Moniek P.M., Jansen, A.J. Gerard, Limper, Maarten, Cremer, Olaf L., Kruip, Marieke J.H.A., Endeman, Henrik, Maas, Coen, de Laat, Bas, Urbanus, Rolf T., van de Beek, D., Brouwer, M.C., de Bruin, S., Coppens, M., van Es, N., van Haaps, T.F., Juffermans, N.P., Muller, M.C.A., Vlaar, A.P.J., Hertogh, C.M.P.M., Heunks, L.M.A., Hugtenburg, J.G., van Kooten, J., Nossent, E.J., Smulders, Y., Tuinman, P.R., Vonk Noordegraaf, A., Grootenboers, M.J.J.H., van Guldener, C., Kant, M., Lansbergen, A., Faber, J., Hajer, G., Stemerdink, A., van den Akker, J., Bierings, R., Endeman, H., Goeijenbier, M., Hunfeld, N.G.M., van Gorp, E.C.M., Gommers, D.A.M.P.J., Koopmans, M.P.G., Kruip, M.J.H.A., Kuiken, T., Langerak, T., Leebeek, Lauw, M.N., de Maat, M.P.M., Noack, D., Paats, M.S., Raadsen, M.P., Rockx, B., Rokx, C., Schurink, C.A.M., Tong‐Minh, K., van den Toorn, L., den Uil, C.A., Visser, C., Boutkourt, F., Roest, T., Douma, R.A., de Haan, L.R., ten Wolde, M., Bemelmans, R.H.H., Festen, B., Stads, S., de Jager, C.P.C., Simons, K.S., Antoni, M.L., Bos, M.H., Burggraaf, J.L.I., Cannegieter, S.C., Eikenboom, H.C.J., den Exter, P.L., Geelhoed, J.J.M., Huisman, M.V., de Jonge, E., Kaptein, F.H.J., Klok, F.A., Kroft, L.J.M., Lijfering, W.M., Nab, L., Ninaber, M.K., Putter, H., Ramai, S.R.S., da Rocha Rondon, A.M., Roukens, A.H.E., Stals, M.A.M., Versteeg, H.H., Vliegen, H.W., van Vlijmen, B.J.M., van de Berg, T., Bruggemann, R., van Bussel, B.C.T., ten Cate, H., ten Cate‐Hoek, A., Hackeng, T.M., Henskens, ir.Y., Hulshof, A., Mulder, M., Olie, R.H., Schurgers, L., Spaetgens, B., Spronk, H., Winckers, K., Nieuwenhuizen, L., Franken, B., Schrover, I.M., de Waal, E.G.M., Beishuizen, A., Cornet, A., Krabbe, J., Kramers, K., Leentjens, J., de Mast, Q., Middeldorp, S., Brouwer, R.E., Ellerbroek, J.L.J., Tijmensen, J., Hovens, M.M C., Oostdijk, E.A.N., Westerhof, B.D., Faber, L.M., van den Biggelaar, M., Meijers, J.C.M., Voorberg, J., Kevenaar, M.E., Soei, Y.L., Wils, E.J., Croles, F.N., de Laat, B., Kamphuisen, P.W., Vink, R., Lisman, T., Meijer, K., van Tichelaar, Y.I.G., Cremer, O.L., Geersing, G., Kaasjager, H.A.H., Kusadasi, N., Huisman, A., Maas, C., Nijkeuter, M., Schutgens, R.E.G., Creveldkliniek, Van, Urbanus, R.T., Westerink, J., Faber, H.J., Koster, S.C.E., van Montfort, P., and van Twist, D.J.L.

Published
2022
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2. In-hospital and 6-month outcomes in patients with COVID-19 supported with extracorporeal membrane oxygenation (EuroECMO-COVID): a multicentre, prospective observational study

