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231 results on '"Ferrarese, M"'

1. Outcome of treatment of MDR-TB or drug-resistant patients treated with bedaquiline and delamanid: Results from a large global cohort

Author

Koirala, S., Borisov, S., Danila, E., Mariandyshev, A., Shrestha, B., Lukhele, N., Dalcolmo, M., Shakya, S.R., Miliauskas, S., Kuksa, L., Manga, S., Aleksa, A., Denholm, J.T., Khadka, H.B., Skrahina, A., Diktanas, S., Ferrarese, M., Bruchfeld, J., Koleva, A., Piubello, A., Koirala, G.S., Udwadia, Z.F., Palmero, D.J., Munoz-Torrico, M., GC, R., Gualano, G., Grecu, V.I., Motta, I., Papavasileiou, A., Li, Y., Hoefsloot, W., Kunst, H., Mazza-Stalder, J., Payen, M.-C., Akkerman, O.W., Bernal, E., Manfrin, V., Matteelli, A., Mustafa Hamdan, H., Nieto Marcos, M., Cadiñanos Loidi, J., Cebrian Gallardo, J.J., Duarte, R., Escobar Salinas, N., Gomez Rosso, R., Laniado-Laborín, R., Martínez Robles, E., Quirós Fernandez, S., Rendon, A., Solovic, I., Tadolini, M., Viggiani, P., Belilovski, E., Boeree, M.J., Cai, Q., Davidavičienė, E., Forsman, L.D., De Los Rios, J., Drakšienė, J., Duga, A., Elamin, S.E., Filippov, A., Garcia, A., Gaudiesiute, I., Gavazova, B., Gayoso, R., Gruslys, V., Jonsson, J., Khimova, E., Madonsela, G., Magis-Escurra, C., Marchese, V., Matei, M., Moschos, C., Nakčerienė, B., Nicod, L., Palmieri, F., Pontarelli, A., Šmite, A., Souleymane, M.B., Vescovo, M., Zablockis, R., Zhurkin, D., Alffenaar, J.-W., Caminero, J.A., Codecasa, L.R., García-García, J.-M., Esposito, S., Saderi, L., Spanevello, A., Visca, D., Tiberi, S., Pontali, E., Centis, R., D'Ambrosio, L., van den Boom, M., Sotgiu, G., and Migliori, G.B.

Published
2021
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3. Translational readthrough at F8 nonsense variants in factor VIII B domain contributes to residual expression and lowers inhibitor association

Author

Testa, M, Lombardi, S, Bernardi, F, Ferrarese, M, Belvini, D, Radossi, P, Castaman, G, Pinotti, M, Branchini, A, Testa, Maria Francesca, Lombardi, Silvia, Bernardi, Francesco, Ferrarese, Mattia, Belvini, Donata, Radossi, Paolo, Castaman, Giancarlo, Pinotti, Mirko, Branchini, Alessio, Testa, M, Lombardi, S, Bernardi, F, Ferrarese, M, Belvini, D, Radossi, P, Castaman, G, Pinotti, M, Branchini, A, Testa, Maria Francesca, Lombardi, Silvia, Bernardi, Francesco, Ferrarese, Mattia, Belvini, Donata, Radossi, Paolo, Castaman, Giancarlo, Pinotti, Mirko, and Branchini, Alessio

Abstract

In hemophilia A, F8 nonsense variants, and particularly those affecting the large factor VIII (FVIII) B domain that is dispensable for coagulant activity, display lower association with replacement therapy-related anti-FVIII inhibitory antibodies as retrieved from multiple international databases. Since null genetic conditions favor inhibitor development, we hypothesized that translational readthrough over premature termination codons (PTC) may contribute to immune tolerance by producing full-length proteins through the insertion of amino acid subset(s). To quantitatively evaluate the readthrough output in vitro, we developed a very sensitive luciferase-based system to detect very low full-length FVIII synthesis from a wide panel (n=45; ~60% patients with PTC) of F8 nonsense variants. PTC not associated with inhibitors displayed higher readthrough-driven expression levels than inhibitor-associated PTC, a novel observation. Particularly, higher levels were detected for B-domain variants (n=20) than for variants in other domains (n=25). Studies on plasma from six hemophilia A patients with PTC, integrated by expression of the corresponding nonsense and readthrough-deriving missense variants, consistently revealed higher FVIII levels for B-domain variants. Only one B-domain PTC (Arg814*) was found among the highly represented PTC not sporadically associated with inhibitors, but with the lowest proportion of inhibitor cases (4 out of 57). These original insights into the molecular genetics of hemophilia A, and particularly into genotype-phenotype relationships related with disease treatment, demonstrate that B-domain features favor PTC readthrough output. This provides a potential molecular mechanism contributing to differential PTC-associated inhibitor occurrence, with translational implications for a novel, experimentally based classification of F8 nonsense variants.

Published
2023

5. Are all people with diabetes and cardiovascular risk factors or microvascular complications at very high risk? Findings from the Risk and Prevention Study

