Author: "Maniscalco G" - Searchworks@Jio Institute Digital Library Search Results

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226 results on '"Maniscalco G"'

101. SMART (Multiple Sclerosis Status of Art), Physician and adherence: Qualitative and quantitative analysis of the therapy management. Prospectic multicenter observational study on patients with relapsing-remitting multiple sclerosis in italian public hospitals. Preliminary results | SMART (Sclerosi Multipla: Stato Dell'arte), medico e aderenza: Analisi qualitativa e quantitativa della gestione della terapia. Risultati preliminari di uno studio osservazionale prospettico multicentrico condotto sui pazienti con sclerosi multipla recidivante remittente nei centri ospedalieri Italiani

Author: Di Battista, G., Bertolotto, A., Gasperini, C., Ghezzi, A., Maimone, D., Claudio Marcello Solaro, Maddestra, M., Coniglio, M. G., Spitalieri, D., Florio, C., Maniscalco, G., Sinisi, L., Mansi, D., Iuliano, G., Neri, W., Jandolo, B., Galiè, E., Koudriatseva, T., Ferraro, E., Ruggieri, S., Tartaglione, A., Parodi, S., Agostoni, E., Balgera, R., Palumbo, R., Guidotti, M., Barrilà, C., Baldini, S., Previdi, P., Tottola, M., Ragno, M., Cacchiò, G., Curatola, L., Dotta, M., L Episcopo, M., Perla, F., Messina, A., Sosso, L., Bucciantini, E., Costantino, G., Grimaldi, L., Vitello, G., Milone, S., Matta, F., Bianca, M., Cappellani, A., Guidi, L., Bartolozzi, M. L., Plewnia, K., Pieri, S., Meucci, G., Fioretti, C., Bartolini, S., Ancona, A. L., Falcini, M., and Sabatini, S.

102. A cylindrical GEM detector with analog readout for the BESIII experiment

Author: Bettoni, D., Cibinetto, G., Fioravanti, E., Garzia, I., Santoro, V., Savriè, M., Carassiti, V., Melchiorri, M., Farinelli, R., Rinchiuso, L., Baldini, R., Bertani, M., Calcaterra, A., Felici, G., Patteri, P., Wang, Y. D., Zallo, F., Pacetti, S., Amoroso, A., Bianchi, F., Giorgio Cotto, Destefanis, M., Mori, F., Fava, L., Greco, M., Hu, J. F., Leng, C., Maggiora, M., Maniscalco, G., Marcello, S., Mezzadri, G., Rivetti, A., Sosio, S., Spataro, S., Zotti, L., Dong, M., Ji, X., Liu, Z., Ouyan, Q., Shen, X., Wang, K., Wang, L., Wu, L., Ye, M., Zhang, Y., Johansson, T., Marciniewski, P., Gradl, W., and Rosner, C.

103. Feasibility study for the measurement of πN transition distribution amplitudes at ¯PANDA in ¯pp→J/ψπ0

Author: Singh, B., Erni, W., Krusche, B., Steinacher, M., Walford, N., Liu, H., Liu, Z., Liu, B., Shen, X., Wang, C., Zhao, J., Albrecht, M., Erlen, T., Fink, M., Heinsius, F. H., Held, T., Holtmann, T., Jasper, S., Keshk, I., Koch, H., Kopf, B., Kuhlmann, M., Kuemmel, M., Leiber, S., Mikirtychyants, M., Musiol, P., Mustafa, A., Pelizaeus, M., Pychy, J., Richter, M., Schnier, C., Schroeder, T., Sowa, C., Steinke, M., Triffterer, T., Wiedner, U., Ball, M., Beck, R., Hammann, C., Ketzer, B., Kube, M., Mahlberg, P., Rossbach, M., Schmidt, C., Schmitz, R., Thoma, U., Urban, M., Walther, D., Wendel, C., Wilson, A., Bianconi, A., Bragadireanu, M., Caprini, M., Pantea, D., Patel, B., Czyzycki, W., Domagala, M., Filo, G., Jaworowski, J., Krawczyk, M., Lisowski, E., Lisowski, F., Michalek, M., Poznanski, P., Plazek, J., Korcyl, K., Kozela, A., Kulessa, P., Lebiedowicz, P., Pysz, K., Schaefer, W., Szczurek, A., Fiutowski, T., Idzik, M., Mindur, B., Przyborowski, D., Swientek, K., Biernat, J., Kamys, B., Kistryn, S., Korcyl, G., Krzemien, W., Magiera, A., Moskal, P., Pyszniak, A., Rudy, Z., Salabura, P., Smyrski, J., Strzempek, P., Wronska, A., Augustin, I., Boehm, R., Lehmann, I., Marinescu, D. Nicmorus, Schmitt, L., Varentsov, V., Al-Turany, M., Belias, A., Deppe, H., Veis, N. Divani, Dzhygadlo, R., Ehret, A., Flemming, H., Gerhardt, A., Goetzen, K., Gromliuk, A., Gruber, L., Karabowicz, R., Kliemt, R., Krebs, M., Kurilla, U., Lehmann, D., Loechner, S., Luehning, J., Lynen, U., Orth, H., Patsyuk, M., Peters, K., Saito, T., Schepers, G., Schmidt, C. J., Schwarz, C., Schwiening, J., Taeschner, A., Traxler, M., Ugur, C., Voss, B., Wieczorek, P., Wilms, A., Zuehlsdorf, M., Abazov, V., Alexeev, G., Arefiev, V. A., Astakhov, V., Barabanov, M. Yu., Batyunya, B. V., Davydov, Y., Dodokhov, V. Kh., Efremov, A., Fechtchenko, A., Fedunov, A. G., Galoyan, A., Grigoryan, S., Koshurnikov, E. K., Lobanov, Y. Yu., Lobanov, V. I., Makarov, A. F., Malinina, L. V., Malyshev, V., Olshevskiy, A. G., Perevalova, E., Piskun, A. A., Pocheptsov, T., Pontecorvo, G., Rodionov, V., Rogov, Y., Salmin, R., Samartsev, A., Sapozhnikov, M. G., Shabratova, G., Skachkov, N. B., Skachkova, A. N., Strokovsky, E. A., Suleimanov, M., Teshev, R., Tokmenin, V., Uzhinsky, V., Vodopianov, A., Zaporozhets, S. A., Zhuravlev, N. I., Zinchenko, A., Zorin, A. G., Branford, D., Glazier, D., Watts, D., Boehm, M., Britting, A., Eyrich, W., Lehmann, A., Pfaffinger, M., Uhlig, F., Dobbs, S., Seth, K., Tomaradze, A., Xiao, T., Bettoni, D., Carassiti, V., Ramusino, A. Cotta, Dalpiaz, P., Drago, A., Fioravanti, E., Garzia, I., Savrie, M., Akishina, V., Kisel, I., Kozlov, G., Pugach, M., Zyzak, M., Gianotti, P., Guaraldo, C., Lucherini, V., Bersani, A., Bracco, G., Macri, M., Parodi, R. F., Biguenko, K., Brinkmann, K. T., Di Pietro, V., Diehl, S., Dormenev, V., Drexler, P., Doern, M., Etzelmller, E., Galuska, M., Gutz, E., Hahn, C., Hayrapetyan, A., Kesselkaul, M., Koehn, W., Kuske, T., Lange, J. S., Liang, Y., Metag, V., Moritz, M., Nanova, M., Nazarenko, S., Novotny, R., Quagli, T., Reiter, S., Riccardi, A., Rieke, J., Rosenbaum, C., Schmidt, M., Schnell, R., Stenzel, H., Thoering, U., Ullrich, T., Wagner, M. N., Wasem, T., Wohlfahrt, B., Zaunick, H. G., Tomasi-Gustafsson, E., Ireland, D., Rosner, G., Seitz, B., Deepak, P. N., Kulkarni, A., Apostolou, A., Babai, M., Kavatsyuk, M., Lemmens, P. J., Lindemulder, M., Loehner, H., Messchendorp, J., Schakel, P., Smit, H., Tiemens, M., Van derweele, J. C., Veenstra, R., Vejdani, S., Dutta, K., Kalita, K., Kumar, A., Roy, A., Sohlbach, H., Bai, M., Bianchi, L., Buescher, M., Cao, L., Cebulla, A., Dosdall, R., Gillitzer, A., Goldenbaum, F., Grunwald, D., Herten, A., Hu, Q., Kemmerling, G., Kleines, H., Lai, A., Lehrach, A., Nellen, R., Ohm, H., Orfanitski, S., Prasuhn, D., Prencipe, E., Puetz, J., Ritman, J., Schadmand, S., Sefzick, T., Serdyuk, V., Sterzenbach, G., Stockmanns, T., Wintz, P., Wuestner, P., Xu, H., Zambanini, A., Li, S., Li, Z., Sun, Z., Rigato, V., Isaksson, L., Achenbach, P., Corell, O., Denig, A., Distler, M., Hoek, M., Karavdina, A., Lauth, W., Merkel, H., Mueller, U., Pochodzalla, J., Sanchez, S., Schlimme, S., Sfienti, C., Thiel, M., Ahmadi, H., Ahmed, S., Bleser, S., Capozza, L., Cardinali, M., Dbeyssi, A., Deiseroth, M., Feldbauer, F., Fritsch, M., Froerllich, B., Kang, D., Khaneft, D., Klasen, R., Leithoff, H. H., Lin, D., Maas, F., Maldaner, S., Martinez, M., Michel, M., Mora Esp, M. C., Morales, C. Morales, Motzko, C., Nerling, F., Noll, O., Pfloeger, S., Pitka, A., Pineiro, D. Rodriguez, Sanchez-Lorente, A., Steinen, M., Valente, R., Weber, T., Zambrana, M., Zimmermann, I., Fedorov, A., Korjik, M., Missevitch, O., Boukharov, A., Malyshev, O., Marishev, I., Balanutsa, V., Balanutsa, P., Chernetsky, V., Demekhin, A., Dolgolenko, A., Fedorets, P., Gerasimov, A., Goryachev, V., Chandratre, V., Datar, V., Dutta, D., Jha, V., Kumawat, H., Mohanty, A. K., Parmar, A., Roy, B., Sonika, G., Fritzsch, C., Grieser, S., Hergemoeller, A. K., Hetz, B., Huesken, N., Khoukaz, A., Wessels, J. P., Khosonthongkee, K., Kobdaj, C., Limphirat, A., Srisawad, P., Yan, Y., Barnyakov, A. Yu., Barnyakov, M., Beloborodov, K., Blinov, V. E., Bobrovnikov, V. S., Kuyanov, I. A., Martin, K., Onuchin, A. P., Serednyakov, S., Sokolov, A., Tikhonov, Y., Blinov, A. E., Kononov, S., Kravchenko, E. A., Atomssa, E., Kunne, R., Ma, B., Marchand, D., Ramstein, B., van de Wiele, J., Wang, Y., Boca, G., Costanza, S., Genova, P., Montagna, P., Rotondi, A., Abramov, V., Belikov, N., Bukreeva, S., Davidenko, A., Derevschikov, A., Goncharenko, Y., Grishin, V., Kachanov, V., Kormilitsin, V., Levin, A., Melnik, Y., Minaev, N., Mochalov, V., Morozov, D., Nogach, L., Poslavskiy, S., Ryazantsev, A., Ryzhikov, S., Semenov, P., Shein, I., Uzunian, A., Vasiliev, A., Yakutin, A., Roy, U., Yabsley, B., Belostotski, S., Gavrilov, G., Izotov, A., Manaenkov, S., Miklukho, O., Veretennikov, D., Zhdanov, A., Baeck, T., Cederwall, B., Makonyi, K., Preston, M., Tegner, P. E., Woelbing, D., Rai, A. K., Godre, S., Calvo, D., Coli, S., De Remigis, P., Filippi, A., Giraudo, G., Lusso, S., Mazza, G., Mignone, M., Rivetti, A., Wheadon, R., Amoroso, A., Bussa, M. P., Busso, L., De Mori, F., Destefanis, M., Fava, L., Ferrero, L., Greco, M., Hu, J., Lavezzi, L., Maggiora, M., Maniscalco, G., Marcello, S., Sosio, S., Spataro, S., Balestra, F., Iazzi, F., Introzzi, R., Lavagno, A., Olave, J., Birsa, R., Bradamante, F., Bressan, A., Martin, A., Calen, H., Andersson, W. Ikegami, Johansson, T., Kupsc, A., Marciniewski, P., Papenbrock, M., Pettersson, J., Schoenning, K., Wolke, M., Galnander, B., Diaz, J., Chackara, V. Pothodi, Chlopik, A., Kesik, G., Melnychuk, D., Slowinski, B., Trzcinski, A., Wojciechowski, M., Wronka, S., Zwieglinski, B., Buehler, P., Marton, J., Steinschaden, D., Suzuki, K., Widmann, E., Zmeskal, J., and Semenov-Tian-Shansky, K. M.
Subjects: 7. Clean energy

104. The game 'The House of Common Values'

Author: Roberta Medda-Windischer, Carlà A, Zeqo E, Pirhofer A, Zeba M, Maniscalco G, Tartarotti M, Stoichita P, Patti Y, and Stecchi V

105. Clinical predictors of dimethil-fumarate response in multiple sclerosis: a real life multicentre study

Author: Signoriello, E., Marcello Moccia, Palladino, R., Carotenuto, A., Maniscalco, G. T., Sacca, F., Bonavita, S., Russo, C. V., Iodice, R., Petruzzo, M., Sinisi, L., Angelis, M., Lavorgna, L., Rosa, A., Romano, F., Orlando, V., Ronga, B., Florio, C., Lus, G., Morra, V. Brescia, and Lanzillo, R.

106. Rationale and methodology of the ICAI study, a randomised clinical trial of alprostadil in the treatment of chronic critical leg ischemia

Author: Belgrano, Ea, Nardella, L., Guala, A., Mazzucchetti, S., Marinoni, V., Calzoni, D., Bedoni, P., Confalonieri, Ma, Agus, Gb, Mondani, P., Deangelis, R., Biasi, Gm, Piglionica, MR, Abbritti, F., Agrifoglio, G., Costantini, A., DellaVedova, MR, Miglierina, L., Marrocu, R., Bragherio, G., Zanoni, Ce, Borin, F., Alderi, G., Emanuelli, G., Flandoli, C., Colzani, M., Ponti, Gb, Berra, S., Bevilacqua, A., Bocca, M., Invernizzi, C., Deangelis, E., Tacconi, A., Dangelo, F., Vaghi, M., Arzini, A., Boccalon, L., Losapio, Gm, Ambrosi, R., Briolini, F., Inzoli, MR, Lombardi, G., Tarantola, P., Zocca, N., Tenchini, P., Bruni, T., Fontanili, M., Guidetti, D., Pedeferri, G., Bordoni, Mc, Catalano, A., Visconti, W., Vedovato, F., Zucchella, M., Bittolo, Bg, Busetto, Mt, Zambon, C., Carlassara, Gb, Barbato, O., Zambelli, V., Mazzilli, G., Lino, M., Pavan, S., Pagnan, A., Visona, A., Perissinotto, C., Tonietto, G., Michelet, I., Agresta, F., Favretti, F., Burigo, E., Delazzer, L., Giansante, C., Fiotti, N., Grego, S., Mozzon, L., Gonano, N., Pfeiffer, P., Petrilli, Gl, Puzzo, A., Giuseppe Baldino, Podesta, A., Guastini, A., Traversaro, A., Zinicola, N., Baglietto, F., Arnuzzo, L., Defabritiis, A., Filippini, M., Ferrari, F., Martini, L., Testoni, P., Accorsi, F., Maurizi, P., Evangelisti, G., Roffi, A., Marzara, G., Fini, C., Coppi, G., Camparini, S., Tusini, N., Tuscano, G., Lonardi, R., Rozza, A., Botta, Gc, Villani, Lg, Pavarini, E., Campanella, P., Moratti, A., Ieran, M., Bertini, D., Pratesi, C., Narcetti, S., Corsi, C., Pollastri, M., Marrapodi, E., Melillo, E., Iabichella, Ml, Setacci, C., Sozio, G., Cao, P., Verzini, F., Mannarino, E., Pasqualini, L., Vaudo, G., Alo, F., Ioannidis, G., Spartera, C., Marino, G., Bafile, G., Anselmi, E., Maniscalco, G., Longo, P., Digiovanni, V., Colli, R., Fabbri, Mc, Bracale, G., Bernardo, B., Perretti, B., Valitutti, P., Vigliotti, G., Cimino, G., Rolli, F., Pascali, M., Sabella, G., Grilli, M., Correra, M., Palese, E., Florena, M., Cassina, I., Cumbo, P., Comande, C., Notarbartolo, A., Novo, S., Belvedere, M., Caruso, R., Verghi, F., Cavallaro, S., Martello, G., Romeo, S., Cormaci, Of, Binaghi, F., Fronteddu, P., Cannas, F., Degaetano, G., Tognoni, G., Avanzini, F., Bertele, V., Digiulio, P., Pangrazzi, J., Roncaglioni, Mc, Colombo, F., Fellin, G., Terzian, E., Coccheri, S., Delfavero, A., Geraci, E., Janzon, L., Vermylen, J., Beghi, E., Coen, D., and Turazza, F.

107. A real-world study of Alemtuzumab in a cohort of Italian patients

Author: Sacca, F., Russo, C. V., Frau, J., Annovazzi, P., Signoriello, E., Bonavita, S., Grasso, R., Clerico, M., Cordioli, C., Laroni, A., Capobianco, M., Clerici, V. Torri, Sartori, A., Cavalla, P., Maniscalco, G. T., La Gioia, S., Caleri, F., Giugno, A., Iodice, R., Carotenuto, A., Cocco, E., Fenu, G., Zaffaroni, M., Baronicini, D., Lus, G., Gallo, A., Mercanti, S. F., Caterina Lapucci, Di Francescantonio, V., Sormani, M. P., and Signori, A.