Author

Lorusso, R, De Piero, M, Mariani, S, Di Mauro, M, Folliguet, T, Taccone, F, Camporota, L, Swol, J, Wiedemann, D, Belliato, M, Broman, L, Vuylsteke, A, Kassif, Y, Scandroglio, A, Fanelli, V, Gaudard, P, Ledot, S, Barker, J, Boeken, U, Maier, S, Kersten, A, Meyns, B, Pozzi, M, Pedersen, F, Schellongowski, P, Kirali, K, Barrett, N, Riera, J, Mueller, T, Belohlavek, J, Lo Coco, V, Van der Horst, I, Van Bussel, B, Schnabel, R, Delnoij, T, Bolotin, G, Lorini, L, Schmiady, M, Schibilsky, D, Kowalewski, M, Pinto, L, Silva, P, Kornilov, I, Blandino Ortiz, A, Vercaemst, L, Finney, S, Roeleveld, P, Di Nardo, M, Hennig, F, Antonini, M, Davidson, M, Jones, T, Staudinger, T, Mair, P, Kilo, J, Krapf, C, Erbert, K, Peer, A, Bonaros, N, Kotheletner, F, Krenner Mag, N, Shestakova, L, Hermans, G, Dauwe, D, Meersseman, P, Stockman, B, Nobile, L, Lhereux, O, Nrasseurs, A, Creuter, J, De Backer, D, Giglioli, S, Michiels, G, Foulon, P, Raes, M, Rodrigus, I, Allegaert, M, Jorens, P, Debeucklare, G, Piagnerelli, M, Biston, P, Peperstraete, H, Vandewiele, K, Germay, O, Vandeweghe, D, Havrin, S, Bourgeois, M, Lagny, M, Alois, G, Lavios, N, Misset, B, Courcelle, R, Timmermans, P, Yilmaz, A, Vantomout, M, Lehaen, J, Jassen, A, Guterman, H, Strauven, M, Lormans, P, Verhamme, B, Vandewaeter, C, Bonte, F, Vionne, D, Balik, M, Blaha, J, Lips, M, Othal, M, Bursa, F, Spacek, R, Christensen, S, Jorgensen, V, Sorensen, M, Madsen, S, Puss, S, Beljantsev, A, Saiydoun, G, Fiore, A, Colson, P, Bazalgette, F, Capdevila, X, Kollen, S, Muller, L, Obadia, J, Dubien, P, Ajrhourh, L, Guinot, P, Zarka, J, Besserve, P, Malfertheiner, M, Dreier, E, Heinze, B, Akhyari, P, Lichtenberg, A, Aubin, H, Assman, A, Saeed, D, Thiele, H, Baumgaertel, M, Schmitto, J, Ruslan, N, Haverich, A, Thielmann, M, Brenner, T, Ruhpawar, A, Benk, C, Czerny, M, Staudacher, D, Beyersdorf, F, Kalbhenn, J, Henn, P, Popov, A, Iuliu, T, Muellenbach, R, Reyher, C, Rolfes, C, Lotz, G, Sonntagbauer, M, Winkels, H, Fichte, J, Stohr, R, Kalverkamp, S, Karagiannidis, C, Schafer, S, Svetlitchny, A, Hopf, H, Jarczak, D, Groesdonk, H, Rommer, M, Hirsch, J, Kaehny, C, Soufleris, D, Gavriilidis, G, Pontikis, K, Kyriakopoulou, M, Kyriakoudi, A, O'Brien, S, Conrick-Martin, I, Carton, E, Makhoul, M, Ben-Ari, J, Hadash, A, Kogan, A, Kassif Lerner, R, Abu-Shakra, A, Matan, M, Balawona, A, Kachel, E, Altshuler, R, Galante, O, Fuchs, L, Almog, Y, Ishay, Y, Lichter, Y, Gal-oz, A, Carmi, U, Nini, A, Soroksky, A, Dekel, H, Rozman, Z, Tayem, E, Ilgiyaev, E, Hochman, Y, Miltau, D, Rapoport, A, Eden, A, Kompanietz, D, Yousif, M, Golos, M, Grazioli, L, Ghitti, D, Loforte, A, Di Luca, D, Baiocchi, M, Pacini, D, Cappai, A, Meani, P, Mondino, M, Russo, C, Ranucci, M, Fina, D, Cotza, M, Ballotta, A, Landoni, G, Nardelli, P, Fominski, E, Brazzi, L, Montrucchio, G, Sales, G, Simonetti, U, Livigni, S, Silengo, D, Arena, G, Sovatzis, S, Degani, A, Riccardi, M, Milanesi, E, Raffa, G, Martucci, G, Arcadipane, A, Panarello, G, Chiarini, G, Cattaneo, S, Puglia, C, Benussi, S, Foti, G, Giani, M, Bombino, M, Costa, M, Rona, R, Avalli, L, Donati, A, Carozza, R, Gasparri, F, Carsetti, A, Piciche, M, Marinello, A, Danzi, V, Zanin, A, Condello, I, Fiore, F, Moscarelli, M, Nasso, G, Speziale, G, Sandrelli, L, Montalto, A, Musumeci, F, Circelli, A, Russo, E, Agnoletti, V, Rociola, R, Milano, A, Pilato, E, Comentale, G, Montisci, A, Alessandri, F, Tosi, A, Pugliese, F, Giordano, G, Carelli, S, Grieco, D, Dell'Anna, A, Antonelli, M, Ramoni, E, Zulueta, J, Del Giglio, M, Petracca, S, Bertini, P, Guarracino, F, De Simone, L, Angeletti, P, Forfori, F, Taraschi, F, Quintiliani, V, Samalavicius, R, Jankuviene, A, Scupakova, N, Urbonas, K, Kapturauskas, J, Soerensen, G, Suwalski, P, Linhares Santos, L, Marques, A, Miranda, M, Teixeira, S, Salgueiro, A, Pereira, F, Ketskalo, M, Tsarenko, S, Shilova, A, Afukov, I, Popugaev, K, Minin, S, Shelukhin, D, Malceva, O, Gleb, M, Skopets, A, Kornelyuk, R, Kulikov, A, Okhrimchuk, V, Turchaninov, A, Petrushin, M, Sheck, A, Mekulov, A, Ciryateva, S, Urusov, D, Gorjup, V, Golicnik, A, Goslar, T, Ferrer, R, Martinez-Martinez, M, Argudo, E, Palmer, N, De Pablo Sanchez, R, Juan Higuera, L, Arnau Blasco, L, Marquez, J, Sbraga, F, Fuset, M, De Gopegui, P, Claraco, L, De Ayala, J, Peiro, M, Ricart, P, Martinez, S, Chavez, F, Fabra, M, Sandoval, E, Toapanta, D, Carraminana, A, Tellez, A, Ososio, J, Milan, P, Rodriguez, J, Andoni, G, Gutierrez, C, Perez de la Sota, E, Eixeres-Esteve, A, Garcia-Maellas, M, Gutierrez-Gutierrez, J, Arboleda-Salazar, R, Santa Teresa, P, Jaspe, A, Garrido, A, Castaneda, G, Alcantara, S, Martinez, N, Perez, M, Villanueva, H, Vidal Gonzalez, A, Paez, J, Santon, A, Perez, C, Lopez, M, Rubio Lopez, M, Gordillo, A, Naranjo-Izurieta, J, Munoz, J, Alcalde, I, Onieva, F, Gimeno Costa, R, Perez, F, Madrid, I, Gordon, M, Albacete Moreno, C, Perez, D, Lopez, N, Martinenz, D, Blanco-Schweizer, P, Diez, C, Prieto, A, Renedo, G, Bustamante, E, Cicuendez, R, Citores, R, Boado, V, Garcia, K, Voces, R, Domezain, M, Nunez Martinez, J, Vicente, R, Martin, D, Andreu, A, Gomez Casal, V, Chico, I, Menor, E, Vara, S, Gamacho, J, Perez-Chomon, H, Javier Gonzales, F, Barrero, I, Martin-Villen, L, Fernandez, E, Mendoza, M, Navarro, J, Colomina Climent, J, Gonzales-Perez, A, Muniz-Albaceita, G, Amado, L, Rodriguez, R, Ruiz, E, Eiras, M, Grins, E, Magnus, R, Kanetoft, M, Eidevald, M, Watson, P, Vogt, P, Steiger, P, Aigner, T, Weber, A, Grunefelder, J, Kunz, M, Grapow, M, Aymard, T, Reser, D, Agus, G, Consiglio, J, Haenggi, M, Hansjoerg, J, Iten, M, Doeble, T, Zenklusen, U, Bechtold, X, Faedda, G, Iafrate, M, Rohjer, A, Bergamaschi, L, Maessen, J, Reis Miranda, D, Endeman, H, Gommers, D, Meuwese, C, Maas, J, Van Gijlswijk, M, Van Berg, R, Candura, D, Van der Linden, M, Kant, M, Van der Heijden, J, Scholten, E, Van Belle-van Haren, N, Lagrand, W, Vlaar, A, De Jong, S, Cander, B, Sargin, M, Ugur, M, Kaygin, M, Daly, K, Agnew, N, Head, L, Kelly, L, Anoma, G, Russell, C, Aquino, V, Scott, I, Flemming, L, Gillon, S, Moore, O, Gelandt, E, Auzinger, G, Patel, S, Loveridge, R, Lorusso R., De Piero M. E., Mariani S., Di Mauro M., Folliguet T., Taccone F. S., Camporota L., Swol J., Wiedemann D., Belliato M., Broman L. M., Vuylsteke A., Kassif Y., Scandroglio A. M., Fanelli V., Gaudard P., Ledot S., Barker J., Boeken U., Maier S., Kersten A., Meyns B., Pozzi M., Pedersen F. M., Schellongowski P., Kirali K., Barrett N., Riera J., Mueller T., Belohlavek J., Lo Coco V., Van der Horst I. C. C., Van Bussel B. C. T., Schnabel R. M., Delnoij T., Bolotin G., Lorini L., Schmiady M. O., Schibilsky D., Kowalewski M., Pinto L. F., Silva P. E., Kornilov I., Blandino Ortiz A., Vercaemst L., Finney S., Roeleveld P. P., Di Nardo M., Hennig F., Antonini M. V., Davidson M., Jones T. J., Staudinger T., Mair P., Kilo J., Krapf C., Erbert K., Peer A., Bonaros N., Kotheletner F., Krenner Mag N., Shestakova L., Hermans G., Dauwe D., Meersseman P., Stockman B., Nobile L., Lhereux O., Nrasseurs A., Creuter J., De Backer D., Giglioli S., Michiels G., Foulon P., Raes M., Rodrigus I., Allegaert M., Jorens P., Debeucklare G., Piagnerelli M., Biston P., Peperstraete H., Vandewiele K., Germay O., Vandeweghe D., Havrin S., Bourgeois M., Lagny M. -G., Alois G., Lavios N., Misset B., Courcelle R., Timmermans P. J., Yilmaz A., Vantomout M., Lehaen J., Jassen A., Guterman H., Strauven M., Lormans P., Verhamme B., Vandewaeter C., Bonte F., Vionne D., Balik M., Blaha J., Lips M., Othal M., Bursa F., Spacek R., Christensen S., Jorgensen V., Sorensen M., Madsen S. A., Puss S., Beljantsev A., Saiydoun G., Fiore A., Colson P., Bazalgette F., Capdevila X., Kollen S., Muller L., Obadia J. -F., Dubien P. -Y., Ajrhourh L., Guinot P. G., Zarka J., Besserve P., Malfertheiner M. V., Dreier E., Heinze B., Akhyari P., Lichtenberg A., Aubin H., Assman A., Saeed D., Thiele H., Baumgaertel M., Schmitto J. D., Ruslan N., Haverich A., Thielmann M., Brenner T., Ruhpawar A., Benk C., Czerny M., Staudacher D. L., Beyersdorf F., Kalbhenn J., Henn P., Popov A. -F., Iuliu T., Muellenbach R., Reyher C., Rolfes C., Lotz G., Sonntagbauer M., Winkels H., Fichte J., Stohr R., Kalverkamp S., Karagiannidis C., Schafer S., Svetlitchny A., Hopf