76 results on '"Donnarumma D"'
Search Results
2. T.02.9: PREVALENCE OF CARBAPENEMASE-PRODUCING ORGANISMS (CPO) COLONIZATION BEFORE AND AFTER ENDOSCOPIC RETROGRADE CHOLANGIOPANCREATOGRAPHY (ERCP)
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Mutignani, M., primary, Bonato, G., additional, Dioscoridi, L., additional, Cottone, I., additional, Cintolo, M., additional, Palermo, A., additional, Bravo, M., additional, Pugliese, F., additional, Capasso, M., additional, Palmeri, E., additional, Donnarumma, D., additional, and Forti, E., additional
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- 2024
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3. Endoscopic papillectomy: results of a tertiary referral center experience
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Donnarumma, D., additional, Dioscoridi, L., additional, Forti, E., additional, Bonato, G., additional, Cintolo, M., additional, Pugliese, F., additional, Bravo, M., additional, Capasso, M., additional, and Mutignani, M., additional
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- 2023
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4. Biliopancreatic adverse events after pancreaticoduodenectomy: preliminary results of endoscopic management with pediatric colonoscope
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Capasso, M., additional, Mutignani, M., additional, Dioscoridi, L., additional, Bravo, M., additional, Pugliese, F., additional, Cintolo, M., additional, Bonato, G., additional, Donnarumma, D., additional, and Forti, E., additional
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- 2023
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5. T.11.4 SAFETY AND EFFICACY OF EUS-GUIDED HEPATICOGASTROSTOMY IN BENIGN BILIARY DISEASE SETTING
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Capasso, M., primary, Mutignani, M., additional, Dioscoridi, L., additional, Cintolo, M., additional, Francesco, P., additional, Bonato, G., additional, Bravo, M., additional, Ksissa, O., additional, Palermo, A., additional, Donnarumma, D., additional, and Forti, E., additional
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- 2023
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6. T.11.2 BILIOPANCREATIC ADVERSE EVENTS AFTER PANCREATICODUODENECTOMY: PRELIMINARY RESULTS OF ENDOSCOPIC MANAGEMENT WITH PEDIATRIC COLONOSCOPE
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Capasso, M., primary, Mutignani, M., additional, Dioscoridi, L., additional, Bravo, M., additional, Pugliese, F., additional, Cintolo, M., additional, Bonato, G., additional, Donnarumma, D., additional, and Forti, E., additional
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- 2023
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7. OC.13.1 THE DIAGNOSTIC YIELD OF SMALL BOWEL CAPSULE ENDOSCOPY IN DIFFERENT CLINICAL SETTINGS DEPENDS ON REFERRING PHYSICIAN
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Sgamato, C., primary, Compare, D., additional, Rocco, A., additional, Palmieri, P., additional, Laurenza, C., additional, Donnarumma, D., additional, and Nardone, G., additional
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- 2023
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8. OC.05.8 ENDOSCOPIC PREDICTORS OF RESPONSE TO OCTREOTIDE THERAPY FOR GASTROINTESTINAL BLEEDING DUE TO SMALL BOWEL ANGIOECTASIAS
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Laurenza, C., primary, Compare, D., additional, Martino, A., additional, Sgamato, C., additional, Donnarumma, D., additional, Rocco, A., additional, and Nardone, G., additional
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- 2021
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9. AF.73 DIFFUSE GASTROINTESTINAL MALT LYMPHOMA IN A PATIENT WITH ULCERATIVE COLITIS IN REMISSION