108. Experimental access to Transition Distribution Amplitudes with the \={P}ANDA experiment at FAIR

Author: Singh, B. P., Erni, W., Keshelashvili, I., Krusche, B., Steinacher, M., Liu, B., Liu, H., Liu, Z., Shen, X., Wang, C., Zhao, J., Albrecht, M., Fink, M., Heinsius, F. H., Held, T., Holtmann, T., Koch, H., Kopf, B., Kümmel, M., KUHL, G., Kuhlmann, M., Leyhe, M., Mikirtychyants, M., Musiol, P., Mustafa, A., Pelizäus, M., Pychy, J., Richter, M., Schnier, C., Schröder, T., Sowa, C., Steinke, M., Triffterer, T., Wiedner, U., Beck, R., Hammann, C., Kaiser, D., Ketzer, B., Kube, M., Mahlberg, P., Rossbach, M., Schmidt, C., Schmitz, R., Thoma, U., Walther, D., Wendel, C., Wilson, A., Bianconi, A., Bragadireanu, M., Caprini, M., Pantea, D., Pietreanu, D., Vasile, M. E., Patel, B., Kaplan, D., Brandys, P., Czyzewski, T., Czyzycki, W., Domagala, M., Hawryluk, M., Filo, G., Krawczyk, M., Kwiatkowski, D., Lisowski, E., Lisowski, F., Fiutowski, T., Idzik, M., Mindur, B., Przyborowski, D., Swientek, K., Czech, B., Kliczewski, S., Korcyl, K., Kozela, A., Kulessa, P., Lebiedowicz, P., Malgorzata, K., Pysz, K., Schäfer, W., Siudak, R., Szczurek, A., Biernat, J., Jowzaee, S., Kamys, B., Kistryn, S., Korcyl, G., Krzemien, W., Magiera, A., Moskal, P., Palka, M., Psyzniak, A., Rudy, Z., Salabura, P., Smyrski, J., Strzempek, P., Wrońska, A., Augustin, I., Lehmann, I., Nicmorus, D., Schepers, G., Schmitt, L., Al-Turany, M., Cahit, U., Capozza, L., Dbeyssi, A., Deppe, H., Dzhygadlo, R., Ehret, A., Flemming, H., Gerhardt, A., Götzen, K., Karabowicz, R., Kliemt, R., Kunkel, J., Kurilla, U., Lehmann, D., Lühning, J., Maas, F., Morales, C. Morales, Espí, M. C. Mora, Nerling, F., Orth, H., Peters, K., Piñeiro, D. Rodríguez, Saito, N., Saito, T., Lorente, A. Sánchez, Schmidt, C. J., Schwarz, C., Schwiening, J., Traxler, M., Valente, R., Voss, B., Wieczorek, P., Wilms, A., Zühlsdorf, M., Abazov, V. M., Alexeev, G., Arefiev, A., Astakhov, V. I., Barabanov, M. Yu., Batyunya, B. V., Davydov, Yu. I., Dodokhov, V. Kh., Efremov, A. A., Fedunov, A. G., Festchenko, A. A., Galoyan, A. S., Grigoryan, S., Karmokov, A., Koshurnikov, E. K., Lobanov, V. I., Lobanov, Yu. Yu., Makarov, A. F., Malinina, L. V., Malyshev, V. L., Mustafaev, G. A., Olshevskiy, A., Pasyuk, M. A., Perevalova, E. A., Piskun, A. A., Pocheptsov, T. A., Pontecorvo, G., Rodionov, V. K., Rogov, Yu. N., Salmin, R. A., Samartsev, A. G., Sapozhnikov, M. G., Shabratova, G. S., Skachkov, N. B., Skachkova, A. N., Strokovsky, E. A., Suleimanov, M. K., Teshev, R. Sh., Tokmenin, V. V., Uzhinsky, V. V., Vodopyanov, A. S., Zaporozhets, S. A., Zhuravlev, N. I., Zorin, A. G., Branford, D., Glazier, D., Watts, D., Woods, P., Britting, A., Eyrich, W., Lehmann, A., Uhlig, F., Dobbs, S., Seth, K., Tomaradze, A., Xiao, T., Bettoni, D., Carassiti, V., Ramusino, A. Cotta, Dalpiaz, P., Drago, A., Fioravanti, E., Garzia, I., Savriè, M., Stancari, G., Akishina, V., Kisel, I., Kulakov, I., Zyzak, M., Arora, R., Bel, T., Gromliuk, A., Kalicy, G., Krebs, M., Patsyuk, M., Zuehlsdorf, M., Bianchi, N., Gianotti, P., Guaraldo, C., Lucherini, V., Pace, E., Bersani, A., Bracco, G., Macri, M., Parodi, R. F., Bianco, S., Bremer, D., Brinkmann, K. T., Diehl, S., Dormenev, V., Drexler, P., Düren, M., Eissner, T., Etzelmüller, E., Föhl, K., Galuska, M., Gessler, T., Gutz, E., Hayrapetyan, A., Hu, J., Kröck, B., Kühn, W., Kuske, T., Lange, S., Liang, Y., Merle, O., Metag, V., Mülhheim, D., Münchow, D., Nanova, M., Novotny, R., Pitka, A., Quagli, T., Rieke, J., Rosenbaum, C., Schnell, R., Spruck, B., Stenzel, H., Thöring, U., Ullrich, T., Wasem, T., Werner, M., Zaunick, H. G., Ireland, D., Rosner, G., Seitz, B., Deepak, P. N., Kulkarni, A. V., Apostolou, A., Babai, M., Kavatsyuk, M., Lemmens, P., Lindemulder, M., Löhner, H., Messchendorp, J., Schakel, P., Smit, H., van der Weele, J. C., Veenstra, R., Tiemens, M., Vejdani, S., Kalita, K., Mohanta, D. P., Kumar, A., Roy, A., Sahoo, R., Sohlbach, H., Büscher, M., Cao, L., Cebulla, A., Deermann, D., Dosdall, R., Esch, S., Georgadze, I., Gillitzer, A., Goerres, A., Goldenbaum, F., Grunwald, D., Herten, A., Hu, Q., Kemmerling, G., Kleines, H., Kozlov, V., Lehrach, A., Leiber, S., Maier, R., Nellen, R., Ohm, H., Orfanitski, S., Prasuhn, D., Prencipe, E., Ritman, J., Schadmand, S., Schumann, J., Sefzick, T., Serdyuk, V., Sterzenbach, G., Stockmanns, T., Wintz, P., Wüstner, P., Xu, H., Li, S., Li, Z., Sun, Z., Rigato, V., Fissum, S., Hansen, K., Isaksson, L., Lundin, M., Schröder, B., Achenbach, P., Bleser, S., Cardinali, M., Corell, O., Deiseroth, M., Denig, A., Distler, M., Feldbauer, F., Fritsch, M., Jasinski, P., Hoek, M., Kangh, D., Karavdina, A., Lauth, W., Leithoff, H., Merkel, H., Michel, M., Motzko, C., Müller, U., Noll, O., Plueger, S., Pochodzalla, J., Sanchez, S., Schlimme, S., Sfienti, C., Steinen, M., Thiel, M., Weber, T., Zambrana, M., Dormenev, V. I., Fedorov, A. A., Korzihik, M. V., Missevitch, O. V., Balanutsa, P., Balanutsa, V., Chernetsky, V., Demekhin, A., Dolgolenko, A., Fedorets, P., Gerasimov, A., Goryachev, V., Varentsov, V., Boukharov, A., Malyshev, O., Marishev, I., Semenov, A., Konorov, I., Paul, S., Grieser, S., Hergemöller, A. K., Khoukaz, A., Köhler, E., Täschner, A., Wessels, J., Dash, S., Jadhav, M., Kumar, S., Sarin, P., Varma, R., Chandratre, V. B., Datar, V., Dutta, D., Jha, V., Kumawat, H., Mohanty, A. K., Roy, B., Yan, Y., Chinorat, K., Khanchai, K., Ayut, L., Pornrad, S., Barnyakov, A. Y., Blinov, A. E., Blinov, V. E., Bobrovnikov, V. S., Kononov, S. A., Kravchenko, E. A., Kuyanov, I. A., Onuchin, A. P., Sokolov, A. A., Tikhonov, Y. A., Atomssa, E., Hennino, T., Imre, M., Kunne, R., Galliard, C. Le, Ma, B., Marchand, D., Ong, S., Ramstein, B., Rosier, P., Tomasi-Gustafsson, E., Van de Wiele, J., Boca, G., Costanza, S., Genova, P., Lavezzi, L., Montagna, P., Rotondi, A., Abramov, V., Belikov, N., Bukreeva, S., Davidenko, A., Derevschikov, A., Goncharenko, Y., Grishin, V., Kachanov, V., Kormilitsin, V., Melnik, Y., Levin, A., Minaev, N., Mochalov, V., Morozov, D., Nogach, L., Poslavskiy, S., Ryazantsev, A., Ryzhikov, S., Semenov, P., Shein, I., Uzunian, A., Vasiliev, A., Yakutin, A., Yabsley, B., Bäck, T., Cederwall, B., Makónyi, K., Tegnér, P. E., von Würtemberg, K. M., Belostotski, S., Gavrilov, G., Izotov, A., Kashchuk, A., Levitskaya, O., Manaenkov, S., Miklukho, O., Naryshkin, Y., Suvorov, K., Veretennikov, D., Zhadanov, A., Rai, A. K., Godre, S. S., Duchat, R., Amoroso, A., Bussa, M. P., Busso, L., De Mori, F., Destefanis, M., Fava, L., Ferrero, L., Greco, M., Maggiora, M., Maniscalco, G., Marcello, S., Sosio, S., Spataro, S., Zotti, L., Calvo, D., Coli, S., De Remigis, P., Filippi, A., Giraudo, G., Lusso, S., Mazza, G., Mingnore, M., Rivetti, A., Wheadon, R., Balestra, F., Iazzi, F., Introzzi, R., Lavagno, A., Younis, H., Birsa, R., Bradamante, F., Bressan, A., Martin, A., Clement, H., Gålnander, B., Balkeståhl, L. Caldeira, Calén, H., Fransson, K., Johansson, T., Kupsc, A., Marciniewski, P., Pettersson, J., Schönning, K., Wolke, M., Zlomanczuk, J., Díaz, J., Ortiz, A., Vinodkumar, P. C., Parmar, A., Chlopik, A., Melnychuk, D., Slowinski, B., Trzcinski, A., Wojciechowski, M., Wronka, S., Zwieglinski, B., Bühler, P., Marton, J., Suzuki, K., Widmann, E., Zmeskal, J., Fröhlich, B., Khaneft, D., Lin, D., Zimmermann, I., Semenov-Tian-Shansky, K., Singh, B. P., Erni, W., Keshelashvili, I., Krusche, B., Steinacher, M., Liu, B., Liu, H., Liu, Z., Shen, X., Wang, C., Zhao, J., Albrecht, M., Fink, M., Heinsius, F. H., Held, T., Holtmann, T., Koch, H., Kopf, B., Kümmel, M., KUHL, G., Kuhlmann, M., Leyhe, M., Mikirtychyants, M., Musiol, P., Mustafa, A., Pelizäus, M., Pychy, J., Richter, M., Schnier, C., Schröder, T., Sowa, C., Steinke, M., Triffterer, T., Wiedner, U., Beck, R., Hammann, C., Kaiser, D., Ketzer, B., Kube, M., Mahlberg, P., Rossbach, M., Schmidt, C., Schmitz, R., Thoma, U., Walther, D., Wendel, C., Wilson, A., Bianconi, A., Bragadireanu, M., Caprini, M., Pantea, D., Pietreanu, D., Vasile, M. E., Patel, B., Kaplan, D., Brandys, P., Czyzewski, T., Czyzycki, W., Domagala, M., Hawryluk, M., Filo, G., Krawczyk, M., Kwiatkowski, D., Lisowski, E., Lisowski, F., Fiutowski, T., Idzik, M., Mindur, B., Przyborowski, D., Swientek, K., Czech, B., Kliczewski, S., Korcyl, K., Kozela, A., Kulessa, P., Lebiedowicz, P., Malgorzata, K., Pysz, K., Schäfer, W., Siudak, R., Szczurek, A., Biernat, J., Jowzaee, S., Kamys, B., Kistryn, S., Korcyl, G., Krzemien, W., Magiera, A., Moskal, P., Palka, M., Psyzniak, A., Rudy, Z., Salabura, P., Smyrski, J., Strzempek, P., Wrońska, A., Augustin, I., Lehmann, I., Nicmorus, D., Schepers, G., Schmitt, L., Al-Turany, M., Cahit, U., Capozza, L., Dbeyssi, A., Deppe, H., Dzhygadlo, R., Ehret, A., Flemming, H., Gerhardt, A., Götzen, K., Karabowicz, R., Kliemt, R., Kunkel, J., Kurilla, U., Lehmann, D., Lühning, J., Maas, F., Morales, C. Morales, Espí, M. C. Mora, Nerling, F., Orth, H., Peters, K., Piñeiro, D. Rodríguez, Saito, N., Saito, T., Lorente, A. Sánchez, Schmidt, C. J., Schwarz, C., Schwiening, J., Traxler, M., Valente, R., Voss, B., Wieczorek, P., Wilms, A., Zühlsdorf, M., Abazov, V. M., Alexeev, G., Arefiev, A., Astakhov, V. I., Barabanov, M. Yu., Batyunya, B. V., Davydov, Yu. I., Dodokhov, V. Kh., Efremov, A. A., Fedunov, A. G., Festchenko, A. A., Galoyan, A. S., Grigoryan, S., Karmokov, A., Koshurnikov, E. K., Lobanov, V. I., Lobanov, Yu. Yu., Makarov, A. F., Malinina, L. V., Malyshev, V. L., Mustafaev, G. A., Olshevskiy, A., Pasyuk, M. A., Perevalova, E. A., Piskun, A. A., Pocheptsov, T. A., Pontecorvo, G., Rodionov, V. K., Rogov, Yu. N., Salmin, R. A., Samartsev, A. G., Sapozhnikov, M. G., Shabratova, G. S., Skachkov, N. B., Skachkova, A. N., Strokovsky, E. A., Suleimanov, M. K., Teshev, R. Sh., Tokmenin, V. V., Uzhinsky, V. V., Vodopyanov, A. S., Zaporozhets, S. A., Zhuravlev, N. I., Zorin, A. G., Branford, D., Glazier, D., Watts, D., Woods, P., Britting, A., Eyrich, W., Lehmann, A., Uhlig, F., Dobbs, S., Seth, K., Tomaradze, A., Xiao, T., Bettoni, D., Carassiti, V., Ramusino, A. Cotta, Dalpiaz, P., Drago, A., Fioravanti, E., Garzia, I., Savriè, M., Stancari, G., Akishina, V., Kisel, I., Kulakov, I., Zyzak, M., Arora, R., Bel, T., Gromliuk, A., Kalicy, G., Krebs, M., Patsyuk, M., Zuehlsdorf, M., Bianchi, N., Gianotti, P., Guaraldo, C., Lucherini, V., Pace, E., Bersani, A., Bracco, G., Macri, M., Parodi, R. F., Bianco, S., Bremer, D., Brinkmann, K. T., Diehl, S., Dormenev, V., Drexler, P., Düren, M., Eissner, T., Etzelmüller, E., Föhl, K., Galuska, M., Gessler, T., Gutz, E., Hayrapetyan, A., Hu, J., Kröck, B., Kühn, W., Kuske, T., Lange, S., Liang, Y., Merle, O., Metag, V., Mülhheim, D., Münchow, D., Nanova, M., Novotny, R., Pitka, A., Quagli, T., Rieke, J., Rosenbaum, C., Schnell, R., Spruck, B., Stenzel, H., Thöring, U., Ullrich, T., Wasem, T., Werner, M., Zaunick, H. G., Ireland, D., Rosner, G., Seitz, B., Deepak, P. N., Kulkarni, A. V., Apostolou, A., Babai, M., Kavatsyuk, M., Lemmens, P., Lindemulder, M., Löhner, H., Messchendorp, J., Schakel, P., Smit, H., van der Weele, J. C., Veenstra, R., Tiemens, M., Vejdani, S., Kalita, K., Mohanta, D. P., Kumar, A., Roy, A., Sahoo, R., Sohlbach, H., Büscher, M., Cao, L., Cebulla, A., Deermann, D., Dosdall, R., Esch, S., Georgadze, I., Gillitzer, A., Goerres, A., Goldenbaum, F., Grunwald, D., Herten, A., Hu, Q., Kemmerling, G., Kleines, H., Kozlov, V., Lehrach, A., Leiber, S., Maier, R., Nellen, R., Ohm, H., Orfanitski, S., Prasuhn, D., Prencipe, E., Ritman, J., Schadmand, S., Schumann, J., Sefzick, T., Serdyuk, V., Sterzenbach, G., Stockmanns, T., Wintz, P., Wüstner, P., Xu, H., Li, S., Li, Z., Sun, Z., Rigato, V., Fissum, S., Hansen, K., Isaksson, L., Lundin, M., Schröder, B., Achenbach, P., Bleser, S., Cardinali, M., Corell, O., Deiseroth, M., Denig, A., Distler, M., Feldbauer, F., Fritsch, M., Jasinski, P., Hoek, M., Kangh, D., Karavdina, A., Lauth, W., Leithoff, H., Merkel, H., Michel, M., Motzko, C., Müller, U., Noll, O., Plueger, S., Pochodzalla, J., Sanchez, S., Schlimme, S., Sfienti, C., Steinen, M., Thiel, M., Weber, T., Zambrana, M., Dormenev, V. I., Fedorov, A. A., Korzihik, M. V., Missevitch, O. V., Balanutsa, P., Balanutsa, V., Chernetsky, V., Demekhin, A., Dolgolenko, A., Fedorets, P., Gerasimov, A., Goryachev, V., Varentsov, V., Boukharov, A., Malyshev, O., Marishev, I., Semenov, A., Konorov, I., Paul, S., Grieser, S., Hergemöller, A. K., Khoukaz, A., Köhler, E., Täschner, A., Wessels, J., Dash, S., Jadhav, M., Kumar, S., Sarin, P., Varma, R., Chandratre, V. B., Datar, V., Dutta, D., Jha, V., Kumawat, H., Mohanty, A. K., Roy, B., Yan, Y., Chinorat, K., Khanchai, K., Ayut, L., Pornrad, S., Barnyakov, A. Y., Blinov, A. E., Blinov, V. E., Bobrovnikov, V. S., Kononov, S. A., Kravchenko, E. A., Kuyanov, I. A., Onuchin, A. P., Sokolov, A. A., Tikhonov, Y. A., Atomssa, E., Hennino, T., Imre, M., Kunne, R., Galliard, C. Le, Ma, B., Marchand, D., Ong, S., Ramstein, B., Rosier, P., Tomasi-Gustafsson, E., Van de Wiele, J., Boca, G., Costanza, S., Genova, P., Lavezzi, L., Montagna, P., Rotondi, A., Abramov, V., Belikov, N., Bukreeva, S., Davidenko, A., Derevschikov, A., Goncharenko, Y., Grishin, V., Kachanov, V., Kormilitsin, V., Melnik, Y., Levin, A., Minaev, N., Mochalov, V., Morozov, D., Nogach, L., Poslavskiy, S., Ryazantsev, A., Ryzhikov, S., Semenov, P., Shein, I., Uzunian, A., Vasiliev, A., Yakutin, A., Yabsley, B., Bäck, T., Cederwall, B., Makónyi, K., Tegnér, P. E., von Würtemberg, K. M., Belostotski, S., Gavrilov, G., Izotov, A., Kashchuk, A., Levitskaya, O., Manaenkov, S., Miklukho, O., Naryshkin, Y., Suvorov, K., Veretennikov, D., Zhadanov, A., Rai, A. K., Godre, S. S., Duchat, R., Amoroso, A., Bussa, M. P., Busso, L., De Mori, F., Destefanis, M., Fava, L., Ferrero, L., Greco, M., Maggiora, M., Maniscalco, G., Marcello, S., Sosio, S., Spataro, S., Zotti, L., Calvo, D., Coli, S., De Remigis, P., Filippi, A., Giraudo, G., Lusso, S., Mazza, G., Mingnore, M., Rivetti, A., Wheadon, R., Balestra, F., Iazzi, F., Introzzi, R., Lavagno, A., Younis, H., Birsa, R., Bradamante, F., Bressan, A., Martin, A., Clement, H., Gålnander, B., Balkeståhl, L. Caldeira, Calén, H., Fransson, K., Johansson, T., Kupsc, A., Marciniewski, P., Pettersson, J., Schönning, K., Wolke, M., Zlomanczuk, J., Díaz, J., Ortiz, A., Vinodkumar, P. C., Parmar, A., Chlopik, A., Melnychuk, D., Slowinski, B., Trzcinski, A., Wojciechowski, M., Wronka, S., Zwieglinski, B., Bühler, P., Marton, J., Suzuki, K., Widmann, E., Zmeskal, J., Fröhlich, B., Khaneft, D., Lin, D., Zimmermann, I., and Semenov-Tian-Shansky, K.
Abstract: We address the possibility of accessing nucleon-to-pion ($\pi N$) Transition Distribution Amplitudes (TDAs) from $\bar{p}p \to e^+e^- \pi^0$ reaction with the future \={P}ANDA detector at the FAIR facility. At high center of mass energy and high invariant mass of the lepton pair $q^2$, the amplitude of the signal channel $\bar{p}p \to e^+e^- \pi^0$ admits a QCD factorized description in terms of $\pi N$ TDAs and nucleon Distribution Amplitudes (DAs) in the forward and backward kinematic regimes. Assuming the validity of this factorized description, we perform feasibility studies for measuring $\bar{p}p \to e^+e^- \pi^0$ with the \={P}ANDA detector. Detailed simulations on signal reconstruction efficiency as well as on rejection of the most severe background channel, {\it i.e.} $\bar{p}p \to \pi^+\pi^- \pi^0$ were performed for the center of mass energy squared $s = 5$ GeV$^2$ and $s = 10$ GeV$^2$, in the kinematic regions $3.0 < q^2 < 4.3$ GeV$^2$ and $5 < q^2 < 9$ GeV$^2$, respectively, with a neutral pion scattered in the forward or backward cone $| \cos\theta_{\pi^0}| > 0.5 $ in the proton-antiproton center of mass frame. Results of the simulation show that the particle identification capabilities of the \={P}ANDA detector will allow to achieve a background rejection factor at the level of $10^8$ ($2\cdot 10^7$) at low (high) $q^2$ while keeping the signal reconstruction efficiency at around $40\%$ and that a clean lepton signal can be reconstructed with the expected statistics corresponding to $2$ fb$^{-1}$ of integrated luminosity. The future measurement of the signal channel cross section with \={P}ANDA will provide a new test of perturbative QCD description of a novel class of hard exclusive reactions and will open the possibility of experimentally accessing $\pi N$ TDAs.

109. Lifestyle and Mediterranean diet adherence in a cohort of Southern Italian patients with Multiple Sclerosis

Author: G. Tedeschi, Alessio Signori, Francesca Trojsi, Simona Bonavita, Luigi Lavorgna, V. Brescia Morra, Antonio Gallo, Simone Cepparulo, Luca Carmisciano, Camilla Russo, Maddalena Sparaco, Elisabetta Signoriello, G. T. Maniscalco, Sabrina Esposito, Giacomo Lus, Francesco Saccà, R Lanzillo, Esposito, S, Sparaco, M, Maniscalco, G T, Signoriello, E, Lanzillo, R, Russo, C, Carmisciano, L, Cepparulo, S, Lavorgna, L, Gallo, A, Trojsi, F, Brescia Morra, V, Lus, G, Tedeschi, G, Saccà, F, Signori, A, Bonavita, S, Esposito, S., Sparaco, M., Maniscalco, G. T., Signoriello, E., Lanzillo, R., Russo, C., Carmisciano, L., Cepparulo, S., Lavorgna, L., Gallo, A., Trojsi, F., Brescia Morra, V., Lus, G., Tedeschi, G., Sacca, F., Signori, A., and Bonavita, S.
Subjects: medicine.medical_specialty, Multiple Sclerosis, Mediterranean diet, Physical examination, Systemic inflammation, Diet, Mediterranean, 03 medical and health sciences, 0302 clinical medicine, Retrospective Studie, Internal medicine, medicine, Outpatient clinic, Humans, Multiple sclerosi, 030212 general & internal medicine, Life Style, Retrospective Studies, Cross-Sectional Studie, Expanded Disability Status Scale, medicine.diagnostic_test, business.industry, Multiple sclerosis, General Medicine, medicine.disease, Cardiovascular risk, Lifestyle, Cross-Sectional Studies, Neurology, Italy, Cohort, Neurology (clinical), medicine.symptom, business, Body mass index, 030217 neurology & neurosurgery, Human
Abstract: Background/objectives Several studies supported the beneficial effects of the Mediterranean diet (MeDi) on chronic diseases. In Multiple Sclerosis (MS), the MeDi might interfere with systemic inflammatory state, gut microbiota, and comorbidities. The Med Diet Score (MDS) estimates the adherence to the MeDi and the cardiovascular (CV) risk. Aims of our study were i) to photograph lifestyle and diet habits of a southern Italy cohort of people with MS (pwMS), and ii) to investigate the impact of the MeDi on MS clinical outcomes. Subjects/methods We conducted a multi-center, cross-sectional study, enrolling 435 consecutive consenting pwMS, attending the outpatient clinics for routine follow-up visits. Participants underwent a clinical examination and a 29-item self-administered questionnaire on life and dietary habits. Disease phenotype, Expanded Disability Status Scale (EDSS), MS Severity Score (MSSS), waist circumference (WC), Body Mass Index (BMI), therapies, and comorbidities, were updated. MDS was assessed and correlated with current and retrospective clinical data. Results 75.8% of respondents were interested in nutrition, 72.8% were non-smokers, 52.9% performed physical activity, and 45.6% used food supplements. MDS was higher in pwMS with normal WC (p = 0.031), and inversely correlated with MSSS (p = 0.013) and EDSS (p = 0.012) at survey time. MDS did not correlate with the total number of relapses (before and after diagnosis) (p = 0.372). Metabolic comorbidities were associated with an increased 10-year CV risk (r = 0.85, p = 0.002). Conclusion Our findings suggest a putative beneficial effect of the MeDi on WC, MS course and disability. Given the role of chronic systemic inflammation in maintenance of autoimmunity and secondary neurodegeneration, both involved in long-term disability, we may suppose a beneficial effect of the MeDi on MS long-term disability outcomes, probably mediated by a modulation of the gut microbiota and the low-grade chronic systemic inflammation.
Published: 2021

110. Is antibody titer useful to verify the immunization after VZV Vaccine in MS patients treated with Fingolimod? A case series

Author: V. Brescia Morra, Elisabetta Signoriello, Leonardo Sinisi, Roberta Lanzillo, Giacomo Lus, Camilla Russo, Francesco Saccà, S. Casertano, Giorgia Teresa Maniscalco, Simona Bonavita, Signoriello, E, Bonavita, S, Sinisi, L, Russo, C, Maniscalco, G T, Casertano, S, Saccà, F, Lanzillo, R, Morra, E Brescia, Lus, G, Signoriello, E., Bonavita, S., Sinisi, L., Russo, C., Maniscalco, G. T., Casertano, S., Sacca, F., Lanzillo, R., Morra, E. B., and Lus, G.
Subjects: Chickenpox, business.industry, viruses, Varicella zoster virus, Antibody titer, virus diseases, General Medicine, biochemical phenomena, metabolism, and nutrition, medicine.disease, Vaccine efficacy, medicine.disease_cause, Fingolimod, Vaccination, 03 medical and health sciences, Titer, 0302 clinical medicine, Neurology, Immunization, Immunology, medicine, 030212 general & internal medicine, Neurology (clinical), business, 030217 neurology & neurosurgery, medicine.drug
Abstract: Background : Fingolimod (FTY720, Gilenya) is a second line therapy to treat relapsing MS not responding to first-line treatments and/or with a high disease activity (according to Italian Regulatory authorities). Before starting Fingolimod, patients’ immunity to varicella zoster virus (VZV) needs to be assessed and seronegative patients vaccinated. To test susceptibility and response, IgG antibodies are tested after immunization. Since Fingolimod determines a reduction of circulating B lymphocytes and immunoglobulins, we aimed at describing the trend of VZV antibodies in seronegative vaccinated patients with MS before and after treatment. Methods : A total of 23 patients vaccinated for VZV before starting Fingolimod treatment, were recruited in this observational retrospective study involving five MS Centers in Campania (Italy). Of these, 12 patients were excluded for missing data. Patients received two doses of Varivax® Vaccine. After vaccination patients were re-tested and were all positive for IgG-VZV. We re-tested IgG-VZV in the same laboratory after a mean time of 2.42 years from Fingolimod therapy start. Results : During Fingolimod therapy we observed a global reduction of antibody titer and a disappearance in 7/11 patients. Titer disappearance was more probable in patients with lower post-vaccination titer. Of the 7 patients with vanishing IgG-VZV, three suspended Fingolimod for adverse event. In two of them, we observed a reappearance of antibody titer after treatment cessation. In one patient chickenpox infection occurred one year later. Discussion and conclusions : Our observational study shows that Fingolimod could influence antibody titer probably through its effect on B lymphocytes, but the efficacy of the vaccination should be verified. In conclusion, it is necessary to pay attention to therapies acting on B lymphocytes as they could influence the antibody titer and efficacy of vaccination making the search for other markers of vaccine efficacy desirable such as cell-mediated immunity with proliferation and induction of memory T lymphocytes in response to viral glycoproteins.
Published: 2020

111. Cost-Effectiveness Analysis of Cannabinoid Oromucosal Spray Use for the Management of Spasticity in Subjects with Multiple Sclerosis

Author: Mantovani, Lg, Cozzolino, P, Cortesi, Pa, Patti, F, Messina, S, Solaro, C, Amato, Mp, Bergamaschi, R, Bonavita, S, Bruno Bossio, R, Brescia Morra, V, Costantino, Gf, Cavalla, P, Centonze, D, Comi, G, Cottone, S, Danni, M, Francia, A, Gajofatto, A, Gasperini, C, Ghezzi, A, Iudice, A, Lus, G, Maniscalco, Gt, Marrosu, Mg, Matta, M, Mirabella, M, Montanari, E, Pozzilli, C, Rovaris, M, Sessa, E, Spitaleri, D, Trojano, M, Valentino, P, Zappia, M, Benedetti, Md, Bertolotto, A, Berra, E, Bianco, A, Buttari, F, Cerqua, R, Florio, C, Fuiani, A, Guareschi, A, Ippolito, D, Nuara, A, Palmieri, V, Paolicelli, D, Petrucci, L, Pontecorvo, S, Sacca, F, Salomone, G, Signoriello, E, Spinicci, G, Russo, M, Tavazzi, E, Trabucco, E, Trotta, M, Zaffaroni, M, Mantovani, L, Cozzolino, P, Cortesi, P, Patti, F, Messina, S, Solaro, C, Amato, M, Bergamaschi, R, Bonavita, S, Bruno Bossio, R, Brescia Morra, V, Costantino, G, Cavalla, P, Centonze, D, Comi, G, Cottone, S, Danni, M, Francia, A, Gajofatto, A, Gasperini, C, Ghezzi, A, Iudice, A, Lus, G, Maniscalco, G, Marrosu, M, Matta, M, Mirabella, M, Montanari, E, Pozzilli, C, Rovaris, M, Sessa, E, Spitaleri, D, Trojano, M, Valentino, P, Zappia, M, Benedetti, M, Bertolotto, A, Berra, E, Bianco, A, Buttari, F, Cerqua, R, Florio, C, Fuiani, A, Guareschi, A, Ippolito, D, Nuara, A, Palmieri, V, Paolicelli, D, Petrucci, L, Pontecorvo, S, Sacca, F, Salomone, G, Signoriello, E, Spinicci, G, Russo, M, Tavazzi, E, Trabucco, E, Trotta, M, Zaffaroni, M, Mantovani, Lorenzo G, Cozzolino, Paolo, Cortesi, Paolo A, Patti, Francesco, Amato, Mp, Costantino, Gf, Maniscalco, Gt, Marrosu, Mg, Benedetti, Md, Saccà, F, Zaffaroni, M., Mantovani, L. G., Cozzolino, P., Cortesi, P. A., Patti, F., Messina, S., Solaro, C., Amato, M. P., Bergamaschi, R., Bonavita, S., Bruno Bossio, R., Brescia Morra, V., Costantino, G. F., Cavalla, P., Centonze, D., Comi, G., Cottone, S., Danni, M., Francia, A., Gajofatto, A., Gasperini, C., Ghezzi, A., Iudice, A., Lus, G., Maniscalco, G. T., Marrosu, M. G., Matta, M., Mirabella, M., Montanari, E., Pozzilli, C., Rovaris, M., Sessa, E., Spitaleri, D., Trojano, M., Valentino, P., Zappia, M., Benedetti, M. D., Bertolotto, A., Berra, E., Bianco, A., Buttari, F., Cerqua, R., Florio, C., Fuiani, A., Guareschi, A., Ippolito, D., Nuara, A., Palmieri, V., Paolicelli, D., Petrucci, L., Pontecorvo, S., Sacca, F., Salomone, G., Signoriello, E., Spinicci, G., Russo, M., Tavazzi, E., Trabucco, E., and Trotta, M.
Subjects: Adult, Male, medicine.medical_specialty, Cost effectiveness, Cost-Benefit Analysis, MEDLINE, 030204 cardiovascular system & hematology, Settore MED/26, multiple sclerosis, 030226 pharmacology & pharmacy, 03 medical and health sciences, 0302 clinical medicine, Quality of life, Cannabidiol, Dronabinol, Drug Combinations, Female, Humans, Italy, Middle Aged, Multiple Sclerosis, Muscle Spasticity, Quality of Life, Quality-Adjusted Life Years, Medicine, Pharmacology (medical), Spasticity, spasticity, multiple sclerosis, cannabinoid, health care economics and organizations, Cost-Effectiveness Analysis, Spasticity, Cannabinoid, Multiple Sclerosis, Cost–benefit analysis, business.industry, Multiple sclerosis, spasticity, General Medicine, Cost-effectiveness analysis, cannabinoid, medicine.disease, Quality-adjusted life year, Settore MED/26 - NEUROLOGIA, Physical therapy, medicine.symptom, business
Abstract: Introduction: Multiple sclerosis (MS) is a highly symptomatic disease, with a wide range of disabilities affecting many bodily functions, even in younger persons with a short disease history. The availability of a cannabinoid oromucosal spray (Sativex) for the management of treatment-resistant MS spasticity has provided a new opportunity for many patients. Objective: Our study aimed to assess the cost effectiveness of Sativex in Italian patients with treatment-resistant MS spasticity. The analysis was based on the real-world data of a large registry of Italian patients. Methods: A cost-utility analysis was conducted using data collected prospectively from an electronic registry of all patients who began to use Sativex for MS-resistant spasticity between January 2014 and February 2015 in 30 specialized MS units across Italy and were followed up for ≤ 6months. Data on drug consumption and spasticity/utility were used to estimate the incremental cost-effectiveness ratio (ICER) of Sativex, as compared with no intervention. No costs or spasticity/utility changes were assumed for no treatment intervention. The ICER was expressed as quality-adjusted life-years (QALYs) gained, using the Italian NHS perspective and a 6-month time horizon. Results: Sativex effectiveness and consumption was estimated analyzing data of 1350 patients from the registry. These patients reported a mean (SD) utility increment of 0.087 (0.069) after 1month of treatment, 0.118 (0.073) after 3months’ treatment and 0.127 (0.080) after 6months’ treatment. The 6-month cost of treating the entire population with Sativex was €1,361,266, with a €1008 cost and 0.0284 QALYs gained per patient. The estimated ICER was €35,516 per QALY gained, with little variability around the central estimate of cost-effectiveness, as shown by the cost-effectiveness acceptability curve. Conclusion: The use of Sativex could improve the quality of life of patients with a reasonable incremental cost resulting as a cost-effective option for patients with MS-resistant spasticity. These results could help clinicians and decision makers to develop improved management strategies for spasticity in patients with MS, optimizing the use of available resources.
Published: 2020

112. A snapshot on patient-reported outcome measures of people with multiple sclerosis on first-line therapies in a real world setting

Author: Luigi Lavorgna, Teresa Costabile, Luca Carmisciano, R Lanzillo, N. Frattaruolo, Giacomo Lus, Alvino Bisecco, Alessio Signori, Simona Bonavita, A. Strianese, G. T. Maniscalco, V. Brescia Morra, Maddalena Sparaco, Elisabetta Signoriello, Simone Cepparulo, Francesco Saccà, Camilla Russo, Lanzillo, R, Sparaco, M, Lavorgna, L, Carmisciano, L, Signoriello, E, Signori, A, Costabile, T, Maniscalco, G T, Saccà, F, Cepparulo, S, Russo, C V, Bisecco, A, Frattaruolo, N, Strianese, A, Lus, G, Brescia Morra, V, Bonavita, S, Lanzillo, R., Sparaco, M., Lavorgna, L., Carmisciano, L., Signoriello, E., Signori, A., Costabile, T., Maniscalco, G. T., Sacca, F., Cepparulo, S., Russo, C. V., Bisecco, A., Frattaruolo, N., Strianese, A., Lus, G., Brescia Morra, V., and Bonavita, S.
Subjects: medicine.medical_specialty, Neurology, Multiple Sclerosis, Disease-modifying therapies, First-line therapies, Multiple sclerosis, Patient-reported outcomes, Dermatology, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Multiple Sclerosis, Relapsing-Remitting, Teriflunomide, medicine, Humans, Multiple sclerosi, Disease-modifying therapie, 030212 general & internal medicine, Effects of sleep deprivation on cognitive performance, Patient Reported Outcome Measures, Glatiramer acetate, First-line therapie, Aged, business.industry, Cognition, General Medicine, Glatiramer Acetate, medicine.disease, humanities, Psychiatry and Mental health, chemistry, Physical therapy, Quality of Life, Patient-reported outcome, Neurology (clinical), Analysis of variance, business, 030217 neurology & neurosurgery, medicine.drug
Abstract: Background: Patient-reported outcomes (PROs) may help patients and clinicians in selecting disease-modifying therapies (DMTs) for multiple sclerosis (MS). Objective: To evaluate PRO differences among first-line DMTs for relapsing-remitting (RR) people with MS (pwMS). Methods: Multicenter study. RR pwMS on first-line DMTs completed Fatigue Severity Scale (FSS), PROs Indices for MS (PRIMUS), 36-item Short-Form Health Survey (SF-36), treatment satisfaction questionnaire for medication (TSQM), Beck Depression Inventory-II (BDI-II), and Symbol Digit Modalities Test (SDMT). Differences among PROs across DMTs were tested by ANOVA. Multivariable linear regressions were used to investigate associations between PROs and the treatment group. Results: Two-hundred eighty pwMS were enrolled: 56% were on interferons (INF), 22% on dimethylfumarate (DMF), 13% on glatiramer acetate, and 9% on teriflunomide (Teri). Compared with INF, pwMS on Teri were the oldest, with higher disability, worst depression at BDI, worst cognitive performances at SDMT (p = 0.001), fatigue at FSS (p = 0.001), and activity limitation and quality of life respectively at PRIMUS (p = 0.005) and SF-36 Mental Composite Score (p < 0.001); pwMS on DMF reported highest side effects and, together with pwMS on Teri, better treatment satisfaction at TSQM. Conclusions: Compared with INF-treated patients, pwMS on DMF and Teri reported the best treatment satisfaction, although DMF-treated pwMS reported higher side effects and those on Teri the worst QoL and fatigue; however, the older age, higher disability and depression, and worse cognitive performance of pwMS on Teri suggest to be careful in evaluating these results.
Published: 2019