Author

Marzona, Irene, Avanzini, Fausto, Lucisano, Giuseppe, Tettamanti, Mauro, Baviera, Marta, Nicolucci, Antonio, Roncaglioni, Maria Carla, Tombesi, M., Tognoni, G., Massa, E., Marrocco, W., Micalella, M., Caimi, V., Longoni, P., Avanzini, F., Franzosi, M. G., Roncaglioni, M. C., Marzona, I., Baviera, M., Monesi, L., Pangrazzi, I., Barlera, S., Milani, V., Nicolis, E., Casola, C., Clerici, F., Palumbo, A., Sgaroni, G., Marchioli, R., Silletta, M. G., Pioggiarella, R., Scarano, M., Marfisi, R. M., Flamminio, A., Macino, L., Ferri, B., Pera, C., Polidoro, A., Abbatino, D., Acquati, M., Addorisio, G., Adinolfi, D., Adreani, L., Agistri, M. R., Agneta, A., Agnolio, M. L., Agostini, N., Agostino, G., Airò, A., Alaimo, N., Albano, M., Albano, N., Alecci, G., Alemanno, S., Alexanian, A., Alfarano, M., Alfè, L., Alonzo, N., Alvino, S., Ancora, A., Andiloro, S., Andreatta, E., Angeli, S., Angiari, F., Angilletti, V., Annicchiarico, C., Anzivino, M., Aprea, R., Aprile, A., Aprile, E., Aprile, I., Aprile, L., Armellani, V., Arnetoli, M., Aronica, A., Autiero, V., Bacca, G., Baccalaro, A. M., Bacci, M., Baglio, G., Bagnani, M., Baiano, A., Baldari, A., Ballarini, L., Banchi, G., Bandera, R., Bandini, F., Baratella, M., Barbieri, A., Barbieri Vita, A., Bardi, M., Barlocchi, M., Baron, P., Bartoli, M., Basile, A., Basile, F., Basile, S., Battaggia, A., Battaglia, A., Baù, A., Beconcini, G., Beggio, R., Belfiore, P. A., Belicchi, M., Bellamoli, S., Bellini, C., Bellomo, M., Benetollo, C., Benetti, R., Beretta, E., Bertalero, P., Bertaso, F. G., Bertolani, U., Bettelli, G., Biagiotti, G., Bianchi, S., Bianco, G., Biccari, F., Bigioli, F., Bindi, M., Bisanti, G., Bitetti, E. M., Blasetti, M. P., Blesi, F., Boato, V., Boga, S., Boidi, E., Boldrin, G., Bollati, A., Bolzan, L., Bolzonella, S., Bonardi, P., Bonato, G. B., Bonci, M., Bonfitto, G., Bonincontro, E., Boninsegna, F., Bonissone, D., Bono, L., Bonollo, E., Borghi, M., Borioli, N., Borsatto, M., Bosco, T., Bosisio Pioltelli, M., Botarelli, C., Botassis, S., Bottini, F., Bottos, C., Bova, G., Bova, V., Bozzani, A., Bozzetto, R. M., Braga, V. T., Braglia, M., Bramati, E., Brazzoli, C., Breglia, G., Brescia, A., Briganti, D., Brigato, G., Brocchi, A., Brosio, F. A., Bruni, E., Buscaglia, E., Bussini, M. D., Bussotti, A., Buzzaccarini, F., Buzzatti, A., Caccamo, G., Cacciavillani, C., Caggiano, G., Caimi, V., Calciano, F. P., Calderisi, M., Calienno, S., Caltagirone, P., Calzolari, I., Cammisa, M., Campanaro, M., Campanella, G. B., Campese, F., Canali, G., Candiani, D. E. L., Canepa, R., Canini, D., Canino, A., Cantoro, E. A., Capilupi, V., Capotosto, P., Cappelli, B., Capraro, G., Carafa, F. A., Carano, Q., Carcaterra, V., Carriero, D., Carrozzo, G., Cartanese, M., Casalena, M., Casarola, M., Caso, C., Casotto, M., Castaldi, F., Castegnaro, R., Castellani, G., Castri, S., Catalano, E., Catinello, N., Caturano, G., Cavallaro, R., Cavallo, A. M., Cavallo, G., Cavion, M. T., Cavirani, G., Cazzaniga, F., Cazzetta, D., Cecconi, V., Cefalo, A., Celebrano, M., Celora, A., Centonze, P., Cerati, D., Cesaretti, D., Checchia, G., Checchin, A., Cherubini, M., Chianese, L., Chiappa, A., Chiappa, M. V., Chiariello, G., Chiavini, G., Chicco, M., Chiumeo, F., Ciacciarelli, A., Ciaci, D., Ciancaglini, R., Cicale, C., Cicale, S., Cipolla, A., Ciruolo, A., Citeri, A. L., Citterio, G., Clerici, M., Coazzoli, E., Collecchia, G., Colletta, F., Colombo, I., Colorio, P., Coluccia, S., Comerio, M., Comoretto, P., Compagni, M., Conte, O., Contri, S., Contrisciani, A., Coppetti, T., Corasaniti, F., Corradi, M. T., Corsano, A., Corsini, A., Corti, N., Costantini, G., Costantino, A., Cotroneo, S., Cozzi, D., Cravello, M. G., Cristiano, E., Cucchi, R., Cusmai, L., D’Errico, G. B., D’Agostino, P., Dal Bianco, L., Dal Mutto, U., Dal Pozzo, G., Dallapiccola, P., Dallatorre, G., Dalle Molle, G., Dalloni, E., D’Aloiso, A., D’Amicis, G., Danese, R., Danieli, D., Danisi, G., D’Anna, M. A., Danti, G., D’Ascanio, S., Davidde, G., De Angeli, D., De Bastiani, R., De Battisti, A., De Bellis, A., De Berardinis, G., De Carlo, F., De Giorgi, D., De Gobbi, R., De Lorenzis, E., De Luca, P., De Martini, G., De Marzi, M., De Matteis, D., De Padova, S., De Polo, P., De Sabato, N., De Stefano, T., De Vita, M. T., De Vito, U., De Zolt, V., Debernardi, F., Del Carlo, A., Del Re, G., Del Zotti, F., D’Elia, R., Della Giovanna, P., Dell’Acqua, L., Dell’Orco, R. L., Demaria, G., Di Benedetto, M. G., Di Chiara, G., Di Corcia, V., Di Domizio, O., Di Donato, P., Di Donato, S., Di Fermo, G., Di Franco, M., Di Giovannantonio, G., Di Lascio, G., Di Lecce, G., Di Lorenzo, N., Di Maro, T., Di Mattia, Q., Di Michele, E., Di Modica, R. S., Di Murro, D., Di Noi, M. C., Di Paoli, V., Di Santi, M., Di Sanzo, A., Di Turi, C., Diazzi, A., Dileo, I., D’Ingianna, A. P., Dolci, A., Donà, G., Donato, C., Donato, P., Donini, A., Donna, M. E., Donvito, T. V., Esposito, L., Esposito, N., Evangelista, M., Faita, G., Falco, M., Falcone, D. A., Falorni, F., Fanciullacci, A., Fanton, L., Fasolo, L., Fassina, R., Fassone, A., Fatarella, P., Fedele, F., Fera, I., Fera, L., Ferioli, S., Ferlini, M. G., Ferlino, R., Ferrante, G., Ferrara, F. N., Ferrarese, M. F., Ferrari, G., Ferrari, O., Ferreri, A., Ferroni, M., Fezzi, G., Figaroli, C., Fina, M. G., Fioretta, A., Fiorucci, C., Firrincieli, R., Fischetti, M., Fischietti, G., Fiume, D. C., Flecchia, G., Forastiere, G., Fossati, B., Franceschi, P. L., Franchi, L., Franzoso, F., Frapporti, G., Frasca, G., Frisotti, A., Fumagalli, G., Fusco, D., Gabriele, P., Gabrieli, A., Gagliano, D., Galimberti, G., Galli, A., Gallicchio, N., Gallio, F., Gallipoli, T., Gallo, P., Galopin, T., Gambarelli, L., Garbin, A., Garozzo, G. M., Gasparri, R., Gastaldo, M., Gatti, E., Gazzaniga, P., Gennachi, N., Gentile, R. V., Germani, P., Gesualdi, F., Gherardi, E., Ghezzi, C., Ghidini, M. G., Ghionda, F., Giacci, L., Gialdini, D., Giampaolo, C., Giancane, R., Giannanti, A., Giannese, S., Giannini, L., Giaretta, M., Giaretta, R., Giavardi, L., Giordano, P., Giordano, E., Giordano, B., Gioria, G. M., Giugliano, R., Grassi, E. A., Greco, A., Greco, L., Grilletti, N., Grimaldi, N., Grisetti, G., Groppelli, G., Gualtieri, L., Guarducci, M., Guastella, G., Guerra, M., Guerrini, F., Guglielmini, A., Guido, A., Gulotta, P., Iacono, E., Iadarola, G., Ianiro, G., Iarussi, V., Ieluzzi, M. L., Ierardi, C., Ingaldi, F., Interlandi, S., Iocca, M., Iorno, A., Ioverno, E., Iurato, R., La Pace, L., La Piscopia, C., La Selva, R., Lafratta, M., Lamparelli, M., Lanaro, G., Lancerotto, R., Larcher, M., Lassandro, M., Lattuada, G., Laurino, P., Lefons, C., Legrottaglie, F., Lemma, A., Leone, D., Leone, F., Leso, A., Leuzzi, G., Levato, G., Libardi, L., Libralesso, N., Licini, P. I., Licursi, G., Lidonnici, F., Lillo, C., Liveri, L., Livio, A., Loiero, R. A., Loison, M., Lombardo, G., Lombardo, T., Lomunno, V., Lomuscio, S., Lonedo, A., Longo, E., Longoni, P., Lora, L., Lotterio, A., Lucatello, L., Luongo, A., Lupoli, M., Macchia, C., Macri, G., Mafessanti, M., Maggialetti, V., Maggioni, A., Magnani, M., Maiellaro, G., Mancuso, A., Maniglio, A. R., Mannari, G. L., Manni, A., Manocchio, B., Mao, M., Maranò, A., Maraone, E., Marascio, D., Marcheselli, P., Marchetto, B., Marchetto, S., Marchi, A., Marchi, G. L., Mariano, C., Marinacci, S., Marinelli, S., Marini, G., Marra, V. C., Marrali, F., Marseglia, C., Martello, G., Martino, C., Martino, G., Martino, M., Marulli, C. F., Maruzzi, G., Marzotti, A., Mascheroni, G., Mascolo, P., Masoch, G., Masone, R., Massa, E., Massa, L., Massafra, M., Massi, M., Massignani, D. M., Matarese, A. M., Matini, G., Mauro, R., Mazzi, M., Mazzillo, A., Mazzocato, E., Mazzoleni, N. S., Mazzone, A., Melacci, A., Mele, E., Meliota, P., Menaspà, S., Meneghello, F., Merola, G., Merone, L., Metrucci, A., Mezzina, V., Micchi, A., Michielon, A., Migliore, N., Minero, G., Minotta, F., Mirandola, C., Mistrorigo, S., Modafferi, L., Moitre, R., Mola, E., Monachese, C., Mongiardini, C., Montagna, F., Montani, M., Montemurno, I., Montolli, R., Montorsi, S., Montresor, M., Monzani, M. G., Morabito, F., Mori, G., Moro, A., Mosca, M. F., Motti, F., Muddolon, L., Mugnai, M., Muscas, F., Naimoli, F., Nanci, G., Nargi, E., Nasorri, R., Nastrini, G., Negossi, M., Negrini, A., Negroni, A., Neola, V., Niccolini, F., Niro, C. M., Nosengo, C., Novella, G., Nuti, C., Obici, F., Olita, C., Oliverio, S. S., Olivieri, I., Oriente, S., Orlando, G., Paci, C., Pagano, G., Pagliara, C., Paita, G., Paladini, G., Paladino, G., Palano, T., Palatella, A., Palermo, P., Palmisano, M., Pando, P., Panessa, P., Panigo, F., Panozzo, G., Panvini, F., Panzieri, F., Panzino, A., Panzitta, F., Paoli, N., Papagna, R., Papaleo, M. G., Papalia, G., Parisi, R., Parotti, N., Parravicini, D., Passarella, P., Pastore, G. A., Patafio, M., Pavone, P., Pedroli, W., Pedroni, M., Pelligra, G., Pellizzari, M., Penati, A., Perlot, M., Perrone, A., Perrone, G., Peruzzi, P., Peselli, C., Petracchini, L., Petrera, L., Petrone, S., Peverelli, C., Pianorsi, F., Piazza, G. P., Piazzolla, G., Picci, A., Pienabarca, G., Pietronigro, T. P., Pignocchino, P., Pilone, R., Pinto, D., Pirovano, E., Pirrotta, D., Pisante, V., Pitotto, P., Pittari, L., Piva, A., Pizzoglio, A., Plantera, O. R., Plebani, W., Plessi, S., Podrecca, D., Poerio, V., Poggiani, F., Pogliani, W., Poli, L., Poloni, F. G., Porcelli, R., Porto, S., Pranzo, L., Prevedello, C., Profeta, C., Profico, D., Punzi, A., Quaglia, G. M., Racano, M., Raccone, A., Radice, F., Raho, C. A., Raimondi, R., Rainò, M., Ramponi, R., Ramunni, A., Ramunni, A. L., Ravasio, F., Ravera, M., Re Sartò, G., Rebustello, G., Regazzoli, S., Restelli, C., Rezzonico, M., Ricchiuto, F., Rigo, S., Rigon, G., Rigon, R., Rinaldi, O. V., Rinaldi, M., Risplendente, P. G., Rispoli, M., Riundi, R., Riva, M. G., Rizzi, A. L., Rizzi, D., Rizzo, L. D., Rocchi, L., Rondinone, B., Rosa, B., Rosati, F., Roselli, F., Rossetti, A., Rossetti, C., Rossi, R., Rossi, P. R., Rossi, A., Rossi, C. L., Rossitto, A., Ruffini, R., Ruffo, A., Ruggio, S., Ruo, M., Russo, B., Russo, L., Russo, R., Russo, S., Russo, U., Russo, V., Ruta, G., Sacchi, F., Sacco Botto, F., Saia, A., Salladini, G., Salmoiraghi, S., Saluzzo, F., Salvatore, C., Salvatori, E., Salvio, G., Sandri, P., Sandrini, T., Sangermano, V., Santoni, N., Saracino, A. D., Saracino, A., Sarasin, P., Sardo Infirri, C., Sarrì, B., Sartori, G., Sartori, N., Sauro, C., Scaglioni, M., Scalfi, C., Scamardella, A. M., Scandale, G., Scandone, L., Scannavini, G., Scarati, R., Scardi, A., Scarpa, F. M., Scazzi, P., Schifone, A., Schiroso, G., Scigliano, G., Scilla, A., Sciortino, M., Scolaro, G., Scollo, E., Scorretti, G., Sellitti, R., Selmo, A., Selvaggio, G., Sempio, A., Seren, F., Serio, L., Serra, C., Serra, L., Siciliano, D., Sideri, A., Sighele, M., Signore, R., Siliberto, F., Silvestro, M., Simioni, G., Simmini, G., Simonato, L., Sinchetto, F., Sizzano, E., Smajato, G., Smaldone, M., Sola, G., Sordillo, L., Sovran, C. S., Spagnul, P., Spanò, F., Sproviero, S., Squintani, A., Stella, L., Stilo, V., Stocchiero, B., Stornello, M. C., Stracka, G., Strada, S., Stranieri, G., Stucci, N., Stufano, N., Suppa, A., Susca, V. G., Sutti, M., Taddei, M., Tagliabue, E., Tagliente, G., Talato, F., Talerico, P., Talia, R., Taranto, R., Tartaglia, M., Tauro, N., Tedesco, A., Tieri, P., Tirelli, M., Tocci, L., Todesco, P., Tognolo, M., Tomba, A., Tonello, P., Tonon, R., Toscano, L., Tosi, A., Tosi, G., Toso, S., Travaglio, P., Tremul, L., Tresso, C., Triacchini, P., Triggiano, L., Trigilio, A., Trimeloni, J., Tripicchio, G., Tritto, G. S., Trono, F., Trotta, E., Trotta, G., Tubertini, A., Turri, C., Turri, L., Tuttolani, M. P., Urago, M., Ursini, G., Valcanover, F., Valente, L., Valenti, M., Valentini, F., Vallone, G., Valz, P., Valzano, L., Vanin, V., Vatteroni, M., Vegetti, L., Vendrame, D., Veramonti, I., Veronelli, G., Vesco, A., Vicariotto, G., Vignale, G., Villa, P. L., Vinciguerra, R., Visco, A., Visentin, G., Visonà, E., Vitali, E., Vitali, S., Vitti, F., Volpone, D. A., Zambon, N., Zammarrelli, A., Zanaboni, A., Zane, D., Zanetti, B., Zanibellato, R., Zappetti, M., Zappone, P., Zerilli, G., Zirino, V., Zoccali, R., Zuin, F., Altomonte, M., Anelli, N., Angiò, F., Annale, P., Antonacci, S., Anzilotta, R., Bano, F., Basadonna, O., Beduschi, L., Becagli, P., Bellotti, G., Blotta, C., Bruno, G., Cappuccini, A., Caramatti, S., Cariolato, M. P., Castellana, M., Castellani, L., Catania, R., Chielli, A., Chinellato, A., Ciaccia, A., Clerici, E., Cocci, A., Costanzo, G., D’Ercole, F., De Stefano, G., Decè, F., Di Cicco, N., Di Marco, A., Donati Sarti, C., Draghi, E., Dusi, G., Esposito, V., Ferraro, L., Ferretti, A., Ferri, E., Foggetti, L., Foglia, A., Fonzi, E., Frau, G., Fuoco, M. R., Furci, G., Gallo, L., Garra, V., Giannini, A., Gris, A., Iacovino, R., Interrigi, R., Joppi, R., Laner, B., La Fortezza, G., La Padula, A., Lista, M. R., Lupi, G., Maffei, D., Maggioni, G., Magnani, L., Marrazzo, E., Marcon, L., Marinò, V., Maroni, A., Martinelli, C., Mastandrea, E., Mastropierro, F., Meo, A. T., Mero, P., Minesso, E., Moschetta, V., Mosele, E., Nanni, C., Negretti, A., Nisticò, C., Orsini, A., Osti, M., Pacilli, M. C., Pennestre, C., Picerno, G., Piol, K., Pivano, L., Pizzuti, E., Poggi, L., Poidomani, I., Pozzetto, M., Presti, M. L., Ravani, R., Recalenda, V., Romagnuolo, F., Rossignoli, S., Rossin, E., Sabatella, C., Sacco, F., Sanità, F., Sansone, E., Servadei, F., Sisto, M. T., Sorio, A., Sorrentino, A., Spinelli, E., Spolaor, A., Squillacioti, A., Stella, P., Talerico, A., Todisco, C., Vadino, M., Zuliani, C., and Risk & Prevention Collaborative Group

Published
2017
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7. Fusion of engineered albumin with factor IX Padua extends half-life and improves coagulant activity

Author

Lombardi, S, Aaen, K, Nilsen, J, Ferrarese, M, Gjølberg, T, Bernardi, F, Pinotti, M, Andersen, J, Branchini, A, Lombardi S., Aaen K. H., Nilsen J., Ferrarese M., Gjølberg T. T., Bernardi F., Pinotti M., Andersen J. T., Branchini A., Lombardi, S, Aaen, K, Nilsen, J, Ferrarese, M, Gjølberg, T, Bernardi, F, Pinotti, M, Andersen, J, Branchini, A, Lombardi S., Aaen K. H., Nilsen J., Ferrarese M., Gjølberg T. T., Bernardi F., Pinotti M., Andersen J. T., and Branchini A.