H. -B., Jarczak D., Groesdonk H., Rommer M., Hirsch J., Kaehny C., Soufleris D., Gavriilidis G., Pontikis K., Kyriakopoulou M., Kyriakoudi A., O'Brien S., Conrick-Martin I., Carton E., Makhoul M., Ben-Ari J., Hadash A., Kogan A., Kassif Lerner R., Abu-Shakra A., Matan M., Balawona A., Kachel E., Altshuler R., Galante O., Fuchs L., Almog Y., Ishay Y. S., Lichter Y., Gal-oz A., Carmi U., Nini A., Soroksky A., Dekel H., Rozman Z., Tayem E., Ilgiyaev E., Hochman Y., Miltau D., Rapoport A., Eden A., Kompanietz D., Yousif M., Golos M., Grazioli L., Ghitti D., Loforte A., Di Luca D., Baiocchi M., Pacini D., Cappai A., Meani P., Mondino M., Russo C. F., Ranucci M., Fina D., Cotza M., Ballotta A., Landoni G., Nardelli P., Fominski E. V., Brazzi L., Montrucchio G., Sales G., Simonetti U., Livigni S., Silengo D., Arena G., Sovatzis S. S., Degani A., Riccardi M., Milanesi E., Raffa G., Martucci G., Arcadipane A., Panarello G., Chiarini G., Cattaneo S., Puglia C., Benussi S., Foti G., Giani M., Bombino M., Costa M. C., Rona R., Avalli L., Donati A., Carozza R., Gasparri F., Carsetti A., Piciche M., Marinello A., Danzi V., Zanin A., Condello I., Fiore F., Moscarelli M., Nasso G., Speziale G., Sandrelli L., Montalto A., Musumeci F., Circelli A., Russo E., Agnoletti V., Rociola R., Milano A. D., Pilato E., Comentale G., Montisci A., Alessandri F., Tosi A., Pugliese F., Giordano G., Carelli S., Grieco D. L., Dell'Anna A. M., Antonelli M., Ramoni E., Zulueta J., Del Giglio M., Petracca S., Bertini P., Guarracino F., De Simone L., Angeletti P. M., Forfori F., Taraschi F., Quintiliani V. N., Samalavicius R., Jankuviene A., Scupakova N., Urbonas K., Kapturauskas J., Soerensen G., Suwalski P., Linhares Santos L., Marques A., Miranda M., Teixeira S., Salgueiro A., Pereira F., Ketskalo M., Tsarenko S., Shilova A., Afukov I., Popugaev K., Minin S., Shelukhin D., Malceva O., Gleb M., Skopets A., Kornelyuk R., Kulikov A., Okhrimchuk V., Turchaninov A., Petrushin M., Sheck A., Mekulov A., Ciryateva S., Urusov D., Gorjup V., Golicnik A., Goslar T., Ferrer R., Martinez-Martinez M., Argudo E., Palmer N., De Pablo Sanchez R., Juan Higuera L., Arnau Blasco L., Marquez J. A., Sbraga F., Fuset M. P., De Gopegui P. R., Claraco L. M., De Ayala J. A., Peiro M., Ricart P., Martinez S., Chavez F., Fabra M., Sandoval E., Toapanta D., Carraminana A., Tellez A., Ososio J., Milan P., Rodriguez J., Andoni G., Gutierrez C., Perez de la Sota E., Eixeres-Esteve A., Garcia-Maellas M. T., Gutierrez-Gutierrez J., Arboleda-Salazar R., Santa Teresa P., Jaspe A., Garrido A., Castaneda G., Alcantara S., Martinez N., Perez M., Villanueva H., Vidal Gonzalez A., Paez J., Santon A., Perez C., Lopez M., Rubio Lopez M. I., Gordillo A., Naranjo-Izurieta J., Munoz J., Alcalde I., Onieva F., Gimeno Costa R., Perez F., Madrid I., Gordon M., Albacete Moreno C. L., Perez D., Lopez N., Martinenz D., Blanco-Schweizer P., Diez C., Prieto A., Renedo G., Bustamante E., Cicuendez R., Citores R., Boado V., Garcia K., Voces R., Domezain M., Nunez Martinez J. M., Vicente R., Martin D., Andreu A., Gomez Casal V., Chico I., Menor E. M., Vara S., Gamacho J., Perez-Chomon H., Javier Gonzales F., Barrero I., Martin-Villen L., Fernandez E., Mendoza M., Navarro J., Colomina Climent J., Gonzales-Perez A., Muniz-Albaceita G., Amado L., Rodriguez R., Ruiz E., Eiras M., Grins E., Magnus R., Kanetoft M., Eidevald M., Watson P., Vogt P. R., Steiger P., Aigner T., Weber A., Grunefelder J., Kunz M., Grapow M., Aymard T., Reser D., Agus G., Consiglio J., Haenggi M., Hansjoerg J., Iten M., Doeble T., Zenklusen U., Bechtold X., Faedda G., Iafrate M., Rohjer A., Bergamaschi L., Maessen J., Reis Miranda D., Endeman H., Gommers D., Meuwese C., Maas J., Van Gijlswijk M. J., Van Berg R. N., Candura D., Van der Linden M., Kant M., Van der Heijden J. J., Scholten E., Van Belle-van Haren N., Lagrand W. K., Vlaar A. P., De Jong S., Cander B., Sargin M., Ugur M., Kaygin M. A., Daly K., Agnew N., Head L., Kelly L., Anoma G., Russell C., Aquino V., Scott I., Flemming L., Gillon S., Moore O., Gelandt E., Auzinger G., Patel S., Loveridge R., Lorusso, R, De Piero, M, Mariani, S, Di Mauro, M, Folliguet, T, Taccone, F, Camporota, L, Swol, J, Wiedemann, D, Belliato, M, Broman, L, Vuylsteke, A, Kassif, Y, Scandroglio, A, Fanelli, V, Gaudard, P, Ledot, S, Barker, J, Boeken, U, Maier, S, Kersten, A, Meyns, B, Pozzi, M, Pedersen, F, Schellongowski, P, Kirali, K, Barrett, N, Riera, J, Mueller, T, Belohlavek, J, Lo Coco, V, Van der Horst, I, Van Bussel, B, Schnabel, R, Delnoij, T, Bolotin, G, Lorini, L, Schmiady, M, Schibilsky, D, Kowalewski, M, Pinto, L, Silva, P, Kornilov, I, Blandino Ortiz, A, Vercaemst, L, Finney, S, Roeleveld, P, Di Nardo, M, Hennig, F, Antonini, M, Davidson, M, Jones, T, Staudinger, T, Mair, P, Kilo, J, Krapf, C, Erbert, K, Peer, A, Bonaros, N, Kotheletner, F, Krenner Mag, N, Shestakova, L, Hermans, G, Dauwe, D, Meersseman, P, Stockman, B, Nobile, L, Lhereux, O, Nrasseurs, A, Creuter, J, De Backer, D, Giglioli, S, Michiels, G, Foulon, P, Raes, M, Rodrigus, I, Allegaert, M, Jorens, P, Debeucklare, G, Piagnerelli, M, Biston, P, Peperstraete, H, Vandewiele, K, Germay, O, Vandeweghe, D, Havrin, S, Bourgeois, M, Lagny, M, Alois, G, Lavios, N, Misset, B, Courcelle, R, Timmermans, P, Yilmaz, A, Vantomout, M, Lehaen, J, Jassen, A, Guterman, H, Strauven, M, Lormans, P, Verhamme, B, Vandewaeter, C, Bonte, F, Vionne, D, Balik, M, Blaha, J, Lips, M, Othal, M, Bursa, F, Spacek, R, Christensen, S, Jorgensen, V, Sorensen, M, Madsen, S, Puss, S, Beljantsev, A, Saiydoun, G, Fiore, A, Colson, P, Bazalgette, F, Capdevila, X, Kollen, S, Muller, L, Obadia, J, Dubien, P, Ajrhourh, L, Guinot, P, Zarka, J, Besserve, P, Malfertheiner, M, Dreier, E, Heinze, B, Akhyari, P, Lichtenberg, A, Aubin, H, Assman, A, Saeed, D, Thiele, H, Baumgaertel, M, Schmitto, J, Ruslan, N, Haverich, A, Thielmann, M, Brenner, T, Ruhpawar, A, Benk, C, Czerny, M, Staudacher, D, Beyersdorf, F, Kalbhenn, J, Henn, P, Popov, A, Iuliu, T, Muellenbach, R, Reyher, C, Rolfes, C, Lotz, G, Sonntagbauer, M, Winkels, H, Fichte, J, Stohr, R, Kalverkamp, S, Karagiannidis, C, Schafer, S, Svetlitchny, A, Hopf, H, Jarczak, D, Groesdonk, H, Rommer, M, Hirsch, J, Kaehny, C, Soufleris, D, Gavriilidis, G, Pontikis, K, Kyriakopoulou, M, Kyriakoudi, A, O'Brien, S, Conrick-Martin, I, Carton, E, Makhoul, M, Ben-Ari, J, Hadash, A, Kogan, A, Kassif Lerner, R, Abu-Shakra, A, Matan, M, Balawona, A, Kachel, E, Altshuler, R, Galante, O, Fuchs, L, Almog, Y, Ishay, Y, Lichter, Y, Gal-oz, A, Carmi, U, Nini, A, Soroksky, A, Dekel, H, Rozman, Z, Tayem, E, Ilgiyaev, E, Hochman, Y, Miltau, D, Rapoport, A, Eden, A, Kompanietz, D, Yousif, M, Golos, M, Grazioli, L, Ghitti, D, Loforte, A, Di Luca, D, Baiocchi, M, Pacini, D, Cappai, A, Meani, P, Mondino, M, Russo, C, Ranucci, M, Fina, D, Cotza, M, Ballotta, A, Landoni, G, Nardelli, P, Fominski, E, Brazzi, L, Montrucchio, G, Sales, G, Simonetti, U, Livigni, S, Silengo, D, Arena, G, Sovatzis, S, Degani, A, Riccardi, M, Milanesi, E, Raffa, G, Martucci, G, Arcadipane, A, Panarello, G, Chiarini, G, Cattaneo, S, Puglia, C, Benussi, S, Foti, G, Giani, M, Bombino, M, Costa, M, Rona, R, Avalli, L, Donati, A, Carozza, R, Gasparri, F, Carsetti, A, Piciche, M, Marinello, A, Danzi, V, Zanin, A, Condello, I, Fiore, F, Moscarelli, M, Nasso, G, Speziale, G, Sandrelli, L, Montalto, A, Musumeci, F, Circelli, A, Russo, E, Agnoletti, V, Rociola, R, Milano, A, Pilato, E, Comentale, G, Montisci, A, Alessandri, F, Tosi, A, Pugliese, F, Giordano, G, Carelli, S, Grieco, D, Dell'Anna, A, Antonelli, M, Ramoni, E, Zulueta, J, Del Giglio, M, Petracca, S, Bertini, P, Guarracino, F, De Simone, L, Angeletti, P, Forfori, F, Taraschi, F, Quintiliani, V, Samalavicius, R, Jankuviene, A, Scupakova, N, Urbonas, K, Kapturauskas, J, Soerensen, G, Suwalski, P, Linhares Santos, L, Marques, A, Miranda, M, Teixeira, S, Salgueiro, A, Pereira, F, Ketskalo, M, Tsarenko, S, Shilova, A, Afukov, I, Popugaev, K, Minin, S, Shelukhin, D, Malceva, O, Gleb, M, Skopets, A, Kornelyuk, R, Kulikov, A, Okhrimchuk, V, Turchaninov, A, Petrushin, M, Sheck, A, Mekulov, A, Ciryateva, S, Urusov, D, Gorjup, V, Golicnik, A, Goslar, T, Ferrer, R, Martinez-Martinez, M, Argudo, E, Palmer, N, De