113. Clinical predictors of Dimethyl Fumarate response in multiple sclerosis: a real life multicentre study

Author: Antonio Carotenuto, Elisabetta Signoriello, Leonardo Sinisi, Giacomo Lus, Rosa Iodice, Luigi Lavorgna, V. Brescia Morra, Martina Petruzzo, B. Ronga, A. De Rosa, G. T. Maniscalco, Marcello Moccia, Camilla Russo, Raffaele Palladino, F. Romano, Simona Bonavita, Ciro Florio, M. De Angelis, Roberta Lanzillo, V. Orlando, Francesco Saccà, Lanzillo, R, Moccia, M, Palladino, R, Signoriello, E, Carotenuto, A, Maniscalco, G T, Saccà, F, Bonavita, S, Russo, C V, Iodice, R, Petruzzo, M, Sinisi, L, De Angelis, M, Lavorgna, L, De Rosa, A, Romano, F, Orlando, V, Ronga, B, Florio, C, Lus, G, Brescia Morra, V, Lanzillo, R., Moccia, M., Palladino, R., Signoriello, E., Carotenuto, A., Maniscalco, G. T., Sacca, F., Bonavita, S., Russo, C. V., Iodice, R., Petruzzo, M., Sinisi, L., De Angelis, M., Lavorgna, L., De Rosa, A., Romano, F., Orlando, V., Ronga, B., Florio, C., Lus, G., and Brescia Morra, V.
Subjects: Adult, Male, medicine.medical_specialty, Multivariate analysis, Time Factors, Efficacy, Dimethyl Fumarate, Real life, Disease, law.invention, Multiple sclerosis, Persistence, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Multiple Sclerosis, Relapsing-Remitting, Randomized controlled trial, law, Recurrence, Internal medicine, Outcome Assessment, Health Care, medicine, Humans, Immunologic Factors, Multiple sclerosi, 030212 general & internal medicine, Prospective Studies, Risk factor, Age of Onset, Retrospective Studies, Expanded Disability Status Scale, Dimethyl fumarate, business.industry, General Medicine, Middle Aged, Multiple Sclerosis, Chronic Progressive, medicine.disease, Dimethyl-fumarate, Neurology, Tolerability, chemistry, Disease Progression, Female, Neurology (clinical), business, 1109 Neurosciences, 030217 neurology & neurosurgery
Abstract: Background: Dimethyl-fumarate (DMF) was effective and safe in relapsing–remitting multiple sclerosis (MS) in randomized clinical trials. We aimed to evaluate the efficacy and safety of DMF and factors related to drug response in real-life setting. Methods: We analysed prospectively collected demographic and clinical data for patients treated with DMF in six multiple sclerosis (MS) centers from 2015 to 2017 in Campania region, Italy. We performed univariate and multivariate analyses to assess relationships between baseline parameters and DMF efficacy outcomes, Annualized Relapse Rate (ARR), Expanded Disability Status Scale (EDSS) progression and No Evidence of Disease Activity (NEDA-3) status. Results: we analyzed data of 456 patients (67% female subjects, mean age 40 ± 12 years, mean disease duration 9 ± 9 years, mean treatment duration 18 ± 11 months, median EDSS 2.5, 0–8). Proportion of Naïve versus pretreated with other DMTs patients was 149/307 (32.7%), with 122 patients switching to DMF for disease activity (26.7%) and 185 for safety and tolerability issues (40.6%). During treatment with DMF, the annualized relapse rate was reduced by 75% respect to the pre-treatment ARR [incidence-rate-ratio (IRR) = 0.25, p < 0.001, CI 0.18–0.33]. Factors influencing ARR rate while on DMF were relapsing remitting (RR) MS course (IRR = 2.0, p =
Published: 2019

114. Fake news, influencers and health-related professional participation on the Web: A pilot study on a social-network of people with Multiple Sclerosis

Author: G. Tedeschi, Daniela Buonanno, Gianmarco Abbadessa, L. Rosa, Luigi Lavorgna, Simona Bonavita, Alvino Bisecco, Francesca Trojsi, Maddalena Sparaco, Marcello Moccia, Domenico Ippolito, M. De Stefano, Marinella Clerico, Sabrina Esposito, V. Brescia Morra, C. Cenci, Giorgia Teresa Maniscalco, Patrizia Montella, R Lanzillo, Lavorgna, L., De Stefano, M., Sparaco, Rosa, Moccia, M., Abbadessa, Pietro, Montella, P., Buonanno, D., Esposito, S., Clerico, M., Cenci, Beniamino, Trojsi, F., Lanzillo, R., Rosa, L., Morra, V. Brescia, Ippolito, D., Maniscalco, G., Bisecco, A., Tedeschi, G., Bonavita, S., Lavorgna, L, De Stefano, M, Sparaco, M, Moccia, M, Abbadessa, G, Montella, P, Buonanno, D, Esposito, S, Clerico, M, Cenci, C, Trojsi, F, Lanzillo, R, Rosa, L, Morra, Vb, Ippolito, D, Maniscalco, G, Bisecco, A, Tedeschi, G, and Bonavita, S
Subjects: Male, Multiple Sclerosis, 020205 medical informatics, Digital health, E-health, Fake news, Influencers, Female, Health Personnel, Humans, Interpersonal Relations, Italy, Pilot Projects, Internet, Physician-Patient Relations, Social Networking, Neurology, Neurology (clinical), Internet privacy, 02 engineering and technology, Computer-assisted web interviewing, Fake new, 03 medical and health sciences, Influencer, 0302 clinical medicine, Multiple Sclerosi, 0202 electrical engineering, electronic engineering, information engineering, Medicine, Confidentiality, Misinformation, Web community, business.industry, Information seeking, General Medicine, Influencer marketing, The Internet, business, 030217 neurology & neurosurgery
Abstract: Background Over the last few decades, patients have increasingly been searching for health information on the Internet. This aspect of information seeking is important, especially for people affected by chronic pathologies and require lifelong treatment and management. These people are usually very well informed about the disease but are nonetheless vulnerable to hopes of being cured or saved, often amplified by misinformation, myths, legends, and therapies that are not always scientifically proven. Many studies suggest that some individuals prefer to rely on the Internet as their main source of information, often hindering the patient-doctor relationship. A professional approach is imperative to maintain confidentiality, honesty, and trust in the medical profession. Objective we aimed to examine, in a medically supervised Italian web community (SMsocialnetwotk.com) dedicated to people with Multiple Sclerosis (pwMS), the posts shared by users and to verify the reliability of contents of posts shared by users pinpointed as Influencers through an online questionnaire. Methods we grouped the posts published on SMsocialnetwork from April to June 2015 into those with medical content (scientifically correct or fake news), and those related to social interactions. Later, we gave a questionnaire to the community asking to identify the three users/Influencers providing the most reliable advice for everyday life with MS and the three users/Influencers providing the most useful information about MS treatments. Results 308 posts reported scientific and relevant medical information, whereas 72 posts included pieces of fake news. 1420 posts were of general interest. Four out of the 6 Influencers had written only posts with correct medical information (3 were pwMS, 1 was a Neurologist) and never any fake news. The remaining 2 appointed Influencers (2 pwMS) had written only posts about general interests. Conclusion the identification of fake news and their authors has shown that the latter are never appointed as Influencers. SMsocialnetwork.com acted as a “web safe environment” where the Influencers contributed by sharing only correct medical information and never fake news. We speculate that the presence of neurologists and psychologists supervising the information flow might have contributed to reduce the risk of fake news spreading and to avoid their acquisition of authoritative meaning.
Published: 2018

115. Clinical activity after fingolimod cessation: Disease reactivation or rebound?

Author: S La Gioia, B Forci, Sabrina Realmuto, Pietro Annovazzi, Arianna Sartori, Roberta Grasso, Cinzia Cordioli, M. L. Stromillo, R Lanzillo, B. Frigeni, Eleonora Cocco, Elisabetta Signoriello, Alessio Signori, Sandro Rossi, Giuseppe Fenu, M. P. Sormani, Damiano Baroncini, G. T. Maniscalco, Sarah Rasia, Jessica Frau, Frau, J., Sormani, M. P., Signori, A., Realmuto, S., Baroncini, D., Annovazzi, P., Signoriello, E., Maniscalco, G. T., La Gioia, S., Cordioli, C., Frigeni, B., Rasia, S., Fenu, G., Grasso, R., Sartori, A., Lanzillo, R., Stromillo, M. L., Rossi, S., Forci, B., Cocco, E., Frau, J, Sormani, M P, Signori, A, Realmuto, S, Baroncini, D, Annovazzi, P, Signoriello, E, Maniscalco, G T, La Gioia, S, Cordioli, C, Frigeni, B, Rasia, S, Fenu, G, Grasso, R, Sartori, A, Lanzillo, R, Stromillo, M L, Rossi, S, Forci, B, and Cocco, E
Subjects: Adult, Male, medicine.medical_specialty, Adolescent, Disease, Cohort Studies, Multiple sclerosis, Immunosuppressive Agent, Young Adult, 03 medical and health sciences, Multiple Sclerosis, Relapsing-Remitting, 0302 clinical medicine, Recurrence, Internal medicine, Humans, Medicine, 030212 general & internal medicine, Fingolimod, Reactivation, Rebound, Neurology, Neurology (clinical), Natural course, Fingolimod Hydrochloride, business.industry, medicine.disease, Magnetic Resonance Imaging, Discontinuation, Italy, Withholding Treatment, multiple sclerosi, Cohort, Female, Cohort Studie, business, Immunosuppressive Agents, 030217 neurology & neurosurgery, Human, medicine.drug
Abstract: Background and purpose There is debate as to whether the apparent rebound after fingolimod discontinuation is related to the discontinuation itself or whether it is due to the natural course of highly active multiple sclerosis (MS). Our aim was to survey the prevalence of severe reactivation and rebound after discontinuation of fingolimod in a cohort of Italian patients with MS. Methods Patients with relapsing-remitting MS who were treated with fingolimod for at least 6 months and who stopped treatment for reasons that were unrelated to inefficacy were included in the analysis. Results A total of 100 patients who had discontinued fingolimod were included in the study. Fourteen patients (14%) had a relapse within 3 months after fingolimod discontinuation, and an additional 12 (12%) had a relapse within 6 months. According to this study's criteria, 10 patients (10%) had a severe reactivation. Amongst these patients, five (5%) had a reactivation that was considered to be a rebound. Conclusions The present study showed that more than 26% of patients are at risk of having a relapse within 6 months after fingolimod discontinuation. Nevertheless, the risk of severe reactivations and rebound is lower than has been previously described.
Published: 2018

116. A real‐world study of alemtuzumab in a cohort of Italian patients

Author: Paola Cavalla, Laura Brambilla, Roberta Grasso, Cinzia Cordioli, Alice Laroni, Alessia Giugno, Valentina Torri Clerici, Maria Pia Sormani, Pietro Annovazzi, Francesco Saccà, Eleonora Cocco, Jessica Frau, Elisabetta Signoriello, Antonio Gallo, Marinella Clerico, Stefania Federica De Mercanti, Antonio Carotenuto, Simona Bonavita, Cinzia Valeria Russo, Giuseppe Fenu, Caterina Lapucci, Giorgia Teresa Maniscalco, Arianna Sartori, Francesca Caleri, Marco Capobianco, Alessio Signori, Rosa Iodice, Sara La Gioia, Giacomo Lus, Mauro Zaffaroni, Damiano Baroncini, Valeria Di Francescantonio, Russo, C. V., Sacca, F., Frau, J., Annovazzi, P., Signoriello, E., Bonavita, S., Grasso, R., Clerico, M., Cordioli, C., Laroni, A., Capobianco, M., Torri Clerici, V., Sartori, A., Cavalla, P., Maniscalco, G. T., La Gioia, S., Caleri, F., Giugno, A., Iodice, R., Carotenuto, A., Cocco, E., Fenu, G., Zaffaroni, M., Baroncini, D., Lus, G., Gallo, A., De Mercanti, S. F., Lapucci, C., Di Francescantonio, V., Brambilla, L., Sormani, M. P., Signori, A., Russo, CINZIA VALERIA, Sacca', Francesco, Frau, Jessica, Annovazzi, Pietro, Signoriello, Elisabetta, Bonavita, Simona, Grasso, Roberta, Clerico, Marinella, Cordioli, Cinzia, Laroni, Alice, Capobianco, Marco, Torri Clerici, Valentina, Sartori, Arianna, Cavalla, Paola, Teresa Maniscalco, Giorgia, La Gioia, Sara, Caleri, Francesca, Giugno, Alessia, Iodice, Rosa, Carotenuto, Antonio, Cocco, Eleonora, Fenu, Giuseppe, Zaffaroni, Mauro, Baroncini, Damiano, Lus, Giacomo, Gallo, Antonio, Federica De Mercanti, Stefania, Lapucci, Caterina, Di Francescantonio, Valeria, Brambilla, Laura, Pia Sormani, Maria, and Signori, Alessio
Subjects: Adult, safety, medicine.medical_specialty, efficacy, Multiple Sclerosis, Relapsing-Remitting, Natalizumab, Internal medicine, alemtuzumab, medicine, Humans, Glatiramer acetate, real-world evidence, Retrospective Studies, Expanded Disability Status Scale, Fingolimod Hydrochloride, business.industry, Multiple sclerosis, Glatiramer Acetate, cohort, medicine.disease, Fingolimod, Neurology, Relative risk, Cohort, Alemtuzumab, Neurology (clinical), business, medicine.drug
Abstract: Background and purpose: Real-world data on alemtuzumab are limited and do not provide evidence of its effectiveness after various disease-modifying therapies (DMTs). Our aim was to provide real-world data on the impact of clinical variables and previous DMTs on clinical response to alemtuzumab. Methods: Sixteen Italian multiple sclerosis centers retrospectively included patients who started alemtuzumab from January 2015 to December 2018, and recorded demographics, previous therapies, washout duration, relapses, Expanded Disability Status Scale (EDSS) score, and magnetic resonance imaging data. Negative binomial regression models were used to assess the effect of factors on annualized relapse (ARR) after alemtuzumab initiation. Results: We studied 322 patients (mean age 36.8years, median EDSS score 3, median follow-up 1.94years). Previous treatments were: fingolimod (106), natalizumab (80), first-line oral agents (56), first-line injectables (interferon/glatiramer acetate; 30), and other drugs (15). Thirty-five patients were treatment-naïve. The pre-alemtuzumab ARR was 0.99 and decreased to 0.13 during alemtuzumab treatment (p&nbsp
Published: 2021

117. Immuno-metabolic impact of the multiple sclerosis patients’ sera on endothelial cells of the blood-brain barrier

Author: S. Mercurio, V. De Rosa, Simon McArthur, Egle Solito, Rodrigo Azevedo Loiola, Giorgia Teresa Maniscalco, Madeeha H Sheikh, Alessandra Colamatteo, Sian M. Henson, Sheikh, M. H., Henson, S. M., Loiola, R. A., Mercurio, S., Colamatteo, A., Maniscalco, G. T., De Rosa, V., Mcarthur, S., and Solito, E.
Subjects: Adult, Male, 0301 basic medicine, medicine.medical_specialty, Endothelium, Immunology, Blood–brain barrier, lcsh:RC346-429, Capillary Permeability, Multiple sclerosis, 03 medical and health sciences, Cellular and Molecular Neuroscience, Multiple Sclerosis, Relapsing-Remitting, 0302 clinical medicine, Immune system, Internal medicine, medicine, Humans, Multiple sclerosi, Cells, Cultured, Tight junction, Cytoskeleton, lcsh:Neurology. Diseases of the nervous system, Blood-brain barrier, Autoimmune disease, Cell adhesion molecule, Chemistry, Research, General Neuroscience, Transendothelial and Transepithelial Migration, medicine.disease, Extravasation, Endothelial stem cell, 030104 developmental biology, Endocrinology, medicine.anatomical_structure, Metabolism, Neurology, Female, Endothelium, Vascular, Signal transduction, 030217 neurology & neurosurgery
Abstract: Background Multiple sclerosis (MS) is an autoimmune disease which results from the invasion of the brain by activated immune cells across the endothelial cells (ECs) of the blood-brain barrier (BBB), due to loss of immune self-tolerance. Many reports define the metabolic profile of immune cells in MS, however little is known about the metabolism of the BBB ECs during the disease. We aim to determine whether circulating factors in MS induce metabolic alterations of the BBB ECs compared to a healthy state, which can be linked with disruption of BBB integrity and subsequent immune cell extravasation. Methods and results In this report, we used an in vitro model to study the effect of sera from naïve-to-treatment, relapsing-remitting MS (RRMS) patients on the human brain microvascular endothelium, comparing effects to age/sex-matched healthy donor (HD) sera. Our data show that RRMS serum components affect brain endothelial cells by impairing intercellular tightness through the down-modulation of occludin and VE-cadherin, and facilitating immune cell extravasation through upregulation of intercellular adhesion molecules (ICAM-1) and P-glycoprotein (P-gp). At a metabolic level, the treatment of the endothelial cells with RRMS sera reduced their glycolytic activity (measured through the extracellular acidification rate-ECAR) and oxygen consumption rate (oxidative phosphorylation rate-OCR). Such changes were associated with the down-modulation of endothelial glucose transporter 1 (GLUT-1) expression and by altered mitochondrial membrane potential. Higher level of reactive oxygen species released from the endothelial cells treated with RRMS sera indicate a pro-inflammatory status of the cells together with the higher expression of ICAM-1, endothelial cell cytoskeleton perturbation (stress fibres) as well as disruption of the cytoskeleton signal transduction MSK1/2 and β-catenin phosphorylation. Conclusions Our data suggest that circulating factors present in RRMS patient serum induce physiological and biochemical alterations to the BBB, namely reducing expression of essential tightness regulators, as well as reduced engagement of glycolysis and alteration of mitochondrial potential. As these last changes have been linked with alterations in nutrient usage and metabolic function in immune cells; we propose that the BBB endothelium of MS patients may similarly undergo metabolic dysregulation, leading to enhanced permeability and increased disease susceptibility.
Published: 2020

118. Effects of THC/CBD oromucosal spray on spasticity-related symptoms in people with multiple sclerosis: results from a retrospective multicenter study

Author: Domenico Ippolito, Giorgia Teresa Maniscalco, Damiano Paolicelli, Daniele Spitaleri, Francesco Patti, Gianfranco Costantino, Margherita Russo, Clara Grazia Chisari, Letizia Castelli, Giovanna Salamone, Roberto Bruno Bossio, Maria Trotta, Claudio Solaro, Eliana Berra, Roberta Lanzillo, Elisabetta Signoriello, Raffaella Cerqua, Isabella Righini, Fabio Buttari, Gabriella Spinicci, Loredana Petrucci, Angelica Guareschi, Manuela Matta, Mario Zappia, Simona Pontecorvo, Maria Donata Benedetti, Paola Cavalla, Assunta Bianco, Claudio Gasperini, Eleonora Tavazzi, Francesco Saccà, Mauro Zaffaroni, Patti, F., Chisari, C. G., Solaro, C., Benedetti, M. D., Berra, E., Bianco, A., Bruno Bossio, R., Buttari, F., Castelli, L., Cavalla, P., Cerqua, R., Costantino, G., Gasperini, C., Guareschi, A., Ippolito, D., Lanzillo, R., Maniscalco, G. T., Matta, M., Paolicelli, D., Petrucci, L., Pontecorvo, S., Righini, I., Russo, M., Saccà, Francesco, Salamone, G., Signoriello, E., Spinicci, G., Spitaleri, D., Tavazzi, E., Trotta, M., Zaffaroni, M., Zappia, M., Patti, Francesco, Grazia Chisari, Clara, Solaro, Claudio, Donata Benedetti, Maria, Berra, Eliana, Bianco, Assunta, Bruno Bossio, Roberto, Buttari, Fabio, Castelli, Letizia, Cavalla, Paola, Cerqua, Raffaella, Costantino, Gianfranco, Gasperini, Claudio, Guareschi, Angelica, Ippolito, Domenico, Lanzillo, Roberta, Teresa Maniscalco, Giorgia, Matta, Manuela, Paolicelli, Damiano, Petrucci, Loredana, Pontecorvo, Simona, Righini, Isabella, Russo, Margherita, Salamone, Giovanna, Signoriello, Elisabetta, Spinicci, Gabriella, Spitaleri, Daniele, Tavazzi, Eleonora, Trotta, Maria, Zaffaroni, Mauro, and Zappia, Mario
Subjects: medicine.medical_specialty, Multiple Sclerosis, THC, Neurology, Dermatology, Clinical practice, Spasticity-related symptom, CBD, Multiple sclerosis, Spasticity-related symptoms, 03 medical and health sciences, 0302 clinical medicine, Rating scale, Internal medicine, medicine, Cannabidiol, Humans, Multiple sclerosi, Dronabinol, 030212 general & internal medicine, Spasticity, Oromucosal spray, Retrospective Studies, Plant Extracts, business.industry, General Medicine, medicine.disease, nervous system diseases, Clinical Practice, Drug Combinations, Psychiatry and Mental health, Italy, Muscle Spasticity, Neurology (clinical), Neurosurgery, medicine.symptom, business, 030217 neurology & neurosurgery, medicine.drug
Abstract: Introduction: The approval of 9-δ-tetrahydocannabinol (THC)+cannabidiol (CBD) oromucosal spray (Sativex®) in Italy as an add-on medication for the management of moderate to severe spasticity in multiple sclerosis (MS) has provided a new opportunity for MS patients with drug-resistant spasticity. We aimed to investigate the improvement of MS spasticity-related symptoms in a large cohort of patients with moderate to severe spasticity in daily clinical practice. Materials and methods: MS patients with drug-resistant spasticity were recruited from 30 Italian MS centers. All patients were eligible for THC:CBD treatment according to the approved label: ≥ 18 years of age, at least moderate spasticity (MS spasticity numerical rating scale [NRS] score ≥ 4) and not responding to the common antispastic drugs. Patients were evaluated at baseline (T0) and after 4 weeks of treatment (T1) with the spasticity NRS scale and were also asked about meaningful improvements in 6 key spasticity-related symptoms. Results: Out of 1615 enrolled patients, 1432 reached the end of the first month trial period (T1). Of these, 1010 patients (70.5%) reached a ≥ 20% NRS score reduction compared with baseline (initial responders; IR). We found that 627 (43.8% of 1432) patients showed an improvement in at least one spasticity-related symptom (SRSr group), 543 (86.6%) of them belonging to the IR group and 84 (13.4%) to the spasticity NRS non-responders group. Conclusion: Our study confirmed that the therapeutic benefit of cannabinoids may extend beyond spasticity, improving spasticity-related symptoms even in non-NRS responder patients. © 2020, Fondazione Società Italiana di Neurologia.
Published: 2020

119. Prognostic Markers of Ocrelizumab Effectiveness in Multiple Sclerosis: A Real World Observational Multicenter Study

Author: Roberta Lanzillo, Antonio Carotenuto, Elisabetta Signoriello, Rosa Iodice, Giuseppina Miele, Alvino Bisecco, Giorgia Teresa Maniscalco, Leonardo Sinisi, Felice Romano, Maria Di Gregorio, Luigi Lavorgna, Francesca Trojsi, Marcello Moccia, Mario Fratta, Nicola Capasso, Raffaele Dubbioso, Maria Petracca, Antonio Luca Spiezia, Antonio Gallo, Martina Petruzzo, Marcello De Angelis, Simona Bonavita, Giacomo Lus, Gioacchino Tedeschi, Vincenzo Brescia Morra, Lanzillo, R., Carotenuto, A., Signoriello, E., Iodice, R., Miele, G., Bisecco, A., Maniscalco, G. T., Sinisi, L., Romano, F., Di Gregorio, M., Lavorgna, L., Trojsi, F., Moccia, M., Fratta, M., Capasso, N., Dubbioso, R., Petracca, M., Spiezia, A. L., Gallo, A., Petruzzo, M., De Angelis, M., Bonavita, S., Lus, G., Tedeschi, G., Morra, V. B., Lanzillo, Roberta, Carotenuto, Antonio, Signoriello, Elisabetta, Iodice, Rosa, Miele, Giuseppina, Bisecco, Alvino, Maniscalco, Giorgia Teresa, Sinisi, Leonardo, Romano, Felice, Di Gregorio, Maria, Lavorgna, Luigi, Trojsi, Francesca, Moccia, Marcello, Fratta, Mario, Capasso, Nicola, Dubbioso, Raffaele, Petracca, Maria, Spiezia, Antonio Luca, Gallo, Antonio, Petruzzo, Martina, De Angelis, Marcello, Bonavita, Simona, Lus, Giacomo, Tedeschi, Gioacchino, and Brescia Morra, Vincenzo
Subjects: real-world, ocrelizumab, multiple sclerosi, disease-modifying treatment, progression, General Medicine, multiple sclerosis
Abstract: Pivotal trials showed the effectiveness of the monoclonal antibody ocrelizumab in relapsing and progressive multiple sclerosis (MS). However, data on everyday practice in MS patients and markers of treatment effectiveness are scarce. We aimed to collect real-world data from ocrelizumab-treated MS patients, relapsing-remitting (RR) and progressive MS patients (PMS), including active secondary progressive MS (aSPMS) and primary progressive MS (PPMS) patients, and to explore potential prognostic factors of clinical outcome. Patients were enrolled at MS centres in the Campania region, Italy. We collected clinic-demographic features retrospectively one year before ocrelizumab start (T−1), at ocrelizumab start (T0), and after one year from ocrelizumab start (T1). We explored possible clinical markers of treatment effectiveness in those patients receiving ocrelizumab treatment for at least one year using multilevel-mixed models. We included a total of 383 MS patients (89 RRMS and 294 PMS; 205 females, mean age: 45.8 ± 11.2, disease duration: 12.7 ± 11.6 years). Patients had a mean follow-up of 12.4 ± 8.2 months, and 217 patients completed one-year ocrelizumab treatment. Overall, EDSS increased from T−1 to T0 (coeff. = 0.30, 95% coefficient interval [CI] = 0.19–0.41, p < 0.001) without a further change between T0 and T1 (p = 0.61). RRMS patients did not show an EDSS change between T−1 and T0 nor between T0 and T1. Conversely, PMS patients showed EDSS increase from T−1 to T0 (coeff. = 0.34, 95% CI = 0.22–0.45, p < 0.001) without a further change between T0 and T1 (p = 0.21). PMS patients with a time from conversion shorter than 2 years showed increased EDSS from T−1 to T0 (coeff. = 0.63, 95% CI = 0.18–1.08, p = 0.006) without a further change between T0 and T1 (p = 0.94), whereas PMS patients with a time from conversion longer than 2 years showed increased EDSS from T0 to T1 (coeff. = 0.30, 95% CI = 0.11–0.49, p = 0.002). Naïve patients showed an EDSS decrease between T0 and T1 (coeff. = −0.30, 95% CI = −0.50–−0.09, p = 0.004). In conclusion, our study highlighted that early ocrelizumab treatment is effective in modifying the disability accrual in MS patients.
Published: 2022

120. Comparing Natural History of Early and Late Onset Pediatric Multiple Sclerosis

Author: Ermelinda De Meo, Massimo Filippi, Maria Trojano, Giancarlo Comi, Francasco Patti, Vincenzo Brescia Morra, Giuseppe Salemi, Marco Onofrj, Giacomo Lus, Eleonora Cocco, Mattia Fonderico, Valentina Torri Clerici, Giorgia Teresa Maniscalco, Paola Valentino, Antonio Bertolotto, Alessandra Lugaresi, Roberto Bergamaschi, Marco Rovaris, Patrizia Sola, Gioacchino Tedeschi, Ilaria Pesci, Umberto Aguglia, Paola Cavalla, Davide Maimone, Franco Granella, Marika Vianello, Marta Simone, Emilio Portaccio, Maria Pia Amato, De Meo, E., Filippi, M., Trojano, M., Comi, G., Patti, F., Brescia Morra, V., Salemi, G., Onofrj, M., Lus, G., Cocco, E., Fonderico, M., Torri Clerici, V., Maniscalco, G. T., Valentino, P., Bertolotto, A., Lugaresi, A., Bergamaschi, R., Rovaris, M., Sola, P., Tedeschi, G., Pesci, I., Aguglia, U., Cavalla, P., Maimone, D., Granella, F., Vianello, M., Simone, M., Portaccio, E., Amato, M. P., De Meo, Ermelinda, Filippi, Massimo, Trojano, Maria, Comi, Giancarlo, Patti, Francasco, Brescia Morra, Vincenzo, Salemi, Giuseppe, Onofrj, Marco, Lus, Giacomo, Cocco, Eleonora, Fonderico, Mattia, Torri Clerici, Valentina, Maniscalco, Giorgia Teresa, Valentino, Paola, Bertolotto, Antonio, Lugaresi, Alessandra, Bergamaschi, Roberto, Rovaris, Marco, Sola, Patrizia, Tedeschi, Gioacchino, Pesci, Ilaria, Aguglia, Umberto, Cavalla, Paola, Maimone, Davide, Granella, Franco, Vianello, Marika, Simone, Marta, Portaccio, Emilio, Amato, Maria Pia, De Meo, E, Filippi, M, Trojano, M, Comi, G, Patti, F, Brescia Morra, V, Salemi, G, Onofrj, M, Lus, G, Cocco, E, Fonderico, M, Torri Clerici, V, Maniscalco, Gt, Valentino, P, Bertolotto, A, Lugaresi, A, Bergamaschi, R, Rovaris, M, Sola, P, Tedeschi, G, Pesci, I, Aguglia, U, Cavalla, P, Maimone, D, Granella, F, Vianello, M, Simone, M, Portaccio, E, and Amato, Mp
Subjects: Male, Natural History of Multiple Sclerosis, Multiple Sclerosis, Neurology, Recurrence, Pediatric Multiple Sclerosis, Disease Progression, Humans, Disabled Persons, Settore MED/26 - Neurologia, Neurology (clinical), Child, Prognosis
Abstract: Objective: This study was undertaken to describe and compare disease course and prognosis of early (ie, disease onset before age 11 years) and late (ie, disease onset after age 11 years) onset pediatric multiple sclerosis. Methods: Prospectively collected clinical information from Italian Multiple Sclerosis Register of 1993 pediatric multiple sclerosis patients, of whom 172 had early onset, was analyzed. Cox models adjusted for sex, baseline Expanded Disability Status Scale score, and disease-modifying treatments and stratified for diagnostic criteria adopted (Poser vs McDonald) were used to assess the risk of reaching irreversible Expanded Disability Status Scale scores of 3, 4, and 6, and conversion to secondary progressive phenotype in early versus late onset pediatric patients. Prognostic factors were also evaluated. Results: A greater proportion of males, isolated brainstem involvement, and longer time interval between first and second clinical episode were observed in early versus late onset pediatric patients. Compared to late onset, early onset pediatric patients took longer from disease onset to convert to secondary progressive phenotype and to reach all disability milestones. Recovery from first demyelinating event, time to first relapse, annualized relapse rate during the first 3 years of disease, and disease-modifying treatment exposure were independent predictors for long-term disability in early onset pediatric patients. In late onset pediatric patients, isolated optic neuritis, multifocal symptoms, and progressive course at disease onset were additional predictors for long-term disability. Interpretation: These findings point toward the existence of a different natural history in early versus late onset pediatric multiple sclerosis patients. ANN NEUROL 2022.
Published: 2022