Abstract

The short half-life of coagulation factor IX (FIX) for haemophilia B (HB) therapy has been prolonged through fusion with human serum albumin (HSA), which drives the neonatal Fc receptor (FcRn)-mediated recycling of the chimera. However, patients would greatly benefit from further FIX-HSA half-life extension. In the present study, we designed a FIX-HSA variant through the engineering of both fusion partners. First, we developed a novel cleavable linker combining the two FIX activation sites, which resulted in improved HSA release. Second, insertion of the FIX R338L (Padua) substitution conferred hyperactive features (sevenfold higher specific activity) as for FIX Padua alone. Furthermore, we exploited an engineered HSA (QMP), which conferred enhanced human (h)FcRn binding [dissociation constant (KD) 0·5 nM] over wild-type FIX-HSA (KD 164·4 nM). In hFcRn transgenic mice, Padua-QMP displayed a significantly prolonged half-life (2·7 days, P < 0·0001) versus FIX-HSA (1 day). Overall, we developed a novel FIX-HSA protein with improved activity and extended half-life. These combined properties may result in a prolonged functional profile above the therapeutic threshold, and thus in a potentially widened therapeutic window able to improve HB therapy. This rational engineering of both partners may pave the way for new fusion strategies for the design of engineered biotherapeutics.

Published
2021

9. An exon-specific small nuclear u1 rna (Exspeu1) improves hepatic otc expression in a splicing-defective spf /ash mouse model of ornithine transcarbamylase deficiency

Author

Balestra, D, Ferrarese, M, Lombardi, S, Ziliotto, N, Branchini, A, Petersen, N, Bosma, P, Pinotti, M, van de Graaf, S, Balestra D., Ferrarese M., Lombardi S., Ziliotto N., Branchini A., Petersen N., Bosma P., Pinotti M., van de Graaf S. F. J., Balestra, D, Ferrarese, M, Lombardi, S, Ziliotto, N, Branchini, A, Petersen, N, Bosma, P, Pinotti, M, van de Graaf, S, Balestra D., Ferrarese M., Lombardi S., Ziliotto N., Branchini A., Petersen N., Bosma P., Pinotti M., and van de Graaf S. F. J.

Abstract

OTC splicing mutations are generally associated with the severest and early disease onset of ornithine transcarbamylase deficiency (OTCD), the most common urea cycle disorder. Noticeably, splicing defects can be rescued by spliceosomal U1snRNA variants, which showed their efficacy in cellular and animal models. Here, we challenged an U1snRNA variant in the OTCD mouse model (spf /ash) carrying the mutation c.386G > A (p.R129H), also reported in OTCD patients. It is known that the R129H change does not impair protein function but affects pre-mRNA splicing since it is located within the 5′ splice site. Through in vitro studies, we identified an Exon Specific U1snRNA (ExSpeU1O3 ) that targets an intronic region downstream of the defective exon 4 and rescues exon inclusion. The adeno-associated virus (AAV8)-mediated delivery of the ExSpeU1O3 to mouse hepatocytes, although in the presence of a modest transduction efficiency, led to increased levels of correct OTC transcripts (from 6.1 ± 1.4% to 17.2 ± 4.5%, p = 0.0033). Consistently, this resulted in increased liver expression of OTC protein, as demonstrated by Western blotting (~3 fold increase) and immunostaining. Altogether data provide the early proof-of-principle of the efficacy of ExSpeU1 in the spf /ash mouse model and encourage further studies to assess the potential of RNA therapeutics for OTCD caused by aberrant splicing.

Published
2020

10. An engineered human albumin enhances half-life and transmucosal delivery when fused to protein-based biologics

Author

Bern, M, Nilsen, J, Ferrarese, M, Sand, K, Gjolberg, T, Lode, H, Davidson, R, Camire, R, Baekkevold, E, Foss, S, Grevys, A, Dalhus, B, Wilson, J, Hoydahl, L, Christianson, G, Roopenian, D, Schlothauer, T, Michaelsen, T, Moe, M, Lombardi, S, Pinotti, M, Sandlie, I, Branchini, A, Andersen, J, Bern M., Nilsen J., Ferrarese M., Sand K. M. K., Gjolberg T. T., Lode H. E., Davidson R. J., Camire R. M., Baekkevold E. S., Foss S., Grevys A., Dalhus B., Wilson J., Hoydahl L. S., Christianson G. J., Roopenian D. C., Schlothauer T., Michaelsen T. E., Moe M. C., Lombardi S., Pinotti M., Sandlie I., Branchini A., Andersen J. T., Bern, M, Nilsen, J, Ferrarese, M, Sand, K, Gjolberg, T, Lode, H, Davidson, R, Camire, R, Baekkevold, E, Foss, S, Grevys, A, Dalhus, B, Wilson, J, Hoydahl, L, Christianson, G, Roopenian, D, Schlothauer, T, Michaelsen, T, Moe, M, Lombardi, S, Pinotti, M, Sandlie, I, Branchini, A, Andersen, J, Bern M., Nilsen J., Ferrarese M., Sand K. M. K., Gjolberg T. T., Lode H. E., Davidson R. J., Camire R. M., Baekkevold E. S., Foss S., Grevys A., Dalhus B., Wilson J., Hoydahl L. S., Christianson G. J., Roopenian D. C., Schlothauer T., Michaelsen T. E., Moe M. C., Lombardi S., Pinotti M., Sandlie I., Branchini A., and Andersen J. T.

Abstract

Needle-free uptake across mucosal barriers is a preferred route for delivery of biologics, but the efficiency of unassisted transmucosal transport is poor. To make administration and therapy efficient and convenient, strategies for the delivery of biologics must enhance both transcellular delivery and plasma half-life. We found that human albumin was transcytosed efficiently across polarized human epithelial cells by a mechanism that depends on the neonatal Fc receptor (FcRn). FcRn also transported immunoglobulin G, but twofold less than albumin. We therefore designed a human albumin variant, E505Q/T527M/K573P (QMP), with improved FcRn binding, resulting in enhanced transcellular transport upon intranasal delivery and extended plasma half-life of albumin in transgenic mice expressing human FcRn. When QMP was fused to recombinant activated coagulation factor VII, the half-life of the fusion molecule increased 3.6-fold compared with the wild-type human albumin fusion, without compromising the therapeutic properties of activated factor VII. Our findings highlight QMP as a suitable carrier of protein-based biologics that may enhance plasma half-life and delivery across mucosal barriers.

Published
2020

11. Long-term Immune Response to SARS-CoV-2 Infection among Children and Adults after Mild Infection

Author

Di Chiara, C, Cantarutti, A, Costenaro, P, Donà, D, Bonfante, F, Cosma, C, Ferrarese, M, Cozzani, S, Raffaella Petrara, M, Carmona, F, Liberati, C, Palma, P, Di Salvo, G, De Rossi, A, Plebani, M, Padoan, A, Giaquinto, C, Di Chiara, C, Cantarutti, A, Costenaro, P, Donà, D, Bonfante, F, Cosma, C, Ferrarese, M, Cozzani, S, Raffaella Petrara, M, Carmona, F, Liberati, C, Palma, P, Di Salvo, G, De Rossi, A, Plebani, M, Padoan, A, and Giaquinto, C

Abstract

Importance: Understanding the long-term immune response against SARS-CoV-2 infection in children is crucial to optimize vaccination strategies. Although it is known that SARS-CoV-2 antibodies may persist in adults 12 months after infection, data are limited in the pediatric population. Objective: To examine long-term anti-SARS-CoV-2 spike receptor-binding domain (S-RBD) IgG kinetics in children after SARS-CoV-2 infection. Design, Setting, and Participants: In this single-center, prospective cohort study, patients were enrolled consecutively from April 1, 2020, to August 31, 2021, at the COVID-19 Family Cluster Follow-up Clinic, Department of Women's and Children's Health, University Hospital of Padua. A cohort of 252 COVID-19 family clusters underwent serologic follow-up at 1 to 4, 5 to 10, and more than 10 months after infection with quantification of anti-S-RBD IgG by chemiluminescent immunoassay. Exposures: SARS-CoV-2 infection. Results: Among 902 study participants, 697 had confirmed SARS-CoV-2 infection, including 351 children or older siblings (mean [SD] age, 8.6 [5.1] years) and 346 parents (mean [SD] age, 42.5 [7.1] years). Among 697 cases, 674 (96.7%) were asymptomatic or mild. Children had significantly higher S-RBD IgG titers than older patients across all follow-up time points, with an overall median S-RBD IgG titer in patients younger than 3 years 5-fold higher than adults (304.8 [IQR, 139.0-516.6] kBAU/L vs 55.6 [24.2-136.0] kBAU/L, P <.001). Longitudinal analysis of 56 study participants sampled at least twice during follow-up demonstrated the persistence of antibodies up to 10 months from infection in all age classes, despite a progressive decline over time. Conclusions and Relevance: In this cohort study of Italian children and adults following SARS-CoV-2 infection different kinetics of SARS-CoV-2 antibodies were found across several age classes of individuals with asymptomatic or mild COVID-19, which could help in optimizing COVID-19 vaccination

Published
2022

12. How to improve TB outpatient service in a TB low-endemic country during SARS-CoV-2 pandemic

Author

Riccardi, N., Rodari, P., Duranti, S., Villa, S., Assante, L. R., Castellotti, P., Ferrarese, M., Martini, M., Zuppini, T., Tessari, R., Calza, C., Codecasa, L., Besozzi, G., and Angheben, A.

Subjects
Ethics, TB-care, SARS-CoV-2, Antitubercular Agents, COVID-19, Italy, Medical ethics, Outpatient care, Tuberculosis, Ambulatory Care, Ethics, Medical, Humans, Outpatient Clinics, Hospital, Pandemics, Telemedicine, Hospital, Medical, Outpatient Clinics, Research Article
Abstract

Summary Despite notable progresses in the recent decades, tuberculosis (TB) continues to remain a public health concern even in Europe. TB prevention and care should be people-centred, improving ambulatory models across countries, in order to expand access to diagnosis and treatment for both TB infection and disease. Even more, during emergencies such as the current pandemic, when seeking of TB care has been replaced by the fear of coronavirus disease 2019 (COVID-19), TB patient’s care is fundamental. In this short communication, we document how was possible to implement a TB outpatient service meanwhile a local outbreak of SARS-CoV-2 transmission was ongoing.

Published
2021

13. The carboxyl-terminal region of human coagulation factor X as a natural linker for fusion strategies

Author

Ferrarese, M, Pignani, S, Lombardi, S, Balestra, D, Bernardi, F, Pinotti, M, Branchini, A, Ferrarese M., Pignani S., Lombardi S., Balestra D., Bernardi F., Pinotti M., Branchini A., Ferrarese, M, Pignani, S, Lombardi, S, Balestra, D, Bernardi, F, Pinotti, M, Branchini, A, Ferrarese M., Pignani S., Lombardi S., Balestra D., Bernardi F., Pinotti M., and Branchini A.

Abstract

Fusion with human serum albumin (HSA), which represents a well-established technique to extend half-life of therapeutic proteins, commonly exploits intervening peptide linkers as key components. Here, we explored the human coagulation factor X (FX) carboxyl-terminal region, previously demonstrated by us to be dispensable for secretion and coagulant activity, as a natural linker for fusion purposes. To test our hypothesis, we compared direct FX-HSA fusion with the designed FX-HSA fusion proteins mimicking the recombinant activated factor VII (rFVIIa)-HSA or factor IX (FIX)-HSA chimeras, both strongly dependent from artificial linkers. Three constructs were produced by direct tandem fusion (FX-HSA) and through flexible (glycine/serine; FX-GS-HSA, mimicking rFVIIa-HSA) or cleavable (incorporating the FX activation site; FX-CL-HSA, mimicking FIX-HSA) linkers. The FX-HSA was efficiently secreted and displayed prolonged plasma persistence in mice. All chimeras possessed remarkable pro-coagulant activity, comparable to FX for FX-HSA (88.7 ± 6.0%) and FX-CL-HSA (98.0 ± 16.4%) or reduced for FX-GS-HSA (55.8 ± 5.4%). Upon incubation with activators, FX-HSA and FX-CL-HSA displayed a correct activation profile while the FX-GS-HSA activation was slightly defective. In fluorogenic-based assays, FX-HSA showed normal activity over time and a specific amidolytic activity (1.0 ± 0.12) comparable to that of FX. Overall, the FX-HSA features indicate that the FX carboxyl-terminal region represents an intrinsic sequence allowing direct tandem fusion. Our results provide the first experimental evidence for i) a coagulation factor fusion protein with biological properties independent from artificial linkers, ii) the suitability of FX carboxyl-terminal region as a natural linker for fusion purposes.