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Sgamato, C., primary, Donnarumma, D., additional, Laurenza, C., additional, Compare, D., additional, De Bonis, L., additional, and Nardone, G., additional
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- 2021
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10. Incidence, Risk Factors and Outcome of Pre-engraftment Gram-Negative Bacteremia After Allogeneic and Autologous Hematopoietic Stem Cell Transplantation: An Italian Prospective Multicenter Survey
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Girmenia, C, Bertaina, A, Piciocchi, A, Perruccio, K, Algarotti, A, Busca, A, Cattaneo, C, Raiola, Am, Guidi, S, Iori, Ap, Candoni, A, Irrera, G, Milone, G, Marcacci, G, Scimè, R, Musso, M, Cudillo, L, Sica, S, Castagna, L, Corradini, P, Marchesi, F, Pastore, D, Alessandrino, Ep, Annaloro, C, Ciceri, F, Santarone, S, Nassi, L, Farina, C, Viscoli, C, Rossolini, Gm, Bonifazi, F, Rambaldi, A, Capria, S, Mastronuzzi, A, Pagliara, D, Bernaschi, P, Amico, L, Carotti, A, Mencacci, A, Bruno, B, Costa, C, Passi, A, Ravizzola, G, Angelucci, E, Marchese, A, Pecile, P, Ventura, G, Fanin, R, Scarparo, C, Barbaro, A, Leotta, S, Marchese, Ae, Becchimanzi, C, Donnarumma, D, Tringali, S, Baldi, Mt, Scalone, R, Picardi, A, Arcese, W, Fontana, C, Giammarco, S, Spanu, T, Crocchiolo, R, Casari, E, Mussetti, A, Conte, E, Ensoli, F, Miragliotta, G, Marone, P, Arghittu, M, Greco, R, Forcina, A, Chichero, P, Di Bartolomeo, P, Fazii, P, Kroumova, V, Decembrino, N, Zecca, M, Pisapia, G, Palazzo, G, Lanino, E, Faraci, M, Castagnola, E, Bandettini, R, Pastano, R, Sammassimo, S, Passerini, R, Stefani, Pm, Gherlinzoni, F, Rigoli, R, Prezioso, L, Cambò, B, Calderaro, A, Carella, Am, Cascavilla, N, Labonia, Mt, Celeghini, I, Mordini, N, Piana, F, Vacca, A, Sanna, M, Podda, G, Corsetti, Mt, Rocchetti, A, Cilloni, D, De Gobbi, M, Bianco, O, Fagioli, F, Carraro, F, De Intinis, G, Severino, A, Proia, A, Parisi, G, Vallisa, D, Confalonieri, M, Russo, D, Malagola, M, Galieni, P, Falcioni, S, Travaglini, V, Raimondi, R, Borghero, C, Pavan, G, Prete, A, Belotti, T, Ambretti, S, Imola, M, Mianulli, Am, Pedna, Mf, Cesaro, S, Lo Cascio, G, Ferrari, A, Piedimonte, M, Santino, I, Calandrelli, M, Olivieri, A, Orecchioni, F, Mirabile, M, Centurioni, R, Gironacci, L, Caravelli, D, Gallo, S, De Filippi, M, Cupelli, L, Dentamaro, T, Falco, S, Eugenio, Os, Marotta, S, Risitano, A, Lula, D, Musto, P, Pietrantuono, G, Traficante, A, Cerchiara, E, Tirindelli, Mc, Dicuonzo, G, Chierichini, A, Anaclerico, B, and Placanica, P.
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- 2017
11. Miglioramenti della qualità di vita correlata alla salute (HRQoL) con Liraglutide 3 mg rispetto a placebo per la gestione del peso
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BUSCEMI, Silvio, Kolotkin, RL, Fujioka, K, Wolden, ML, Brett, J, Donnarumma, D, Bjorner, JB, Buscemi, S, Kolotkin, RL, Fujioka, K, Wolden, ML, Brett, J, Donnarumma, D, and Bjorner, JB
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Liraglutide, quality of life, obesity - Abstract