121. An unusual neurological presentation in a patient with primary hypereosinophilic syndrome

Author: E. Spina, G.T. Maniscalco, A. Petraroli, A. Detoraki, G. Servillo, A. Ranieri, A. De Mase, R. Renna, P. Candelaresi, A. De Paulis, V. Andreone, Spina, E, Maniscalco, G T, Petraroli, A, Detoraki, A, Servillo, G, Ranieri, A, De Mase, A, Renna, R, Candelaresi, P, De Paulis, A, and Andreone, V
Subjects: Stroke, Vasculitis, Rehabilitation, Surgery, Neurology (clinical), Hypereosinophilia, Hypereosinophilic syndrome, Cardiology and Cardiovascular Medicine
Abstract: Hypereosinophilic syndromes are characterized by an increased number of blood eosinophils (usually more than 1.5 × 109) infiltrating tissues and causing organ damage through over-production of pro-inflammatory cytokines with heterogeneous clinical presentation. Here we present a case of a 47 years old male, with an unremarkable previous medical history, with a sudden onset of subungual hemorrhage and low back pain. Admitted for right arm weakness and vomiting, was raised the suspicion of acute cerebrovascular syndrome, but a brain CT scan with angiogram and perfusion sequences did not show any signs of early ischaemic lesions; conversely, lab tests revealed an increased peripheral eosinophil blood count. Clinical conditions rapidly worsened and a brain MRI showed multiple sub-acute ischaemic lesions compatible with vasculitis while EEG was in favor of widespread cortical distress. Diagnosis of the hypereosinophilic syndrome was made through peripheral blood smear and osteo-medullar biopsy, which showed a rich prevalence of eosinophils. The molecular biology testing showed FIP1L1-PDGRA gene mutation. Despite the prompt therapy beginning with intravenous corticosteroids and tyrosine-kinase inhibitors with normalization of cell blood count in a few days, the patient remained in minimal consciousness. When facing unusual symptoms onset (low back pain with weakness in one limb) and a highly impaired WBC not consistent with other courses (such as infections, vasculitis, allergies, and other diseases involving the immune system) clinicians should take into account the possibility of a hematological disorder and treat it as soon as possible to avoid a poor prognosis.
Published: 2022

122. Severe Multiple Sclerosis Relapse After COVID-19 Vaccination: A Case Report

Author: Giorgia T. Maniscalco, Valentino Manzo, Maria E. Di Battista, Simona Salvatore, Ornella Moreggia, Cristina Scavone, Annalisa Capuano, Maniscalco, G. T., Manzo, V., Di Battista, M. E., Salvatore, S., Moreggia, O., Scavone, C., and Capuano, A.
Subjects: Pediatrics, medicine.medical_specialty, Weakness, Coronavirus disease 2019 (COVID-19), Neurological examination, cladribine, multiple sclerosis, medicine, case report, RC346-429, Cladribine, acute relapse, medicine.diagnostic_test, business.industry, Multiple sclerosis, medicine.disease, Vaccination, Neurology, Methylprednisolone, Relative risk, Neurology. Diseases of the nervous system, Neurology (clinical), medicine.symptom, business, COVID-19 vaccine, medicine.drug
Abstract: We describe a case of acute relapse in a woman with Multiple Sclerosis (MS) shortly after the mRNA COVID-19 vaccination. The patient received a diagnosis of MS in November 2016 at the MS Centre of the A. Cardarelli Hospital (South of Italy). Since that moment, her clinical conditions and pharmacological therapies have been managed at this MS centre where, according to national recommendations, in April 2021, the patient received the BNT162b2 vaccine. Almost 48 h after receiving the vaccine, the patient developed paraesthesia and weakness in her left arm and limbs. The neurological examination revealed walking difficulties while the MRI showed three new voluminous enhancing lesions. After having received methylprednisolone iv for 5 days, the patient's neurological symptoms fully recovered. Along with the implementation of COVID-19 vaccination programmes among vulnerable population, further studies are needed in order to improve our knowledge on the benefit/risk ratio of COVID-19 vaccines.
Published: 2021

123. Influenza Vaccine Hesitancy in Patients with Multiple Sclerosis: A Monocentric Observational Study

Author: Stefano Barbato, Maria Elena Di Battista, Giorgia Teresa Maniscalco, Ornella Moreggia, Antonio Rosario Ziello, Simona Salvatore, Lia Allegorico, Anna Sagnelli, Valentino Manzo, Annalisa Capuano, Daniele Di Giulio Cesare, Cristina Scavone, Ziello, A., Scavone, C., Di Battista, M. E., Salvatore, S., Giulio Cesare, D. D., Moreggia, O., Allegorico, L., Sagnelli, A., Barbato, S., Manzo, V., Capuano, A., and Maniscalco, G. T.
Subjects: Pediatrics, medicine.medical_specialty, Influenza vaccine, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Neurosciences. Biological psychiatry. Neuropsychiatry, multiple sclerosis, Article, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Natalizumab, Teriflunomide, medicine, Multiple sclerosi, In patient, 030212 general & internal medicine, business.industry, General Neuroscience, Multiple sclerosis, medicine.disease, Vaccination, chemistry, Observational study, observational study, hesitancy, influenza vaccine, business, 030217 neurology & neurosurgery, RC321-571, medicine.drug
Abstract: Background. The so-called “vaccine hesitancy” still represents a common phenomenon that undermines the effectiveness of vaccination campaigns. In 2020, the Italian Medicines Agency recommended to bring forward the flu vaccination campaign, whose importance was also emphasized for patients with Multiple Sclerosis (MS). We aimed to assess vaccination behavior in patients with MS to prepare for the upcoming SARS-CoV-2 vaccination challenge. Methods. This is an observational study carried out in one MS clinical Centre that enrolled all MS patients who were eligible for any of the flu vaccines recommended by the Italian medicines Agency. Results. 194 patients were enrolled. Patients’ mean age was 43.9 years and 66% were female. Comorbidities, mainly represented by non-autoimmune diseases, were identified in 52% of patients. Almost all patients were receiving a DMT during the study period, mainly dimethyl fumarate, natalizumab, teriflunomide, and interferon. Out of 194 patients, 58.2% accepted to be vaccinated. No statistically significant differences were found, except for the use of natalizumab, which was higher among vaccinated patients. Conclusion. The results of our study emphasize the importance of education and communication campaigns addressed both to healthcare providers and patients with MS, especially considering that MS patients are currently receiving COVID-19 vaccinations.
Published: 2021

124. Transition to secondary progression in relapsing-onset multiple sclerosis: Definitions and risk factors

Author: Simonetta Galgani, Giuseppe Lucisano, Matilde Inglese, Giacomo Lus, M. Achille, V. Lovato, M. Zaffaroni, V. Brescia Morra, Giuseppe Salemi, Marco Salvetti, Carlo Pozzilli, G. T. Maniscalco, Maria Trojano, Francesco Patti, Diana Ferraro, Massimo Filippi, Maria Pia Amato, Pietro Iaffaldano, Alessandra Lugaresi, G. Marrazzo, Roberto Bergamaschi, G. De Luca, Antonella Conte, Marco Rovaris, F. O. Logullo, G. Comi, Damiano Paolicelli, Eleonora Cocco, Iaffaldano, Pietro, Lucisano, Giuseppe, Patti, Francesco, Brescia Morra, Vincenzo, De Luca, Giovanna, Lugaresi, Alessandra, Zaffaroni, Mauro, Inglese, Matilde, Salemi, Giuseppe, Cocco, Eleonora, Conte, Antonella, Ferraro, Diana, Galgani, Simonetta, Bergamaschi, Roberto, Pozzilli, Carlo, Salvetti, Marco, Lus, Giacomo, Rovaris, Marco, Maniscalco, Giorgia Teresa, Logullo, Francesco Ottavio, Paolicelli, Damiano, Achille, Mariaclara, Marrazzo, Giuseppina, Lovato, Valeria, Comi, Giancarlo, Filippi, Massimo, Amato, Maria Pia, Trojano, Maria, Iaffaldano P., Lucisano G., Patti F., Brescia Morra V., De Luca G., Lugaresi A., Zaffaroni M., Inglese M., Salemi G., Cocco E., Conte A., Ferraro D., Galgani S., Bergamaschi R., Pozzilli C., Salvetti M., Lus G., Rovaris M., Maniscalco G.T., Logullo F.O., Paolicelli D., Achille M., Marrazzo G., Lovato V., Comi G., Filippi M., Amato M.P., Trojano M., Iaffaldano, P., Lucisano, G., Patti, F., Brescia Morra, V., De Luca, G., Lugaresi, A., Zaffaroni, M., Inglese, M., Salemi, G., Cocco, E., Conte, A., Ferraro, D., Galgani, S., Bergamaschi, R., Pozzilli, C., Salvetti, M., Lus, G., Rovaris, M., Maniscalco, G. T., Logullo, F. O., Paolicelli, D., Achille, M., Marrazzo, G., Lovato, V., Comi, G., Filippi, M., Amato, M. P., and Trojano, M.
Subjects: Oncology, medicine.medical_specialty, Relapsing-Remitting, Multiple sclerosis, 03 medical and health sciences, Multiple Sclerosis, Relapsing-Remitting, 0302 clinical medicine, Disease registry, Recurrence, Risk Factors, big data, Internal medicine, medicine, Humans, data-driven algorithm, Multiple sclerosi, 030212 general & internal medicine, disease registry, prognosis, secondary progressive, Disease Progression, Multiple Sclerosis, Multiple Sclerosis, Chronic Progressive, Secondary progressive, Transition (genetics), business.industry, medicine.disease, Chronic Progressive, Neurology, Settore MED/26 - Neurologia, Neurology (clinical), business, prognosi, 030217 neurology & neurosurgery
Abstract: Background: No uniform criteria for a sensitive identification of the transition from relapsing–remitting multiple sclerosis (MS) to secondary-progressive multiple sclerosis (SPMS) are available. Objective: To compare risk factors of SPMS using two definitions: one based on the neurologist judgment (ND) and an objective data-driven algorithm (DDA). Methods: Relapsing-onset MS patients ( n = 19,318) were extracted from the Italian MS Registry. Risk factors for SPMS and for reaching irreversible Expanded Disability Status Scale (EDSS) 6.0, after SP transition, were estimated using multivariable Cox regression models. Results: SPMS identified by the DDA ( n = 2343, 12.1%) were older, more disabled and with a faster progression to severe disability ( p 40 years, higher baseline EDSS score and a higher number of relapses; the most consistent protective factor was the disease-modifying therapy (DMT) exposure. DMT exposure during SP did not impact the risk of reaching irreversible EDSS 6.0. Conclusion: A DDA definition of SPMS identifies more aggressive progressive patients. DMT exposure reduces the risk of SPMS conversion, but it does not prevent the disability accumulation after the SP transition.
Published: 2021

125. Injectable Versus Oral First-Line Disease-Modifying Therapies: Results from the Italian MS Register

Author: Marco Onofrj, Giacomo Lus, Damiano Paolicelli, Matilde Inglese, Giorgia Teresa Maniscalco, Massimo Filippi, Emanuele D'Amico, M. Vianello, Simonetta Galgani, Vincenzo Brescia Morra, Francesco Patti, Antonio Gallo, Aurora Zanghì, Paolo Confalonieri, Giuseppe Salemi, Giovanna De Luca, Maria Trojano, Carlo Avolio, Maria Pia Amato, Eleonora Cocco, Marzia Romeo, D'Amico, E., Zanghi, A., Romeo, M., Cocco, E., Maniscalco, G. T., Brescia Morra, V., Paolicelli, D., De Luca, G., Galgani, S., Amato, M. P., Salemi, G., Inglese, M., Confalonieri, P. A., Lus, G., Avolio, C., Gallo, A., Vianello, M., Onofrj, M., Filippi, M., Trojano, M., Patti, F., D'Amico, Emanuele, Zanghì, Aurora, Romeo, Marzia, Cocco, Eleonora, Maniscalco, Giorgia Teresa, Brescia Morra, Vincenzo, Paolicelli, Damiano, De Luca, Giovanna, Galgani, Simonetta, Amato, Maria Pia, Salemi, Giuseppe, Inglese, Matilde, Confalonieri, Paolo Agostino, Lus, Giacomo, Avolio, Carlo, Gallo, Antonio, Vianello, Marika, Onofrj, Marco, Filippi, Massimo, Trojano, Maria, and Patti, Francesco
Subjects: Male, oral DMTs, oral DMT, Administration, Oral, Disease, Relapsing-Remitting, Cohort Studies, 0302 clinical medicine, Immunologic, injectable DMT, Pharmacology (medical), 030212 general & internal medicine, Registries, Subcutaneous, Middle Aged, Italy, EDSS score, injectable DMTs, Multiple sclerosis, real-world setting, Adjuvants, Immunologic, Adult, Female, Follow-Up Studies, Glatiramer Acetate, Humans, Immunologic Factors, Injections, Subcutaneous, Interferon-beta, Multiple Sclerosis, Relapsing-Remitting, Retrospective Studies, Administration, Cohort, Settore MED/26 - Neurologia, Original Article, Neurosurgery, Cohort study, Oral, medicine.medical_specialty, Lower risk, Injections, 03 medical and health sciences, Internal medicine, medicine, Multiple sclerosi, Adjuvants, Pharmacology, business.industry, medicine.disease, Discontinuation, Observational study, Neurology (clinical), business, 030217 neurology & neurosurgery
Abstract: The current study aims to compare injectable and oral first-line disease-modifying therapies (DMTs) for time to first relapse, time to confirmed disability progression (CDP), and time to discontinuation using a cohort of relapsing remitting multiple sclerosis (RRMS) patients, with data extracted from the Italian MS Register. This multicenter, observational, retrospectively acquired, and propensity-adjusted cohort study utilized RRMS-naïve patients from the Italian MS Register who started either injectable or oral first-line DMTs between January 1, 2010, and December 31, 2017, to evaluate the impact on disability outcomes in patients. Enrolled patients were divided into two groups, namely the injectable group (IG) and the oral group (OG). Of a cohort of 11,416 patients, 4602 were enrolled (3919 in the IG and 683 in the OG). The IG had a higher rate of women (67.3% vs 63.4%, p p p p = 0.941), while a lower risk of DMT was found in the OG (HR = 0.72; CI 95% 0.58–0.88, p = 0.002) for the event time to discontinuation. Real-world data from the Italian MS Register suggests that first-line oral DMTs are associated with a lower risk of experiencing a new relapse and of therapy discontinuation compared to injectable DMTs.
Published: 2021

126. Signals of pseudo-starvation unveil the amino acid transporter SLC7A11 as key determinant in the control of Treg cell proliferative potential

Author: Maria Lepore, Dario Di Silvestre, Fabio Buttari, Claudia La Rocca, Antonio Uccelli, Paola de Candia, Giuseppe Matarese, Danila Vella, Alessandra Colamatteo, Giusy De Rosa, Pierluigi Mauri, Sarah Grossi, Claudia Russo, Roberta Lanzillo, Vincenzo Brescia Morra, Mario Galgani, Maria Mottola, Giorgia Teresa Maniscalco, Paola Campomenosi, Claudio Procaccini, Diego Centonze, Marco Salvetti, Silvia Garavelli, Deriggio Faicchia, Bruno Zuccarelli, Francesco Prattichizzo, Fortunata Carbone, Dario Greco, Procaccini, C., Garavelli, S., Carbone, F., Di Silvestre, D., La Rocca, C., Greco, D., Colamatteo, A., Lepore, M. T., Russo, C., De Rosa, G., Faicchia, D., Prattichizzo, F., Grossi, S., Campomenosi, P., Buttari, F., Mauri, P., Uccelli, A., Salvetti, M., Brescia Morra, V., Vella, D., Galgani, M., Mottola, M., Zuccarelli, B., Lanzillo, R., Maniscalco, G. T., Centonze, D., de Candia, P., and Matarese, G.
Subjects: 0301 basic medicine, Male, Antiporter, T-Lymphocytes, SLC7A11, Relapsing-Remitting, medicine.disease_cause, T-Lymphocytes, Regulatory, Autoimmunity, 0302 clinical medicine, Immunology and Allergy, Homeostasis, Cells, Cultured, Cultured, dimethyl fumarate, biology, autoimmunity, Glutamate receptor, hemic and immune systems, Regulatory, Transmembrane protein, Cell biology, Infectious Diseases, 030220 oncology & carcinogenesis, multiple sclerosi, Female, Human, leptin, metabolism, multiple sclerosis, proliferation, starvation, Treg cells, xCT, Adult, Amino Acid Transport System y+, Cell Proliferation, Humans, Immune Tolerance, Multiple Sclerosis, Relapsing-Remitting, NF-E2-Related Factor 2, Multiple Sclerosis, Cells, Immunology, chemical and pharmacologic phenomena, Settore MED/26, 03 medical and health sciences, Homeostasi, medicine, Amino acid transporter, Treg cell, Solute carrier family, 030104 developmental biology, biology.protein
Abstract: Summary Human CD4+CD25hiFOXP3+ regulatory T (Treg) cells are key players in the control of immunological self-tolerance and homeostasis. Here, we report that signals of pseudo-starvation reversed human Treg cell in vitro anergy through an integrated transcriptional response, pertaining to proliferation, metabolism, and transmembrane solute carrier transport. At the molecular level, the Treg cell proliferative response was dependent on the induction of the cystine/glutamate antiporter solute carrier (SLC)7A11, whose expression was controlled by the nuclear factor erythroid 2-related factor 2 (NRF2). SLC7A11 induction in Treg cells was impaired in subjects with relapsing-remitting multiple sclerosis (RRMS), an autoimmune disorder associated with reduced Treg cell proliferative capacity. Treatment of RRMS subjects with dimethyl fumarate (DMF) rescued SLC7A11 induction and fully recovered Treg cell expansion. These results suggest a previously unrecognized mechanism that may account for the progressive loss of Treg cells in autoimmunity and unveil SLC7A11 as major target for the rescue of Treg cell proliferation.
Published: 2021

127. Disease-Modifying Therapies and Coronavirus Disease 2019 Severity in Multiple Sclerosis

Author: Sormani, Maria P., Nicola De Rossi, Irene, Schiavetti, Luca, Carmisciano, Cinzia, Cordioli, Lucia, Moiola, Marta, Radaelli, Paolo, Immovilli, Marco, Capobianco, Maria, Trojano, Paola, Zaratin, Gioacchino, Tedeschi, Giancarlo, Comi, Battaglia, Mario A., Francesco, Patti, Marco, Salvetti, Agostino, Nozzolillo, Alessandra, Bellacosa, Alessandra, Protti, Alessia Di Sapio, Alessio, Signori, Alfredo, Petrone, Alvino, Bisecco, Aniello, Iovino, Anna, Dutto, Anna Maria Repice, Antonella, Conte, Antonio, Bertolotto, Antonio, Bosco, Antonio, Gallo, Antonio, Zito, Arianna, Sartori, Bruno, Giometto, Carla, Tortorella, Carlo, Antozzi, Carlo, Pozzilli, Chiara Rosa Mancinelli, Chiara, Zanetta, Christian, Cordano, Cinzia, Scandellari, Clara, Guaschino, Claudio, Gasperini, Claudio, Solaro, Cristina, Fioretti, Daiana, Bezzini, Damiano, Marastoni, Damiano, Paolicelli, Domizia, Vecchio, Doriana, Landi, Elisabetta, Bucciantini, Elisabetta, Pedrazzoli, Elisabetta, Signoriello, Elvira, Sbragia, Emanuela Laura Susani, Erica, Curti, Eva, Milano, Fabiana, Marinelli, Federico, Camilli, Filippo Martinelli Boneschi, Flora, Govone, Francesca, Bovis, Francesca, Calabria, Francesca, Caleri, Francesca, Rinaldi, Francesca, Vitetta, Francesco, Corea, Francesco, Crescenzo, Francesco, Teatini, Giulietta, Tabiadon, Franco, Granella, Giacomo, Boffa, Giacomo, Lus, Giampaolo, Brichetto, Giorgia Teresa Maniscalco, Giovanna, Borriello, Giovanna De Luca, Giovanna, Konrad, Giovanna, Vaula, Girolama Alessandra Marfia, Giulia, Mallucci, Giuseppe, Liberatore, Giuseppe, Salemi, Giuseppina, Miele, Grazia, Sibilia, Ilaria, Pesci, Laura, Brambilla, Leonardo, Lopiano, Leonardo, Sinisi, Pasquali, Livia, Lorenzo, Saraceno, Luca, Chiveri, Luca, Mancinelli, Grimaldi, Luigi M. E., Luisa Maria Caniatti, Marco Della Cava, Marco, Onofrj, Marco, Rovaris, Marco, Vercellino, Margherita Monti Bragadin, Maria, Buccafusca, Maria Chiara Buscarinu, Maria Grazia Celani, Maria Grazia Grasso, Maria Laura Stromillo, Maria, Petracca, Maria Pia Amato, Maria Pia Sormani, Maria Rita L'Episcopo, Maria, Sessa, Maria Teresa Ferrò, Maria Vittoria Ercolani, Mariangela, Bianco, Marianna Lo Re, Marika, Vianello, Marinella, Clerico, Mario Alberto Battaglia, Mario di Napoli, Marta, Ponzano, Marta Zaffira Conti, Massimiliano, Calabrese, Massimiliano, Mirabella, Massimo, Filippi, Matilde, Inglese, Matteo, Lucchini, Matteo, Pozzato, Maura Chiara Danni, Mauro, Zaffaroni, Mauro, Zampolini, Michela, Ponzio, Milena De Riz, Nicola De Stefano, Paola, Cavalla, Paola De Mitri, Paola, Grossi, Paolo, Confalonieri, Paolo, Gallo, Paolo, Ragonese, Patrizia, Sola, Pietro, Annovazzi, Pietro, Iaffaldano, Raffaele, Nardone, Raffaella, Cerqua, Raffaella, Clerici, Roberta, Lanzillo, Roberta, Motta, Roberto, Balgera, Roberto, Bergamaschi, Rocco, Totaro, Rosa, Iodice, Ruggero, Capra, Sabrina, Marangoni, Sabrina, Realmuto, Salvatore, Cottone, Sara, Montepietra, Sarah, Rasia, Sebastiano, Arena, Sebastiano, Bucello, Silvia, Banfi, Simona, Bonavita, Simona, Malucchi, Simone, Tonietti, Stefano, Vollaro, Susanna, Cordera, Umberto, Aguglia, Valentina Torri Clerici, Valeria, Barcella, Valeria, Bergamaschi, Vincenzo Brescia Morra, Vincenzo, Dattola, and Vittorio Mantero, Sormani, M. P., De Rossi, N., Schiavetti, I., Carmisciano, L., Cordioli, C., Moiola, L., Radaelli, M., Immovilli, P., Capobianco, M., Trojano, M., Zaratin, P., Tedeschi, G., Comi, G., Battaglia, M. A., Patti, F., Salvetti, M., P Sormani, Maria, De Rossi, Nicola, Schiavetti, Irene, Carmisciano, Luca, Cordioli, Cinzia, Moiola, Lucia, Radaelli, Marta, Immovilli, Paolo, Capobianco, Marco, Trojano, Maria, Zaratin, Paola, Tedeschi, Gioacchino, Comi, Giancarlo, A Battaglia, Mario, Patti, Francesco, Salvetti, Marco, Nozzolillo, Agostino, Bellacosa, Alessandra, Protti, Alessandra, Di Sapio, Alessia, Signori, Alessio, Petrone, Alfredo, Bisecco, Alvino, Iovino, Aniello, Dutto, Anna, Maria Repice, Anna, Conte, Antonella, Bertolotto, Antonio, Bosco, Antonio, Gallo, Antonio, Zito, Antonio, Sartori, Arianna, Giometto, Bruno, Tortorella, Carla, Antozzi, Carlo, Pozzilli, Carlo, Rosa Mancinelli, Chiara, Zanetta, Chiara, Cordano, Christian, Scandellari, Cinzia, Guaschino, Clara, Gasperini, Claudio, Solaro, Claudio, Fioretti, Cristina, Bezzini, Daiana, Marastoni, Damiano, Paolicelli, Damiano, Vecchio, Domizia, Landi, Doriana, Bucciantini, Elisabetta, Pedrazzoli, Elisabetta, Signoriello, Elisabetta, Sbragia, Elvira, Laura Susani, Emanuela, Curti, Erica, Milano, Eva, Marinelli, Fabiana, Camilli, Federico, Martinelli Boneschi, Filippo, Govone, Flora, Bovis, Francesca, Calabria, Francesca, Caleri, Francesca, Rinaldi, Francesca, Vitetta, Francesca, Corea, Francesco, Crescenzo, Francesco, Teatini, Francesco, Tabiadon, Giulietta, Granella, Franco, Boffa, Giacomo, Lus, Giacomo, Brichetto, Giampaolo, Teresa Maniscalco, Giorgia, Borriello, Giovanna, De Luca, Giovanna, Konrad, Giovanna, Vaula, Giovanna, Alessandra Marfia, Girolama, Mallucci, Giulia, Liberatore, Giuseppe, Salemi, Giuseppe, Miele, Giuseppina, Sibilia, Grazia, Pesci, Ilaria, Brambilla, Laura, Lopiano, Leonardo, Sinisi, Leonardo, Pasquali, Livia, Saraceno, Lorenzo, Chiveri, Luca, Mancinelli, Luca, E Grimaldi, Luigi M, Maria Caniatti, Luisa, Della Cava, Marco, Onofrj, Marco, Rovaris, Marco, Vercellino, Marco, Monti Bragadin, Margherita, Buccafusca, Maria, Chiara Buscarinu, Maria, Grazia Celani, Maria, Grazia Grasso, Maria, Laura Stromillo, Maria, Petracca, Maria, Pia Amato, Maria, Pia Sormani, Maria, Rita L'Episcopo, Maria, Sessa, Maria, Teresa Ferrò, Maria, Vittoria Ercolani, Maria, Bianco, Mariangela, Lo Re, Marianna, Vianello, Marika, Clerico, Marinella, Alberto Battaglia, Mario, di Napoli, Mario, Ponzano, Marta, Zaffira Conti, Marta, Calabrese, Massimiliano, Mirabella, Massimiliano, Filippi, Massimo, Inglese, Matilde, Lucchini, Matteo, Pozzato, Matteo, Chiara Danni, Maura, Zaffaroni, Mauro, Zampolini, Mauro, Ponzio, Michela, De Riz, Milena, De Stefano, Nicola, Cavalla, Paola, De Mitri, Paola, Grossi, Paola, Confalonieri, Paolo, Gallo, Paolo, Ragonese, Paolo, Sola, Patrizia, Annovazzi, Pietro, Iaffaldano, Pietro, Nardone, Raffaele, Cerqua, Raffaella, Clerici, Raffaella, Lanzillo, Roberta, Motta, Roberta, Balgera, Roberto, Bergamaschi, Roberto, Totaro, Rocco, Iodice, Rosa, Capra, Ruggero, Marangoni, Sabrina, Realmuto, Sabrina, Cottone, Salvatore, Montepietra, Sara, Rasia, Sarah, Arena, Sebastiano, Bucello, Sebastiano, Banfi, Silvia, Bonavita, Simona, Malucchi, Simona, Tonietti, Simone, Vollaro, Stefano, Cordera, Susanna, Aguglia, Umberto, Torri Clerici, Valentina, Barcella, Valeria, Bergamaschi, Valeria, Brescia Morra, Vincenzo, Dattola, Vincenzo, Mantero, Vittorio, Mp, Sormani, N, De Rossi, I, Schiavetti, L, Carmisciano, C, Cordioli, L, Moiola, M, Radaelli, P, Immovilli, M, Capobianco, M, Trojano, P, Zaratin, G, Tedeschi, G, Comi, Ma, Battaglia, F, Patti, M, Salvetti, Study Group Agostino Nozzolillo, Musc-19, Grimaldi, Luigi M. E., Vittorio Mantero, And, Nozzolillo, A., Bellacosa, A., Protti, A., Di Sapio, A., Signori, A., Petrone, A., Bisecco, A., Iovino, A., Dutto, A., Repice, A. M., Conte, A., Bertolotto, A., Bosco, A., Gallo, A., Zito, A., Sartori, A., Giometto, B., Tortorella, C., Antozzi, C., Pozzilli, C., Mancinelli, C. R., Zanetta, C., Cordano, C., Scandellari, C., Guaschino, C., Gasperini, C., Solaro, C., Fioretti, C., Bezzini, D., Marastoni, D., Paolicelli, D., Vecchio, D., Landi, D., Bucciantini, E., Pedrazzoli, E., Signoriello, E., Sbragia, E., Susani, E. L., Curti, E., Milano, E., Marinelli, F., Camilli, F., Boneschi, F. M., Govone, F., Bovis, F., Calabria, F., Caleri, F., Rinaldi, F., Vitetta, F., Corea, F., Crescenzo, F., Teatini, F., Tabiadon, G., Granella, F., Boffa, G., Lus, G., Brichetto, G., Maniscalco, G. T., Borriello, G., De Luca, G., Konrad, G., Vaula, G., Marfia, G. A., Mallucci, G., Liberatore, G., Salemi, G., Miele, G., Sibilia, G., Pesci, I., Brambilla, L., Lopiano, L., Sinisi, L., Pasquali, L., Saraceno, L., Chiveri, L., Mancinelli, L., Grimaldi, L. M. E., Caniatti, L. M., Cava, M. D., Onofrj, M., Rovaris, M., Vercellino, M., Bragadin, M. M., Buccafusca, M., Buscarinu, M. C., Celani, M. G., Grasso, M. G., Stromillo, M. L., Petracca, M., Amato, M. P., L'Episcopo, M. R., Sessa, M., Ferro, M. T., Ercolani, M. V., Bianco, M., Re, M. L., Vianello, M., Clerico, M., di Napoli, M., Ponzano, M., Conti, M. Z., Calabrese, M., Mirabella, M., Filippi, M., Inglese, M., Lucchini, M., Pozzato, M., Danni, M. C., Zaffaroni, M., Zampolini, M., Ponzio, M., De Riz, M., De Stefano, N., Cavalla, P., De Mitri, P., Grossi, P., Confalonieri, P., Gallo, P., Ragonese, P., Sola, P., Annovazzi, P., Iaffaldano, P., Nardone, R., Cerqua, R., Clerici, R., Lanzillo, R., Motta, R., Balgera, R., Bergamaschi, R., Totaro, R., Iodice, R., Capra, R., Marangoni, S., Realmuto, S., Cottone, S., Montepietra, S., Rasia, S., Arena, S., Bucello, S., Banfi, S., Bonavita, S., Malucchi, S., Tonietti, S., Vollaro, S., Cordera, S., Aguglia, U., Clerici, V. T., Barcella, V., Bergamaschi, V., Morra, V. B., Dattola, V., Mantero, V., Sormani M.P., De Rossi N., Schiavetti I., Carmisciano L., Cordioli C., Moiola L., Radaelli M., Immovilli P., Capobianco M., Trojano M., Zaratin P., Tedeschi G., Comi G., Battaglia M.A., Patti F., Salvetti M., Nozzolillo A., Bellacosa A., Protti A., Di Sapio A., Signori A., Petrone A., Bisecco A., Iovino A., Dutto A., Repice A.M., Conte A., Bertolotto A., Bosco A., Gallo A., Zito A., Sartori A., Giometto B., Tortorella C., Antozzi C., Pozzilli C., Mancinelli C.R., Zanetta C., Cordano C., Scandellari C., Guaschino C., Gasperini C., Solaro C., Fioretti C., Bezzini D., Marastoni D., Paolicelli D., Vecchio D., Landi D., Bucciantini E., Pedrazzoli E., Signoriello E., Sbragia E., Susani E.L., Curti E., Milano E., Marinelli F., Camilli F., Boneschi F.M., Govone F., Bovis F., Calabria F., Caleri F., Rinaldi F., Vitetta F., Corea F., Crescenzo F., Teatini F., Tabiadon G., Granella F., Boffa G., Lus G., Brichetto G., Maniscalco G.T., Borriello G., De Luca G., Konrad G., Vaula G., Marfia G.A., Mallucci G., Liberatore G., Salemi G., Miele G., Sibilia G., Pesci I., Brambilla L., Lopiano L., Sinisi L., Pasquali L., Saraceno L., Chiveri L., Mancinelli L., Grimaldi L.M.E., Caniatti L.M., Cava M.D., Onofrj M., Rovaris M., Vercellino M., Bragadin M.M., Buccafusca M., Buscarinu M.C., Celani M.G., Grasso M.G., Stromillo M.L., Petracca M., Amato M.P., L'Episcopo M.R., Sessa M., Ferro M.T., Ercolani M.V., Bianco M., Re M.L., Vianello M., Clerico M., di Napoli M., Ponzano M., Conti M.Z., Calabrese M., Mirabella M., Filippi M., Inglese M., Lucchini M., Pozzato M., Danni M.C., Zaffaroni M., Zampolini M., Ponzio M., De Riz M., De Stefano N., Cavalla P., De Mitri P., Grossi P., Confalonieri P., Gallo P., Ragonese P., Sola P., Annovazzi P., Iaffaldano P., Nardone R., Cerqua R., Clerici R., Lanzillo R., Motta R., Balgera R., Bergamaschi R., Totaro R., Iodice R., Capra R., Marangoni S., Realmuto S., Cottone S., Montepietra S., Rasia S., Arena S., Bucello S., Banfi S., Bonavita S., Malucchi S., Tonietti S., Vollaro S., Cordera S., Aguglia U., Clerici V.T., Barcella V., Bergamaschi V., Morra V.B., Dattola V., and Mantero V.
Subjects: Male, 0301 basic medicine, Dimethyl Fumarate, Neurodegenerative, multiple sclerosis, coronavirus, pneumonia, Severity of Illness Index, law.invention, Immunosuppressive Agent, Immunologic Factor, 0302 clinical medicine, Natalizumab, law, Monoclonal, Multiple Sclerosi, 80 and over, Lung, Humanized, Research Articles, Aged, 80 and over, Middle Aged, Intensive care unit, Hospitalization, Settore MED/26 - NEUROLOGIA, Intensive Care Units, Neurology, Methylprednisolone, Neurological, Pneumonia & Influenza, Interferon, Female, Immunosuppressive Agents, Research Article, Human, medicine.drug, Adult, medicine.medical_specialty, Musc-19 Study Group, Multiple Sclerosis, Adolescent, Clinical Sciences, Intensive Care Unit, Clinical Neurology, Settore MED/26, Antibodies, Monoclonal, Humanized, Autoimmune Disease, Antibodies, Young Adult, 03 medical and health sciences, Clinical Research, Internal medicine, Severity of illness, medicine, Humans, Immunologic Factors, Mortality, Aged, COVID-19, Fingolimod Hydrochloride, Interferons, SARS-CoV-2, Neurology & Neurosurgery, Expanded Disability Status Scale, business.industry, Multiple sclerosis, Neurosciences, Pneumonia, Odds ratio, medicine.disease, Brain Disorders, Good Health and Well Being, 030104 developmental biology, Ocrelizumab, Neurology (clinical), business, 030217 neurology & neurosurgery
Abstract: Objective: This study was undertaken to assess the impact of immunosuppressive and immunomodulatory therapies on the severity of coronavirus disease 2019 (COVID-19) in people with multiple sclerosis (PwMS). Methods: We retrospectively collected data of PwMS with suspected or confirmed COVID-19. All the patients had complete follow-up to death or recovery. Severe COVID-19 was defined by a 3-level variable: mild disease not requiring hospitalization versus pneumonia or hospitalization versus intensive care unit (ICU) admission or death. We evaluated baseline characteristics and MS therapies associated with severe COVID-19 by multivariate and propensity score (PS)-weighted ordinal logistic models. Sensitivity analyses were run to confirm the results. Results: Of 844 PwMS with suspected (n = 565) or confirmed (n = 279) COVID-19, 13 (1.54%) died; 11 of them were in a progressive MS phase, and 8 were without any therapy. Thirty-eight (4.5%) were admitted to an ICU; 99 (11.7%) had radiologically documented pneumonia; 96 (11.4%) were hospitalized. After adjusting for region, age, sex, progressive MS course, Expanded Disability Status Scale, disease duration, body mass index, comorbidities, and recent methylprednisolone use, therapy with an anti-CD20 agent (ocrelizumab or rituximab) was significantly associated (odds ratio [OR] = 2.37, 95% confidence interval [CI] = 1.18–4.74, p = 0.015) with increased risk of severe COVID-19. Recent use (
Published: 2021