Published
2019

15. Outcome of treatment of MDR-TB or drug-resistant patients treated with bedaquiline and delamanid: Results from a large global cohort

Author

Koirala, S, Borisov, S, Danila, E, Mariandyshev, A, Shrestha, B, Lukhele, N, Dalcolmo, M, Shakya, SR, Miliauskas, S, Kuksa, L, Manga, S, Aleksa, A, Denholm, JT, Khadka, HB, Skrahina, A, Diktanas, S, Ferrarese, M, Bruchfeld, J, Koleva, A, Piubello, A, Koirala, GS, Udwadia, ZF, Palmero, DJ, Munoz-Torrico, M, Gc, R, Gualano, G, Grecu, V, Motta, I, Papavasileiou, A, Li, Y, Hoefsloot, W, Kunst, H, Mazza-Stalder, J, Payen, M-C, Akkerman, OW, Bernal, E, Manfrin, V, Matteelli, A, Hamdan, HM, Marcos, MN, Cadinanos Loidi, J, Cebrian Gallardo, JJ, Duarte, R, Escobar Salinas, N, Gomez Rosso, R, Laniado-Laborin, R, Martinez Robles, E, Quiros Fernandez, S, Rendon, A, Solovic, I, Tadolini, M, Viggiani, P, Belilovski, E, Boeree, MJ, Cai, Q, Davidaviciene, E, Forsman, LD, De Los Rios, J, Draksiene, J, Duga, A, Elamin, SE, Filippov, A, Garcia, A, Gaudiesiute, I, Gavazova, B, Gayoso, R, Gruslys, V, Jonsson, J, Khimova, E, Madonsela, G, Magis-Escurra, C, Marchese, V, Matei, M, Moschos, C, Nakceriene, B, Nicod, L, Palmieri, F, Pontarelli, A, Smite, A, Souleymane, MB, Vescovo, M, Zablockis, R, Zhurkin, D, Alffenaar, J-W, Caminero, JA, Codecasa, LR, Garcia-Garcia, J-M, Esposito, S, Saderi, L, Spanevello, A, Visca, D, Tiberi, S, Pontali, E, Centis, R, D'Ambrosio, L, van den Boom, M, Sotgiuw, G, Migliori, GB, Koirala, S, Borisov, S, Danila, E, Mariandyshev, A, Shrestha, B, Lukhele, N, Dalcolmo, M, Shakya, SR, Miliauskas, S, Kuksa, L, Manga, S, Aleksa, A, Denholm, JT, Khadka, HB, Skrahina, A, Diktanas, S, Ferrarese, M, Bruchfeld, J, Koleva, A, Piubello, A, Koirala, GS, Udwadia, ZF, Palmero, DJ, Munoz-Torrico, M, Gc, R, Gualano, G, Grecu, V, Motta, I, Papavasileiou, A, Li, Y, Hoefsloot, W, Kunst, H, Mazza-Stalder, J, Payen, M-C, Akkerman, OW, Bernal, E, Manfrin, V, Matteelli, A, Hamdan, HM, Marcos, MN, Cadinanos Loidi, J, Cebrian Gallardo, JJ, Duarte, R, Escobar Salinas, N, Gomez Rosso, R, Laniado-Laborin, R, Martinez Robles, E, Quiros Fernandez, S, Rendon, A, Solovic, I, Tadolini, M, Viggiani, P, Belilovski, E, Boeree, MJ, Cai, Q, Davidaviciene, E, Forsman, LD, De Los Rios, J, Draksiene, J, Duga, A, Elamin, SE, Filippov, A, Garcia, A, Gaudiesiute, I, Gavazova, B, Gayoso, R, Gruslys, V, Jonsson, J, Khimova, E, Madonsela, G, Magis-Escurra, C, Marchese, V, Matei, M, Moschos, C, Nakceriene, B, Nicod, L, Palmieri, F, Pontarelli, A, Smite, A, Souleymane, MB, Vescovo, M, Zablockis, R, Zhurkin, D, Alffenaar, J-W, Caminero, JA, Codecasa, LR, Garcia-Garcia, J-M, Esposito, S, Saderi, L, Spanevello, A, Visca, D, Tiberi, S, Pontali, E, Centis, R, D'Ambrosio, L, van den Boom, M, Sotgiuw, G, and Migliori, GB

Abstract

The World Health Organization (WHO) recommends countries introduce new anti-TB drugs in the treatment of multidrug-resistant tuberculosis. The aim of the study is to prospectively evaluate the effectiveness of bedaquiline (and/or delamanid)- containing regimens in a large cohort of consecutive TB patients treated globally. This observational, prospective study is based on data collected and provided by Global Tuberculosis Network (GTN) centres and analysed twice a year. All consecutive patients (including children/adolescents) treated with bedaquiline and/or delamanid were enrolled, and managed according to WHO and national guidelines. Overall, 52 centres from 29 countries/regions in all continents reported 883 patients as of January 31st 2021, 24/29 countries/regions providing data on 100% of their consecutive patients (10-80% in the remaining 5 countries). The drug-resistance pattern of the patients was severe (>30% with extensively drug-resistant -TB; median number of resistant drugs 5 (3-7) in the overall cohort and 6 (4-8) among patients with a final outcome). For the patients with a final outcome (477/883, 54.0%) the median (IQR) number of months of anti-TB treatment was 18 (13-23) (in days 553 (385-678)). The proportion of patients achieving sputum smear and culture conversion ranged from 93.4% and 92.8% respectively (whole cohort) to 89.3% and 88.8% respectively (patients with a final outcome), a median (IQR) time to sputum smear and culture conversion of 58 (30-90) days for the whole cohort and 60 (30-100) for patients with a final outcome and, respectively, of 55 (30-90) and 60 (30-90) days for culture conversion. Of 383 patients treated with bedaquiline but not delamanid, 284 (74.2%) achieved treatment success, while 25 (6.5%) died, 11 (2.9%) failed and 63 (16.5%) were lost to follow-up.

Published
2021

18. Therapeutic strategies and outcomes of MDR and pre-XDR-TB in Italy: a nationwide study

Author

Riccardi, N., primary, Saderi, L., additional, Borroni, E., additional, Tagliani, E., additional, Cirillo, D. M., additional, Marchese, V., additional, Matteelli, A., additional, Piana, A., additional, Castellotti, P., additional, Ferrarese, M., additional, Gualano, G., additional, Palmieri, F., additional, Girardi, E., additional, Codecasa, L., additional, and Sotgiu, G., additional

Published
2021
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19. The chaperone-like sodium phenylbutyrate improves factor IX intracellular trafficking and activity impaired by the frequent p.R294Q mutation

Author

Pignani, S, Todaro, A, Ferrarese, M, Marchi, S, Lombardi, S, Balestra, D, Pinton, P, Bernardi, F, Pinotti, M, Branchini, A, Pignani, S., Todaro, A., Ferrarese, M., Marchi, S., Lombardi, S., Balestra, D., Pinton, P., Bernardi, F., Pinotti, M., Branchini, A., Pignani, S, Todaro, A, Ferrarese, M, Marchi, S, Lombardi, S, Balestra, D, Pinton, P, Bernardi, F, Pinotti, M, Branchini, A, Pignani, S., Todaro, A., Ferrarese, M., Marchi, S., Lombardi, S., Balestra, D., Pinton, P., Bernardi, F., Pinotti, M., and Branchini, A.

Abstract

Essentials Missense mutations often impair protein folding, and thus intracellular trafficking and secretion. Cellular models of severe type I hemophilia B were challenged with chaperone-like compounds. Sodium phenylbutyrate improved intracellular trafficking and secretion of the frequent p.R294Q. The increased coagulant activity levels (∼3%) of p.R294Q would ameliorate the bleeding phenotype. Summary: Background Missense mutations often impair protein folding and intracellular processing, which can be improved by small compounds with chaperone-like activity. However, little has been done in coagulopathies, where even modest increases of functional levels could have therapeutic implications. Objectives To rescue the expression of factor IX (FIX) variants affected by missense mutations associated with type I hemophilia B (HB) through chaperone-like compounds. Methods Expression studies of recombinant (r)FIX variants and evaluation of secreted levels (ELISA), intracellular trafficking (immunofluorescence) and activity (coagulant assays) before and after treatment of cells with chaperone-like compounds. Results As a model we chose the most frequent HB mutation (p.R294Q, ~100 patients), compared with other recurrent mutations associated with severe/moderate type I HB. Immunofluorescence studies revealed retention of rFIX variants in the endoplasmic reticulum and negligible localization in the Golgi, thus indicating impaired intracellular trafficking. Consistently, and in agreement with coagulation phenotypes in patients, all missense mutations resulted in impaired secretion (< 1% wild-type rFIX). Sodium phenylbutyrate (NaPBA) quantitatively improved trafficking to the Golgi and dose dependently promoted secretion (from 0.3 ± 0.1% to 1.5 ± 0.3%) only of the rFIX-294Q variant. Noticeably, this variant displayed a specific coagulant activity that was higher (~2.0 fold) than that of wild-type rFIX in all treatment conditions. Importantly, coagulant activity was concurren

Published
2018

21. Real-life evaluation of clinical outcomes in patients undergoing treatment for non-tuberculous mycobacteria lung disease: A ten-year cohort study

Author

Aliberti, S., Sotgiu, G., Castellotti, P., Ferrarese, M., Pancini, L., Pasat, A., Vanoni, N., Spotti, M., Mazzola, E., Gramegna, A., Saderi, L., Perno, C.F., Ingen, J. van, Codecasa, L.R., Blasi, F., Aliberti, S., Sotgiu, G., Castellotti, P., Ferrarese, M., Pancini, L., Pasat, A., Vanoni, N., Spotti, M., Mazzola, E., Gramegna, A., Saderi, L., Perno, C.F., Ingen, J. van, Codecasa, L.R., and Blasi, F.

Abstract

Item does not contain fulltext, Outcome recognition is a crucial step in the management of non-tuberculous mycobacteria lung disease (NTM-LD). In order to explore NTM-LD outcomes in a real-life setting, an observational, retrospective study enrolling consecutive adults who received treatment for NTM-LD in Milan, Italy, from 2007 to 2017 was conducted. Among 170 patients (68.2% females; median age: 68 years), NTM-LD was mainly due to M. avium complex (MAC) (71.2%), M. kansasii (9.4%) and M. xenopi (7.1%). Along a median follow-up of 31 months, adverse events occurred in 37.6% of the patients. Treatment outcomes of the entire study population included an unsuccessful outcome in 35.3% of the patients, including treatment halted in 13.5%, recurrence in 11.2%, re-infection in 5.3%, treatment failure in 4.1% and relapse in 1.2%. The main reason for treatment halted was drug intolerance. No differences were detected between patients with MAC-LD vs. those with other NTM-LD in terms of unsuccessful outcome in general (35.5% vs. 34.7%). A significantly higher prevalence of patients who underwent treatment halted was found in patients with NTM-LD other than MAC in comparison to patients with MAC-LD (22.4% vs. 9.9%, p = 0.030). One third of adults undergoing treatment for a NTM-LD experiences an unsuccessful outcome with adverse events and treatment discontinuation being major challenges in patients' management.

Published
2020

22. A compensatory U1snRNA partially rescues FAH splicing and protein expression in a splicing-defective mouse model of tyrosinemia type I

Author

Balestra, D, Scalet, D, Ferrarese, M, Lombardi, S, Ziliotto, N, C. Croes, C, Petersen, N, Bosma, P, Riccardi, F, Pagani, F, Pinotti, M, van de Graaf, S, Balestra, Dario, Scalet, Daniela, Ferrarese, Mattia, Lombardi, Silvia, Ziliotto, Nicole, C. Croes, Chrystal, Petersen, Naomi, Bosma, Piter, Riccardi, Federico, Pagani, Franco, Pinotti, Mirko, van de Graaf, Stan F. J., Balestra, D, Scalet, D, Ferrarese, M, Lombardi, S, Ziliotto, N, C. Croes, C, Petersen, N, Bosma, P, Riccardi, F, Pagani, F, Pinotti, M, van de Graaf, S, Balestra, Dario, Scalet, Daniela, Ferrarese, Mattia, Lombardi, Silvia, Ziliotto, Nicole, C. Croes, Chrystal, Petersen, Naomi, Bosma, Piter, Riccardi, Federico, Pagani, Franco, Pinotti, Mirko, and van de Graaf, Stan F. J.

Abstract

The elucidation of aberrant splicing mechanisms, frequently associated with disease has led to the development of RNA therapeutics based on the U1snRNA, which is involved in 5′ splice site (5′ss) recognition. Studies in cellular models have demonstrated that engineered U1snRNAs can rescue different splicing mutation types. However, the assessment of their correction potential in vivo is limited by the scarcity of animal models with the targetable splicing defects. Here, we challenged the U1snRNA in the FAH5961SB mouse model of hepatic fumarylacetoacetate hydrolase (FAH) deficiency (Hereditary Tyrosinemia type I, HT1) due to the FAH c.706G>A splicing mutation. Through minigene expression studies we selected a compensatory U1snRNA (U1F) that was able to rescue this mutation. Intriguingly, adeno-associated virus-mediated delivery of U1F (AAV8-U1F), but not of U1wt, partially rescued FAH splicing in mouse hepatocytes. Consistently, FAH protein was detectable only in the liver of AAV8-U1F treated mice, which displayed a slightly prolonged survival. Moreover, RNA sequencing revealed the negligible impact of the U1F on the splicing profile and overall gene expression, thus pointing toward gene specificity. These data provide early in vivo proof-of-principle of the correction potential of compensatory U1snRNAs in HTI and encourage further optimization on a therapeutic perspective, and translation to other splicing-defective forms of metabolic diseases.