Pablo Sanchez, R, Juan Higuera, L, Arnau Blasco, L, Marquez, J, Sbraga, F, Fuset, M, De Gopegui, P, Claraco, L, De Ayala, J, Peiro, M, Ricart, P, Martinez, S, Chavez, F, Fabra, M, Sandoval, E, Toapanta, D, Carraminana, A, Tellez, A, Ososio, J, Milan, P, Rodriguez, J, Andoni, G, Gutierrez, C, Perez de la Sota, E, Eixeres-Esteve, A, Garcia-Maellas, M, Gutierrez-Gutierrez, J, Arboleda-Salazar, R, Santa Teresa, P, Jaspe, A, Garrido, A, Castaneda, G, Alcantara, S, Martinez, N, Perez, M, Villanueva, H, Vidal Gonzalez, A, Paez, J, Santon, A, Perez, C, Lopez, M, Rubio Lopez, M, Gordillo, A, Naranjo-Izurieta, J, Munoz, J, Alcalde, I, Onieva, F, Gimeno Costa, R, Perez, F, Madrid, I, Gordon, M, Albacete Moreno, C, Perez, D, Lopez, N, Martinenz, D, Blanco-Schweizer, P, Diez, C, Prieto, A, Renedo, G, Bustamante, E, Cicuendez, R, Citores, R, Boado, V, Garcia, K, Voces, R, Domezain, M, Nunez Martinez, J, Vicente, R, Martin, D, Andreu, A, Gomez Casal, V, Chico, I, Menor, E, Vara, S, Gamacho, J, Perez-Chomon, H, Javier Gonzales, F, Barrero, I, Martin-Villen, L, Fernandez, E, Mendoza, M, Navarro, J, Colomina Climent, J, Gonzales-Perez, A, Muniz-Albaceita, G, Amado, L, Rodriguez, R, Ruiz, E, Eiras, M, Grins, E, Magnus, R, Kanetoft, M, Eidevald, M, Watson, P, Vogt, P, Steiger, P, Aigner, T, Weber, A, Grunefelder, J, Kunz, M, Grapow, M, Aymard, T, Reser, D, Agus, G, Consiglio, J, Haenggi, M, Hansjoerg, J, Iten, M, Doeble, T, Zenklusen, U, Bechtold, X, Faedda, G, Iafrate, M, Rohjer, A, Bergamaschi, L, Maessen, J, Reis Miranda, D, Endeman, H, Gommers, D, Meuwese, C, Maas, J, Van Gijlswijk, M, Van Berg, R, Candura, D, Van der Linden, M, Kant, M, Van der Heijden, J, Scholten, E, Van Belle-van Haren, N, Lagrand, W, Vlaar, A, De Jong, S, Cander, B, Sargin, M, Ugur, M, Kaygin, M, Daly, K, Agnew, N, Head, L, Kelly, L, Anoma, G, Russell, C, Aquino, V, Scott, I, Flemming, L, Gillon, S, Moore, O, Gelandt, E, Auzinger, G, Patel, S, Loveridge, R, Lorusso R., De Piero M. E., Mariani S., Di Mauro M., Folliguet T., Taccone F. S., Camporota L., Swol J., Wiedemann D., Belliato M., Broman L. M., Vuylsteke A., Kassif Y., Scandroglio A. M., Fanelli V., Gaudard P., Ledot S., Barker J., Boeken U., Maier S., Kersten A., Meyns B., Pozzi M., Pedersen F. M., Schellongowski P., Kirali K., Barrett N., Riera J., Mueller T., Belohlavek J., Lo Coco V., Van der Horst I. C. C., Van Bussel B. C. T., Schnabel R. M., Delnoij T., Bolotin G., Lorini L., Schmiady M. O., Schibilsky D., Kowalewski M., Pinto L. F., Silva P. E., Kornilov I., Blandino Ortiz A., Vercaemst L., Finney S., Roeleveld P. P., Di Nardo M., Hennig F., Antonini M. V., Davidson M., Jones T. J., Staudinger T., Mair P., Kilo J., Krapf C., Erbert K., Peer A., Bonaros N., Kotheletner F., Krenner Mag N., Shestakova L., Hermans G., Dauwe D., Meersseman P., Stockman B., Nobile L., Lhereux O., Nrasseurs A., Creuter J., De Backer D., Giglioli S., Michiels G., Foulon P., Raes M., Rodrigus I., Allegaert M., Jorens P., Debeucklare G., Piagnerelli M., Biston P., Peperstraete H., Vandewiele K., Germay O., Vandeweghe D., Havrin S., Bourgeois M., Lagny M. -G., Alois G., Lavios N., Misset B., Courcelle R., Timmermans P. J., Yilmaz A., Vantomout M., Lehaen J., Jassen A., Guterman H., Strauven M., Lormans P., Verhamme B., Vandewaeter C., Bonte F., Vionne D., Balik M., Blaha J., Lips M., Othal M., Bursa F., Spacek R., Christensen S., Jorgensen V., Sorensen M., Madsen S. A., Puss S., Beljantsev A., Saiydoun G., Fiore A., Colson P., Bazalgette F., Capdevila X., Kollen S., Muller L., Obadia J. -F., Dubien P. -Y., Ajrhourh L., Guinot P. G., Zarka J., Besserve P., Malfertheiner M. V., Dreier E., Heinze B., Akhyari P., Lichtenberg A., Aubin H., Assman A., Saeed D., Thiele H., Baumgaertel M., Schmitto J. D., Ruslan N., Haverich A., Thielmann M., Brenner T., Ruhpawar A., Benk C., Czerny M., Staudacher D. L., Beyersdorf F., Kalbhenn J., Henn P., Popov A. -F., Iuliu T., Muellenbach R., Reyher C., Rolfes C., Lotz G., Sonntagbauer M., Winkels H., Fichte J., Stohr R., Kalverkamp S., Karagiannidis C., Schafer S., Svetlitchny A., Hopf H. -B., Jarczak D., Groesdonk H., Rommer M., Hirsch J., Kaehny C., Soufleris D., Gavriilidis G., Pontikis K., Kyriakopoulou M., Kyriakoudi A., O'Brien S., Conrick-Martin I., Carton E., Makhoul M., Ben-Ari J., Hadash A., Kogan A., Kassif Lerner R., Abu-Shakra A., Matan M., Balawona A., Kachel E., Altshuler R., Galante O., Fuchs L., Almog Y., Ishay Y. S., Lichter Y., Gal-oz A., Carmi U., Nini A., Soroksky A., Dekel H., Rozman Z., Tayem E., Ilgiyaev E., Hochman Y., Miltau D., Rapoport A., Eden A., Kompanietz D., Yousif M., Golos M., Grazioli L., Ghitti D., Loforte A., Di Luca D., Baiocchi M., Pacini D., Cappai A., Meani P., Mondino M., Russo C. F., Ranucci M., Fina D., Cotza M., Ballotta A., Landoni G., Nardelli P., Fominski E. V., Brazzi L., Montrucchio G., Sales G., Simonetti U., Livigni S., Silengo D., Arena G., Sovatzis S. S., Degani A., Riccardi M., Milanesi E., Raffa G., Martucci G., Arcadipane A., Panarello G., Chiarini G., Cattaneo S., Puglia C., Benussi S., Foti G., Giani M., Bombino M., Costa M. C., Rona R., Avalli L., Donati A., Carozza R., Gasparri F., Carsetti A., Piciche M., Marinello A., Danzi V., Zanin A., Condello I., Fiore F., Moscarelli M., Nasso G., Speziale G., Sandrelli L., Montalto A., Musumeci F., Circelli A., Russo E., Agnoletti V., Rociola R., Milano A. D., Pilato E., Comentale G., Montisci A., Alessandri F., Tosi A., Pugliese F., Giordano G., Carelli S., Grieco D. L., Dell'Anna A. M., Antonelli M., Ramoni E., Zulueta J., Del Giglio M., Petracca S., Bertini P., Guarracino F., De Simone L., Angeletti P. M., Forfori F., Taraschi F., Quintiliani V. N., Samalavicius R., Jankuviene A., Scupakova N., Urbonas K., Kapturauskas J., Soerensen G., Suwalski P., Linhares Santos L., Marques A., Miranda M., Teixeira S., Salgueiro A., Pereira F., Ketskalo M., Tsarenko S., Shilova A., Afukov I., Popugaev K., Minin S., Shelukhin D., Malceva O., Gleb M., Skopets A., Kornelyuk R., Kulikov A., Okhrimchuk V., Turchaninov A., Petrushin M., Sheck A., Mekulov A., Ciryateva S., Urusov D., Gorjup V., Golicnik A., Goslar T., Ferrer R., Martinez-Martinez M., Argudo E., Palmer N., De Pablo Sanchez R., Juan Higuera L., Arnau Blasco L., Marquez J. A., Sbraga F., Fuset M. P., De Gopegui P. R., Claraco L. M., De Ayala J. A., Peiro M., Ricart P., Martinez S., Chavez F., Fabra M., Sandoval E., Toapanta D., Carraminana A., Tellez A., Ososio J., Milan P., Rodriguez J., Andoni G., Gutierrez C., Perez de la Sota E., Eixeres-Esteve A., Garcia-Maellas M. T., Gutierrez-Gutierrez J., Arboleda-Salazar R., Santa Teresa P., Jaspe A., Garrido A., Castaneda G., Alcantara S., Martinez N., Perez M., Villanueva H., Vidal Gonzalez A., Paez J., Santon A., Perez C., Lopez M., Rubio Lopez M. I., Gordillo A., Naranjo-Izurieta J., Munoz J., Alcalde I., Onieva F., Gimeno Costa R., Perez F., Madrid I., Gordon M., Albacete Moreno C. L., Perez D., Lopez N., Martinenz D., Blanco-Schweizer P., Diez C., Prieto A., Renedo G., Bustamante E., Cicuendez R., Citores R., Boado V., Garcia K., Voces R., Domezain M., Nunez Martinez J. M., Vicente R., Martin D., Andreu A., Gomez Casal V., Chico I., Menor E. M., Vara S., Gamacho J., Perez-Chomon H., Javier Gonzales F., Barrero I., Martin-Villen L., Fernandez E., Mendoza M., Navarro J., Colomina Climent J., Gonzales-Perez A., Muniz-Albaceita G., Amado L., Rodriguez R., Ruiz E., Eiras M., Grins E., Magnus R., Kanetoft M., Eidevald M., Watson P., Vogt P. R., Steiger P., Aigner T., Weber A., Grunefelder J., Kunz M., Grapow M., Aymard T., Reser D., Agus G., Consiglio J., Haenggi M., Hansjoerg J., Iten M., Doeble T., Zenklusen U., Bechtold X., Faedda G., Iafrate M., Rohjer A., Bergamaschi L., Maessen J., Reis Miranda D., Endeman H., Gommers D., Meuwese C., Maas J., Van Gijlswijk M. J., Van Berg R. N., Candura D., Van der Linden M., Kant M., Van der Heijden J. J., Scholten E., Van Belle-van Haren N., Lagrand W. K., Vlaar A. P., De Jong S., Cander B., Sargin M., Ugur M., Kaygin M. A., Daly K., Agnew N., Head L., Kelly L., Anoma G., Russell C., Aquino V., Scott I., Flemming L., Gillon S., Moore O., Gelandt E., Auzinger G., Patel S., and Loveridge R.