128. Switch from sequestering to anti-CD20 depleting treatment: disease activity outcomes during wash-out and in the first 6 months of ocrelizumab therapy

Author: Maria Pia Sormani, Antonio Carotenuto, Jessica Frau, Doriana Landi, Girolama Alessandra Marfia, Alessio Signori, Erica Curti, Francesco Saccà, Giorgia Teresa Maniscalco, Simone Cepparulo, Elisabetta Signoriello, Francesca Caleri, Mauro Zaffaroni, Damiano Baroncini, Carolina Gabri Nicoletti, Simona Bonavita, Giacomo Lus, Roberta Lanzillo, Viviana Nociti, Arianna Sartori, Signoriello, E., Lus, G., Bonavita, S., Lanzillo, R., Sacca, F., Landi, D., Frau, J., Baroncini, D., Zaffaroni, M., Maniscalco, G. T., Curti, E., Sartori, A., Cepparulo, S., Marfia, G. A., Nicoletti, C. G., Carotenuto, A., Nociti, V., Caleri, F., Sormani, M. P., Signori, A., Signoriello, Elisabetta, Lus, Giacomo, Bonavita, Simona, Lanzillo, Roberta, Sacc??, Francesco, Landi, Doriana, Frau, Jessica, Baroncini, Damiano, Zaffaroni, Mauro, Teresa Maniscalco, Giorgia, Curti, Erica, Sartori, Arianna, Cepparulo, Simone, Alessandra Marfia, Girolama, Gabri Nicoletti, Carolina, Carotenuto, Antonio, Nociti, Viviana, Caleri, Francesca, Pia Sormani, Maria, and Signori, Alessio
Subjects: Oncology, medicine.medical_specialty, Antibodies, Monoclonal, Humanized, Settore MED/26, Disease activity, Multiple sclerosis, 03 medical and health sciences, 0302 clinical medicine, Natalizumab, Multiple Sclerosis, Relapsing-Remitting, natalizumab, ocrelizumab, Internal medicine, medicine, Humans, Multiple sclerosi, 030212 general & internal medicine, Anti cd20, fingolimod, switch, Retrospective Studies, business.industry, Fingolimod Hydrochloride, medicine.disease, Fingolimod, Disease control, Neurology, Ocrelizumab, Neurology (clinical), business, 030217 neurology & neurosurgery, Immunosuppressive Agents, medicine.drug
Abstract: Objectives: Switching between treatments is an opportunity for patients with multiple sclerosis (MS) to ameliorate disease control or safety. The aim of this study was to investigate the impact of switching from fingolimod (FTY) or natalizumab (NTZ) to ocrelizumab (OCR) on disease activity. Methods: We retrospectively enrolled 165 patients treated with OCR from 11 MS centres. We assessed the association of demographic and clinical characteristics on relapse rate (RR) and activity on magnetic resonance imaging (MRI) during wash-out and after 6 months of treatment with OCR through univariable and multivariable negative binomial regression models. Results: We registered a total of 35 relapses during the wash-out period. Previous treatment with FTY, relapses in the previous year, and relapsing-remitting course were associated with higher RR. In the first 6 months of OCR, 12 patients had clinical or MRI disease activity. Higher Expanded Disability Status Scale (EDSS) and higher lymphocyte count at OCR start were associated with a reduced probability of relapse. Discussion and Conclusion: This study confirms that withdrawal from sequestering agents as FTY increases the risk of relapses in the wash-out period. Nevertheless, starting OCR before achieving complete immune reconstitution could limit its effectiveness in the first 6 months probably because trapped lymphocytes escape the CD20-mediated depletion.
Published: 2021

129. Characteristics and treatment of Multiple Sclerosis-related trigeminal neuralgia: An Italian multi-centre study

Author: Giorgia Teresa Maniscalco, Cinzia Cordioli, Maria Chiara Buscarinu, Diana Ferraro, Massimiliano Calabrese, Claudio Gasperini, Marcello Moccia, Alberto Gajofatto, Antonio Gallo, Eleonora Cocco, Valentina Camera, Pietro Annovazzi, Roberta Fantozzi, Marta Radaelli, Giovanna De Luca, Valentina Tomassini, Roberta Lanzillo, Claudio Solaro, Lorena Lorefice, Carla Tortorella, Federica Pinardi, Fabio Buttari, Paolo Ragonese, Paola Cavalla, Viviana Nociti, Salvatore Lo Fermo, Laura Boffa, Rirems, Damiano Paolicelli, Massimiliano Di Filippo, Ferraro, D., Annovazzi, P., Moccia, M., Lanzillo, R., De Luca, G., Nociti, V., Fantozzi, R., Paolicelli, D., Ragonese, P., Gajofatto, A., Boffa, L., Cavalla, P., Lo Fermo, S., Buscarinu, M. C., Lorefice, L., Cordioli, C., Calabrese, M., Gallo, A., Pinardi, F., Tortorella, C., Di Filippo, M., Camera, V., Maniscalco, G. T., Radaelli, M., Buttari, F., Tomassini, V., Cocco, E., Gasperini, C., Solaro, C., Ferraro D., Annovazzi P., Moccia M., Lanzillo R., De Luca G., Nociti V., Fantozzi R., Paolicelli D., Ragonese P., Gajofatto A., Boffa L., Cavalla P., Lo Fermo S., Buscarinu M.C., Lorefice L., Cordioli C., Calabrese M., Gallo A., Pinardi F., Tortorella C., Di Filippo M., Camera V., Maniscalco G.T., Radaelli M., Buttari F., Tomassini V., Cocco E., Gasperini C., and Solaro C.
Subjects: Pediatrics, medicine.medical_treatment, multiple sclerosis, microvascular decompression surgery, time factors, 0302 clinical medicine, Radiofrequency thermocoagulation, Trigeminal neuralgia, Multiple Sclerosi, Outcome Assessment, Health Care, italy, middle aged, pain, 030212 general & internal medicine, Oxcarbazepine, humans, education.field_of_study, trigeminal neuralgia, adult, Disability, Multiple Sclerosis, Pain, radiosurgery, General Medicine, Analgesics, Non-Narcotic, health care, follow-up studies, Settore MED/26 - NEUROLOGIA, aged, retrospective studies, female, Neurology, disability, analgesics, non-narcotic, male, severity of illness index, sex factors, neurosurgical procedures, outcome assessment, health care, analgesics, medicine.drug, medicine.medical_specialty, Population, Microvascular decompression, 03 medical and health sciences, medicine, education, outcome assessment, business.industry, Multiple sclerosis, Carbamazepine, medicine.disease, Discontinuation, non-narcotic, Neurology (clinical), business, 030217 neurology & neurosurgery
Abstract: Background The prevalence of trigeminal neuralgia (TN) in Multiple Sclerosis (MS) patients is higher than in the general population and its management can be particularly challenging. Our aim is to describe the characteristics, treatment and prognostic factors of MS-related TN in a retrospective multicentre study. Methods Neurologists members of the RIREMS group (Rising Researchers in MS) enrolled MS patients with a TN diagnosis and filled out a spreadsheet comprising their clinical data. Results Population consisted of 298 patients. First-choice preventive treatments were carbamazepine and oxcarbazepine. A surgical procedure was performed in 81 (30%) patients, most commonly gamma knife stereotactic radiosurgery (37%), followed by microvascular decompression (22%) and radiofrequency thermocoagulation (21%); one third of patients underwent at least two procedures. Surgery was associated with higher disability, male sex and longer interval between MS and TN onset. Patients (77%) who stayed on at least one preventive medication at most recent follow-up, after a mean period of 8 years, had a higher disability compared to the untreated group. Furthermore, patients with higher disability at TN onset were less likely to discontinue their first preventive medication due to pain remission, had bilateral TN more frequently and underwent surgical interventions earlier. Conclusion MS patients with a higher disability at TN onset and with a longer interval between MS and TN onset had differing clinical features and outcomes: pain was more frequently bilateral, surgery was more frequent and anticipated, and preventive medication discontinuation due to pain remission was less common.
Published: 2020

130. Cladribine vs other drugs in MS: Merging randomized trial with real-life data

Author: Domenico Ippolito, Sara La Gioia, Sabrina Esposito, Valentina Torri Clerici, Giorgia Teresa Maniscalco, Cinzia Cordioli, Lorena Pareja-Gutierrez, Elisabetta Signoriello, Cinzia Valeria Russo, Roberta Grasso, Doriana Landi, B. Frigeni, Andrea Visconti, Caterina Barrilà, Valeria Barcella, Raffaella Cerqua, Alice Laroni, Simona Bonavita, Stefania Barone, P. Perini, Sarah Rasia, Arianna Sartori, Maria Laura Stromillo, Roberta Lanzillo, Damiano Baroncini, Jessica Frau, Francesco Saccà, Luigi Lavorgna, Alessio Signori, Ignazio Roberto Zarbo, Giorgia Mataluni, Eleonora Cocco, Maria Pia Sormani, E Binello, Pietro Annovazzi, M Clerico, Simona Pontecorvo, Giuseppe Fenu, Alessia Di Sapio, Anna Maria Repice, Signori, A., Sacca, F., Lanzillo, R., Maniscalco, G. T., Signoriello, E., Repice, A. M., Annovazzi, P., Baroncini, D., Clerico, M., Binello, E., Cerqua, R., Mataluni, G., Perini, P., Bonavita, S., Lavorgna, L., Zarbo, I. R., Laroni, A., Pareja-Gutierrez, L., La Gioia, S., Frigeni, B., Barcella, V., Frau, J., Cocco, E., Fenu, G., Clerici, V. T., Sartori, A., Rasia, S., Cordioli, C., Stromillo, M. L., Di Sapio, A., Pontecorvo, S., Grasso, R., Barone, S., Barrila, C., Russo, C. V., Esposito, S., Ippolito, D., Landi, D., Visconti, A., Sormani, M. P., Signori, Alessio, Saccà, Francesco, Lanzillo, Roberta, Maniscalco, Giorgia Teresa, Signoriello, Elisabetta, Repice, Anna Maria, Annovazzi, Pietro, Baroncini, Damiano, Clerico, Marinella, Binello, Eleonora, Cerqua, Raffaella, Mataluni, Giorgia, Perini, Paola, Bonavita, Simona, Lavorgna, Luigi, Zarbo, Ignazio Roberto, Laroni, Alice, Pareja-Gutierrez, Lorena, La Gioia, Sara, Frigeni, Barbara, Barcella, Valeria, Frau, Jessica, Cocco, Eleonora, Fenu, Giuseppe, Clerici, Valentina Torri, Sartori, Arianna, Rasia, Sarah, Cordioli, Cinzia, Stromillo, Maria Laura, Di Sapio, Alessia, Pontecorvo, Simona, Grasso, Roberta, Barone, Stefania, Barrilà, Caterina, Russo, Cinzia Valeria, Esposito, Sabrina, Ippolito, Domenico, Landi, Doriana, Visconti, Andrea, and Sormani, Maria Pia
Subjects: Adult, Male, medicine.medical_specialty, Databases, Factual, Datasets as Topic, Settore MED/26, Placebo, Severity of Illness Index, law.invention, Multiple Sclerosis, Relapsing-Remitting, Natalizumab, Randomized controlled trial, law, Internal medicine, Outcome Assessment, Health Care, Severity of illness, medicine, Humans, Immunologic Factors, Multicenter Studies as Topic, Glatiramer acetate, Cladribine, Randomized Controlled Trials as Topic, Retrospective Studies, business.industry, Middle Aged, Fingolimod, Observational Studies as Topic, Neurology, Propensity score matching, Disease Progression, Female, Neurology (clinical), business, medicine.drug
Abstract: ObjectiveCladribine tablets were tested against placebo in randomized controlled trials (RCTs). In this study, the effectiveness of cladribine vs other approved drugs in patients with relapsing-remitting MS (RRMS) was compared by matching RCT to observational data.MethodsData from the pivotal trial assessing cladribine tablets vs placebo (CLARITY) were propensity score matched to data from the Italian multicenter database i-MuST. This database included 3,150 patients diagnosed between 2010 and 2018 at 24 Italian MS centers who started a disease-modifying drug. The annualized relapse rate (ARR) over 2 years from treatment start and the 24-week confirmed disability progression were compared between patients treated with cladribine and other approved drugs (interferon, glatiramer acetate, fingolimod, natalizumab, and dimethyl fumarate), with comparisons with placebo as a reference. Treatment effects were estimated by the inverse probability weighting negative binomial regression model for ARR and Cox model for disability progression. The treatment effect has also been evaluated according to baseline disease activity.ResultsAll weighted baseline characteristics were well balanced between groups. All drugs tested had an effect vs placebo close to that detected in the RCT. Patients treated with cladribine had a significantly lower ARR compared with interferon (relapse ratio [RR] = 0.48; p < 0.001), glatiramer acetate (RR = 0.49; p < 0.001), and dimethyl fumarate (RR = 0.6; p = 0.001); a similar ARR to that with fingolimod (RR = 0.74; p = 0.24); and a significantly higher ARR than natalizumab (RR = 2.13; p = 0.014), confirming results obtained by indirect treatment comparisons from RCTs (network meta-analyses). The relative effect of cladribine tablets 10 mg (cumulative dose 3.5 mg/kg over 2 years) was higher in patients with high disease activity vs all treatments except fingolimod and natalizumab. Effects on disability progression were largely nonsignificant, probably due to lack of power for such analysis.ConclusionIn patients with RRMS, cladribine tablets showed lower ARR compared with matched patients who started interferon, glatiramer acetate, or dimethyl fumarate; was similar to fingolimod; and was higher than natalizumab. The beneficial effect of cladribine tablets was generally amplified in the subgroup of patients with high disease activity.Classification of evidenceThis study provides Class III evidence that for patients with RRMS, cladribine-treated patients had lower ARR compared with interferon, glatiramer acetate, or dimethyl fumarate; similar ARR compared with fingolimod; and higher ARR compared with natalizumab.
Published: 2020

131. Treatment of multiple sclerosis with rituximab: A multicentric Italian–Swiss experience

Author: Antonio Gallo, Gianmarco Abbadessa, Chiara Zecca, Giancarlo Coghe, Giuseppe Salemi, Antonio Uccelli, Marco Capobianco, Stefania Barone, Rosaria Sacco, Lorena Lorefice, Claudia Mechi, Giorgia Mataluni, Elio Prestipino, Jessica Frau, Claudio Gobbi, Alessandro Barilaro, Giorgia Teresa Maniscalco, Erica Curti, E. Magnani, Bahia Hakiki, Maria Malentacchi, Simona Bonavita, Alessia Di Sapio, Francesca Bovis, Maria Cellerino, Franco Granella, Roberta Lanzillo, Anna Maria Repice, Marcello De Angelis, Isabella Maraffi, Laura Brambilla, Giuseppe Fenu, Elisabetta Signoriello, Alessio Signori, Paola Cavalla, Maria Pia Sormani, Agostino Nozzolillo, Giacomo Boffa, Simona Malucchi, Maria Pia Amato, Giovanni Novi, Sabrina Realmuto, Francesca Sperli, Ilaria Maietta, Vincenzo Brescia Morra, Zecca, C., Bovis, F., Novi, G., Capobianco, M., Lanzillo, R., Frau, J., Repice, A. M., Hakiki, B., Realmuto, S., Bonavita, S., Curti, E., Brambilla, L., Mataluni, G., Cavalla, P., Di Sapio, A., Signoriello, E., Barone, S., Maniscalco, G. T., Maietta, I., Maraffi, I., Boffa, G., Malucchi, S., Nozzolillo, A., Coghe, G., Mechi, C., Salemi, G., Gallo, A., Sacco, R., Cellerino, M., Malentacchi, M., De Angelis, M., Lorefice, L., Magnani, E., Prestipino, E., Sperli, F., Brescia Morra, V., Fenu, G., Barilaro, A., Abbadessa, G., Signori, A., Granella, F., Amato, M. P., Uccelli, A., Gobbi, C., Sormani, M. P., Zecca, Chiara, Bovis, Francesca, Novi, Giovanni, Capobianco, Marco, Lanzillo, Roberta, Frau, Jessica, Repice, Anna Maria, Hakiki, Bahia, Realmuto, Sabrina, Bonavita, Simona, Curti, Erica, Brambilla, Laura, Mataluni, Giorgia, Cavalla, Paola, Di Sapio, Alessia, Signoriello, Elisabetta, Barone, Stefania, Maniscalco, Giorgia T, Maietta, Ilaria, Maraffi, Isabella, Boffa, Giacomo, Malucchi, Simona, Nozzolillo, Agostino, Coghe, Giancarlo, Mechi, Claudia, Salemi, Giuseppe, Gallo, Antonio, Sacco, Rosaria, Cellerino, Maria, Malentacchi, Maria, De Angelis, Marcello, Lorefice, Lorena, Magnani, Eliana, Prestipino, Elio, Sperli, Francesca, Brescia Morra, Vincenzo, Fenu, Giuseppe, Barilaro, Alessandro, Abbadessa, Gianmarco, Signori, Alessio, Granella, Franco, Amato, Maria Pia, Uccelli, Antonio, Gobbi, Claudio, and Sormani, Maria Pia
Subjects: Multiple Sclerosis, medicine.drug_class, Lymphocyte depletion, relapsing–remitting, Monoclonal antibody, Primary progressive, 03 medical and health sciences, 0302 clinical medicine, Multiple Sclerosis, Relapsing-Remitting, real life, medicine, Humans, Immunologic Factors, 030212 general & internal medicine, Secondary progressive, Retrospective Studies, primary progressive, business.industry, Multiple sclerosis, Rituximab, multiple sclerosis, secondary progressive, Treatment options, medicine.disease, Neurology, Relapsing remitting, Italy, multiple sclerosi, Immunology, Settore MED/26 - Neurologia, Neurology (clinical), business, 030217 neurology & neurosurgery, Switzerland, medicine.drug
Abstract: Background: Rituximab, an anti-CD20 monoclonal antibody leading to B lymphocyte depletion, is increasingly used as an off-label treatment option for multiple sclerosis (MS). Objective: To investigate the effectiveness and safety of rituximab in relapsing–remitting (RR) and progressive MS. Methods: This is a multicenter, retrospective study on consecutive MS patients treated off-label with rituximab in 22 Italian and 1 Swiss MS centers. Relapse rate, time to first relapse, Expanded Disability Status Scale (EDSS) progression, incidence of adverse events, and radiological outcomes from 2009 to 2019 were analyzed. Results: A total of 355/451 enrolled subjects had at least one follow-up visit and were included in the outcome analysis. Annualized relapse rate significantly decreases after rituximab initiation versus the pre-rituximab start year in RRMS (from 0.86 to 0.09, p Conclusion: Consistently with other observational studies, our data show effectiveness of rituximab in reducing disease activity in patients with MS.
Published: 2020

132. Molecular Mechanisms Controlling Foxp3 Expression in Health and Autoimmunity: From Epigenetic to Post-translational Regulation

Author: Alessandra Colamatteo, Fortunata Carbone, Sara Bruzzaniti, Mario Galgani, Clorinda Fusco, Giorgia Teresa Maniscalco, Francesca Di Rella, Paola de Candia, Veronica De Rosa, Colamatteo, A., Carbone, F., Bruzzaniti, S., Galgani, M., Fusco, C., Maniscalco, G. T., Di Rella, F., de Candia, P., and De Rosa, V.
Subjects: 0301 basic medicine, lcsh:Immunologic diseases. Allergy, genetic structures, Cellular differentiation, Immunology, chemical and pharmacologic phenomena, Review, [object Object], Biology, T-Lymphocytes, Regulatory, epigenetic regulation, Epigenesis, Genetic, 03 medical and health sciences, 0302 clinical medicine, T-Lymphocyte Subsets, Transcriptional regulation, Immunology and Allergy, Animals, Humans, Epigenetics, Enhancer, Transcription factor, Regulation of gene expression, Foxp3 stability, autoimmunity, FOXP3, Cell Differentiation, Forkhead Transcription Factors, hemic and immune systems, Chromatin, Cell biology, 030104 developmental biology, Gene Expression Regulation, Foxp3, lcsh:RC581-607, Treg cells, 030215 immunology
Abstract: The discovery of the transcription factor Forkhead box-p3 (Foxp3) has shed fundamental insights into the understanding of the molecular determinants leading to generation and maintenance of T regulatory (Treg) cells, a cell population with a key immunoregulatory role. Work over the past few years has shown that fine-tuned transcriptional and epigenetic events are required to ensure stable expression of Foxp3 in Treg cells. The equilibrium between phenotypic plasticity and stability of Treg cells is controlled at the molecular level by networks of transcription factors that bind regulatory sequences, such as enhancers and promoters, to regulate Foxp3 expression. Recent reports have suggested that specific modifications of DNA and histones are required for the establishment of the chromatin structure in conventional CD4+T (Tconv) cells for their future differentiation into the Treg cell lineage. In this review, we discuss the molecular events that control Foxp3 gene expression and address the associated alterations observed in human diseases. Also, we explore how Foxp3 influences the gene expression programs in Treg cells and how unique properties of Treg cell subsets are defined by other transcription factors. Progetto giovani ricercatori [GR-2016-02363725] dal titolo: "Immune Tolerance, Metabolism and Multiple Sclerosis: Novel Molecular Tools to Monitor Disease Pathogenesis and Progression" &nbsp
Published: 2020