Published
2020

23. Worldwide Effects of Coronavirus Disease Pandemic on Tuberculosis Services, January-April 2020

Author

Migliori, GB, Thong, PM, Akkerman, O, Alffenaar, J-W, Alvarez-Navascues, F, Assao-Neino, MM, Bernard, PV, Biala, JS, Blanc, F-X, Bogorodskaya, EM, Borisov, S, Buonsenso, D, Calnan, M, Castellotti, PF, Centis, R, Chakaya, JM, Cho, J-G, Codecasa, LR, D'Ambrosio, L, Denholm, J, Enwerem, M, Ferrarese, M, Galvao, T, Garcia-Clemente, M, Garcia-Garcia, J-M, Gualano, G, Gullon-Blanco, JA, Inwentarz, S, Ippolito, G, Kunst, H, Maryandyshev, A, Melazzini, M, de Queiroz Mello, FC, Munoz-Torrico, M, Njungfiyini, PB, Palmero, DJ, Palmieri, F, Piccioni, P, Piubello, A, Rendon, A, Sabri, J, Saporiti, M, Scognamiglio, P, Sharma, S, Silva, DR, Souleymane, MB, Spanevello, A, Tabernero, E, Tadolini, M, Tchangou, ME, Thornton, ABY, Tiberi, S, Udwadia, ZF, Sotgiu, G, Ong, CWM, Goletti, D, Migliori, GB, Thong, PM, Akkerman, O, Alffenaar, J-W, Alvarez-Navascues, F, Assao-Neino, MM, Bernard, PV, Biala, JS, Blanc, F-X, Bogorodskaya, EM, Borisov, S, Buonsenso, D, Calnan, M, Castellotti, PF, Centis, R, Chakaya, JM, Cho, J-G, Codecasa, LR, D'Ambrosio, L, Denholm, J, Enwerem, M, Ferrarese, M, Galvao, T, Garcia-Clemente, M, Garcia-Garcia, J-M, Gualano, G, Gullon-Blanco, JA, Inwentarz, S, Ippolito, G, Kunst, H, Maryandyshev, A, Melazzini, M, de Queiroz Mello, FC, Munoz-Torrico, M, Njungfiyini, PB, Palmero, DJ, Palmieri, F, Piccioni, P, Piubello, A, Rendon, A, Sabri, J, Saporiti, M, Scognamiglio, P, Sharma, S, Silva, DR, Souleymane, MB, Spanevello, A, Tabernero, E, Tadolini, M, Tchangou, ME, Thornton, ABY, Tiberi, S, Udwadia, ZF, Sotgiu, G, Ong, CWM, and Goletti, D

Abstract

Coronavirus disease has disrupted tuberculosis services globally. Data from 33 centers in 16 countries on 5 continents showed that attendance at tuberculosis centers was lower during the first 4 months of the pandemic in 2020 than for the same period in 2019. Resources are needed to ensure tuberculosis care continuity during the pandemic.

Published
2020

26. Next generation factor VIIa with enhanced half-life

Author

Ferrarese, M., Nilsen, J., Pinotti, M., Bern, M., Davidson, R. J., Camire, R. M., Lode, H. E., Roopenian, D. C., Sandlie, I., Lombardi, Silvia, Castaman, G., Andersen, J. T., and Branchini, A.

Subjects
Socio-culturale
Published
2019

28. Surveillance of adverse events in the treatment of drug-resistant tuberculosis: first global report

Author

Borisov, S., Danila, E., Maryandyshev, A., Dalcolmo, M., Miliauskas, S., Kuksa, L., Manga, S., Skrahina, A., Diktanas, S., Codecasa, L.R., Aleksa, A., Bruchfeld, J., Koleva, A., Piubello, A., Udwadia, Z.F., Akkerman, O.W., Belilovski, E., Bernal, E., Boeree, M.J., Loidi, J., Cai, Q., Gallardo, J.J. Cebrian, Dara, M., Davidaviciene, E., Forsman, L.D., Rios, J. De Los, Denholm, J., Draksiene, J., Duarte, R., Elamin, S.E., Salinas, N. Escobar, Ferrarese, M., Filippov, A., Garcia, A., Garcia-Garcia, J.M., Gaudiesiute, I., Gavazova, B., Gayoso, R., Rosso, R., Gruslys, V., Gualano, G., Hoefsloot, W., Jonsson, J., Khimova, E., Kunst, H., Laniado-Laborin, R., Li, Y, Magis-Escurra, C., Manfrin, V., Marchese, V., Robles, E. Martinez, Matteelli, A., Mazza-Stalder, J., Moschos, C., Munoz-Torrico, M., Hamdan, H. Mustafa, Nakceriene, B., Nicod, L., Marcos, M., Palmero, D.J., Palmieri, F., Papavasileiou, A., Payen, M.C., Pontarelli, A., Quiros, S., Rendon, A., Saderi, L., Smite, A., Solovic, I., Souleymane, M.B., Tadolini, M., Boom, M. van den, Vescovo, M., Viggiani, P., Yedilbayev, A., Zablockis, R., Zhurkin, D., Zignol, M., Visca, D., Spanevello, A., Caminero, J.A., Alffenaar, J.W.C., Tiberi, S., Centis, R., D'Ambrosio, L., Pontali, E., Sotgiu, G., Migliori, G.B., Borisov, S., Danila, E., Maryandyshev, A., Dalcolmo, M., Miliauskas, S., Kuksa, L., Manga, S., Skrahina, A., Diktanas, S., Codecasa, L.R., Aleksa, A., Bruchfeld, J., Koleva, A., Piubello, A., Udwadia, Z.F., Akkerman, O.W., Belilovski, E., Bernal, E., Boeree, M.J., Loidi, J., Cai, Q., Gallardo, J.J. Cebrian, Dara, M., Davidaviciene, E., Forsman, L.D., Rios, J. De Los, Denholm, J., Draksiene, J., Duarte, R., Elamin, S.E., Salinas, N. Escobar, Ferrarese, M., Filippov, A., Garcia, A., Garcia-Garcia, J.M., Gaudiesiute, I., Gavazova, B., Gayoso, R., Rosso, R., Gruslys, V., Gualano, G., Hoefsloot, W., Jonsson, J., Khimova, E., Kunst, H., Laniado-Laborin, R., Li, Y, Magis-Escurra, C., Manfrin, V., Marchese, V., Robles, E. Martinez, Matteelli, A., Mazza-Stalder, J., Moschos, C., Munoz-Torrico, M., Hamdan, H. Mustafa, Nakceriene, B., Nicod, L., Marcos, M., Palmero, D.J., Palmieri, F., Papavasileiou, A., Payen, M.C., Pontarelli, A., Quiros, S., Rendon, A., Saderi, L., Smite, A., Solovic, I., Souleymane, M.B., Tadolini, M., Boom, M. van den, Vescovo, M., Viggiani, P., Yedilbayev, A., Zablockis, R., Zhurkin, D., Zignol, M., Visca, D., Spanevello, A., Caminero, J.A., Alffenaar, J.W.C., Tiberi, S., Centis, R., D'Ambrosio, L., Pontali, E., Sotgiu, G., and Migliori, G.B.

Abstract

Item does not contain fulltext, The World Health Organization (WHO) recommends that countries implement pharmacovigilance and collect information on active drug safety monitoring (aDSM) and management of adverse events.The aim of this prospective study was to evaluate the frequency and severity of adverse events to anti-tuberculosis (TB) drugs in a cohort of consecutive TB patients treated with new (i.e. bedaquiline, delamanid) and repurposed (i.e. clofazimine, linezolid) drugs, based on the WHO aDSM project. Adverse events were collected prospectively after attribution to a specific drug together with demographic, bacteriological, radiological and clinical information at diagnosis and during therapy. This interim analysis included patients who completed or were still on treatment at time of data collection.Globally, 45 centres from 26 countries/regions reported 658 patients (68.7% male, 4.4% HIV co-infected) treated as follows: 87.7% with bedaquiline, 18.4% with delamanid (6.1% with both), 81.5% with linezolid and 32.4% with clofazimine. Overall, 504 adverse event episodes were reported: 447 (88.7%) were classified as minor (grade 1-2) and 57 (11.3%) as serious (grade 3-5). The majority of the 57 serious adverse events reported by 55 patients (51 out of 57, 89.5%) ultimately resolved. Among patients reporting serious adverse events, some drugs held responsible were discontinued: bedaquiline in 0.35% (two out of 577), delamanid in 0.8% (one out of 121), linezolid in 1.9% (10 out of 536) and clofazimine in 1.4% (three out of 213) of patients. Serious adverse events were reported in 6.9% (nine out of 131) of patients treated with amikacin, 0.4% (one out of 221) with ethionamide/prothionamide, 2.8% (15 out of 536) with linezolid and 1.8% (eight out of 498) with cycloserine/terizidone.The aDSM study provided valuable information, but implementation needs scaling-up to support patient-centred care.

Published
2019

29. Surveillance of adverse events in the treatment of drug-resistant tuberculosis: A global feasibility study

Author

Akkerman, O., Aleksa, A., Alffenaar, J.W.C., Al-Marzouqi, N.H., Arias-Guillen, M., Belilovski, E., Bernal, E., Boeree, M.J., Borisov, S.E., Bruchfeld, J., Loidi, J., Cai, Q., Caminero, J.A., Gallardo, J.J. Cebrian, Centis, R., Codecasa, L.R., D'Ambrosio, L., Dalcolmo, M., Danila, E., Dara, M., Davidaviciene, E., Forsman, L. Davies, Jefe, J. De Los Rios, Denholm, J., Duarte, R., Elamin, S.E., Ferrarese, M., Filippov, A., Ganatra, S., Garcia, A., Garcia-Garcia, J.M., Gayoso, R., Montoya, A.M. Giraldo, Rosso, R.G. Gomez, Gualano, G., Hoefsloot, W., Ilievska-Poposka, B., Jonsson, J., Khimova, E., Kuksa, L., Kunst, H., Laniado-Laborin, R., Li, Y., Magis-Escurra, C., Manfrin, V., Manga, S., Marchese, V., Robles, E. Martinez, Maryandyshev, A., Matteelli, A., Migliori, G.B., Mullerpattan, J.B., Munoz-Torrico, M., Hamdan, H. Mustafa, Marcos, M., Noordin, N.M., Palmero, D.J., Palmieri, F., Payen, M.C., Piubello, A., Pontali, E., Pontarelli, A., Quiros, S., Rendon, A., Skrahina, A., Smite, A., Solovic, I., Sotgiu, G., Souleymane, M.B., Spanevello, A., Stosic, M., Tadolini, M., Tiberi, S., Udwadia, Z.F., Boom, M. van den, Vescovo, M., Viggiani, P., Visca, D., Zhurkin, D., Zignol, M., Akkerman, O., Aleksa, A., Alffenaar, J.W.C., Al-Marzouqi, N.H., Arias-Guillen, M., Belilovski, E., Bernal, E., Boeree, M.J., Borisov, S.E., Bruchfeld, J., Loidi, J., Cai, Q., Caminero, J.A., Gallardo, J.J. Cebrian, Centis, R., Codecasa, L.R., D'Ambrosio, L., Dalcolmo, M., Danila, E., Dara, M., Davidaviciene, E., Forsman, L. Davies, Jefe, J. De Los Rios, Denholm, J., Duarte, R., Elamin, S.E., Ferrarese, M., Filippov, A., Ganatra, S., Garcia, A., Garcia-Garcia, J.M., Gayoso, R., Montoya, A.M. Giraldo, Rosso, R.G. Gomez, Gualano, G., Hoefsloot, W., Ilievska-Poposka, B., Jonsson, J., Khimova, E., Kuksa, L., Kunst, H., Laniado-Laborin, R., Li, Y., Magis-Escurra, C., Manfrin, V., Manga, S., Marchese, V., Robles, E. Martinez, Maryandyshev, A., Matteelli, A., Migliori, G.B., Mullerpattan, J.B., Munoz-Torrico, M., Hamdan, H. Mustafa, Marcos, M., Noordin, N.M., Palmero, D.J., Palmieri, F., Payen, M.C., Piubello, A., Pontali, E., Pontarelli, A., Quiros, S., Rendon, A., Skrahina, A., Smite, A., Solovic, I., Sotgiu, G., Souleymane, M.B., Spanevello, A., Stosic, M., Tadolini, M., Tiberi, S., Udwadia, Z.F., Boom, M. van den, Vescovo, M., Viggiani, P., Visca, D., Zhurkin, D., and Zignol, M.