Obiettivo: L'obesità ha un impatto negativo sulla qualità di vita correlata alla salute (HRQoL), la cui gravità dipende dalla severità dell’obesità. Lo studio SCALE (Satiety and Clinical Adiposity - Liraglutide Evidence) Obesity and Prediabetes ha valutato l’efficacia di Liraglutide 3 mg in aggiunta a dieta ed esercizio fisico sulla HRQoL in soggetti con sovrappeso o obesità, con o senza prediabete. Metodi: I soggetti (BMI ≥ 27 kg/m2 con ≥ 1 comorbidità o ≥ 30 kg/m2) sono stati randomizzati (2:1), a ricevere liraglutide 3 mg (n = 2487) o placebo (n = 1244) una volate al giorno s.c., in aggiunta ad un programma di intervento sullo stile di vita (dieta ipocalorica con deficit di 500 Kcal/die e 150 min/settimana di esercizio fisico). La qualità di vita correlata alla salute (HRQoL) è stata valutata utilizzando i questionari IWQOL-Lite (Impatto del peso sulla qualità della vita-Lite) e SF-36 v2 (Short-Form 36) al basale, a 6 mesi e a 1 anno (fine dello studio). Il questionario TRIM-Weight (Impatto correlato al trattamento specifico per il peso) è stato completato 6 mesi e alla fine dello studio. I dati sono stati riportati come media ± deviazione standard (DS). Analisi statistiche condotte: ANCOVA con LOCF. Risultati: Caratteristiche al basale: 78,5% femmine, età 45,1 anni, peso kg 106,2, BMI 38,3 kg/m2. I soggetti trattati con liraglutide 3 mg hanno mostrato miglioramenti significativamente maggiori nel punteggio totale dell’ IWQOL-Lite [(10.6±13.3) vs placebo (7.6±12.8; ED 3.1 [95% IC: 2.2; 4.0]; p
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- 2015
12. Human protective response induced by meningococcus B vaccine is mediated by the synergy of multiple bactericidal epitopes
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Giuliani, M., primary, Bartolini, E., additional, Galli, B., additional, Santini, L., additional, Lo Surdo, P., additional, Buricchi, F., additional, Bruttini, M., additional, Benucci, B., additional, Pacchiani, N., additional, Alleri, L., additional, Donnarumma, D., additional, Pansegrau, W., additional, Peschiera, I., additional, Ferlenghi, I., additional, Cozzi, R., additional, Norais, N., additional, Giuliani, M. M., additional, Maione, D., additional, Pizza, M., additional, Rappuoli, R., additional, Finco, O., additional, and Masignani, V., additional
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- 2018
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13. Dynamic behaviour of multilamellar vesicles under Poiseuille flow
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Pommella, A., primary, Donnarumma, D., additional, Caserta, S., additional, and Guido, S., additional
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- 2017
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14. New developments in ultrasound-modulated optical tomography made by heterodyne holography
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Brodoline, A., primary, Donnarumma, D., additional, and Gross, M., additional
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- 2016
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15. High numerical aperture holographic microscopy reconstruction with extended z range
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Verrier, N., primary, Donnarumma, D., additional, Tessier, G., additional, and Gross, M., additional
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- 2015
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16. Early interim 2-(1)fluoro-2-deoxy-D-glucose positron emission tomography is prognostically superior to peripheral blood lymphocyte/monocyte ratio at diagnosis in classical Hodgkin's lymphoma
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Romano, A., primary, Vetro, C., additional, Donnarumma, D., additional, Forte, S., additional, Ippolito, M., additional, and Di Raimondo, F., additional
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- 2012
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17. Endoscopic ultrasonography in gastric lymphomas: appraisal on reliability in long-term follow-up.
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Vetro C, Romano A, Chiarenza A, Conticello C, Donnarumma D, Gorgone A, Coppolino F, Palumbo GA, Bonanno G, Di Raimondo F, Vetro, Calogero, Romano, Alessandra, Chiarenza, Annalisa, Conticello, Concetta, Donnarumma, Daniela, Gorgone, Ausilia, Coppolino, Francesco, Palumbo, Giuseppe Alberto, Bonanno, Giacomo, and Di Raimondo, Francesco