133. Extending the Interval of Natalizumab Dosing: Is Efficacy Preserved?

Author: Marco Iudicello, Cinzia Cordioli, Marinella Clerico, Giorgia Teresa Maniscalco, Luigi Lavorgna, Martina Petruzzo, Giorgia Mataluni, Giacomo Lus, Massimiliano Mirabella, Rita Frangiamore, Damiano Baroncini, Erica Curti, Alice Laroni, Paola Cavalla, Eleonora Cocco, Ruggero Capra, Alessio Signori, Roberta Lanzillo, Gianfranco Costantini, Maria Pia Sormani, Stefania Federica De Mercanti, Viviana Nociti, Simona Bonavita, Ilaria Gandoglia, Arianna Sartori, Doriana Landi, Lorena Lorefice, Elisabetta Signoriello, Clerico, Marinella, De Mercanti, Stefania Federica, Signori, Alessio, Iudicello, Marco, Cordioli, Cinzia, Signoriello, Elisabetta, Lus, Giacomo, Bonavita, Simona, Lavorgna, Luigi, Maniscalco, Giorgia Teresa, Curti, Erica, Lorefice, Lorena, Cocco, Eleonora, Nociti, Viviana, Mirabella, Massimiliano, Baroncini, Damiano, Mataluni, Giorgia, Landi, Doriana, Petruzzo, Martina, Lanzillo, Roberta, Gandoglia, Ilaria, Laroni, Alice, Frangiamore, Rita, Sartori, Arianna, Cavalla, Paola, Costantini, Gianfranco, Sormani, Maria Pia, Capra, Ruggero, Clerico, M., De Mercanti, S. F., Signori, A., Iudicello, M., Cordioli, C., Signoriello, E., Lus, G., Bonavita, S., Lavorgna, L., Maniscalco, G. T., Curti, E., Lorefice, L., Cocco, E., Nociti, V., Mirabella, M., Baroncini, D., Mataluni, G., Landi, D., Petruzzo, M., Lanzillo, R., Gandoglia, I., Laroni, A., Frangiamore, R., Sartori, A., Cavalla, P., Costantini, G., Sormani, M. P., and Capra, R.
Subjects: 0301 basic medicine, Standard interval, Adult, Male, medicine.medical_specialty, efficacy, progressive multifocal leukoencephalopathy, law.invention, Cohort Studies, Multiple sclerosis, 03 medical and health sciences, 0302 clinical medicine, Natalizumab, natalizumab, Randomized controlled trial, law, Recurrence, Internal medicine, medicine, Humans, Immunologic Factors, Pharmacology (medical), Multiple sclerosi, extended dose, Dosing, Retrospective Studies, Pharmacology, business.industry, Progressive multifocal leukoencephalopathy, Leukoencephalopathy, Progressive Multifocal, Retrospective cohort study, medicine.disease, Settore MED/26 - NEUROLOGIA, 030104 developmental biology, Treatment Outcome, Italy, Observational study, Female, Original Article, Neurology (clinical), business, 030217 neurology & neurosurgery, medicine.drug, Cohort study
Abstract: Extending the natalizumab interval after the 24th administration could reduce the risk of progressive multifocal leukoencephalopathy (PML). The objective is to evaluate the noninferiority of the efficacy of an extended interval dosing (EID) compared with the standard interval dosing (SID) of natalizumab. It is an observational, multicenter (14 Italian centers), retrospective cohort study, starting from the 24th natalizumab infusion to the loss of follow-up or 2 years after baseline. Patients were grouped in 2 categories according to the mean number of weeks between doses
Published: 2020

134. First therapy choice in newly diagnosed Multiple Sclerosis patients: A multicenter Italian study

Author: Roberta Grasso, Doriana Landi, Luca Carmisciano, Simona Bonavita, Domenico Ippolito, Sara La Gioia, Marinella Clerico, Cinzia Valeria Russo, A. Repice, Maria Laura Stromillo, Roberta Lanzillo, Raffaella Cerqua, Alice Laroni, Lorena Pareja Gutierrez, Stefania Barone, Maria Pia Sormani, Simona Pontecorvo, E Binello, Pietro Annovazzi, Valentina Torri Clerici, Giorgia Mataluni, Cinzia Cordioli, Elisabetta Signoriello, Jessica Frau, Alessio Signori, Sarah Rasia, Arianna Sartori, Gabriella Turano, Francesco Saccà, Damiano Baroncini, Alessia Di Sapio, Ignazio Roberto Zarbo, Eleonora Cocco, Paola Perini, Luigi Lavorgna, Caterina Barrilà, Giorgia Teresa Maniscalco, B. Frigeni, Maniscalco, G. T., Sacca, F., Lanzillo, R., Annovazzi, P., Baroncini, D., Binello, E., Repice, A., Perini, P., Clerico, M., Mataluni, G., Bonavita, S., La Gioia, S., Gutierrez, L. P., Laroni, A., Frau, J., Cocco, E., Torri Clerici, V., Zarbo, I. R., Sartori, A., Signoriello, E., Rasia, S., Cordioli, C., Stromillo, M. L., Cerqua, R., Pontecorvo, S., Di Sapio, A., Grasso, R., Barone, S., Lavorgna, L., Barrila, C., Landi, D., Russo, C. V., Frigeni, B., Ippolito, D., Turano, G., Carmisciano, L., Sormani, M. P., and Signori, A.
Subjects: Male, medicine.medical_specialty, Dimethyl Fumarate, Settore MED/26, Logistic regression, Multiple sclerosis, 03 medical and health sciences, chemistry.chemical_compound, Multiple Sclerosis, Relapsing-Remitting, 0302 clinical medicine, Natalizumab, Internal medicine, Teriflunomide, Immunomodulatory therapy, Humans, Medicine, Relapsing-remitting, Multiple sclerosi, 030212 general & internal medicine, Glatiramer acetate, Determinants first therapy, Naive, Aged, Dimethyl fumarate, Fingolimod Hydrochloride, business.industry, General Medicine, medicine.disease, Fingolimod, Italy, Neurology, chemistry, Cohort, Neurology (clinical), business, Immunosuppressive Agents, 030217 neurology & neurosurgery, medicine.drug
Abstract: Background: The approval of an increasing number of disease modifying drugs for the treatment of Multiple Sclerosis (MS) creates new challenges for patients and clinicians on the first treatment choice. The main aim of this study was to assess factors impacting first therapy choice in a large Italian MS cohort. Methods: Newly diagnosed relapsing-remitting (RR) MS patients (2010-2018) followed in 24 Italian MS centres were included in the study. We evaluated the association of baseline demographics, clinical and MRI characteristics to the first treatment choice by logistic regression models applied to pre-defined binary alternatives: dimethyl fumarate vs injectables (interferon and glatiramer acetate), teriflunomide vs injectables, fingolimod vs dimethyl fumarate and fingolimod vs natalizumab. Results: We enrolled 3025 patients in the period between January 2010 and June 2018. Relapses in the previous year (OR = 2.75; p = 0.001), presence of spinal cord lesions (OR = 1.80; p = 0.002) and higher number (>9) of T2 lesions on the baseline brain MRI scan (OR = 1.65; p = 0.022) were the factors associated to dimethyl fumarate choice as first therapy vs an injectable drug. Older age (OR = 1.06; p < 0.001), male sex (OR = 2.29; p = 0.001) and higher EDSS (OR = 1.36; p < 0.001) were the factors associated with the choice of teriflunomide vs injectables. In more recent years, dimethyl fumarate (OR = 3.23; p < 0.001) and teriflunomide (OR = 2.53; p < 0.001) were chosen more frequently than injectables therapies. The main determinant for the choice of fingolimod as compared with dimethyl fumarate was a higher EDSS (OR = 1.56; p = 0.001), while there was a weak association with a longer disease duration (p = 0.068) and a longer time from onset to diagnosis (p = 0.085). Compared to fingolimod, natalizumab was preferred in patients with a younger age (OR = 0.95; p = 0.003) and higher EDSS (OR = 1.45; p = 0.007) and a shorter disease duration (OR = 0.52; p = 0.076). Conclusion: Many factors guided therapeutic decision for our Italian cohort of MS patients; they are mainly related to MS disease activity, baseline EDSS, disease duration and age.
Published: 2020

135. Outcomes after fingolimod to alemtuzumab treatment shift in relapsing–remitting MS patients: a multicentre cohort study

Author: Francesco Saccà, Giuseppe Fenu, Alessio Signori, Sara La Gioia, Simona Bonavita, Jessica Frau, Marinella Clerico, Cinzia Valeria Russo, Marco Capobianco, Arianna Sartori, Maria Pia Sormani, Damiano Baroncini, Pietro Annovazzi, Caterina Lapucci, Eleonora Cocco, Alice Laroni, Antonio Carotenuto, Elisabetta Signoriello, Antonio Gallo, Giorgia Teresa Maniscalco, Frau, J., Sacca, F., Signori, A., Baroncini, D., Fenu, G., Annovazzi, P., Capobianco, M., Signoriello, E., Laroni, A., La Gioia, S., Sartori, A., Maniscalco, G. T., Bonavita, S., Clerico, M., Russo, C. V., Gallo, A., Lapucci, C., Carotenuto, A., Sormani, M. P., and Cocco, E.
Subjects: Adult, Male, medicine.medical_specialty, Multiple Sclerosis, Outcome Assessment, Alemtuzumab, Fingolimod, NEDA, Real life, Real life, NEDA, Relapsing-Remitting, Gastroenterology, Severity of Illness Index, 03 medical and health sciences, 0302 clinical medicine, Multiple Sclerosis, Relapsing-Remitting, Fingolimod Hydrochloride, Internal medicine, Alemtuzumab, Fingolimod, Female, Humans, Immunologic Factors, Magnetic Resonance Imaging, Middle Aged, Retrospective Studies, Outcome Assessment, Health Care, medicine, 030212 general & internal medicine, Expanded Disability Status Scale, business.industry, Multiple sclerosis, Retrospective cohort study, medicine.disease, Discontinuation, Health Care, Neurology, Cohort, Neurology (clinical), business, 030217 neurology & neurosurgery, medicine.drug
Abstract: Background: A high reactivation of multiple sclerosis (MS) was reported in patients treated with alemtuzumab after fingolimod. We aimed to understand whether this shift enhanced the risk for reactivation in a real-life cohort. Methods: Subjects with relapsing MS, shifting from fingolimod to alemtuzumab were enrolled. We collected the following data: age, sex, disease duration, relapses after fingolimod withdrawal, new T2/gadolinium (Gd)-enhancing lesions in the last magnetic resonance imaging (MRI) during fingolimod and in the first, while on alemtuzumab, lymphocyte counts at alemtuzumab start, and Expanded Disability Status Scale (EDSS) before and after alemtuzumab. Results: We enrolled 77 patients (women 61 (79%); mean age 36.2years (SD 9.6), and disease duration 12.3years (SD 6.8) at fingolimod discontinuation; median washout 1.8months). The annualised relapse rate was 0.89 during fingolimod, 1.32 during washout, and 0.15 after alemtuzumab (p = 0.001). The EDSS changed from a median of 3 (IQR 2–4) at the end of fingolimod to 2.5 after alemtuzumab (IQR 1.5–4) (p = 0.013). The washout length and the lymphocyte count before alemtuzumab were not associated with EDSS change after alemtuzumab (p = 0.59 and p = 0.33, respectively). MRI activity decreased after alemtuzumab compared to that during fingolimod (p = 0.001). At alemtuzumab start, lymphocyte counts were < 0.8 × 103/mL in 21 patients. Conclusions: In our cohort, alemtuzumab reduced relapse, new T2/Gd-enhancing lesions, and EDSS score, as compared to the previous periods (fingolimod/washout). These results were not related to washout length or lymphocyte counts. Therefore, a rapid initiation of alemtuzumab after fingolimod does not seem to be a risk factor for MS reactivation.
Published: 2019

136. MRI activity and extended interval of Natalizumab dosing regimen: a multicentre Italian study

Author: Doriana Landi, Gianmarco Abbadessa, Gianfranco Costantini, Giacomo Lus, Stefania Federica De Mercanti, Cinzia Cordioli, Simona Bonavita, Giorgia Mataluni, Massimiliano Mirabella, Maria Pia Sormani, Ilaria Gandoglia, Giorgia Teresa Maniscalco, Martina Petruzzo, Rita Frangiamore, Eleonora Cocco, Erica Curti, Damiano Baroncini, Ruggero Capra, Elisabetta Signoriello, Paola Cavalla, Luigi Lavorgna, Lorena Lorefice, Alice Laroni, Marinella Clerico, Viviana Nociti, Alessio Signori, Arianna Sartori, Roberta Lanzillo, De Mercanti, Stefania Federica, Signori, Alessio, Cordioli, Cinzia, Signoriello, Elisabetta, Lus, Giacomo, Bonavita, Simona, Abbadessa, Gianmarco, Lavorgna, Luigi, Maniscalco, Giorgia Teresa, Curti, Erica, Lorefice, Lorena, Cocco, Eleonora, Nociti, Viviana, Mirabella, Massimiliano, Baroncini, Damiano, Mataluni, Giorgia, Landi, Doriana, Petruzzo, Martina, Lanzillo, Roberta, Gandoglia, Ilaria, Laroni, Alice, Frangiamore, Rita, Sartori, Arianna, Cavalla, Paola, Costantini, Gianfranco, Capra, Ruggero, Sormani, Maria Pia, Clerico, Marinella, De Mercanti, S. F., Signori, A., Cordioli, C., Signoriello, E., Lus, G., Bonavita, S., Abbadessa, G., Lavorgna, L., Maniscalco, G. T., Curti, E., Lorefice, L., Cocco, E., Nociti, V., Mirabella, M., Baroncini, D., Mataluni, G., Landi, D., Petruzzo, M., Lanzillo, R., Gandoglia, I., Laroni, A., Frangiamore, R., Sartori, A., Cavalla, P., Costantini, G., Capra, R., Sormani, M. P., and Clerico, M.
Subjects: medicine.medical_specialty, Efficacy, Progressive Multifocal, Relapsing-Remitting, Settore MED/26, law.invention, Multiple sclerosis, 03 medical and health sciences, Magnetic resonance imaging, Immunologic Factor, Multiple Sclerosis, Relapsing-Remitting, 0302 clinical medicine, Natalizumab, Randomized controlled trial, Leukoencephalopathy, Retrospective Studie, law, Internal medicine, Multiple Sclerosi, Humans, Immunologic Factors, Medicine, 030212 general & internal medicine, Dosing, Retrospective Studies, Extended dose, medicine.diagnostic_test, business.industry, Progressive multifocal leukoencephalopathy, Leukoencephalopathy, Progressive Multifocal, Retrospective cohort study, medicine.disease, Settore MED/26 - NEUROLOGIA, Regimen, Italy, Neurology, Magnetic Resonance Imaging, Multiple Sclerosis, Neurology (clinical), business, 030217 neurology & neurosurgery, Human, medicine.drug
Abstract: Background: To minimize the risk of Progressive Multifocal Leukoencephalopathy and rebound in JCV-positive multiple sclerosis (MS) patients after 24 natalizumab doses, it has been proposed to extend the administrations interval. The objective is to evaluate the EID efficacy on MRI activity compared with the standard interval dosing (SID). Methods: Observational, multicentre, retrospective cohort study, starting from the 24th natalizumab infusion to the loss of follow-up or 2 years after baseline. Three hundred and sixteen patients were enrolled. The median dose interval (MDI) following the 24th infusion was 5 weeks, with a bimodal distribution (modes at 4 and 6 weeks). Patients were grouped into 2 categories according to the mean number of weeks between doses: < 5 weeks, SID; ≥ 5 weeks, EID. Results: One hundred and eighty-seven patients were in the SID group (MDI = 4.5 weeks) and 129 in the EID group (MDI 6.1 weeks). The risk to develop active lesions on MRI is similar in SID and EID groups during the 6 and 12 months after the 24th natalizumab infusion, respectively 4.27% (95% CI:0.84–7.70) vs 4.71% (95% CI:0.16–9.25%) [p = 0.89] and 8.50% (95% CI:4.05–12.95) vs 6.55% (95% CI:2.11–11.00%) [p = 0.56]. The EID regimen does not appear to increase the occurrence of MRI activity during follow-up. Conclusion: There is no evidence of the reduced efficacy of natalizumab in an EID setting regarding the MRI activity. This observation supports the need for a bigger randomized study to assess the need to change the standard of the natalizumab dosing schedule, to better manage JCV-positive patients.
Published: 2021

137. A multicenter survey on access to care in Multiple Sclerosis-related trigeminal neuralgia

Author: Ilaria Pesci, Pietro Annovazzi, Claudio Solaro, Alberto Gajofatto, Cinzia Cordioli, G. T. Maniscalco, Eleonora Cocco, Roberta Fantozzi, Antonio Gallo, Marta Radaelli, Maria Chiara Buscarinu, Federica Pinardi, M. Di Filippo, Damiano Paolicelli, Valentina Tomassini, Diana Ferraro, Massimiliano Calabrese, G. De Luca, R Lanzillo, Paolo Ragonese, Paola Cavalla, S. Lo Fermo, C. Gasperini, Marcello Moccia, C. Tortorella, Viviana Nociti, Valentina Camera, Ferraro, D., Annovazzi, P., Lanzillo, R., Calabrese, M., Fantozzi, R., De Luca, G., Cordioli, C., Paolicelli, D., Ragonese, P., Gajofatto, A., Lo Fermo, S., Cavalla, P., Tortorella, C., Pesci, I., Gallo, A., Pinardi, F., Di Filippo, M., Maniscalco, G. T., Nociti, V., Radaelli, M., Tomassini, V., Buscarinu, M. C., Moccia, M., Camera, V., Cocco, E., Gasperini, C., Solaro, C., Ferraro D., Annovazzi P., Lanzillo R., Calabrese M., Fantozzi R., De Luca G., Cordioli C., Paolicelli D., Ragonese P., Gajofatto A., Lo Fermo S., Cavalla P., Tortorella C., Pesci I., Gallo A., Pinardi F., Di Filippo M., Maniscalco G.T., Nociti V., Radaelli M., Tomassini V., Buscarinu M.C., Moccia M., Camera V., Cocco E., Gasperini C., and Solaro C.
Subjects: medicine.medical_specialty, Multiple Sclerosis, multiple sclerosis, trigeminal neuralgia, Cross-sectional study, medicine.medical_treatment, Population, Microvascular decompression, Health Services Accessibility, 03 medical and health sciences, 0302 clinical medicine, Retrospective Studie, Trigeminal neuralgia, Multiple Sclerosi, medicine, Humans, 030212 general & internal medicine, Intensive care medicine, education, Oxcarbazepine, Retrospective Studies, Cross-Sectional Studie, education.field_of_study, business.industry, Multiple sclerosis, Retrospective cohort study, Trigeminal Neuralgia, medicine.disease, Cross-Sectional Studies, Treatment Outcome, Italy, Neurology, Multicenter survey, Neurology (clinical), business, 030217 neurology & neurosurgery, Human, medicine.drug
Abstract: The prevalence of trigeminal neuralgia (TN) in patients with Multiple Sclerosis (MS) is higher than in the general population and its management can be particularly challenging due to a number of reasons including high recurrence rates, lack of MS-specific treatment guidelines and uncertainties about pain pathophysiology. Aim of this cross-sectional, multicentre survey was to gather information on the current treatment modalities and options of MS-related TN across 23 Italian MS centres. Initial medical management (carbamazepine or oxcarbazepine) of MS-related TN was fairly homogeneous throughout Italian centres. The most commonly available surgical procedure was microvascular decompression, but the frequency and types of surgical procedures available locally differed considerably throughout MS centers, and were unavailable in one quarter of them. This survey reveals some of the issues that could hamper an optimal patient management and underlines the need for a consensus on MS-related TN to support health-care professionals in their approach to this challenging condition and to facilitate the development of local guidelines aimed at ensuring equity in access to care and treatment optimization.
Published: 2021

138. Reversion studies with known mutagens in V79 Chinese hamster cells

Author: Mariani, L., Randazzo, R., Maniscalco, G., Di Leonardo, A., Bonatti, S., Fiorio, R., Mazzaccaro, A., and Abbondandolo, A.
Published: 1980
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139. Early neutropenia with thrombocytopenia following alemtuzumab treatment for multiple sclerosis: case report and review of literature

Author: Giorgia Teresa Maniscalco, Giovanni Improta, Ciro Florio, V. Abate, M. Napolitano, Ilaria Cerillo, Giovanni Guarcello, G. Servillo, Maniscalco, G. T., Cerillo, I., Servillo, G., Napolitano, M., Guarcello, G., Abate, V., Improta, Giovanni, and Florio, C.
Subjects: Adult, medicine.medical_specialty, Neutropenia, CD52, medicine.drug_class, Monoclonal antibody, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Antineoplastic Agents, Immunological, Multiple Sclerosis, Relapsing-Remitting, hemic and lymphatic diseases, Internal medicine, medicine, Humans, Platelet, Multiple sclerosi, Alemtuzumab, business.industry, Multiple sclerosis, 030208 emergency & critical care medicine, General Medicine, medicine.disease, Thrombocytopenia, Purpura, Treatment Outcome, Surgery, Female, Neurology (clinical), medicine.symptom, business, 030217 neurology & neurosurgery, medicine.drug, Haematological disorders, Human
Abstract: Alemtuzumab is a monoclonal antibody targeting the CD52 antigen used in the treatment of relapsing-remitting multiple sclerosis (RRMS). CD52 is expressed by lymphocytes and monocytes but less by neutrophils and not by platelets. We present a case of a 38-year-old woman with RRMS who developed early neutropenia with thrombocytopenia after alemtuzumab infusion. She had no fever or symptoms of infection or purpura. After two weeks her haematological disorders spontaneously resolved. We reported the first case of neutropenia and thrombocytopenia as a possible event occurring after alemtuzumab infusion in MS patients, even if in a mild grade. So, we recommend to not underestimate these two conditions.
Published: 2018

140. Long-term adherence of patients with relapsing-remitting multiple sclerosis to subcutaneous self-injections of interferon β-1a using an electronic device: the RIVER study

Author: Vincenzo Brescia Morra, Stefano Borghesan, Marinella Clerico, Giorgia Teresa Maniscalco, Francesca De Robertis, Diego Centonze, Alessandra Lugaresi, Lugaresi, A, De Robertis, F, Clerico, M, BRESCIA MORRA, Vincenzo, Centonze, D, Borghesan, S, Maniscalco, G. T., Lugaresi, Alessandra, De Robertis, Francesca, Clerico, Marinella, Brescia Morra, Vincenzo, Centonze, Diego, Borghesan, Stefano, and Maniscalco, Giorgia Teresa
Subjects: Adult, Male, medicine.medical_specialty, Injections, Subcutaneous, Observation period, Pharmaceutical Science, patient outcome assessment, multiple sclerosis, Auto-injection device, drug delivery system, interferon β-1a, long-term adherence, patient outcome assessments, 3003, 03 medical and health sciences, Multiple Sclerosis, Relapsing-Remitting, 0302 clinical medicine, Internal medicine, medicine, Humans, Prospective Studies, 030212 general & internal medicine, Prospective cohort study, Retrospective Studies, business.industry, Extension study, Multiple sclerosis, Interferon beta-1a, Retrospective cohort study, Middle Aged, medicine.disease, Surgery, Interferon β 1a, Relapsing remitting, multiple sclerosi, Patient Compliance, Female, Settore MED/26 - Neurologia, business, 030217 neurology & neurosurgery, Follow-Up Studies, medicine.drug
Abstract: Objectives: The BRIDGE study has previously shown a high short-term (12 weeks) adherence rate (>85%) of patients with relapsing-remitting multiple sclerosis (RRMS) to subcutaneous self-injections of interferon β-1a using an electronic auto-injection device (RebiSmart®). The primary goal of the RIVER study was to investigate in a real-life setting the long-term adherence to the use of RebiSmart among patients enrolled in the parent BRIDGE study. Methods: The RIVER study was designed as a real-life extension study of the BRIDGE trial. RRMS patients who completed BRIDGE and still had an indication for treatment were included. Data were collected prospectively through the RebiSmart device, and analyzed retrospectively. Long term adherence (administration of ≥ 80% of injections) to and safety of RebiSmart were assessed. The expected follow-up period ranged from 19 to 26 months. Results: A total of 57 RRMS patients participated in the follow-up study. The mean observation period was 20.5 ± 5.7 months. The overall adherence to the use of RebiSmart in the entire study cohort was 79.8% (median = 85.2%, range = 16–100%). There were 36 patients (63.2%) who completed at least 80% of the scheduled injections. No statistically significant differences were found between adherent and non-adherent patients in terms of age, sex, duration of the observation period, and occurrence of relapses. No serious treatment-related adverse events occurred. Conclusions: This study showed a high level of long-term adherence to the use of RebiSmart, with 63.2% of participants meeting the criterion for adherence to treatment. © 2016 Informa UK Limited, trading as Taylor & Francis Group .
Published: 2016

141. Treatment withdrawal in relapsing-remitting multiple sclerosis: a retrospective cohort study

Author: Giacomo Lus, G. T. Maniscalco, Elisabetta Signoriello, Simona Signoriello, Ciro Gallo, Simona Bonavita, Lus, Giacomo, Signoriello, E, Maniscalco, G. T, Bonavita, Simona, Signoriello, Simona, and Gallo, Ciro
Subjects: Adult, Male, medicine.medical_specialty, 03 medical and health sciences, Drug withdrawal, 0302 clinical medicine, Multiple Sclerosis, Relapsing-Remitting, Adjuvants, Immunologic, Recurrence, Internal medicine, Outcome Assessment, Health Care, medicine, Humans, 030212 general & internal medicine, Glatiramer acetate, Retrospective Studies, Expanded Disability Status Scale, business.industry, Multiple sclerosis, treatment withdrawal, Retrospective cohort study, Glatiramer Acetate, medicine.disease, Confidence interval, Surgery, Neurology, multiple sclerosi, Cohort, Observational study, Female, Neurology (clinical), business, 030217 neurology & neurosurgery, Interferon beta-1a, medicine.drug, Follow-Up Studies, Interferon beta-1b
Abstract: Background To investigate the effect of drug withdrawal on the course of relapsing−remitting multiple sclerosis (RR-MS). Methods An observational cohort retrospective study was performed to compare the time to relapse of patients who discontinued disease-modifying therapy (1a or 1b beta-interferons or glatiramer acetate) with the patients who did not. One hundred and twenty-eight RR-MS patients were investigated using a time-dependent approach. Results Over a median follow-up of 108 months, 60 patients discontinued treatment and 89 relapses were observed. The time to relapse was shorter in patients who discontinued treatment compared with those who did not (P
Published: 2015

142. The Framingham cardiovascular risk score in multiple sclerosis

Author: Raffaele Palladino, A. De Rosa, Roberta Lanzillo, Emanuela Postiglione, Camilla Russo, Marcello Moccia, Oreste Caporale, Maria Triassi, V. Brescia Morra, Marco Massarelli, Antonio Carotenuto, Giorgia Teresa Maniscalco, Moccia, M, Lanzillo, Roberta, Palladino, R., Maniscalco, G. T., DE ROSA, Anna, Russo, C., Massarelli, M., Carotenuto, A., Postiglione, E., Caporale, O., Triassi, Maria, and BRESCIA MORRA, Vincenzo
Subjects: Gerontology, Adult, Male, Risk, medicine.medical_specialty, Adolescent, Cardiovascular risk factors, Comorbidity, Cardiovascular, Severity of Illness Index, Young Adult, Multiple Sclerosis, Relapsing-Remitting, Cardiovascular Disease, Internal medicine, Linear regression, medicine, Humans, Multiple sclerosi, Framingham, Aged, Expanded Disability Status Scale, Framingham Risk Score, business.industry, Medicine (all), Multiple sclerosis, Middle Aged, Multiple Sclerosis, Chronic Progressive, medicine.disease, Blood pressure, Neurology, Cardiovascular Diseases, Case-Control Studies, Disease Progression, Smoking status, Female, Comorbiditie, Neurology (clinical), Case-Control Studie, business, Body mass index, Human
Abstract: Background and purpose Cardiovascular risk factors can increase the risk of multiple sclerosis (MS) and modify its course. However, such factors possibly interact, determining a global cardiovascular risk. Our aim was to compare the global cardiovascular risk of subjects with and without MS with the simplified 10-year Framingham General Cardiovascular Disease Risk Score (FR) and to evaluate its importance on MS-related outcomes. Methods Age, gender, smoking status, body mass index, systolic blood pressure, type II diabetes and use of antihypertensive medications were recorded in subjects with and without MS to estimate the FR, an individualized percentage risk score estimating the 10-year likelihood of cardiovascular events. Results In total, 265 MS subjects were identified with 530 matched controls. A t test showed similar FR in cases and controls (P = 0.212). Secondary progressive MS presented significantly higher FR compared to relapsing−remitting MS (P
Published: 2015