Abstract

Background: Extracorporeal membrane oxygenation (ECMO) has been widely used in patients with COVID-19, but uncertainty remains about the determinants of in-hospital mortality and data on post-discharge outcomes are scarce. The aims of this study were to investigate the variables associated with in-hospital outcomes in patients who received ECMO during the first wave of COVID-19 and to describe the status of patients 6 months after ECMO initiation. Methods: EuroECMO-COVID is a prospective, multicentre, observational study developed by the European Extracorporeal Life Support Organization. This study was based on data from patients aged 16 years or older who received ECMO support for refractory COVID-19 during the first wave of the pandemic—from March 1 to Sept 13, 2020—at 133 centres in 21 countries. In-hospital mortality and mortality 6 months after ECMO initiation were the primary outcomes. Mixed-Cox proportional hazards models were used to investigate associations between patient and management-related variables (eg, patient demographics, comorbidities, pre-ECMO status, and ECMO characteristics and complications) and in-hospital deaths. Survival status at 6 months was established through patient contact or institutional charts review. This study is registered with ClinicalTrials.gov, NCT04366921, and is ongoing. Findings: Between March 1 and Sept 13, 2020, 1215 patients (942 [78%] men and 267 [22%] women; median age 53 years [IQR 46–60]) were included in the study. Median ECMO duration was 15 days (IQR 8–27). 602 (50%) of 1215 patients died in hospital, and 852 (74%) patients had at least one complication. Multiorgan failure was the leading cause of death (192 [36%] of 528 patients who died with available data). In mixed-Cox analyses, age of 60 years or older, use of inotropes and vasopressors before ECMO initiation, chronic renal failure, and time from intubation to ECMO initiation of 4 days or more were associated with higher in-hospital mortality. 613 patients

Published
2023

3. Validation of mitotic cell quantification via microscopy and multiple whole-slide scanners

Author

Kazuhiro Tabata, Naohiro Uraoka, Jamal Benhamida, Matthew G. Hanna, Sahussapont Joseph Sirintrapun, Brandon D. Gallas, Qi Gong, Rania G. Aly, Katsura Emoto, Kant M. Matsuda, Meera R. Hameed, David S. Klimstra, and Yukako Yagi

Subjects
Whole slide imaging, Microscopy, eeDAP, Multiple whole slide scanner, Mitotic cell quantification, Validation study, Pathology, RB1-214
Abstract

Abstract Background The establishment of whole-slide imaging (WSI) as a medical diagnostic device allows that pathologists may evaluate mitotic activity with this new technology. Furthermore, the image digitalization provides an opportunity to develop algorithms for automatic quantifications, ideally leading to improved reproducibility as compared to the naked eye examination by pathologists. In order to implement them effectively, accuracy of mitotic figure detection using WSI should be investigated. In this study, we aimed to measure pathologist performance in detecting mitotic figures (MFs) using multiple platforms (multiple scanners) and compare the results with those obtained using a brightfield microscope. Methods Four slides of canine oral melanoma were prepared and digitized using 4 WSI scanners. In these slides, 40 regions of interest (ROIs) were demarcated, and five observers identified the MFs using different viewing modes: microscopy and WSI. We evaluated the inter- and intra-observer agreements between modes with Cohen’s Kappa and determined “true” MFs with a consensus panel. We then assessed the accuracy (agreement with truth) using the average of sensitivity and specificity. Results In the 40 ROIs, 155 candidate MFs were detected by five pathologists; 74 of them were determined to be true MFs. Inter- and intra-observer agreement was mostly “substantial” or greater (Kappa = 0.594–0.939). Accuracy was between 0.632 and 0.843 across all readers and modes. After averaging over readers for each modality, we found that mitosis detection accuracy for 3 of the 4 WSI scanners was significantly less than that of the microscope (p = 0.002, 0.012, and 0.001). Conclusions This study is the first to compare WSIs and microscopy in detecting MFs at the level of individual cells. Our results suggest that WSI can be used for mitotic cell detection and offers similar reproducibility to the microscope, with slightly less accuracy.

Published
2019
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5. Transport study of charged current interactions in neutrino-nucleus reactions

Author

Cassing, W., Kant, M., Langanke, K., and Vogel, P.

Subjects
Nuclear Theory
Abstract

Within a dynamical transport approach we investigate charged current interactions in neutrino-nucleus reactions for neutrino energies of 0.3 - 1.5 GeV with particular emphasis on resonant pion production channels via the $\Delta_{33}(1232)$ resonance. The final-state-interactions of the resonance as well as of the emitted pions are calculated explicitly for $^{12}C$ and $^{56}Fe$ nuclei and show a dominance of pion suppression at moderate momenta $p_\pi >$ 0.2 GeV/c. A comparison to integrated $\pi^+$ spectra for $\nu_\mu + ^{12}C$ reactions with the available (preliminary) data demonstrates a reasonable agreement., Comment: 13 pages incl. 6 eps-figures; computational error in final state interactions corrected; to be published in Phys. Lett. B

Published
2006
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7. High treatment adherence, satisfaction, motivation, and health-related quality of life with fingolimod in patients with relapsing-remitting multiple sclerosis – results from a 24-month, multicenter, open-label Danish study

Author

Schreiber K, Kant M, Pfleger C, Jensen HB, Oesterberg O, Hald AR, Nielsen FK, and Rubak S

Subjects
Gilenya®, multiple sclerosis, treatment adherence, motivational interview, quality of life, Treatment Satisfaction Questionnaire for Medication, Medicine (General), R5-920
Abstract