- Abstract
The reliability of endoscopic ultrasonography (EUS) in follow-up management of gastric lymphomas has not been clearly validated. We conducted a retrospective analysis on 23 patients, 12 affected by mucosa-associated lymphoid tissue (MALT) lymphoma, eight by diffuse large B-cell lymphoma, and three by high-grade lymphoma with low-grade component, all treated with a stomach-conservative approach. One hundred and twenty matched evaluations with both EUS and endoscopy with biopsy (E-Bx) were performed, according to validated guidelines and clinical judgment. At a median follow-up of 87 months ranged between 9.5 and 166 months, the analysis of progression-free survival and disease-free survival showed a strict relationship between the persistence of EUS abnormalities and the clinical outcome in patients with MALT lymphoma (p = 0.0079; p = 0.02) but not in patients with high-grade lymphoma. In conclusion, EUS evaluation does not seem reliable in follow-up management of high-grade lymphomas, although it could have a great clinical impact in the management of MALT lymphoma. [ABSTRACT FROM AUTHOR]
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- 2012
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18. Bortezomib-thalidomide-dexamethasone is superior to thalidomide-dexamethasone as consolidation therapy following autologous hematopoietic stem-cell transplantation in patients with newly diagnosed multiple myeloma
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Cavo, Michele, Pantani, Lucia, Petrucci, Maria Teresa, Patriarca, Francesca, Zamagni, Elena, Donnarumma, Daniela, Crippa, Claudia, Boccadoro, Mario, Perrone, Giulia, Falcone, Antonietta, Nozzoli, Chiara, Zambello, Renato, Masini, Luciano, Furlan, Anna, Brioli, Annamaria, Derudas, Daniele, Ballanti, Stelvio, Dessanti, Maria Laura, De Stefano, Valerio, Carella, Angelo Michele, Marcatti, Magda, Nozza, Andrea, Ferrara, Felicetto, Callea, Vincenzo, Califano, Catello, Pezzi, Annalisa, Baraldi, Anna, Grasso, Mariella, Musto, Pellegrino, Palumbo, Antonio COLLABORATORI: Tosi, P, Motta, Mr, Rizzi, S, Fanin, R, Buttignol, S, Foà, R, Levi, A, Calabrese, E, Rambaldi, A, Galli, M, Rossi, G, Ferrari, S, Bringhen, S, Leoni, P, Offidani, M, Polloni, C, Corradini, P, Montefusco, V, Torelli, G, Narni, Franco, Fioritoni, G, Spadano, A, Cortelazzo, S, Pescosta, N, Billio, A, Lambertenghi Deliliers, G, Baldini, L, Onida, F, Annaloro, C, La Nasa, G, Ledda, A, Zaccaria, A, Cellini, C, De Fabritiis, P, Caravita, T, Siniscalchi, A, Cascavilla, N, Bosi, A, Semenzato, G, Gugliotta, L, Merli, F, Gherlinzoni, F, Angelucci, E, Martelli, M, Petti, Mc, Pisani, F, Leone, G, Rossi, E, Za, T, Fianchi, L, Catania, G, Spriano, M, Ciceri, F, Peccatori, J, Girlanda, S, Santoro, A, Castagna, L, Palmieri, S, Nobile, F, D'Arco, Am, Levis, A, Primon, V, Tamiazzo, S, Guardigni, L, Pasini, S, Gallamini, A, Pietrantuono, G, Martorelli, Mc, Fattori, P, Pasquini, E, Galieni, P, Ruggieri, M, Morandi, S, Tajana, M, Amadori, D, Ronconi, S, Cangini, D, Ceccolini, M, Gobbi, M, Ballerini, F, Pane, F, Catalano, L, Cangialosi, C, Vallisa, D, Lazzaro, A, Paladini, G, De Sabbata, G, Mozzana, R, Ciambelli, F, Pinotti, G, Rodeghiero, F, Elice, F, Cantore, N, Volpe, S, Pavone, V, Mele, A, Pogliani, E, Rossini, F, Liberati, A, Majolino, I, De Rosa, L, Amadori, S, Rizzo, M, Lauria, F, Gozzetti, A, Aglietta, M, Capaldi, A, Quarta, G, Mele, G, Storti, S, Fraticelli, V, Morabito, F, Gentile, C, Capalbo, S, Gianni, A, Magni, M, Mettivier, V, Nunziata, G, Rizzoli, V, Giuliani, N, Crugnola, M, Bernasconi, C, Fregoni, V, Visani, G, Olivieri, A, Pizzuti, M, La