Abstract

Contains fulltext : 207083.pdf (publisher's version ) (Open Access), The World Health Organization launched a global initiative, known as aDSM (active TB drug safety monitoring and management) to better describe the safety profile of new treatment regimens for drug-resistant tuberculosis (TB) in real-world settings. However, comprehensive surveillance is difficult to implement in several countries. The aim of the aDSM project is to demonstrate the feasibility of implementing national aDSM registers and to describe the type and the frequency of adverse events (AEs) associated with exposure to the new anti-TB drugs. Following a pilot study carried out in 2016, official involvement of TB reference centres/countries into the project was sought and cases treated with bedaquiline- and/or delamanid-containing regimens were consecutively recruited. AEs were prospectively collected ensuring potential attribution of the AE to a specific drug based on its known safety profile. A total of 309 cases were fully reported from 41 centres in 27 countries (65% males; 268 treated with bedaquiline, 20 with delamanid, and 21 with both drugs) out of an estimated 781 cases the participating countries had committed to report by the first quarter of 2019.

Published
2019

32. Differential functional readthrough over homozygous nonsense mutations contributes to the bleeding phenotype in coagulation factor VII deficiency

Author

Branchini, A, Ferrarese, M, Lombardi, S, Mari, R, Bernardi, F, Pinotti, M, Branchini A., Ferrarese M., Lombardi S., Mari R., Bernardi F., Pinotti M., Branchini, A, Ferrarese, M, Lombardi, S, Mari, R, Bernardi, F, Pinotti, M, Branchini A., Ferrarese M., Lombardi S., Mari R., Bernardi F., and Pinotti M.

Abstract

Essentials Potentially null homozygous Factor(F)7 nonsense mutations are associated to variable bleeding symptoms. Readthrough of p.Ser112X (life-threatening) and p.Cys132X (moderate) stop codons was investigated. Readthrough-mediated insertion of wild-type or tolerated residues produce functional proteins. Functional readthrough over homozygous F7 nonsense mutations contributes to the bleeding phenotype. Summary: Background Whereas the rare homozygous nonsense mutations causing factor (F)VII deficiency may predict null conditions that are almost completely incompatible with life, they are associated with appreciable differences in hemorrhagic symptoms. The misrecognition of premature stop codons (readthrough) may account for variable levels of functional full-length proteins. Objectives To experimentally evaluate the basal and drug-induced levels of FVII resulting from the homozygous p.Cys132X and p.Ser112X nonsense mutations that are associated with moderate (132X) or life-threatening (112X) symptoms, and that are predicted to undergo readthrough with (132X) or without (112X) production of wild-type FVII. Methods We transiently expressed recombinant FVII (rFVII) nonsense and missense variants in human embryonic kidney 293 cells, and evaluated secreted FVII protein and functional levels by ELISA, activated FX generation, and coagulation assays. Results The levels of functional FVII produced by p.Cys132X and p.Ser112X mutants (rFVII-132X, 1.1% ± 0.2% of wild-type rFVII; rFVII-112X, 0.5% ± 0.1% of wild-type rFVII) were compatible with the occurrence of spontaneous readthrough, which was magnified by the addition of G418 – up to 12% of the wild-type value for the rFVII-132X nonsense variant. The predicted missense variants arising from readthrough abolished (rFVII-132Trp/Arg) or reduced (rFVII-112Trp/Cys/Arg, 22–45% of wild-type levels) secretion and function. These data suggest that the appreciable rescue of p.Cys132X function was driven by reinsertion of the wild-ty

Published
2016

33. Extensively drug-resistant tuberculosis, Italy and Germany

Author

Migliori, Giovanni Battista, Ortmann, Johannes, Girardi, Enrico, Besozzi, Giorgio, Lange, Christoph, Cirillo, Daniela M., Ferrarese, M., De laco, Giuseppina, Gori, Andrea, and Raviglione, Mario C.

Subjects
Tuberculosis -- Research, Prevalence studies (Epidemiology) -- Reports
Abstract

To the Editor: Twenty-three countries have reported [greater than or equal to] 1 case of extensively drug-resistant tuberculosis (XDR TB) (1); however, information about XDR TB is still incomplete. In [...]

Published
2007

34. The Italian registry of pulmonary non-tuberculous mycobacteria - IRENE: The study protocol

Author

Aliberti, S., Codecasa, L. R., Gori, A., Sotgiu, G., Spotti, M., Di Biagio, A., Calcagno, A., Nardini, S., Assael, B. M., Tortoli, E., Besozzi, G., Ferrarese, M., Matteelli, A., Girardi, E., De Lorenzo, S., Seia, M., Gramegna, A., Del Prato, B., Terranova, L., Oriano, M., Sverzellati, N., Mirsaeidi, M., Chalmers, J. D., Haworth, C. S., Loebinger, M. R., Aksamit, T., Winthrop, K., Ringshausen, F. C., Previdi, G., Blasi, F., Fusetti, G., Martorana, M., Colella, G., Verga, G., Carbone, G., Damilano, I., Nava, F., Pancini, L., Pasat, A., and Vanoni, N.

Subjects
Pulmonary and Respiratory Medicine, medicine.medical_specialty, M. Avium, Atypical mycobacteria, Bronchiectasis, COPD, Cystic fibrosis, HIV, Lung transplant, M. Intracellulare, NTM, NTM-PD, Disease, 03 medical and health sciences, 0302 clinical medicine, Epidemiology, medicine, Original Research Article, 030212 general & internal medicine, Case report form, lcsh:RC705-779, business.industry, lcsh:Diseases of the respiratory system, bacterial infections and mycoses, medicine.disease, Biobank, 030228 respiratory system, Infectious disease (medical specialty), Emergency medicine, NTM-PD, Observational study, NTM, business, Cohort study
Abstract

Background A substantial increase in pulmonary and extra-pulmonary diseases due to non-tuberculous mycobacteria (NTM) has been documented worldwide, especially among subjects suffering from chronic respiratory diseases and immunocompromised patients. Many questions remain regarding the epidemiology of pulmonary disease due to NTM (NTM-PD) mainly because reporting of NTM-PD to health authorities is not mandated in several countries, including Italy. This manuscript describes the protocol of the first Italian registry of adult patients with respiratory infections caused by NTM (IRENE). Methods IRENE is an observational, multicenter, prospective, cohort study enrolling consecutive adult patients with either a NTM respiratory isolate or those with NTM-PD. A total of 41 centers, including mainly pulmonary and infectious disease departments, joined the registry so far. Adult patients with all of the following are included in the registry: 1) at least one positive culture for any NTM species from any respiratory sample; 2) at least one positive culture for NTM isolated in the year prior the enrolment and/or prescribed NTM treatment in the year prior the enrolment; 3) given consent to inclusion in the study. No exclusion criteria are applied to the study. Patients are managed according to standard operating procedures implemented in each IRENE clinical center. An online case report form has been developed to collect patients’ demographics, comorbidities, microbiological, laboratory, functional, radiological, clinical, treatment and outcome data at baseline and on an annual basis. An IRENE biobank has also been developed within the network and linked to the clinical data of the registry. Conclusions IRENE has been developed to inform the clinical and scientific community on the current management of adult patients with NTM respiratory infections in Italy and acts as a national network to increase the disease’s awareness. Trial registration Clinicaltrial.gov: NCT03339063.

Published
2018

41. Are all people with diabetes and cardiovascular risk factors or microvascular complications at very high risk? Findings from the Risk and Prevention Study