Karen Schreiber,1 Matthias Kant,2 Claudia Pfleger,3 Henrik Boye Jensen,4 Ole Oesterberg,5 Anne Rieper Hald,5 Frederik K Nielsen,5 Sune Rubak6 1Department of Neurology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark; 2Department of Neurology, Hospital of Southern Jutland, Soenderborg, Denmark; 3Department of Neurology, Aalborg University Hospital, Denmark; 4Department of Neurology, Kolding Hospital, Kolding, Denmark; 5Novartis Pharmaceutical, Copenhagen, Denmark; 6Department of Child and Adolescent Health, Aarhus University Hospital Skejby, Aarhus Denmark Purpose: Treatment adherence is a prerequisite for treatment success and therefore an important consideration to assure that therapeutic goals are achieved both from a patient point of view and for optimal health care resource utilization. Published data on treatment adherence with fingolimod (Gilenya®) are limited. Therefore, this study investigated treatment adherence in patients with relapsing-remitting multiple sclerosis (RRMS) treated with fingolimod in Denmark. Patients and methods: This was a 24-month, multicenter, open-label study, investigating treatment adherence, satisfaction, motivation, and health-related quality of life (QoL) in RRMS patients treated with fingolimod. In addition, the effect of a motivational interview support program on these measures was evaluated. Treatment adherence was assessed by pill count. Treatment satisfaction, motivation, and QoL were assessed by patient-reported outcomes (PROs). Results: A total of 195 patients were enrolled in the study. A very high treatment adherence was observed during the entire study with no statistically significant difference between study visits before (99%) and after (97%) the motivational interview. In accordance, a high level of treatment satisfaction was found in the Treatment Satisfaction Questionnaire for Medication 9, which was scored high throughout the study with the highest scores seen for the convenience domain (ranging from 94.51 to 95.78). Furthermore, additional PROs demonstrated a high health-related QoL, a self-determined form of motivation for taking medication, and a patient perception of an autonomy supportive approach provided by the health care provider, at all study visits. Conclusion: High levels of treatment adherence, satisfaction, motivation, and QoL were observed in Danish RRMS patients treated with fingolimod. As these positive measures were observed at all study visits and throughout the study, no effect of the motivational interview support program was found. Keywords: Gilenya®, multiple sclerosis, treatment adherence, motivational interview, quality of life, Treatment Satisfaction Questionnaire for Medication

Published
2018

8. Predictors of treatment switching in the Big Multiple Sclerosis Data Network.

Author

Spelman, T, Magyari, M, Butzkueven, H, Van Der Walt, A, Vukusic, S, Trojano, M, Iaffaldano, P, Horáková, D, Drahota, J, Pellegrini, F, Hyde, R, Duquette, P, Lechner-Scott, J, Sajedi, SA, Lalive, P, Shaygannejad, V, Ozakbas, S, Eichau, S, Alroughani, R, Terzi, M, Girard, M, Kalincik, T, Grand'Maison, F, Skibina, O, Khoury, SJ, Yamout, B, Sa, MJ, Gerlach, O, Blanco, Y, Karabudak, R, Oreja-Guevara, C, Altintas, A, Hughes, S, McCombe, P, Ampapa, R, de Gans, K, McGuigan, C, Soysal, A, Prevost, J, John, N, Inshasi, J, Stawiarz, L, Manouchehrinia, A, Forsberg, L, Sellebjerg, F, Glaser, A, Pontieri, L, Joensen, H, Rasmussen, PV, Sejbaek, T, Poulsen, MB, Christensen, JR, Kant, M, Stilund, M, Mathiesen, H, Hillert, J, Big MS Data Network: a collaboration of the Czech MS Registry, the Danish MS Registry, Italian MS Registry, Swedish MS Registry, MSBase Study Group, and OFSEP, Spelman, T, Magyari, M, Butzkueven, H, Van Der Walt, A, Vukusic, S, Trojano, M, Iaffaldano, P, Horáková, D, Drahota, J, Pellegrini, F, Hyde, R, Duquette, P, Lechner-Scott, J, Sajedi, SA, Lalive, P, Shaygannejad, V, Ozakbas, S, Eichau, S, Alroughani, R, Terzi, M, Girard, M, Kalincik, T, Grand'Maison, F, Skibina, O, Khoury, SJ, Yamout, B, Sa, MJ, Gerlach, O, Blanco, Y, Karabudak, R, Oreja-Guevara, C, Altintas, A, Hughes, S, McCombe, P, Ampapa, R, de Gans, K, McGuigan, C, Soysal, A, Prevost, J, John, N, Inshasi, J, Stawiarz, L, Manouchehrinia, A, Forsberg, L, Sellebjerg, F, Glaser, A, Pontieri, L, Joensen, H, Rasmussen, PV, Sejbaek, T, Poulsen, MB, Christensen, JR, Kant, M, Stilund, M, Mathiesen, H, Hillert, J, and Big MS Data Network: a collaboration of the Czech MS Registry, the Danish MS Registry, Italian MS Registry, Swedish MS Registry, MSBase Study Group, and OFSEP

Abstract

BACKGROUND: Treatment switching is a common challenge and opportunity in real-world clinical practice. Increasing diversity in disease-modifying treatments (DMTs) has generated interest in the identification of reliable and robust predictors of treatment switching across different countries, DMTs, and time periods. OBJECTIVE: The objective of this retrospective, observational study was to identify independent predictors of treatment switching in a population of relapsing-remitting MS (RRMS) patients in the Big Multiple Sclerosis Data Network of national clinical registries, including the Italian MS registry, the OFSEP of France, the Danish MS registry, the Swedish national MS registry, and the international MSBase Registry. METHODS: In this cohort study, we merged information on 269,822 treatment episodes in 110,326 patients from 1997 to 2018 from five clinical registries. Patients were included in the final pooled analysis set if they had initiated at least one DMT during the relapsing-remitting MS (RRMS) stage. Patients not diagnosed with RRMS or RRMS patients not initiating DMT therapy during the RRMS phase were excluded from the analysis. The primary study outcome was treatment switching. A multilevel mixed-effects shared frailty time-to-event model was used to identify independent predictors of treatment switching. The contributing MS registry was included in the pooled analysis as a random effect. RESULTS: Every one-point increase in the Expanded Disability Status Scale (EDSS) score at treatment start was associated with 1.08 times the rate of subsequent switching, adjusting for age, sex, and calendar year (adjusted hazard ratio [aHR] 1.08; 95% CI 1.07-1.08). Women were associated with 1.11 times the rate of switching relative to men (95% CI 1.08-1.14), whilst older age was also associated with an increased rate of treatment switching. DMTs started between 2007 and 2012 were associated with 2.48 times the rate of switching relative to DMTs that began between 1

Published
2023

9. Rituximab vs Ocrelizumab in Relapsing-Remitting Multiple Sclerosis

Author

Roos, I, Hughes, S, McDonnell, G, Malpas, CB, Sharmin, S, Boz, C, Alroughani, R, Ozakbas, S, Buzzard, K, Skibina, O, van der Walt, A, Butzkueven, H, Lechner-Scott, J, Kuhle, J, Terzi, M, Laureys, G, Van Hijfte, L, John, N, Grammond, P, Grand'Maison, F, Soysal, A, Jensen, AV, Rasmussen, PV, Svendsen, KB, Barzinji, I, Nielsen, HH, Sejbaek, T, Prakash, S, Stilund, MLM, Weglewski, A, Issa, NM, Kant, M, Sellebjerg, F, Gray, O, Magyari, M, Kalincik, T, MSBase, SG, Danish, MSRSG, Roos, I, Hughes, S, McDonnell, G, Malpas, CB, Sharmin, S, Boz, C, Alroughani, R, Ozakbas, S, Buzzard, K, Skibina, O, van der Walt, A, Butzkueven, H, Lechner-Scott, J, Kuhle, J, Terzi, M, Laureys, G, Van Hijfte, L, John, N, Grammond, P, Grand'Maison, F, Soysal, A, Jensen, AV, Rasmussen, PV, Svendsen, KB, Barzinji, I, Nielsen, HH, Sejbaek, T, Prakash, S, Stilund, MLM, Weglewski, A, Issa, NM, Kant, M, Sellebjerg, F, Gray, O, Magyari, M, Kalincik, T, MSBase, SG, and Danish, MSRSG

Abstract

IMPORTANCE: Ocrelizumab, a humanized monoclonal antibody targeted against CD20+ B cells, reduces the frequency of relapses by 46% and disability worsening by 40% compared with interferon beta 1a in relapsing-remitting multiple sclerosis (MS). Rituximab, a chimeric monoclonal anti-CD20 agent, is often prescribed as an off-label alternative to ocrelizumab. OBJECTIVE: To evaluate whether the effectiveness of rituximab is noninferior to ocrelizumab in relapsing-remitting MS. DESIGN, SETTING, AND PARTICIPANTS: This was an observational cohort study conducted between January 2015 and March 2021. Patients were included in the treatment group for the duration of study therapy and were recruited from the MSBase registry and Danish MS Registry (DMSR). Included patients had a history of relapsing-remitting MS treated with ocrelizumab or rituximab, a minimum 6 months of follow-up, and sufficient data to calculate the propensity score. Patients with comparable baseline characteristics were 1:6 matched with propensity score on age, sex, MS duration, disability (Expanded Disability Status Scale), prior relapse rate, prior therapy, disease activity (relapses, disability accumulation, or both), magnetic resonance imaging lesion burden (missing values imputed), and country. EXPOSURE: Treatment with ocrelizumab or rituximab after 2015. MAIN OUTCOMES AND MEASURES: Noninferiority comparison of annualized rate of relapses (ARRs), with a prespecified noninferiority margin of 1.63 rate ratio. Secondary end points were relapse and 6-month confirmed disability accumulation in pairwise-censored groups. RESULTS: Of the 6027 patients with MS who were treated with ocrelizumab or rituximab, a total of 1613 (mean [SD] age; 42.0 [10.8] years; 1089 female [68%]) fulfilled the inclusion criteria and were included in the analysis (898 MSBase, 715 DMSR). A total of 710 patients treated with ocrelizumab (414 MSBase, 296 DMSR) were matched with 186 patients treated with rituximab (110 MSBase, 76 DMSR). O