143. Experimental access to Transition Distribution Amplitudes with the P̄ANDA experiment at FAIR

Author: M. C. Mora Espí, Pawel Marciniewski, K. Makonyi, Yupeng Yan, S. Wronka, D. Pietreanu, Shaji Kumar, N. Belikov, D. I. Glazier, A. Gillitzer, K. Khanchai, Ajay Kumar Rai, M. Steinen, D. Calvo, Yury Tikhonov, A. A. Derevschikov, T. A. Pocheptsov, R.A. Salmin, P. Balanutsa, B. J. Liu, P. N. Deepak, A. E. Blinov, S. Lange, S. Ryzhikov, G. Kalicy, Arpit Parmar, P. Musiol, G. D. Alexeev, D. P. Watts, Lennart Isaksson, Tobias Stockmanns, E. Gutz, P. F. Dalpiaz, Zhi Liu, D. Marchand, S. Grieser, A. Gerhardt, D. Kangh, L. Fava, A. A. Festchenko, Harphool Kumawat, I. Zimmermann, M. Albrecht, B. Krusche, A. Sanchez Lorente, E. A. Strokovsky, M. A. Pasyuk, J. Ritman, P. C. Vinodkumar, T. Quagli, M.G. Sapozhnikov, Ashok Kumar, Herbert Koch, V. I. Astakhov, V. Serdyuk, K. M. von Würtemberg, D. Münchow, Hans-Georg Zaunick, S. Marcello, M. Ullrich, A. Mustafa, Paola Gianotti, T. Kuske, Michaela Thiel, Kamal K. Seth, S. Schlimme, C. Schwarz, M. Savrie, B. Ketzer, Jerzy Smyrski, E. Etzelmüller, A. G. Fedunov, H. Sohlbach, K. Malgorzata, Victor Bobrovnikov, R.Sh. Teshev, L. Ayut, V.M. Abazov, B. Spruck, B. Kamys, D. Mülhheim, Krzysztof Swientek, S. Schadmand, M. V. Korzihik, Zbigniew Rudy, Matei Eugen Vasile, T. Wasem, J. Schwiening, D. Lehmann, M. Patsyuk, Karin Schönning, W. Czyzycki, M. Zühlsdorf, V. N. Goryachev, A. G. Zorin, A. Davidenko, W. Lauth, B. Fröhlich, A. Amoroso, V. Lucherini, P. Schakel, Grzegorz Korcyl, G.A. Mustafaev, Smbat Grigoryan, Ajit Kumar Mohanty, Grzegorz Filo, R. Veenstra, P. Wüstner, J. Marton, Boris Batyunya, L. Ferrero, A. N. Skachkova, Edward Lisowski, I. Garzia, D. Bremer, T. Eissner, D. Lin, Y.M. Goncharenko, Soumen Paul, A.A. Efremov, Dipanwita Dutta, Alberto Rotondi, M. Michel, B. Slowinski, A. Arefiev, Philip Woods, I. Augustin, Yan Liang, A. Karavdina, M. Greco, P. Rosier, Antoni Szczurek, N. Saito, K. Föhl, T. Schröder, B. Singh, Mariana Nanova, Andreas Herten, Oleg V. Missevitch, S.A. Zaporozhets, K.-T. Brinkmann, Sukanta Dash, A. Filippi, A. Trzcinski, Marek Idzik, M. O. Distler, J. Schumann, C. Sowa, I. Konorov, J. C. van der Weele, Mathias Fink, A. E. Yakutin, B. Kopf, E. Atomssa, A. Pitka, R. Karabowicz, H. H. Leithoff, Angelo Rivetti, S. Pornrad, S. Diehl, M. Maggiora, B. Kröck, R. Duchat, O. Levitskaya, Gianluigi Boca, Krzysztof Korcyl, Gianangelo Bracco, Harald Kleines, F. Nerling, L. Caldeira Balkeståhl, S. Coli, E. Perevalova, T. Gessler, Klaus Peters, A. Magiera, Vassili Kachanov, M. Hawryluk, S. Ong, R. Varma, X. Shen, T. Czyzewski, M. Domagala, S. Godre, M. Zyzak, J. Pettersson, F. Uhlig, F. De Mori, P.J.J. Lemmens, Alexander D. Vasiliev, Mohammed Al-Turany, Q. Hu, Andrzej Kupsc, R. Schmitz, P. Mahlberg, P. De Remigis, C. Schnier, S. Lusso, R. Dosdall, L. Zotti, J. Van de Wiele, A. Britting, S. Fissum, Zhigang Li, Jozef Zlomanczuk, Amiran Tomaradze, S. Spataro, U. Müller, R. Valente, V. Uzhinsky, Giulio Stancari, G. S. Shabratova, I. Keshelashvili, S. Jowzaee, Harald Merkel, C. Guaraldo, S. Li, Christian Schmidt, M. Steinacher, V. Kozlov, Yu.N. Rogov, A. Bianconi, T. Held, V. Datar, Andrei Fedorov, H. Orth, T. Weber, A. Kozela, Piotr Salabura, M. Destefanis, Andrea Lavagno, M. Kuhlmann, B. Ma, J. Pychy, Piotr Lebiedowicz, L. Capozza, Dominik Kwiatkowski, Andrew Levin, A. Wilms, Germán Mazza, Matthias Richter, Wojciech Krzemien, Sean A Dobbs, J. Pochodzalla, I. Shein, H. Ohm, Paolo Montagna, Paul Alois Buhler, Y. Naryshkin, Hans Calén, A. Apostolou, S. Orfanitski, V. Grishin, A. Kashchuk, V. Kormilitsin, Tomasz Fiutowski, M. Mingnore, M. Krebs, A. Dolgolenko, E. Fioravanti, P.-E. Tegnér, A. Chlopik, A. Gromliuk, Andreas Lehrach, I. Georgadze, B. Czech, B. Zwieglinski, Kurt Hansen, W. Schäfer, C. Motzko, R. Kunne, P. Genova, J. Lühning, A. Psyzniak, S. Bianco, H. Smit, Nicola Bianchi, Felice Iazzi, J. Rieke, M. Fritsch, R. Dzhygadlo, O. Corell, E. Pace, S. I. Manaenkov, V. Chandratre, S. Sosio, A. Olshevskiy, T. Johansson, S. Sanchez, Concettina Sfienti, R. F. Parodi, D. Walther, T. Saito, E. Köhler, Zhi Sun, Markus Büscher, P. Kulessa, Magnus Wolke, I. Kisel, V. Tokmenin, Alexander Vodopyanov, J.H. Zhao, C. Wang, M. Kube, M. Kavatsyuk, T. Hennino, Johann Zmeskal, V. Varentsov, C. Morales Morales, S. Esch, R. Kliemt, G. Schepers, S. Poslavskiy, Alessandro Drago, Dan Pantea, M. Imre, W. Eyrich, D. Melnychuk, M.P. Bussa, Dirk Grunwald, I. Lehmann, D. Rodríguez Piñeiro, Kjell Fransson, A. P. Onuchin, Valery Dormenev, M. Rossbach, F. E. Maas, Giuseppe Giraudo, M. Pelizäus, D. P. Mohanta, H. Deppe, C. Rosenbaum, M. Cardinali, A. G. Denig, A. Boukharov, V. Abramov, A. Hayrapetyan, K. Pysz, Vladimir Blinov, A. K. Hergemöller, A. Ryazantsev, K. Kalita, P. Wintz, Raghunath Sahoo, V. Akishina, P. A. Semenov, V. Balanutsa, Mikael Lundin, M. M. Macri, Anne-Laure Martin, A. Karmokov, U. Cahit, A. Demekhin, G. Rosner, W. Erni, S. Plueger, S. Leiber, Michael Werner, L. Schmitt, S. Costanza, Bent Schröder, R. Arora, D. Deermann, M. Leyhe, S.A. Kononov, S. Belostotski, Ulrich Wiedner, Maria Krawczyk, L. V. Malinina, M. Tiemens, Yu.M. Mel'nik, Ch. Schmidt, O. Merle, U. Thoma, M. Babai, A. Semenov, R. Maier, Ankhi Roy, Michael Düren, L. V. Nogach, E. Widmann, A. Zhadanov, Valentino Rigato, Stanisław Kistryn, P. Fedorets, K. Suzuki, D. A. Morozov, Franco Bradamante, Torbjörn Bäck, L. Busso, C. Le Galliard, Bhavin Patel, Alessandro Bressan, K. Chinorat, M. Wojciechowski, A. Lehmann, A.F. Makarov, A. Galoyan, P. Wieczorek, T. Holtmann, Bernd Voss, Aleksandra Wrońska, J. S. Díaz, M. Hoek, D. Veretennikov, F. H. Heinsius, P. Brandys, F. Balestra, H. Flemming, F. Lisowski, H. Younis, Paweł Moskal, G. Maniscalco, P. Jasinski, V. K. Rodionov, J. G. Messchendorp, R. Schnell, O. Miklukho, D. Prasuhn, M. Zambrana, M. Kümmel, L. Cao, I. Marishev, A. Bersani, Bo Cederwall, K. Götzen, L. Lavezzi, S. Vejdani, N. G. Minaev, Herbert Löhner, V. Metag, R. W. Novotny, E. Tomasi-Gustafsson, N. B. Skachkov, A. Cebulla, Bartosz Mindur, V. Chernetsky, B. Seitz, Daniel M. Kaplan, E. K. Koshurnikov, B. Ramstein, A. Kulkarni, B. J. Roy, T. Sefzick, D. Khaneft, D. Branford, A. A. Piskun, Reinhard Beck, S. Bleser, Yu. Yu. Lobanov, R. Siudak, V. I. Lobanov, E. A. Kravchenko, S. Bukreeva, A. Samartsev, U. Thöring, F. Feldbauer, Ting Xiao, Patrick Achenbach, Hongwei Liu, Johannes Peter Wessels, D. Bettoni, Yu.I. Davydov, V. I. Dormenev, Genady Gavrilov, Ch. Wendel, M. Yu. Barabanov, Kirill M. Semenov-Tian-Shansky, R. Birsa, T. Bel, Günter Kemmerling, A. Khoukaz, V. Carassiti, B. Galnander, Jifeng Hu, M. Bragadireanu, I. A. Kuyanov, Bruce Yabsley, Andrey V. Izotov, O. Noll, J. Kunkel, A. Dbeyssi, K. Suvorov, Vivekanand Jha, Wolfgang Kuhn, Hasko Stenzel, O. Malyshev, A. A. Sokolov, U. Kurilla, G. Kuhl, D. Kaiser, P. Strzempek, A. Goerres, J. Biernat, D. G. Ireland, H. Xu, M. K. Suleimanov, G. Sterzenbach, E. Prencipe, A. Ortiz, N. I. Zhuravlev, A. Täschner, A. Gerasimov, T. Triffterer, M. Deiseroth, A. Wilson, Marek Palka, M. Lindemulder, A. Y. Barnyakov, V.Kh. Dodokhov, D. Nicmorus, Andrey Uzunian, A. Ehret, R. Nellen, Ch. Hammann, M. Steinke, V. L. Malyshev, P. Drexler, Richard Wheadon, A. Cotta Ramusino, P. Sarin, Riccardo Introzzi, H. Clement, I. Kulakov, M. Zuehlsdorf, M. Galuska, S. Kliczewski, G.B. Pontecorvo, D. Przyborowski, Mihai Caprini, V. V. Mochalov, M. Jadhav, M. Mikirtychyants, M. Traxler, Frank Goldenbaum, Research unit Nuclear & Hadron Physics, The PANDA Collaboration, Null, Singh, B. P, Erni, W., Keshelashvili, I., Krusche, B., Steinacher, M., Liu, B., Liu, H., Liu, Z., Shen, X., Wang, C., Zhao, J., Albrecht, M., Fink, M., Heinsius, F. H., Held, T., Holtmann, T., Koch, H., Kopf, B., Kümmel, M., Kuhl, G., Kuhlmann, M., Leyhe, M., Mikirtychyants, M., Musiol, P., Mustafa, A., Pelizäus, M., Pychy, J., Richter, M., Schnier, C., Schröder, T., Sowa, C., Steinke, M., Triffterer, T., Wiedner, U., Beck, R., Hammann, C., Kaiser, D., Ketzer, B., Kube, M., Mahlberg, P., Rossbach, M., Schmidt, C., Schmitz, R., Thoma, U., Walther, D., Wendel, C., Wilson, A., Bianconi, A., Bragadireanu, M., Caprini, M., Pantea, D., Pietreanu, D., Vasile, M. E., Patel, B., Kaplan, D., Brandys, P., Czyzewski, T., Czyzycki, W., Domagala, M., Hawryluk, M., Filo, G., Krawczyk, M., Kwiatkowski, D., Lisowski, E., Lisowski, F., Fiutowski, T., Idzik, M., Mindur, B., Przyborowski, D., Swientek, K., Czech, B., Kliczewski, S., Korcyl, K., Kozela, A., Kulessa, P., Lebiedowicz, P., Malgorzata, K., Pysz, K., Schäfer, W., Siudak, R., Szczurek, A., Biernat, J., Jowzaee, S., Kamys, B., Kistryn, S., Korcyl, G., Krzemien, W., Magiera, A., Moskal, P., Palka, M., Psyzniak, A., Rudy, Z., Salabura, P., Smyrski, J., Strzempek, P., Wrońska, A., Augustin, I., Lehmann, I., Nicmorus, D., Schepers, G., Schmitt, L., Al Turany, M., Cahit, U., Capozza, L., Dbeyssi, A., Deppe, H., Dzhygadlo, R., Ehret, A., Flemming, H., Gerhardt, A., Götzen, K., Karabowicz, R., Kliemt, R., Kunkel, J., Kurilla, U., Lehmann, D., Lühning, J., Maas, F., Morales Morales, C., Mora Espí, M. C., Nerling, F., Orth, H., Peters, K., Rodríguez Piñeiro, D., Saito, N., Saito, T., Sánchez Lorente, A., Schmidt, C. J., Schwarz, C., Schwiening, J., Traxler, M., Valente, R., Voss, B., Wieczorek, P., Wilms, A., Zühlsdorf, M., Abazov, V. M., Alexeev, G., Arefiev, A., Astakhov, V. I., Barabanov, M. Y. u., Batyunya, B. V., Davydov, Y. u. I., Dodokhov, V. K. h., Efremov, A. A., Fedunov, A. G., Festchenko, A. A., Galoyan, A. S., Grigoryan, S., Karmokov, A., Koshurnikov, E. K., Lobanov, V. I., Lobanov, Y. u. Y. u., Makarov, A. F., Malinina, L. V., Malyshev, V. L., Mustafaev, G. A., Olshevskiy, A., Pasyuk, M. A., Perevalova, E. A., Piskun, A. A., Pocheptsov, T. A., Pontecorvo, G., Rodionov, V. K., Rogov, Y. u. N., Salmin, R. A., Samartsev, A. G., Sapozhnikov, M. G., Shabratova, G. S., Skachkov, N. B., Skachkova, A. N., Strokovsky, E. A., Suleimanov, M. K., Teshev, R. S. h., Tokmenin, V. V., Uzhinsky, V. V., Vodopyanov, A. S., Zaporozhets, S. A., Zhuravlev, N. I., Zorin, A. 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Subjects: Particle physics, (P)Over-Baranda, Nuclear and High Energy Physics, Electroproduction, Hadron, Annihilation, FOS: Physical sciences, 7. Clean energy, 01 natural sciences, Particle identification, Nucleon, NO, Nuclear physics, High Energy Physics - Experiment (hep-ex), High Energy Physics - Phenomenology (hep-ph), Factorization, 0103 physical sciences, Fysik, Invariant mass, ddc:530, Meson Production, Monte-Carlo, Nuclear Experiment (nucl-ex), 010306 general physics, Nuclear Experiment, Physics, Quantum chromodynamics, 010308 nuclear & particles physics, Perturbative QCD, Qcd, Physical Sciences, Exclusive Processes, High Energy Physics::Experiment, Pi(0), Cross-Sections, Energy (signal processing)
Abstract: Baryon-to-meson Transition Distribution Amplitudes (TDAs) encoding valuable new information on hadron structure appear as building blocks in the collinear factorized description for several types of hard exclusive reactions. In this paper, we address the possibility of accessing nucleon-to-pion ($��N$) TDAs from $\bar{p}p \to e^+e^- ��^0$ reaction with the future PANDA detector at the FAIR facility. At high center of mass energy and high invariant mass squared of the lepton pair $q^2$, the amplitude of the signal channel $\bar{p}p \to e^+e^- ��^0$ admits a QCD factorized description in terms of $��N$ TDAs and nucleon Distribution Amplitudes (DAs) in the forward and backward kinematic regimes. Assuming the validity of this factorized description, we perform feasibility studies for measuring $\bar{p}p \to e^+e^- ��^0$ with the PANDA detector. Detailed simulations on signal reconstruction efficiency as well as on rejection of the most severe background channel, i.e. $\bar{p}p \to ��^+��^- ��^0$ were performed for the center of mass energy squared $s = 5$ GeV$^2$ and $s = 10$ GeV$^2$, in the kinematic regions $3.0 < q^2 < 4.3$ GeV$^2$ and $5 < q^2 < 9$ GeV$^2$, respectively, with a neutral pion scattered in the forward or backward cone $| \cos��_{��^0}| > 0.5 $ in the proton-antiproton center of mass frame. Results of the simulation show that the particle identification capabilities of the PANDA detector will allow to achieve a background rejection factor of $5\cdot 10^7$ ($1\cdot 10^7$) at low (high) $q^2$ for $s=5$ GeV$^2$, and of $1\cdot 10^8$ ($6\cdot 10^6$) at low (high) $q^2$ for $s=10$ GeV$^2$, while keeping the signal reconstruction efficiency at around $40\%$. At both energies, a clean lepton signal can be reconstructed with the expected statistics corresponding to $2$ fb$^{-1}$ of integrated luminosity. (.../...), 19 pages, 7 figures (some multiple), 2 tables (each double), preprint of an article for epj - v2
Published: 2015

144. Embodied energy and environmental impacts of a biomass boiler: a life cycle approach

Author: Francesco Guarino, Massimo Morale, Sonia Longo, Giuseppe Maniscalco, Vincenzo La Rocca, Maurizio Cellura, Longo, S., Cellura, M., Guarino, F., La Rocca, V., Maniscalco, G., and Morale, M.
Subjects: Engineering, Energy Engineering and Power Technology, environmental impact, renewable energy technology, Energy development, life cycle assessment, lcsh:TK1001-1841, Life-cycle assessment, Settore ING-IND/11 - Fisica Tecnica Ambientale, Waste management, Renewable Energy, Sustainability and the Environment, business.industry, greenhouse gas emissions, Environmental engineering, Environmental impact of the energy industry, Energy consumption, environmental impacts, embodied energy, biomass boiler, Renewable energy, Energy conservation, lcsh:Production of electric energy or power. Powerplants. Central stations, Fuel Technology, business, Embodied energy, Efficient energy use
Abstract: The 2030 policy framework for climate and energy, proposed by the European Commission, aims towards the reduction of European greenhouse gas emissions by 40% in comparison to the 1990 level and to increase the share of renewable energy of at least the 27% of the European's energy consumption of 2030. The use of biomass as sustainable and renewable energy source may be a viable tool for achieving the above goals. However, renewable energy technologies are not totally clean because they cause energy and environmental impacts during their life cycle, and in particular they are responsible of air pollutant emissions. In this context, the paper assesses the energy and environmental impacts of a 46 kW biomass boiler by applying the Life Cycle Assessment methodology, as regulated by the international standards of series ISO 14040, ISO 21930 and EN 15804. The following life-cycle steps are included in the analysis: raw materials and energy supply, manufacturing, installation, operation, transport, and end-of-life. The results of the analysis, showing a life-cycle primary energy consumption of about 2,622 GJ and emissions of about 21,664 kg CO2eq, can be used as a basis for assessing the real advantages due to the use of biomass boilers for heating and hot water production.
Published: 2015