Author

Marzona, I., Avanzini, F., Lucisano, G., Tettamanti, M., Baviera, M., Nicolucci, A., Roncaglioni, M. C., Tombesi, M., Tognoni, G., Massa, E., Marrocco, W., Micalella, M., Caimi, V., Longoni, P., Franzosi, M. G., Monesi, L., Pangrazzi, I., Barlera, S., Milani, V., Nicolis, E., Casola, C., Clerici, F., Palumbo, A., Sgaroni, G., Marchioli, R., Silletta, M. G., Pioggiarella, R., Scarano, M., Marfisi, R. M., Flamminio, A., Macino, L., Ferri, B., Pera, C., Polidoro, A., Abbatino, D., Acquati, M., Addorisio, G., Adinolfi, D., Adreani, L., Agistri, M. R., Agneta, A., Agnolio, M. L., Agostini, N., Agostino, G., Airo, A., Alaimo, N., Albano, M., Albano, N., Alecci, G., Alemanno, S., Alexanian, A., Alfarano, M., Alfe, L., Alonzo, N., Alvino, S., Ancora, A., Andiloro, S., Andreatta, E., Angeli, S., Angiari, F., Angilletti, V., Annicchiarico, C., Anzivino, M., Aprea, R., Aprile, A., Aprile, E., Aprile, I., Aprile, L., Armellani, V., Arnetoli, M., Aronica, A., Autiero, V., Bacca, G., Baccalaro, A. M., Bacci, M., Baglio, G., Bagnani, M., Baiano, A., Baldari, A., Ballarini, L., Banchi, G., Bandera, R., Bandini, F., Baratella, M., Barbieri, A., Barbieri Vita, A., Bardi, M., Barlocchi, M., Baron, P., Bartoli, M., Basile, A., Basile, F., Basile, S., Battaggia, A., Battaglia, A., Bau, A., Beconcini, G., Beggio, R., Belfiore, P. A., Belicchi, M., Bellamoli, S., Bellini, C., Bellomo, M., Benetollo, C., Benetti, R., Beretta, E., Bertalero, P., Bertaso, F. G., Bertolani, U., Bettelli, G., Biagiotti, G., Bianchi, S., Bianco, G., Biccari, F., Bigioli, F., Bindi, M., Bisanti, G., Bitetti, E. M., Blasetti, M. P., Blesi, F., Boato, V., Boga, S., Boidi, E., Boldrin, G., Bollati, A., Bolzan, L., Bolzonella, S., Bonardi, P., Bonato, G. B., Bonci, M., Bonfitto, G., Bonincontro, E., Boninsegna, F., Bonissone, D., Bono, L., Bonollo, E., Borghi, M., Borioli, N., Borsatto, M., Bosco, T., Bosisio Pioltelli, M., Botarelli, C., Botassis, S., Bottini, F., Bottos, C., Bova, G., Bova, V., Bozzani, A., Bozzetto, R. M., Braga, V. T., Braglia, M., Bramati, E., Brazzoli, C., Breglia, G., Brescia, A., Briganti, D., Brigato, G., Brocchi, A., Brosio, F. A., Bruni, E., Buscaglia, E., Bussini, M. D., Bussotti, A., Buzzaccarini, F., Buzzatti, A., Caccamo, G., Cacciavillani, C., Caggiano, G., Calciano, F. P., Calderisi, M., Calienno, S., Caltagirone, P., Calzolari, I., Cammisa, M., Campanaro, M., Campanella, G. B., Campese, F., Canali, G., Candiani, D. E. L., Canepa, R., Canini, D., Canino, A., Cantoro, E. A., Capilupi, V., Capotosto, P., Cappelli, B., Capraro, G., Carafa, F. A., Carano, Q., Carcaterra, V., Carriero, D., Carrozzo, G., Cartanese, M., Casalena, M., Casarola, M., Caso, C., Casotto, M., Castaldi, F., Castegnaro, R., Castellani, G., Castri, S., Catalano, E., Catinello, N., Caturano, G., Cavallaro, R., Cavallo, A. M., Cavallo, G., Cavion, M. T., Cavirani, G., Cazzaniga, F., Cazzetta, D., Cecconi, V., Cefalo, A., Celebrano, M., Celora, A., Centonze, P., Cerati, D., Cesaretti, D., Checchia, G., Checchin, A., Cherubini, M., Chianese, L., Chiappa, A., Chiappa, M. V., Chiariello, G., Chiavini, G., Chicco, M., Chiumeo, F., Ciacciarelli, A., Ciaci, D., Ciancaglini, R., Cicale, C., Cicale, S., Cipolla, A., Ciruolo, A., Citeri, A. L., Citterio, G., Clerici, M., Coazzoli, E., Collecchia, G., Colletta, F., Colombo, I., Colorio, P., Coluccia, S., Comerio, M., Comoretto, P., Compagni, M., Conte, O., Contri, S., Contrisciani, A., Coppetti, T., Corasaniti, F., Corradi, M. T., Corsano, A., Corsini, A., Corti, N., Costantini, G., Costantino, A., Cotroneo, S., Cozzi, D., Cravello, M. G., Cristiano, E., Cucchi, R., Cusmai, L., D'Errico, G. B., D'Agostino, P., Dal Bianco, L., Dal Mutto, U., Dal Pozzo, G., Dallapiccola, P., Dallatorre, G., Dalle Molle, G., Dalloni, E., D'Aloiso, A., D'Amicis, G., Danese, R., Danieli, D., Danisi, G., D'Anna, M. A., Danti, G., D'Ascanio, S., Davidde, G., De Angeli, D., De Bastiani, R., De Battisti, A., De Bellis, A., De Berardinis, G., De Carlo, F., De Giorgi, D., De Gobbi, R., De Lorenzis, E., De Luca, P., De Martini, G., De Marzi, M., De Matteis, D., De Padova, S., De Polo, P., De Sabato, N., De Stefano, T., De Vita, M. T., De Vito, U., De Zolt, V., Debernardi, F., Del Carlo, A., Del Re, G., Del Zotti, F., D'Elia, R., Della Giovanna, P., Dell'Acqua, L., Dell'Orco, R. L., Demaria, G., Di Benedetto, M. G., Di Chiara, G., Di Corcia, V., Di Domizio, O., Di Donato, P., Di Donato, S., Di Fermo, G., Di Franco, M., Di Giovannantonio, G., Di Lascio, G., Di Lecce, G., Di Lorenzo, N., Di Maro, T., Di Mattia, Q., Di Michele, E., Di Modica, R. S., Di Murro, D., Di Noi, M. C., Di Paoli, V., Di Santi, M., Di Sanzo, A., Di Turi, C., Diazzi, A., Dileo, I., D'Ingianna, A. P., Dolci, A., Dona, G., Donato, C., Donato, P., Donini, A., Donna, M. E., Donvito, T. V., Esposito, L., Esposito, N., Evangelista, M., Faita, G., Falco, M., Falcone, D. A., Falorni, F., Fanciullacci, A., Fanton, L., Fasolo, L., Fassina, R., Fassone, A., Fatarella, P., Fedele, F., Fera, I., Fera, L., Ferioli, S., Ferlini, M. G., Ferlino, R., Ferrante, G., Ferrara, F. N., Ferrarese, M. F., Ferrari, G., Ferrari, O., Ferreri, A., Ferroni, M., Fezzi, G., Figaroli, C., Fina, M. G., Fioretta, A., Fiorucci, C., Firrincieli, R., Fischetti, M., Fischietti, G., Fiume, D. C., Flecchia, G., Forastiere, G., Fossati, B., Franceschi, P. L., Franchi, L., Franzoso, F., Frapporti, G., Frasca, G., Frisotti, A., Fumagalli, G., Fusco, D., Gabriele, P., Gabrieli, A., Gagliano, D., Galimberti, G., Galli, A., Gallicchio, N., Gallio, F., Gallipoli, T., Gallo, P., Galopin, T., Gambarelli, L., Garbin, A., Garozzo, G. M., Gasparri, R., Gastaldo, M., Gatti, E., Gazzaniga, P., Gennachi, N., Gentile, R. V., Germani, P., Gesualdi, F., Gherardi, E., Ghezzi, C., Ghidini, M. G., Ghionda, F., Giacci, L., Gialdini, D., Giampaolo, C., Giancane, R., Giannanti, A., Giannese, S., Giannini, L., Giaretta, M., Giaretta, R., Giavardi, L., Giordano, P., Giordano, E., Giordano, B., Gioria, G. M., Giugliano, R., Grassi, E. A., Greco, A., Greco, L., Grilletti, N., Grimaldi, N., Grisetti, G., Groppelli, G., Gualtieri, L., Guarducci, M., Guastella, G., Guerra, M., Guerrini, F., Guglielmini, A., Guido, A., Gulotta, P., Iacono, E., Iadarola, G., Ianiro, G., Iarussi, V., Ieluzzi, M. L., Ierardi, C., Ingaldi, F., Interlandi, S., Iocca, M., Iorno, A., Ioverno, E., Iurato, R., La Pace, L., La Piscopia, C., La Selva, R., Lafratta, M., Lamparelli, M., Lanaro, G., Lancerotto, R., Larcher, M., Lassandro, M., Lattuada, G., Laurino, P., Lefons, C., Legrottaglie, F., Lemma, A., Leone, D., Leone, F., Leso, A., Leuzzi, G., Levato, G., Libardi, L., Libralesso, N., Licini, P. I., Licursi, G., Lidonnici, F., Lillo, C., Liveri, L., Livio, A., Loiero, R. A., Loison, M., Lombardo, G., Lombardo, T., Lomunno, V., Lomuscio, S., Lonedo, A., Longo, E., Lora, L., Lotterio, A., Lucatello, L., Luongo, A., Lupoli, M., Macchia, C., Macri, G., Mafessanti, M., Maggialetti, V., Maggioni, A., Magnani, M., Maiellaro, G., Mancuso, A., Maniglio, A. R., Mannari, G. L., Manni, A., Manocchio, B., Mao, M., Marano, A., Maraone, E., Marascio, D., Marcheselli, P., Marchetto, B., Marchetto, S., Marchi, A., Marchi, G. L., Mariano, C., Marinacci, S., Marinelli, S., Marini, G., Marra, V. C., Marrali, F., Marseglia, C., Martello, G., Martino, C., Martino, G., Martino, M., Marulli, C. F., Maruzzi, G., Marzotti, A., Mascheroni, G., Mascolo, P., Masoch, G., Masone, R., Massa, L., Massafra, M., Massi, M., Massignani, D. M., Matarese, A. M., Matini, G., Mauro, R., Mazzi, M., Mazzillo, A., Mazzocato, E., Mazzoleni, N. S., Mazzone, A., Melacci, A., Mele, E., Meliota, P., Menaspa, S., Meneghello, F., Merola, G., Merone, L., Metrucci, A., Mezzina, V., Micchi, A., Michielon, A., Migliore, N., Minero, G., Minotta, F., Mirandola, C., Mistrorigo, S., Modafferi, L., Moitre, R., Mola, E., Monachese, C., Mongiardini, C., Montagna, F., Montani, M., Montemurno, I., Montolli, R., Montorsi, S., Montresor, M., Monzani, M. G., Morabito, F., Mori, G., Moro, A., Mosca, M. F., Motti, F., Muddolon, L., Mugnai, M., Muscas, F., Naimoli, F., Nanci, G., Nargi, E., Nasorri, R., Nastrini, G., Negossi, M., Negrini, A., Negroni, A., Neola, V., Niccolini, F., Niro, C. M., Nosengo, C., Novella, G., Nuti, C., Obici, F., Olita, C., Oliverio, S. S., Olivieri, I., Oriente, S., Orlando, G., Paci, C., Pagano, G., Pagliara, C., Paita, G., Paladini, G., Paladino, G., Palano, T., Palatella, A., Palermo, P., Palmisano, M., Pando, P., Panessa, P., Panigo, F., Panozzo, G., Panvini, F., Panzieri, F., Panzino, A., Panzitta, F., Paoli, N., Papagna, R., Papaleo, M. G., Papalia, G., Parisi, R., Parotti, N., Parravicini, D., Passarella, P., Pastore, G. A., Patafio, M., Pavone, P., Pedroli, W., Pedroni, M., Pelligra, G., Pellizzari, M., Penati, A., Perlot, M., Perrone, A., Perrone, G., Peruzzi, P., Peselli, C., Petracchini, L., Petrera, L., Petrone, S., Peverelli, C., Pianorsi, F., Piazza, G. P., Piazzolla, G., Picci, A., Pienabarca, G., Pietronigro, T. P., Pignocchino, P., Pilone, R., Pinto, D., Pirovano, E., Pirrotta, D., Pisante, V., Pitotto, P., Pittari, L., Piva, A., Pizzoglio, A., Plantera, O. R., Plebani, W., Plessi, S., Podrecca, D., Poerio, V., Poggiani, F., Pogliani, W., Poli, L., Poloni, F. G., Porcelli, R., Porto, S., Pranzo, L., Prevedello, C., Profeta, C., Profico, D., Punzi, A., Quaglia, G. M., Racano, M., Raccone, A., Radice, F., Raho, C. A., Raimondi, R., Raino, M., Ramponi, R., Ramunni, A., Ramunni, A. L., Ravasio, F., Ravera, M., Re Sarto, G., Rebustello, G., Regazzoli, S., Restelli, C., Rezzonico, M., Ricchiuto, F., Rigo, S., Rigon, G., Rigon, R., Rinaldi, O. V., Rinaldi, M., Risplendente, P. G., Rispoli, M., Riundi, R., Riva, M. G., Rizzi, A. L., Rizzi, D., Rizzo, L. D., Rocchi, L., Rondinone, B., Rosa, B., Rosati, F., Roselli, F., Rossetti, A., Rossetti, C., Rossi, R., Rossi, P. R., Rossi, A., Rossi, C. L., Rossitto, A., Ruffini, R., Ruffo, A., Ruggio, S., Ruo, M., Russo, B., Russo, L., Russo, R., Russo, S., Russo, U., Russo, V., Ruta, G., Sacchi, F., Sacco Botto, F., Saia, A., Salladini, G., Salmoiraghi, S., Saluzzo, F., Salvatore, C., Salvatori, E., Salvio, G., Sandri, P., Sandrini, T., Sangermano, V., Santoni, N., Saracino, A. D., Saracino, A., Sarasin, P., Sardo Infirri, C., Sarri, B., Sartori, G., Sartori, N., Sauro, C., Scaglioni, M., Scalfi, C., Scamardella, A. M., Scandale, G., Scandone, L., Scannavini, G., Scarati, R., Scardi, A., Scarpa, F. M., Scazzi, P., Schifone, A., Schiroso, G., Scigliano, G., Scilla, A., Sciortino, M., Scolaro, G., Scollo, E., Scorretti, G., Sellitti, R., Selmo, A., Selvaggio, G., Sempio, A., Seren, F., Serio, L., Serra, C., Serra, L., Siciliano, D., Sideri, A., Sighele, M., Signore, R., Siliberto, F., Silvestro, M., Simioni, G., Simmini, G., Simonato, L., Sinchetto, F., Sizzano, E., Smajato, G., Smaldone, M., Sola, G., Sordillo, L., Sovran, C. S., Spagnul, P., Spano, F., Sproviero, S., Squintani, A., Stella, L., Stilo, V., Stocchiero, B., Stornello, M. C., Stracka, G., Strada, S., Stranieri, G., Stucci, N., Stufano, N., Suppa, A., Susca, V. G., Sutti, M., Taddei, M., Tagliabue, E., Tagliente, G., Talato, F., Talerico, P., Talia, R., Taranto, R., Tartaglia, M., Tauro, N., Tedesco, A., Tieri, P., Tirelli, M., Tocci, L., Todesco, P., Tognolo, M., Tomba, A., Tonello, P., Tonon, R., Toscano, L., Tosi, A., Tosi, G., Toso, S., Travaglio, P., Tremul, L., Tresso, C., Triacchini, P., Triggiano, L., Trigilio, A., Trimeloni, J., Tripicchio, G., Tritto, G. S., Trono, F., Trotta, E., Trotta, G., Tubertini, A., Turri, C., Turri, L., Tuttolani, M. P., Urago, M., Ursini, G., Valcanover, F., Valente, L., Valenti, M., Valentini, F., Vallone, G., Valz, P., Valzano, L., Vanin, V., Vatteroni, M., Vegetti, L., Vendrame, D., Veramonti, I., Veronelli, G., Vesco, A., Vicariotto, G., Vignale, G., Villa, P. L., Vinciguerra, R., Visco, A., Visentin, G., Visona, E., Vitali, E., Vitali, S., Vitti, F., Volpone, D. A., Zambon, N., Zammarrelli, A., Zanaboni, A., Zane, D., Zanetti, B., Zanibellato, R., Zappetti, M., Zappone, P., Zerilli, G., Zirino, V., Zoccali, R., Zuin, F., Altomonte, M., Anelli, N., Angio, F., Annale, P., Antonacci, S., Anzilotta, R., Bano, F., Basadonna, O., Beduschi, L., Becagli, P., Bellotti, G., Blotta, C., Bruno, G., Cappuccini, A., Caramatti, S., Cariolato, M. P., Castellana, M., Castellani, L., Catania, R., Chielli, A., Chinellato, A., Ciaccia, A., Clerici, E., Cocci, A., Costanzo, G., D'Ercole, F., De Stefano, G., Dece, F., Di Cicco, N., Di Marco, A., Donati Sarti, C., Draghi, E., Dusi, G., Esposito, V., Ferraro, L., Ferretti, A., Ferri, E., Foggetti, L., Foglia, A., Fonzi, E., Frau, G., Fuoco, M. R., Furci, G., Gallo, L., Garra, V., Giannini, A., Gris, A., Iacovino, R., Interrigi, R., Joppi, R., Laner, B., La Fortezza, G., La Padula, A., Lista, M. R., Lupi, G., Maffei, D., Maggioni, G., Magnani, L., Marrazzo, E., Marcon, L., Marino, V., Maroni, A., Martinelli, C., Mastandrea, E., Mastropierro, F., Meo, A. T., Mero, P., Minesso, E., Moschetta, V., Mosele, E., Nanni, C., Negretti, A., Nistico, C., Orsini, A., Osti, M., Pacilli, M. C., Pennestre, C., Picerno, G., Piol, K., Pivano, L., Pizzuti, E., Poggi, L., Poidomani, I., Pozzetto, M., Presti, M. L., Ravani, R., Recalenda, V., Romagnuolo, F., Rossignoli, S., Rossin, E., Sabatella, C., Sacco, F., Sanita, F., Sansone, E., Servadei, F., Sisto, M. T., Sorio, A., Sorrentino, A., Spinelli, E., Spolaor, A., Squillacioti, A., Stella, P., Talerico, A., Todisco, C., Vadino, M., and Zuliani, C.