Published
2023

12. Quantitative Ex Vivo MRI Changes due to Progressive Formalin Fixation in Whole Human Brain Specimens: Longitudinal Characterization of Diffusion, Relaxometry, and Myelin Water Fraction Measurements at 3T

Author

Anwar S. Shatil, Md Nasir Uddin, Kant M. Matsuda, and Chase R. Figley

Subjects
ex vivo, fixation, formalin, longitudinal, postmortem, human brain, Medicine (General), R5-920
Abstract

PurposePostmortem MRI can be used to reveal important pathologies and establish radiology–pathology correlations. However, quantitative MRI values are altered by tissue fixation. Therefore, the purpose of this study was to investigate time-dependent effects of formalin fixation on MRI relaxometry (T1 and T2), diffusion tensor imaging (fractional anisotropy, FA; and mean diffusivity, MD), and myelin water fraction (MWF) measurements throughout intact human brain specimens.MethodsTwo whole, neurologically-healthy human brains were immersed in 10% formalin solution and scanned at 13 time points between 0 and 1,032 h. Whole-brain maps of longitudinal (T1) and transverse (T2) relaxation times, FA, MD, and MWF were generated at each time point to illustrate spatiotemporal changes, and region-of-interest analyses were then performed in eight brain structures to quantify temporal changes with progressive fixation.ResultsAlthough neither of the diffusion measures (FA nor MD) showed significant changes as a function of formalin fixation time, both T1 and T2-relaxation times significantly decreased, and MWF estimates significantly increased with progressive fixation until (and likely beyond) our final measurements were taken at 1,032 h.ConclusionThese results suggest that T1-relaxation, T2-relaxation and MWF estimates must be performed quite early in the fixation process to avoid formalin-induced changes compared to in vivo values; and furthermore, that different ex vivo scans within an experiment must be acquired at consistent (albeit still early) fixation intervals to avoid fixative-related differences between samples. Conversely, ex vivo diffusion measures (FA and MD) appear to depend more on other factors (e.g., pulse sequence optimization, sample temperature, etc.).

Published
2018
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18. A Method for Whole Brain Ex Vivo Magnetic Resonance Imaging with Minimal Susceptibility Artifacts

Author

Anwar S. Shatil, Kant M. Matsuda, and Chase R. Figley

Subjects
Neuroimaging, human brain, MRI, ex vivo, fixation, postmortem, Neurology. Diseases of the nervous system, RC346-429
Abstract

Magnetic resonance imaging (MRI) is a non-destructive technique that is capable of localizing pathologies and assessing other anatomical features (e.g., tissue volume, microstructure, white matter connectivity) in postmortem, ex vivo human brains. However, when brains are removed from the skull and cerebrospinal fluid (i.e., their normal in vivo magnetic environment), air bubbles and air-tissue interfaces typically cause magnetic susceptibility artifacts that severely degrade the quality of ex vivo MRI data. In this report, we describe a relatively simple and cost-effective experimental set-up for acquiring artifact-free ex vivo brain images using a clinical MRI system with standard hardware. In particular, we outline the necessary steps, from collecting an ex vivo human brain to the MRI scanner setup, and have also described changing the formalin (as might be necessary in longitudinal postmortem studies). Finally, we share some representative ex vivo MRI images that have been acquired using the proposed setup in order to demonstrate the efficacy of this approach. We hope that this protocol will provide both clinicians and researchers with a straight-forward and cost-effective solution for acquiring ex vivo MRI data from whole postmortem human brains.

Published
2016
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19. The impact of lung ultrasound on clinical-decision making across departments: a systematic review

Author

Heldeweg, MLA, Vermue, L, Kant, M, Brouwer, M, Girbes, ARJ, Haaksma, ME, Heunks, LMA, Mousa, A, Smit, JM, Smits, TW, Paulus, F, Ket, JCF, Schultz, MJ, and Tuinman, PR

Subjects
Medical physics. Medical radiology. Nuclear medicine, Clinical-decision making, Radiological and Ultrasound Technology, Chest, R895-920, Radiology, Nuclear Medicine and imaging, Review, Lung, Ultrasonography, Management
Abstract

Background Lung ultrasound has established itself as an accurate diagnostic tool in different clinical settings. However, its effects on clinical-decision making are insufficiently described. This systematic review aims to investigate the impact of lung ultrasound, exclusively or as part of an integrated thoracic ultrasound examination, on clinical-decision making in different departments, especially the emergency department (ED), intensive care unit (ICU), and general ward (GW). Methods This systematic review was registered at PROSPERO (CRD42021242977). PubMed, EMBASE, and Web of Science were searched for original studies reporting changes in clinical-decision making (e.g. diagnosis, management, or therapy) after using lung ultrasound. Inclusion criteria were a recorded change of management (in percentage of cases) and with a clinical presentation to the ED, ICU, or GW. Studies were excluded if examinations were beyond the scope of thoracic ultrasound or to guide procedures. Mean changes with range (%) in clinical-decision making were reported. Methodological data on lung ultrasound were also collected. Study quality was scored using the Newcastle–Ottawa scale. Results A total of 13 studies were included: five studies on the ED (546 patients), five studies on the ICU (504 patients), two studies on the GW (1150 patients), and one study across all three wards (41 patients). Lung ultrasound changed the diagnosis in mean 33% (15–44%) and 44% (34–58%) of patients in the ED and ICU, respectively. Lung ultrasound changed the management in mean 48% (20–80%), 42% (30–68%) and 48% (48–48%) of patients in the ED, in the ICU and in the GW, respectively. Changes in management were non-invasive in 92% and 51% of patients in the ED and ICU, respectively. Lung ultrasound methodology was heterogeneous across studies. Risk of bias was moderate to high in all studies. Conclusions Lung ultrasound, exclusively or as a part of thoracic ultrasound, has substantial impact on clinical-decision making by changing diagnosis and management in the EDs, ICUs, and GWs. The current evidence level and methodological heterogeneity underline the necessity for well-designed trials and standardization of methodology.

Published
2022
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23. Validation of mitotic cell quantification via microscopy and multiple whole-slide scanners

Author

Katsura Emoto, Yukako Yagi, Naohiro Uraoka, Meera Hameed, Rania G. Aly, Kant M. Matsuda, Jamal Benhamida, Sahussapont Joseph Sirintrapun, Matthew G. Hanna, Qi Gong, Brandon D. Gallas, David S. Klimstra, and Kazuhiro Tabata

Subjects
0301 basic medicine, Medical diagnostic, Pathology, medicine.medical_specialty, Histology, Microscope, Computer science, eeDAP, Mitosis, Pathology and Forensic Medicine, law.invention, 03 medical and health sciences, Dogs, 0302 clinical medicine, law, Image Interpretation, Computer-Assisted, Microscopy, medicine, lcsh:Pathology, Animals, Dog Diseases, Whole slide imaging, Melanoma, Observer Variation, Oral melanoma, Reproducibility, Research, Reproducibility of Results, Validation study, General Medicine, Pathologists, 030104 developmental biology, Mitotic cell quantification, Mitotic cell, Multiple whole slide scanner, 030220 oncology & carcinogenesis, Mitotic Figure, Mouth Neoplasms, Kappa, Biomedical engineering, lcsh:RB1-214
Abstract

Background: The establishment of whole-slide imaging (WSI) as a medical diagnostic device allows that pathologists may evaluate mitotic activity with this new technology. Furthermore, the image digitalization provides an opportunity to develop algorithms for automatic quantifications, ideally leading to improved reproducibility as compared to the naked eye examination by pathologists. In order to implement them effectively, accuracy of mitotic figure detection using WSI should be investigated. In this study, we aimed to measure pathologist performance in detecting mitotic figures (MFs) using multiple platforms (multiple scanners) and compare the results with those obtained using a brightfield microscope. Methods: Four slides of canine oral melanoma were prepared and digitized using 4 WSI scanners. In these slides, 40 regions of interest (ROIs) were demarcated, and five observers identified the MFs using different viewing modes: microscopy and WSI. We evaluated the inter- and intra-observer agreements between modes with Cohen’s Kappa and determined “true” MFs with a consensus panel. We then assessed the accuracy (agreement with truth) using the average of sensitivity and specificity. Results: In the 40 ROIs, 155 candidate MFs were detected by five pathologists; 74 of them were determined to be true MFs. Inter- and intra-observer agreement was mostly “substantial” or greater (Kappa?=?0.594?0.939). Accuracy was between 0.632 and 0.843 across all readers and modes. After averaging over readers for each modality, we found that mitosis detection accuracy for 3 of the 4 WSI scanners was significantly less than that of the microscope (p =?0.002, 0.012, and 0.001). Conclusions: This study is the first to compare WSIs and microscopy in detecting MFs at the level of individual cells. Our results suggest that WSI can be used for mitotic cell detection and offers similar reproducibility to the microscope, with slightly less accuracy., Diagnostic Pathology, 14(1), art.no.65; 2019

Published
2019
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41. Teri-LIFE: an observational study of quality of life in patients with relapsing remitting multiple sclerosis treated with teri-flunomide in the Nordic region

Author

Hestvik, A. L., Frederiksen, J., Helle Hvilsted Nielsen, Torkildsen, O., Eek, C., Huang-Link, Y., Haghighi, S., Poole, E. M., Tsai, J. A., and Kant, M.