145. Heart failure and chronic kidney disease in a registry of internal medicine wards

Author: Rosa Di Costanzo, Roberto Corinaldesi, Federica Quaglia, Umberto Vespasiani Gentilucci, Giancarlo Agnelli, M. Vanoli, Roberta Forlano, Valeria Savojardo, Luca Bertone, Elisa Fabbri, Antonino Di Pino, Claudia Amolini, Giampiera Bertolino, Paolo Cavallo Perin, Paola Bonara, Tommaso Barnini, Fabrizio Fabris, Paola Di Corato, Maria Rosaria Barbella, Francesco Franceschi, Elisabetta Bergami, Roberto Manfredini, Sonia Seghezzi, Enrico Strocchi, Maria Domenica Cappellini, Antonio Manucra, Alberto Tedeschi, Maurizio Corsi, Gabriella Gruden, Giuseppe Licata, Marianna Zardo, Emanuela Marchesini, Luca Pasina, Maria Ester Modeo, Mosè Bartone, Barbara Nardo, Umberto Gualtieri, Sabbatini Marta, Caterina Cenci, Alessia Coralli, Giorgio Annoni, Lucrezia De Feudis, V. Monti, Pietro Serra, Anna Maria Stanzial, Antonio Bonelli, Gianpaolo Reboldi, Francesco Paciullo, Ferdinando Massari, Graziana Lupattelli, Giorgio Sesti, Silvia Fargion, Angela Sciacqua, Giovanna Fabio, Silvia Di Carlo, Maria Grazia Serra, Emanuele Durante Mangoni, Salvatore Corrao, Maria Angela Becchi, Margherita Migone De Amicis, Francesco Gullo, Silvia Cappelli, Flora Peyvandi, Paolo Gallo, Chiara Mazzarelli, Daniela Calipari, Ferdinando Carlo Sasso, Carlo Cagnoni, Laura Carassale, Donatella Renna, Paola Loria, Davide Ghelfi, Alessandra Quercioli, Maria Teresa Guagnano, Luana Castoldi, Massimo Delfino, Cosimo Morabito, Giuseppe Musca, Francesca Turatto, Silvia Prolo, Lina Falanga, Michela Zanetti, Antonio Perciccante, Francesco Purrello, Marco Cicardi, Maria Beatrice Secchi, Mauro Tettamanti, Maria Rosaria Rizzo, Luigi Anastasio, C. Masala, Andrea Maria Maresca, Elena Silvestri, Domenico Prisco, Filippo Pedrazzoli, Marco Bertolotti, Guido De Marco, Giancarlo Traisci, Maria Carmela Carbone, Filippo Rossi Fanelli, Maria Valenti, Ilenia Pepe, Deborah Melis, Christian Bracco, Giorgio Maniscalco, Antonella Gallo, Daniela D'Angelo, Alfonso Iorio, Gianfranco Martucci, Tatiana Tonella, Ilaria Serio, Wu Sheng Chin, Michela Quagliolo, Cordischi Chiara, Andrea Sacco, Pietro Tizzani, Antonio Mammarella, Donatella Setti, Damiano Rizzoni, Lucia Gottardo, Olga Cuccurullo, Gino Roberto Corazza, Rinaldo Striuli, Elmo Mannarino, Guido Moreo, Luana Castiglioni, G. Vaudo, Teresa Salvatore, Maurizio Bicchi, Raffaella Rossio, Francesco Violi, Donatella Magalotti, Giuseppe Zuccalà, Luca Puccetti, Luigi Fenoglio, Daniela Tirotta, Alessandra Fiorentini, Oliviero Olivieri, Christian Folli, Alberto Buratti, Francesco Saverio Vella, Vincenzo Fontana, Giulia Grignani, Laura Gasbarrone, Sara Zazzetta, Antonio Brucato, Marco Zoli, Michele Cortellaro, Stella Provini, Claudio Borghi, Mario Barbagallo, Rodolfo Tassara, Sara Contini, Elisa Rebecca Rinaldi, Lidia Plances, Stefano Volpato, Alessandra Barreca, Ludovica Perri, Stefania Alborghetti, Chiara Valentina Luglio, Donatella Padula, Codjo Djignefa Djade, Maria Rachele Meroni, Mara Bulgheroni, Giuseppe Riccardo Centenaro, Chiara Bagnato, Salvatore Piro, Nicola Lucio Liberato, Luigi Bolondi, Franco Ricci, Annalisa Spalluti, Luciano Ottonello, Giordano Bernasconi, Antonio Picardi, Michela Carlon, Riccardo Utili, Maria Alice Ferri, Roberto Valenti, Francesca Veltri, Giorgio Menardo, Giuliana Micale, Maria Cristina Baroni, Piergiorgio Gaudenzi, Pallante Raffaele, Simona Sestili, Giuseppe Romanelli, Roberto De Giorgio, L. Rasciti, Franco Arturi, Marta Bovio, Alessandro Squizzato, Leonella Pasqualini, Pier Leopoldo Capecchi, Alfredo Postiglione, Maura Marcucci, Antonio Amoroso, Sarah Damanti, Lucia Sofia, E Mannarino, Francesca Perego, Silvia Caporotundo, Giuseppe Delitala, Gaetano Serviddio, Barbara Ferrari, Lorenzo Mauro Carozza, Raffaella Salmi, Giacomo Fera, Pier Mannuccio Mannucci, Daniela Mari, Pasquale Mansueto, Carlotta Franchi, Silvia Li Bassi, Luca Santi, Michele Quero, Graziella Bruno, Elsa Sferrazzo, Martino Bellusci, Sebastiana Atzori, Mauro Maurantonio, Mauro Bernardi, Maria Sole Lilleri, Maria Loreta Di Luca, Carlo Sabbà, Luigi Cricco, Mancuso G, Alessia Valentina Giraudo, Giovanni Battista Bianchi, Valentina Grasso, Chiara Mussi, Giovanni Murialdo, Chiara Brignone, Marco Pala, Marina Magenta, Franco Dallegri, Giuseppe Montrucchio, Pamela Rondelli, Carlo L. Balduini, P. M. Mannucci, Giampiero Benetti, Fabio Fabbian, Massimo Gunelli, Fabio Pignatti, Emanuela Miceli, Tiziana Tognin, Stefania Pugliese, Franco Laghi Pasini, Francesco Salerno, Alessandra Marengoni, Rosa Scipioni, A. Nobili, Maria Antonietta Bleve, Gianluca Casella, Francesca Meda, Elisabetta Greco, Antonio Gidaro Marina Magenta, Fabio Magrini, Elena Succurro, Emanuela Rizzioli, Valeria Raparelli, Susanna Gamberini, Caterina Pirali, Ligia J. Dominguez, Stefania Basili, Matteo Pirro, Luigi Calvo, Bartolomeo Lorenzati, Ranuccio Nuti, Francesco Perticone, Claudio Ferri, Giovanbattista Rini, Christian Molino, Stefano Carta, Marta Molaro, Francesco De Stefano, Maria Teresa Laieta, Annamaria Aquilino, Sabrina Giaquinto Ospedale, Gaetano Dentamaro, Martina Ruvio, Raffaele Landolfi, Renzo Rozzini, Mauro Serra, Giovanni Davì, Carlo Selmi, Renato Fellin, G. Lupattelli, Silvia Ghidoni, Marco Vincenzo Lenti, Alberto Auteri, Alessandro Giordano, Eleonora Sparacio, Marco Falcone, Roberto Fava, Anna Laura Pasqui, Giuseppe Palasciano, Daniela Di Pinto, Gianfranco Guarnieri, Rosa Lombardi, F. 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Savojardo, V, Folli, C, Magnini, M, Mari, D, Rossi, P, Damanti, S, Prolo, S, Lilleri, M, Micale, G, Podda, M, Selmi, C, Meda, F, Accordino, S, Conca, A, Monti, V, Corazza, G, Miceli, E, Lenti, M, Padula, D, Balduini, C, Bertolino, G, Provini, S, Quaglia, F, Murialdo, G, Bovio, M, Dallegri, F, Ottonello, L, Quercioli, A, Barreca, A, Secchi, M, Ghelfi, D, Chin, W, Carassale, L, Caporotundo, S, Anastasio, L, Sofia, L, Carbone, M, Traisci, G, De Feudis, L, Di Carlo, S, Davì, G, Guagnano, M, Sestili, S, Bergami, E, Rizzioli, E, Cagnoni, C, Bertone, L, Manucra, A, Buratti, A, Tognin, T, Liberato, N, Bernasconi, G, Nardo, B, Bianchi, G, Ospedale, S, Benetti, G, Quagliolo, M, Centenaro, G, Purrello, F, Di Pino, A, Piro, S, Mancuso, G, Calipari, D, Bartone, M, Gullo, F, Cortellaro, M, Magenta, M, Perego, F, Meroni, M, Cicardi, M, Magenta, A, Sacco, A, Bonelli, A, Dentamaro, G, Rozzini, R, Falanga, L, Giordano, A, Perin, P, Lorenzati, B, Gruden, G, Bruno, G, Montrucchio, G, Greco, E, Tizzani, P, Fera, G, Di Luca, M, Renna, D, Perciccante, A, Coralli, A, Tassara, R, Melis, D, Rebella, L, Menardo, G, Bottone, S, Sferrazzo, E, Ferri, C, Striuli, R, Scipioni, R, Salmi, R, Gaudenzi, P, Gamberini, S, Ricci, F, Morabito, C, Fava, R, Semplicini, A, Gottardo, L, Vendemiale, G, Serviddio, G, Forlano, R, Bolondi, L, Rasciti, L, Serio, I, Masala, C, Mammarella, A, Raparelli, V, Fanelli, F, Delfino, M, Amoroso, A, Violi, F, Basili, S, Perri, L, Serra, P, Fontana, V, Falcone, M, Landolfi, R, Grieco, A, Gallo, A, Zuccalà, G, Franceschi, F, De Marco, G, Chiara, C, Marta, S, Bellusci, M, Setti, D, Pedrazzoli, F, Romanelli, G, Pirali, C, Amolini, C, Rosei, E, Rizzoni, D, Castoldi, L, Picardi, A, Gentilucci, U, Mazzarelli, C, Gallo, P, Guasti, L, Castiglioni, L, Maresca, A, Squizzato, A, Contini, S, Molaro, M, Annoni, G, Corsi, M, Zazzetta, S, Bertolotti, M, Mussi, C, Scotto, R, Ferri, M, Veltri, F, Arturi, F, Succurro, E, Sesti, G, Gualtieri, U, Perticone, F, Sciacqua, A, Quero, M, Bagnato, C, Loria, P, Becchi, M, Martucci, G, Fantuzzi, A, Maurantonio, M, Corinaldesi, R, De Giorgio, R, Grasso, V, Ruggeri, E, Carozza, L, Pignatti, F, Reboldi, G, Vaudo, G, Pirro, M, Pasqualini, L, Mannucci, Pier Mannuccio, Nobili, Alessandro, Tettamanti, Mauro, Pasina, Luca, Franchi, Carlotta, Salerno, Francesco, Corrao, Salvatore, Marengoni, Alessandra, Iorio, Alfonso, Marcucci, Maura, Sparacio, Eleonora, Alborghetti, Stefania, Di Costanzo, Rosa, Djade, Codjo Djignefa, Prisco, Domenico, Silvestri, Elena, Cenci, Caterina, Barnini, Tommaso, Delitala, Giuseppe, Carta, Stefano, Atzori, Sebastiana, Guarnieri, Gianfranco, Zanetti, Michela, Spalluti, Annalisa, Serra, Maria Grazia, Bleve, Maria Antonietta, Vanoli, Massimo, Grignani, Giulia, Casella, Gianluca, Gasbarrone, Laura, Maniscalco, Giorgio, Gunelli, Massimo, Tirotta, Daniela, Brucato, Antonio, Ghidoni, Silvia, Di Corato, Paola, Bernardi, Mauro, Li Bassi, Silvia, Santi, Luca, Agnelli, Giancarlo, Marchesini, Emanuela, Mannarino, Elmo, Lupattelli, Graziana, Rondelli, Pamela, Paciullo, Francesco, Fabris, Fabrizio, Carlon, Michela, Turatto, Francesca, Baroni, Maria Cristina, Zardo, Marianna, Manfredini, Roberto, Molino, Christian, Pala, Marco, Fabbian, Fabio, Nuti, Ranuccio, Valenti, Roberto, Ruvio, Martina, Cappelli, Silvia, Paolisso, Giuseppe, Rizzo, Maria Rosaria, Laieta, Maria Teresa, Salvatore, Teresa, Sasso, Ferdinando Carlo, Utili, Riccardo, Mangoni, Emanuele Durante, Pinto, Daniela, Olivieri, Oliviero, Stanzial, Anna Maria, Fellin, Renato, Volpato, Stefano, Fotini, Siouli, Barbagallo, Mario, Dominguez, Ligia, Plances, Lidia, D'Angelo, Daniela, Rini, Giovanbattista, Mansueto, Pasquale, Pepe, Ilenia, Licata, Giuseppe, Calvo, Luigi, Valenti, Maria, Borghi, Claudio, Strocchi, Enrico, Rinaldi, Elisa Rebecca, Zoli, Marco, Fabbri, Elisa, Magalotti, Donatella, Auteri, Alberto, Pasqui, Anna Laura, Puccetti, Luca, Pasini, Franco Laghi, Capecchi, Pier Leopoldo, Bicchi, Maurizio, Sabbà, Carlo, Vella, Francesco Saverio, Marseglia, Alessandro, Luglio, Chiara Valentina, Palasciano, Giuseppe, Modeo, Maria Ester, Aquilino, Annamaria, Raffaele, Pallante, Pugliese, Stefania, Capobianco, Caterina, Postiglione, Alfredo, Barbella, Maria Rosaria, De Stefano, Francesco, Fenoglio, Luigi, Brignone, Chiara, Bracco, Christian, Giraudo, Alessia, Musca, Giuseppe, Cuccurullo, Olga, Cricco, Luigi, Fiorentini, Alessandra, Cappellini, Maria Domenica, Fabio, Giovanna, Seghezzi, Sonia, De Amicis, Margherita Migone, Fargion, Silvia, Bonara, Paola, Bulgheroni, Mara, Lombardi, Rosa, Magrini, Fabio, Massari, Ferdinando, Tonella, Tatiana, Peyvandi, Flora, Tedeschi, Alberto, Rossio, Raffaella, Moreo, Guido, Ferrari, Barbara, Roncari, Luisa, Monzani, Valter, Savojardo, Valeria, Folli, Christian, Magnini, Maria, Mari, Daniela, Rossi, Paolo Dionigi, Damanti, Sarah, Prolo, Silvia, Lilleri, Maria Sole, Micale, Giuliana, Podda, Mauro, Selmi, Carlo, Meda, Francesca, Accordino, Silvia, Conca, Alessio, Monti, Valentina, Corazza, Gino Roberto, Miceli, Emanuela, Lenti, Marco Vincenzo, Padula, Donatella, Balduini, Carlo L., Bertolino, Giampiera, Provini, Stella, Quaglia, Federica, Murialdo, Giovanni, Bovio, Marta, Dallegri, Franco, Ottonello, Luciano, Quercioli, Alessandra, Barreca, Alessandra, Secchi, Maria Beatrice, Ghelfi, Davide, Chin, Wu Sheng, Carassale, Laura, Caporotundo, Silvia, Anastasio, Luigi, Sofia, Lucia, Carbone, Maria, Traisci, Giancarlo, De Feudis, Lucrezia, Di Carlo, Silvia, Davì, Giovanni, Guagnano, Maria Teresa, Sestili, Simona, Bergami, Elisabetta, Rizzioli, Emanuela, Cagnoni, Carlo, Bertone, Luca, Manucra, Antonio, Buratti, Alberto, Tognin, Tiziana, Liberato, Nicola Lucio, Bernasconi, Giordano, Nardo, Barbara, Bianchi, Giovanni Battista, Ospedale, Sabrina Giaquinto, Benetti, Giampiero, Quagliolo, Michela, Centenaro, Giuseppe Riccardo, Purrello, Francesco, Di Pino, Antonino, Piro, Salvatore, Mancuso, Gerardo, Calipari, Daniela, Bartone, Mosè, Gullo, Francesco, Cortellaro, Michele, Magenta, Marina, Perego, Francesca, Meroni, Maria Rachele, Cicardi, Marco, Magenta, Antonio Gidaro Marina, Sacco, Andrea, Bonelli, Antonio, Dentamaro, Gaetano, Rozzini, Renzo, Falanga, Lina, Giordano, Alessandro, Perin, Paolo Cavallo, Lorenzati, Bartolomeo, Gruden, Gabriella, Bruno, Graziella, Montrucchio, Giuseppe, Greco, Elisabetta, Tizzani, Pietro, Fera, Giacomo, Di Luca, Maria Loreta, Renna, Donatella, Perciccante, Antonio, Coralli, Alessia, Tassara, Rodolfo, Melis, Deborah, Rebella, Lara, Menardo, Giorgio, Bottone, Stefania, Sferrazzo, Elsa, Ferri, Claudio, Striuli, Rinaldo, Scipioni, Rosa, Salmi, Raffaella, Gaudenzi, Piergiorgio, Gamberini, Susanna, Ricci, Franco, Morabito, Cosimo, Fava, Roberto, Semplicini, Andrea, Gottardo, Lucia, Vendemiale, Gianluigi, Serviddio, Gaetano, Forlano, Roberta, Bolondi, Luigi, Rasciti, Leonardo, Serio, Ilaria, Masala, Cesare, Mammarella, Antonio, Raparelli, Valeria, Fanelli, Filippo Rossi, Delfino, Massimo, Amoroso, Antonio, Violi, Francesco, Basili, Stefania, Perri, Ludovica, Serra, Pietro, Fontana, Vincenzo, Falcone, Marco, Landolfi, Raffaele, Grieco, Antonio, Gallo, Antonella, Zuccalà, Giuseppe, Franceschi, Francesco, De Marco, Guido, Chiara, Cordischi, Marta, Sabbatini, Bellusci, Martino, Setti, Donatella, Pedrazzoli, Filippo, Romanelli, Giuseppe, Pirali, Caterina, Amolini, Claudia, Rosei, Enrico Agabiti, Rizzoni, Damiano, Castoldi, Luana, Picardi, Antonio, Gentilucci, Umberto Vespasiani, Mazzarelli, Chiara, Gallo, Paolo, Guasti, Luigina, Castiglioni, Luana, Maresca, Andrea, Squizzato, Alessandro, Contini, Sara, Molaro, Marta, Annoni, Giorgio, Corsi, Maurizio, Zazzetta, Sara, Bertolotti, Marco, Mussi, Chiara, Scotto, Roberto, Ferri, Maria Alice, Veltri, Francesca, Arturi, Franco, Succurro, Elena, Sesti, Giorgio, Gualtieri, Umberto, Perticone, Francesco, Sciacqua, Angela, Quero, Michele, Bagnato, Chiara, Loria, Paola, Becchi, Maria Angela, Martucci, Gianfranco, Fantuzzi, Alessandra, Maurantonio, Mauro, Corinaldesi, Roberto, De Giorgio, Roberto, Serra, Mauro, Grasso, Valentina, Ruggeri, Eugenio, Carozza, Lorenzo Mauro, Pignatti, Fabio, Lupattelli, G., Reboldi, G., Paciullo, F., Vaudo, G., Pirro, M., Pasqualini, L., Nobili, A., Mannucci, P. M., Mannarino, E., Mannucci, PM, REPOSI, Investigators, Barbagallo, M, and Dominguez Rodríguez, LJ
Subjects: medicine.medical_specialty, Chronic kidney disease, Elderly, Heart failure, REPOSI, Gerontology, Geriatrics and Gerontology, Humans, Sleep Apnea Syndromes, Noninvasive Ventilation, Renal function, chronic kidney disease, elderly, registry, Tertiary care, Sleep Apnea Syndrome, Internal medicine, Epidemiology, medicine, business.industry, medicine.disease, Heart failure, Elderly, Chronic kidney disease, REPOSI, Icd codes, business, Clinical record, Body mass index, Kidney disease, Human
Abstract: Background: The aim of the present study was to evaluate the association between heart failure (HF) and chronic kidney disease (CKD) in tertiary care centers using the clinical records of patients enrolled in internal medicine departments.Patients and methods: We used the clinical records of 1380 elderly patients to identify patients with a history of HF and CKD using admission ICD codes and glomerular filtration rate (GFR) formulas. Magnitude and strength of such associations were investigated by univariable and multivariable analysis.Results: Of the 1380 patients enrolled, 27.9% had HF (age 80 ± 7, BMI 27 ± 6 kg/m2) and 17.4% CKD (age 81 ± 7, BMI 26.8 ± 6 kg/m2). Both groups were significantly older (P
Published: 2014

146. Tumor Necrosis Factor-alpha and Insulin-Like Growth Factor-1 Levels in Patients with Relapsing–Remitting Multiple Sclerosis Receiving Interferon-beta1a

Author: Giacomo Lus, Mario Fratta, Roberto Cotrufo, Giuseppina Di Biase, Giorgia Teresa Maniscalco, Lus, Giacomo, DI BIASE, G., Fratta, M., Maniscalco, G., and Cotrufo, R.
Subjects: Adult, Male, Insulin-Like Growth Factor-1, Multiple Sclerosis, Adolescent, medicine.medical_treatment, Immunology, Insulin-like growth factor, Interferon, Recurrence, Virology, medicine, Humans, In patient, Tumor Necrosis Factor-?, Insulin-Like Growth Factor I, Tumor necrosis factor α, Interferon β1a, Interferon-beta1a, business.industry, Tumor Necrosis Factor-alpha, Multiple sclerosis, Cell Biology, Middle Aged, medicine.disease, Magnetic Resonance Imaging, Relapsing remitting, Tumor necrosis factor alpha, Female, business, medicine.drug
Abstract: To examine the effect of high-dose interferon (IFN)-beta1a [44 microg administered subcutaneously (sc) 3 times weekly (tiw)] on tumor necrosis factor-alpha (TNF-alpha) and insulin-like growth factor-1 (IGF-1) levels in patients with relapsing-remitting multiple sclerosis (RRMS), and any correlation with clinical and magnetic resonance imaging (MRI) data. Previously treatment-naive patients with RRMS and an Expanded Disability Status Scale scoreor = 3.5 were enrolled. At baseline, monthly for the first 5 months, and then after 12 months of treatment with 44 microg sc tiw of IFN-beta1a, all patients underwent clinical examination, assessment of serum TNF-alpha and IGF-1 levels and baseline, 5th, and 12th months to MRI scanning. Mean TNF-alpha values decreased significantly from months 0 to 12 of the study (P = 0.003), but mean IGF-1 values showed a nonsignificant reduction (P = 0.265). Serum levels of TNF-alpha and IGF-1 were sometimes correlated throughout the study, but no significant interactions were observed between serum TNF-alpha or IGF-1 and clinical or MRI findings. A borderline significant trend toward higher basal TNF-alpha levels was found in patients who developed new T1 lesions at 12 months compared with those who did not (P = 0.057). Interferon-beta1a therapy may reduce serum TNF-alpha levels in patients with RRMS, without a clear correlation with disease activity.
Published: 2009

147. Validation of an iPad version of the Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS).

Author: Costabile T, Signoriello E, Lauro F, Altieri M, Ziello AR, D'Ambrosio A, Bisecco A, Maniscalco G, Bonavita S, Gallo A, Brescia Morra V, Lus G, Saccà F, and Russo CV
Subjects: Humans, Reproducibility of Results, Neuropsychological Tests, Cognition, Multiple Sclerosis complications, Multiple Sclerosis diagnosis, Multiple Sclerosis psychology, Cognitive Dysfunction diagnosis, Cognitive Dysfunction etiology
Abstract: Background: The Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) is the most widely used screening tool for cognitive impairment in Multiple Sclerosis (MS). However, the administration and scoring procedures of the paper version are time consuming and prone to errors. Aim of our study was to develop a tablet version of BICAMS (iBICAMS), and to assess its reliability compared to the paper version., Methods: We administered both BICAMS and iBICAMS to 139 MS patients in two different sessions. We compared scores on both versions using a paired t-test. We used a repeated measures ANOVA to test the impact of rater, order of administration and test-retest time on test-retest performances. We used the Intraclass Correlation Coefficient (ICC) to assess the reliability between BICAMS and iBICAMS., Results: All three sub-tests of the BICAMS (SDMT, CVLT-II and BVMT-R) were different between the paper and the tablet versions. Order of administration influenced test-retest performances at the SDMT (p<0.001), CVLT- II (p<0.001) and BVMT-R (p<0.001). Intraclass coefficient correlation (ICC) revealed a high level of agreement between the paper BICAMS and the iPad version for all three tests: SDMT (0.92), CVLT-II (0.83) and BVMT-R (0.82)., Conclusions: We found a high reliability between BICAMS and iBICAMS. Considering the inherent advantages of automated scoring, digital storage of data, standardized timing, the iBICAMS could become a standard in clinical practice., Competing Interests: Declaration of Competing Interest F.S. received public speaking honoraria from Alexion, Argenx, Biogen, Mylan, Novartis, Roche, Sanofi, Teva; he also received compensation for Advisory boards or consultation fees from Alexion, Almirall, Argenx, Avexis, Biogen, Forward Pharma, Lexeo Therapeutics, Merk, Novartis, Novatek, Roche, Sanofi, Takeda. The other authors report no conflict of interest., (Copyright © 2023. Published by Elsevier B.V.)
Published: 2023
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148. Patients with multiple sclerosis choose a collaborative role in making treatment decision: results from the Italian multicenter SWITCH study.

Author: Patti F, Chisari CG, Toscano S, Annovazzi P, Banfi P, Bergamaschi R, Clerici R, Conti MZ, Cortese A, Fantozzi R, Ferraro D, Fischetti M, Frigo M, Gatto M, Immovilli P, Leoni S, Malucchi S, Maniscalco G, Marfia GA, Paolicelli D, Perini P, Serrati C, Totaro R, Turano G, Valentino P, Zaffaroni M, Zuliani C, and Centonze D
Subjects: Humans, Female, Adult, Middle Aged, Male, Cross-Sectional Studies, Decision Making, Patient Preference, Italy, Multiple Sclerosis psychology
Abstract: Background: Clinicians are increasingly recognizing the importance of shared decision-making in complex treatment choices, highlighting the importance of the patient's rationale and motivation for switching therapies. This study aimed to evaluate the association between different modalities of changing multiple sclerosis (MS) treatments, cognitive profile and attitude and preferences of patients concerning treatment choice., Methods: This multicenter cross-sectional study was conducted at 28 Italian MS centers in the period between June 2016 and June 2017. We screened all MS patients treated with any DMT, with a treatment compliance of at least 80% of therapy administered during the 3 last months who needed to modify MS therapy because of efficacy, safety or other reasons during a follow-up visit. At the time of switching the symbol digit modalities test (SDMT) and the Control Preference Scale (CPS) were evaluated. According to the CPS, patients were classified as "active" (i.e. who prefer making the medical decision themselves), "collaborative" (i.e. who prefer decisions be made jointly with the physician), or "passive" (i.e. who prefer the physician make the decision)., Results: Out of 13,657 patients recorded in the log, 409 (3%) changed therapy. Of these, 336 (2.5%) patients, 69.6% were female and with mean age 40.6 ± 10.5 years, were enrolled. According to the CPS score evaluation, a significant high percentage of patients (51.1%) were considered collaborative, 74 patients (22.5%) were passive, and 60 (18.2%) patients were active. Stratifying according to CPS results, we found a higher SDMT score among collaborative patients compared to active and passive ones (45.8 ± 12.3 versus 41.0 ± 13.2 versus 41.7 ± 12.8, p < 0.05)., Conclusion: In this study, the CPS evaluation showed that more than 50% of patients who needed to change therapy chose a "collaborative" role in making treatment decision. Cognitive profile with SDMT seems to correlate with patients' preference on treatment decision, showing better scores in collaborative patients., Competing Interests: Declaration of Competing Interest Francesco Patti has received honoraria for speaking activities by Almirall, Bayer Schering, Biogen Idec, Merck Serono, Novartis, Roche, Sanofi Genzyme, and TEVA; he also served as advisory board member the following companies: Bayer Schering, Biogen Idec, Merck Serono, Novartis, Roche, Sanofi Genzyme, and TEVA; he was also funded by Pfizer and FISM for epidemiological studies; he received grants for congress participation from Almirall, Bayer Shering, Biogen Idec, Merck Serono, Novartis, Roche, Sanofi Genzyme, and TEVA. Clara G. Chisari has received grants for congress participation from Almirall, Biogen Idec, Merck Serono, Novartis, Roche, Sanofi Genzyme, and TEVA. Simona Toscano declares no conflict of interest. Pietro Annovazzi has received honoraria for lecturing and participation in advisory boards, and/or travel expenses for attending congresses and meetings from Almirall, Biogen Idec, Merck Serono, Mylan, Novartis, Roche, Sanofi Genzyme, and TEVA. Paola Banfi has received support for attendance to scientific meetings from Biogen Idec, Merck Serono, Novartis, and Sanofi Genzyme. Roberto Bergamaschi has received honoraria for lectures, travel and registration coverage for attending several national or international congresses or symposia from Almirall, Bayer Shering, Biogen Idec, Merck Serono, Novartis, Roche, Sanofi Aventis, Sanofi Genzyme, and TEVA. Raffaella Clerici has received speaker's honoraria, consulting fees, honoraria in advisory boards, support for attendance of scientific meetings from Meck Serono, Novartis, and Sanofi Genzyme. Marta Zaffira Conti declares there is no conflict of interest. Antonio Cortese has received speaker honoraria, travel grants, advisory boards member honoraria from Biogen Idec, Merck Serono, Novartis, Sanofi Genzyme, and TEVA. Roberta Fantozzi has received consulting fees and honoraria for advisory boards from Biogen Idec, Merck Serono, Novartis, Roche, and TEVA Diana Ferraro declares there is no conflict of interest. Mariano Fischetti declares there is no conflict of interest. Maura Frigo declares there is no conflict of interest. Maurizia Gatto declares there is no conflict of interest. Paolo Immovilli has received speaking honoraria, consulting fees, advisory board honoraria from Biogen Idec, Merck Serono, Novartis, Roche, Sanofi Genzyme, and TEVA. Stefania Leoni declares there is no conflict of interest. Simona Malucchi has received speaker's honoraria and consulting fees, honoraria in advisory boards from Biogen Idec, Merck Serono, Novartis, Sanofi Genzyme, and TEVA Giorgia Maniscalco has received honoraria for public speaking and advisory boards from Biogen, Novartis, and Merck Serono. Girolama Alessandra Marfia is an Advisory Board member of Biogen Idec, Sanofi Genzyme, Merck-Serono, Novartis, and TEVA, and received honoraria for speaking or consultation fees from Almirall, Bayer Schering, Biogen Idec, Merck Serono, Novartis, Sanofi-Genzyme, and TEVA. She is the principal investigator in clinical trials for Actelion, Biogen Idec, Merck Serono, Mitsubishi, Novartis, Roche, Sanofi-Genzyme, and TEVA Damiano Paolicelli has received honoraria for consultancy and/or speaking from Almirall, Bayer Shering, Biogen Idec, Merck Serono, Novartis, Roche, Sanofi Genzyme, and TEVA. Paola Perini has received speaker honoraria and consulting fees from Biogen, Merck Serono, Novartis, Roche, Sanofi Genzyme, and TEVA. Carlo Serrati declares no conflict of interest. Rocco Totaro has received speaker's honoraria, consulting fee, honoraria for advisory boards, support for attendance of scientific meetings from Alfa Wasserman, Biogen Idec, Merck Serono, Novartis, Roche, Sanofi genzyme, and TEVA. Gabriella Turano has received support for attendance to scientific meetings from Almirall, Biogen Idec, Merck Serono, Novartis, and Sanofi Genzyme. Paola Valentino has received speaker's honoraria and consulting fee, honoraria for advisory boards from Biogen Idec, Novartis, Merck Serono, Sanofi Genzyme, and TEVA. Mauro Zaffaroni has received honoraria for lecturing or participating for advisory boards or travel funding from Almirall, Biogen, Merck Serono, Novartis, Sanofi Genzyme, and TEVA. Cristina Zuliani has received speaker's honoraria and consulting fees, honoraria for advisory boards, support for attendance of scientific meetings from Almirall, Bayer Shering, Biogen Idec, Merck Serono, Novartis, Roche, Sanofi Genzyme, and TEVA. Diego Centonze is an Advisory Board member of Almirall, Bayer Schering, Biogen Idec, GW Pharmaceuticals, Merck Serono, Novartis, Roche, Sanofi Genzyme, and TEVA, and received honoraria for speaking or consultation fees from Almirall, Bayer Schering, Biogen, GW Pharmaceuticals, Merck Serono, Novartis, Roche, Sanofi-Genzyme, and TEVA. He is also the principal investigator in clinical trials for Bayer Schering, Biogen, Merck Serono, Mitsubishi, Novartis, Roche, Sanofi Genzyme, and TEVA. His preclinical and clinical research was supported by grants from Bayer Schering, Biogen Idec, Celgene, Merck Serono, Novartis, Roche, Sanofi Genzyme and TEVA., (Copyright © 2022. Published by Elsevier B.V.)
Published: 2023
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149. An unusual neurological presentation in a patient with primary hypereosinophilic syndrome.

Author: Spina E, Maniscalco GT, Petraroli A, Detoraki A, Servillo G, Ranieri A, De Mase A, Renna R, Candelaresi P, De Paulis A, and Andreone V
Subjects: Humans, Male, Middle Aged, Adrenal Cortex Hormones therapeutic use, Cytokines, Tyrosine, Low Back Pain, Hypereosinophilic Syndrome complications, Hypereosinophilic Syndrome diagnosis, Hypereosinophilic Syndrome drug therapy, Vasculitis drug therapy
Abstract: Hypereosinophilic syndromes are characterized by an increased number of blood eosinophils (usually more than 1.5 × 10 9 ) infiltrating tissues and causing organ damage through over-production of pro-inflammatory cytokines with heterogeneous clinical presentation. Here we present a case of a 47 years old male, with an unremarkable previous medical history, with a sudden onset of subungual hemorrhage and low back pain. Admitted for right arm weakness and vomiting, was raised the suspicion of acute cerebrovascular syndrome, but a brain CT scan with angiogram and perfusion sequences did not show any signs of early ischaemic lesions; conversely, lab tests revealed an increased peripheral eosinophil blood count. Clinical conditions rapidly worsened and a brain MRI showed multiple sub-acute ischaemic lesions compatible with vasculitis while EEG was in favor of widespread cortical distress. Diagnosis of the hypereosinophilic syndrome was made through peripheral blood smear and osteo-medullar biopsy, which showed a rich prevalence of eosinophils. The molecular biology testing showed FIP1L1-PDGRA gene mutation. Despite the prompt therapy beginning with intravenous corticosteroids and tyrosine-kinase inhibitors with normalization of cell blood count in a few days, the patient remained in minimal consciousness. When facing unusual symptoms onset (low back pain with weakness in one limb) and a highly impaired WBC not consistent with other courses (such as infections, vasculitis, allergies, and other diseases involving the immune system) clinicians should take into account the possibility of a hematological disorder and treat it as soon as possible to avoid a poor prognosis., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interests., (Copyright © 2022 Elsevier Inc. All rights reserved.)
Published: 2022
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150. Oral Cladribine in Patients who Change From First-Line Disease Modifying Treatments for Multiple Sclerosis: Protocol of a Prospective Effectiveness and Safety Study (CLAD CROSS).

Author: Tsivgoulis G, Deftereos S, Gobbi C, Gulowsen Celius E, Kulakowska A, Maniscalco G, Mendes I, and Grigoriadis N
Abstract: Background: Recently, the number of available disease modifying therapies for multiple sclerosis (MS) has increased. However, a proportion of patients treated with these agents continue to experience relapses and disease progression. Cladribine tablets, approved in 2017 for highly active relapsing MS, comprise a sparsely administered oral treatment which exerts its therapeutic effect through a reduction and subsequent repletion of the lymphocyte population., Purpose/study Sample: Here we describe the design of CLAD CROSS, a prospective, non-interventional, multicenter, Phase IV study in patients with a confirmed diagnosis of RRMS who switch from first-line disease modifying drugs (DMDs) to treatment with cladribine tablets in routine clinical practice. 242 adult patients will be recruited in 61 sites (6 countries) over 30 months and will be followed up for 2 years following prescription of cladribine tablets per the decision of the treating physicians., Research Design: The primary endpoint is the change in annualized relapse rate (ARR) between the 12-month pre-baseline period and over the 12-month period before end of study. Secondary endpoints are the percentage of patients with 6-month disability progression or improvement at the end of the study, measured by the Expanded Disability Status Scale, Timed 25 Foot Walk and 9-Hole Peg Test scales and quality of life, treatment satisfaction, and healthcare resource utilization, measured through the MSIS-29, TSQM 1.4, and EQ-5D-3L scales, respectively. MRI lesions will be compared in the exploratory setting between the 12-month pre-baseline period, baseline, and at years 1 and 2. Adverse events will be monitored throughout the study. Interim analyses are pre-planned when 30% and 60% of patients will complete the 12-month follow-up visit., Conclusions: CLAD CROSS will provide efficacy data on cladribine tablets, used as a follow-up treatment to first-line DMDs in the real-world setting, will further establish its safety profile and will collect information to support pharmacoeconomic studies., Competing Interests: Declaration of Conflicting Interests: SD in an employee of Merck AE, Greece. All remaining authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2022.)
Published: 2022
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