Subjects
Male, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, Population, 030209 endocrinology & metabolism, 030204 cardiovascular system & hematology, Overweight, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Prediction model, Internal medicine, Diabetes mellitus, Internal Medicine, Diabetes Mellitus, Medicine, Humans, Multicenter Studies as Topic, Myocardial infarction, Risk factor, education, Stroke, Aged, Randomized Controlled Trials as Topic, education.field_of_study, Lifestyle habits, business.industry, Major cardiovascular events, Atrial fibrillation, General Medicine, Middle Aged, medicine.disease, Cardiovascular Diseases, Heart failure, Physical therapy, Female, medicine.symptom, business, Diabetic Angiopathies
Abstract

To verify whether it is possible, in people with diabetes mellitus (DM) considered at very high cardiovascular (CV) risk, stratify this risk better and identify significant modifiable risk factor (including lifestyle habits) to help patients and clinicians improve CV prevention. People with DM and microvascular diseases or one or more CV risk factors (hypertension, hyperlipidemia, smoking, poor dietary habits, overweight, physical inactivity) included in the Risk and Prevention study were selected. We considered the combined endpoint of non-fatal acute myocardial infarction and stroke and CV death. A multivariate Cox proportional analysis was carried out to identify relevant predictors. We also used the RECPAM method to identify subgroups of patients at higher risk. In our study, the rate of major CV events was lower than expected (5 % in 5 years). Predictors of CV events were age, male, sex, heart failure, previous atherosclerotic disease, atrial fibrillation, insulin treatment, high HbA1c, heart rate and other CV diseases while being physically active was protective. RECPAM analysis indicated that history of atherosclerotic diseases and a low BMI defined worse prognosis (HR 4.51 95 % CI 3.04–6.69). Among subjects with no previous atherosclerotic disease, men with HbA1c more than 8 % were at higher CV risk (HR 2.77; 95 % CI 1.86–4.14) with respect to women. In this population, the rate of major CV events was lower than expected. This prediction model could help clinicians identify people with DM at higher CV risk and support them in achieving goals of physical activity and HbA1c.

Published
2016

42. Resistance to second-line injectables and treatment outcomes in multidrug-resistant and extensively drug-resistant tuberculosis cases

Author

Migliori, G. B., Lange, C., Centis, R., Sotgiu, G., Mutterlein, R., Hoffmann, H., Kliiman, K., De Iaco, G., Lauria, F. N., Richardson, M. D., Spanevello, A., Cirillo, D. M., Ortmann, J., Kirsten, D., Ruesch Gerdes, S., Piana, F., Gori, A., Codecasa, L. R., Ferrarese, M., Toungoussova, O. S., Ferrara, Giovanni, Matteelli, A., De Lorenzo, S., Troupioti, P., Besozzi, G., Fattorini, L., Iona, E., Gualano, A., De Mori, P., Bevilacqua, N., Girardi, E., Danilovits, M., Hollo, V., and Mariandyshev, A.

Subjects
Estonia, Pulmonary and Respiratory Medicine, Drug, medicine.medical_specialty, Tuberculosis, Settore MED/17 - Malattie Infettive, Capreomycin, FLUOROQUINOLONES, Extensively Drug-Resistant Tuberculosis, media_common.quotation_subject, Drug Resistance, Antitubercular Agents, Drug resistance, Injections, Russia, Mycobacterium tuberculosis, Multidrug-resistant tuberculosis, Drug Resistance, Multiple, Bacterial, Germany, Internal medicine, tuberculosis MYCOBACTERIUM-TUBERCULOSIS, Humans, Medicine, Registries, Treatment Failure, XDR-TB, media_common, biology, business.industry, Bacterial, Extensively drug-resistant tuberculosis, Odds ratio, biology.organism_classification, medicine.disease, Survival Analysis, Injectable second-line drugs, Injections, Intravenous, Italy, Surgery, Multiple drug resistance, drug resistance, extensively drug-resistant tuberculosis, injectable second-line drugs, multidrug-resistant tuberculosis, tuberculosis MYCOBACTERIUM-TUBERCULOSIS, XDR-TB, FLUOROQUINOLONES, Intravenous, business, Multiple, medicine.drug
Abstract

No information is currently available on the influence of injectable second-line drugs on treatment outcomes of multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis (TB) patients. To investigate this issue, a large series of MDR- and XDR-TB cases diagnosed in Estonia, Germany, Italy and the Russian Federation (Archangels Oblast) between 1999 and 2006 were analysed. All study sites performed drug susceptibility testing for first- and second-line anti-TB drugs, laboratory quality assurance and treatment delivery according to World Health Organization recommendations. Out of 4,583 culture-confirmed cases, 240 MDR- and 48 XDR-TB cases had a definitive outcome recorded (treatment success, death, failure). Among MDR- and XDR-TB cases, capreomycin resistance yielded a higher proportion of failure and death than capreomycin-susceptible cases. Resistance to capreomycin was independently associated with unfavourable outcome (logistic regression analysis: odds ratio 3.51). In the treatment of patients with multidrug-resistant and extensively drug-resistant tuberculosis, resistance to the injectable drug capreomycin was an independent predictor for therapy failure in this cohort. As Mycobacterium tuberculosis drug resistance is increasing worldwide, there is an urgent need for novel interventions in the fight against tuberculosis.

Published
2008

48. Presentazione

Author

Cacciari, M., Irti, N., Menghi, Carlo, Zaccaria, G., Ferrarese, M. R., Spada, P., Sartor, G., Degli Antoni, G., Galgano, F., Palombella, G., Marconi, P., Ferrara, A., Cubeddu, R., Azzoni, G., Chiodi, G. M., La Torre, M., De Sanctis, F., Baldassarre, A., Ferrari, V., Lombardi Vallauri, L., Maffettone, S., and Vari, M.

Published
2008

49. Clinical and operational value of the extensively drug-resistant tuberculosis definition

Author

Migliori, G. B., Besozzi, G., Girardi, E., Kliiman, K., Lange, C., Toungoussova, O. S., Ferrara, G., Cirillo, D. M., Gori, A., Matteelli, A., Spanevello, A., Codecasa, L. R., Raviglione, M. C., Ortmann, J., Kirsten, D., Ruesch-Gerdes, S., Piana, F., Ferrarese, M., De Iaco, G., De Lorenzo, S., Troupioti, P., Fattorini, L., Iona, E., Gualano, A., De Mori, P., Centis, R., Danilovits, M., Hollo, V., and Mariandyshev, A.

Subjects
Pulmonary and Respiratory Medicine, Risk, medicine.medical_specialty, Tuberculosis, Time Factors, medicine.medical_treatment, Extensively Drug-Resistant Tuberculosis, Antitubercular Agents, Drug Resistance, Drug resistance, Global Health, Communicable Diseases, Russia, Multidrug-resistant tuberculosis, Isoniazid, Medicine, tuberculosis MYCOBACTERIUM-TUBERCULOSIS, Humans, Clinical value, Extensively drug-resistant tuberculosis, Drug Resistance, Multiple, Population Surveillance, Public Health, Rifampin, Treatment Outcome, Intensive care medicine, Ethambutol, business.industry, Pyrazinamide, medicine.disease, Surgery, clinical value, drug resistance, extensively drug-resistant tuberculosis, multidrug-resistant tuberculosis, tuberculosis MYCOBACTERIUM-TUBERCULOSIS, Tuberculosis management, business, Multiple, Rifampicin, medicine.drug
Abstract

Currently, no information is available on the effect of resistance/susceptibility to first-line drugs different from isoniazid and rifampicin in determining the outcome of extensively drug-resistant tuberculosis (XDR-TB) patients, and whether being XDR-TB is a more accurate indicator of poor clinical outcome than being resistant to all first-line anti-tuberculosis (TB) drugs. To investigate this issue, a large series of multidrug-resistant TB (MDR-TB) and XDR-TB cases diagnosed in Estonia, Germany, Italy and the Russian Federation during the period 1999-2006 were analysed. Drug-susceptibility testing for first- and second-line anti-TB drugs, quality assurance and treatment delivery was performed according to World Health Organization recommendations in all study sites. Out of 4,583 culture-positive TB cases analysed, 361 (7.9%) were MDR and 64 (1.4%) were XDR. XDR-TB cases had a relative risk (RR) of 1.58 to have an unfavourable outcome compared with MDR-TB cases resistant to all first-line drugs (isoniazid, rifampicin ethambutol, streptomycin and, when tested, pyrazinamide), and an RR of 2.61 compared with "other" MDR-TB cases (those susceptible to at least one first-line anti-TB drug among ethambutol, pyrazinamide and streptomycin, regardless of resistance to the second-line drugs not defining XDR-TB). The emergence of extensively drug-resistant tuberculosis confirms that problems in tuberculosis management are still present in Europe. While waiting for new tools which will facilitate management of extensively drug-resistant tuberculosis, accessibility to quality diagnostic and treatment services should be urgently ensured and adequate public health policies should be rapidly implemented to prevent further development of drug resistance.

Published
2007

50. Use of a T-cell interferon-γ release assay for the diagnosis of tuberculous pleurisy

Author

Losi, Monica, Bossink, A., Codecasa, L., Jafari, C., Ernst, M., Thijsen, S., Cirillo, D., Ferrarese, M., Greinert, U., Fabbri, Leonardo, Richeldi, Luca, Lange, C., and European Tuberculosis Network

Subjects
Pulmonary and Respiratory Medicine, Adult, Male, Tuberculosis, Pleural effusion, T-Lymphocytes, Interferon gamma release assay, Mycobacterium tuberculosis, Pleural disease, Interferon-gamma, Bacterial Proteins, medicine, Humans, Culture filtrate protein-10, Early secretory antigenic target-6, Pleurisy, T-cell interferon-γ release assay, Aged, Aged, 80 and over, Antigens, Bacterial, biology, business.industry, Diagnostic Tests, Routine, ELISPOT, Respiratory disease, Tuberculosis, Pleural, Middle Aged, biology.organism_classification, medicine.disease, Case-Control Studies, Immunology, Female, business
Abstract

The diagnosis of pleural tuberculosis (plTB) by the analysis of pleural effusions (PEs) with standard diagnostic tools is difficult. In routine clinical practice, the present authors evaluated the performance of a commercially available Mycobacterium tuberculosis (MTB)-specific enzyme-linked immunospot assay on peripheral blood mononuclear cells (PBMCs) and pleural effusion mononuclear cells (PEMCs) in patients with suspect plTB. The T-SPOT.TB test (Oxford Immunotec Ltd, Abingdon, UK) was performed on PBMCs and PEMCs in 20 patients with a clinical and radiological suspect of plTB and in 21 control subjects with a diagnosis of PE of nontuberculous origin at four centres participating in the European Tuberculosis Network. In total, 18 (90%) out of 20 patients with plTB tested T-SPOT.TB-positive on PBMCs and 19 (95%) out of 20 on PEMCs. Among controls, T-SPOT.TB was positive in seven out of 21 (33%) patients when performed on PBMCs (these patients were assumed to be latently infected with MTB) and five (23%) out of 21 when performed on PEMCs. Sensitivity and specificity of T-SPOT.TB for the diagnosis of active plTB when performed on PEMCs were 95 and 76%, respectively. Enumerating Mycobacterium tuberculosis-specific T-cells in pleural effusion mononuclear cells by ELISPOT is feasible in routine clinical practice and may be useful for a rapid and accurate diagnosis of pleural tuberculosis.

Published
2007

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