Abstract

Title (max. 250 characters including spaces): 151 Teri-LIFE: An observational study of quality of life in patients with relapsing remitting multiple sclerosis treated with teriflunomide in the Nordic region Authors: Hestvik AL,1 Frederiksen J,2 Nielsen HH,3 Torkildsen Ø,4 Eek C,5 Huang-Link Y,6 Haghighi S,7 Poole EM,8 Tsai JA,9 Kant M3 1Sanofi, Lysaker, Norway 2University of Copenhagen, Copenhagen, Denmark 3University of Southern Denmark, Odense, Denmark 4Haukeland University Hospital, Bergen, Norway 5Drammen Hospital, Drammen, Norway 6 Linköping University Hospital, Linköping, Sweden 7Department of Neurology, Motala Hospital, Motala, Sweden 8Sanofi, Cambridge, MA, USA 9Sanofi, Stockholm, Sweden Abstract character count (max. 2500 including spaces, excluding disclosures): 2441 Introduction Teriflunomide is a once-daily oral immunomodulator approved for the treatment of relapsing forms of multiple sclerosis (MS) or relapsing remitting MS (RRMS), depending on the local label. Objective To report the results of Teri-LIFE, a non-interventional, real-world study of quality of life (QoL) in patients with RRMS treated with teriflunomide in the Nordic region. Methods Teri-LIFE recruited patients from Norway, Sweden, and Denmark between June 2015 and December 2016. Patients ≥18 years of age with RRMS who had already chosen to initiate treatment with teriflunomide 14 mg were eligible. Patients were followed per routine clinical practice for 24 months, with follow-up every 6 months. The primary endpoint was QoL measured by the Short Form-36 (SF-36) questionnaire. Secondary endpoints included clinical efficacy, safety, and adherence. Results Two hundred patients were recruited, 68% were treatment-naïve. The majority (71%) were female, mean (standard deviation [SD]) age was 44.1 (10.4) years. Mean (SD) time since diagnosis was 3.6 (5.9) years. Median (upper quartile, lower quartile) Expanded Disability Status Scale score was 2.0 (1.0, 2.5). Mean (SD) number of relapses in the prior 2 years was 0.8 (0.7); 69/197 (35%) patients reported no relapses during this time. A total of 118 (59%) patients remained on teriflunomide during the 24-month study period; 22% discontinued due to adverse events (AEs), 9% due to lack of efficacy, and 10% due to other reasons. Mean (SD) SF-36 scores at baseline and months 6, 12, 18 and 24 were 46.5 (10.0), 46.7 (10.4), 47.5 (9.7), 47.6 (10.5), and 47.7 (10.4), respectively, for the physical component score (PCS), and 46.6 (11.8), 48.6 (11.9), 48.4 (11.1), 48.4 (11.2), and 48.8 (10.3), respectively, for the mental component score (MCS). A repeated measures analysis of covariance showed no significant change except for baseline to 24 months on the PCS (P=0.0038). The on-treatment annualised relapse rate (95% confidence interval) was 0.17 (0.13, 0.23); 79% of patients experienced no relapses. AEs were reported by 93.5% of patients, the most common being hair thinning (26.5%), diarrhoea (23%), and fatigue (20%). Serious AEs were reported by 11% of patients. Conclusions QoL was stable over 24 months in teriflunomide-treated patients. The benefit–risk ratio, and safety and tolerability profile of teriflunomide were consistent with those observed in clinical trials. Disclosures: ALH: Employee of Sanofi JF: Served on scientific advisory boards for and received funding for travel related to these activities as well as honoraria from Biogen Idec, Merck Serono, Sanofi-Aventis, Teva, Novartis and Almirall. Received speaker honoraria from Biogen Idec, Teva and Novartis. HHN: Accepted financial compensation and travel reimbursements from Teva, Biogen Idec, Sanofi-Genzyme, Novartis and Roche. ØT: Served on the scientific advisory boards for and received speaker honoraria from Novartis, Biogen, Genzyme, Roche and Merck. CE: Received honorarium from Merck and contributed to sponsored research. YL: Financial support from Sanofi for research (Teri-LIFE study) SH: The Teri-LIFE project received financial support from Sanofi. EMP: Employee of Sanofi with ownership interest JAT: Employee of Sanofi with ownership interest MK: Support for congress participation from Biogen, Genzyme, Teva, Roche, and Novartis Study supported by Sanofi Submission details Type: Oral or poster presentation Abstract category: Clinical aspects of MS 1. Diagnosis and differential diagnosis 2. MS Variants 3. Paediatric MS 4. Progressive MS 5. Natural course 6. Epidemiology 7. MS and gender 8. Pregnancy in MS 9. MS symptoms 10. Clinical assessment tools 11. Patient reported outcomes 12. Economic burden 13. Neuro-ophthalmology 14. Comorbidity Pathology and pathogenesis of MS 15. Pathology 16. Experimental models 17. Genetics/ Epigenetics 18. Immunology 19. Microbiology and virology 20. Environmental factors 21. Neurobiology 22. Neurodegeneration 23. Repairing mechanisms 24. MRI and PET 25. OCT 26. Neuropsychology 27. Biomarkers Therapy 28. Immunomodulation/ Immunosuppression 29. Neuroprotection & repair 30. Long-term treatment monitoring 31. Risk management for disease modifying treatments 32. Tools for detecting therapeutic response 33. Symptomatic treatment 34. Others RIMS 35. Multi-disciplinary rehabilitation 36. Symptoms management (including cognition, fatigue, imbalance) 37. Neurobiology & rehabilitation Presenting author details: Anne Lise Hestvik, Sanofi, Prof Kohtsvei 5–17, 1366 Lysaker, Norway. Email: annelise.hestvik@sanofi.com. Telephone: +47 97 48 99 64.

Published
2019
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50. Ex vivo tissue imaging of human glioblastoma using a small bore 7T MRI and correlation with digital pathology and proteomics profiling

Author

Melanie Martin, Kant M. Matsuda, Thalia A. K. Magyar, Richard Buist, Ana Lopes-Calcas, and Zoe O’Brien-Moran

Subjects
0301 basic medicine, medicine.medical_specialty, Pathology, medicine.diagnostic_test, Imaging biomarker, business.industry, Digital pathology, Magnetic resonance imaging, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, medicine, Medical imaging, Effective diffusion coefficient, Medical physics, business, Ex vivo, Preclinical imaging, Diffusion MRI
Abstract

Recent advancement in MRI established multi-parametric imaging for in vivo characterization of pathologic changes in brain cancer, which is expected to play a role in imaging biomarker development. Diffusion Tensor Imaging (DTI) is a prime example, which has been deployed for assessment of therapeutic response via analysis of apparent diffusion coefficient (ADC) / mean diffusivity (MD) values. They have been speculated to reflect apoptosis/necrosis. As newer medical imaging emerges, it is essential to verify that apparent abnormal features in imaging correlate with histopathology. Furthermore, the feasibility of imaging correlation with molecular profile should be explored in order to enhance the potential of biomedical imaging as a reliable biomarker. We focus on glioblastoma, which is an aggressive brain cancer. Despite the increased number of studies involving DTI in glioblastoma; however, little has been explored to bridge the gap between the molecular biomarkers and DTI data. Due to spatial heterogeneity in, MRI signals, pathologic change and protein expression, precise correlation is required between DTI, pathology and proteomics data in a histoanatomically identical manner. The challenge is obtaining an identical plane from in vivo imaging data that exactly matches with histopathology section. Thus, we propose to incorporate ex vivo tissue imaging to bridge between in vivo imaging data and histopathology. With ex vivo scan of removed tissue, it is feasible to use high-field 7T MRI scanner, which can achieve microscopic resolution. Once histology section showing the identical plane, it is feasible to correlate protein expression by a unique technology, “multiplex tissue immunoblotting”.

Published
2017
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