Verde, G, Moscetti, A, Avvisati, G, Tirindelli, M, Longinotti, M, Podda, L, Gallo, E, Pregno, P, Dammacco, F, Perosa, F, Russo, D, Roccaro, A, Bacigalupo, A, Dominietto, A, Musolino, C, Quartarone, E., Cavo M, Pantani L, Petrucci MT, Patriarca F, Zamagni E, Donnarumma D, Crippa C, Boccadoro M, Perrone G, Falcone A, Nozzoli C, Zambello R, Masini L, Furlan A, Brioli A, Derudas D, Ballanti S, Dessanti ML, De Stefano V, Carella AM, Marcatti M, Nozza A, Ferrara F, Callea V, Califano C, Pezzi A, Baraldi A, Grasso M, Musto P, Palumbo A., Cavo, Michele, Pantani, Lucia, Petrucci, Maria Teresa, Patriarca, Francesca, Zamagni, Elena, Donnarumma, Daniela, Crippa, Claudia, Boccadoro, Mario, Perrone, Giulia, Falcone, Antonietta, Nozzoli, Chiara, Zambello, Renato, Masini, Luciano, Furlan, Anna, Brioli, Annamaria, Derudas, Daniele, Ballanti, Stelvio, Dessanti, Maria Laura, De Stefano, Valerio, Carella, Angelo Michele, Marcatti, Magda, Nozza, Andrea, Ferrara, Felicetto, Callea, Vincenzo, Califano, Catello, Pezzi, Annalisa, Baraldi, Anna, Grasso, Mariella, Musto, Pellegrino, Palumbo, Antonio, Cavo, M, Pantani, L, Petrucci, M, Patriarca, F, Zamagni, E, Donnarumma, D, Crippa, C, Boccadoro, M, Perrone, G, Falcone, A, Nozzoli, C, Zambello, R, Masini, L, Furlan, A, Brioli, A, Derudas, D, Ballanti, S, Dessanti, M, De Stefano, V, Carella, A, Marcatti, M, Nozza, A, Ferrara, F, Callea, V, Califano, C, Pezzi, A, Baraldi, A, Grasso, M, Musto, P, Palumbo, A, Tosi, P, Motta, M, Rizzi, S, Fanin, R, Buttignol, S, Foà, R, Levi, A, Calabrese, E, Rambaldi, A, Galli, M, Rossi, G, Ferrari, S, Bringhen, S, Leoni, P, Offidani, M, Polloni, C, Corradini, P, Montefusco, V, Torelli, G, Narni, F, Fioritoni, G, Spadano, A, Cortelazzo, S, Pescosta, N, Billio, A, Lambertenghi Deliliers, G, Baldini, L, Onida, F, Annaloro, C, La Nasa, G, Ledda, A, Zaccaria, A, Cellini, C, De Fabritiis, P, Caravita, T, Siniscalchi, A, Cascavilla, N, Bosi, A, Semenzato, G, Gugliotta, L, Merli, F, Gherlinzoni, F, Angelucci, E, Martelli, M, Petti, M, Pisani, F, Leone, G, Rossi, E, Za, T, Fianchi, L, Catania, G, Spriano, M, Ciceri, F, Peccatori, J, Girlanda, S, Santoro, A, Castagna, L, Palmieri, S, Nobile, F, D'Arco, A, Levis, A, Primon, V, Tamiazzo, S, Guardigni, L, Pasini, S, Gallamini, A, Pietrantuono, G, Martorelli, M, Fattori, P, Pasquini, E, Galieni, P, Ruggieri, M, Morandi, S, Tajana, M, Amadori, D, Ronconi, S, Cangini, D, Ceccolini, M, Gobbi, M, Ballerini, F, Pane, F, Catalano, L, Cangialosi, C, Vallisa, D, Lazzaro, A, Paladini, G, De Sabbata, G, Mozzana, R, Ciambelli, F, Pinotti, G, Rodeghiero, F, Elice, F, Cantore, N, Volpe, S, Pavone, V, Mele, A, Pogliani, E, Rossini, F, Liberati, A, Majolino, I, De Rosa, L, Amadori, S, Rizzo, M, Lauria, F, Gozzetti, A, Aglietta, M, Capaldi, A, Quarta, G, Mele, G, Storti, S, Fraticelli, V, Morabito, F, Gentile, C, Capalbo, S, Gianni, A, Magni, M, Mettivier, V, Nunziata, G, Rizzoli, V, Giuliani, N, Crugnola, M, Bernasconi, C, Fregoni, V, Visani, G, Olivieri, A, Pizzuti, M, La Verde, G, Moscetti, A, Avvisati, G, Tirindelli, M, Longinotti, M, Podda, L, Gallo, E, Pregno, P, Dammacco, F, Perosa, F, Russo, D, Roccaro, A, Bacigalupo, A, Dominietto, A, Musolino, C, and Quartarone, E
- Subjects
Male ,Boronic Acid ,medicine.medical_treatment ,PLUS DEXAMETHASONE ,Phases of clinical research ,Kaplan-Meier Estimate ,Hematopoietic stem cell transplantation ,Biochemistry ,Antineoplastic Agent ,Bortezomib-thalidomide-dexamethasone ,Bortezomib ,Immunosuppressive Agent ,Autologous stem-cell transplantation ,MULTIPLE MYELOMA ,Antineoplastic Combined Chemotherapy Protocols ,thalidomide-dexamethasone ,Multiple myeloma ,RANDOMIZED PHASE-3 ,LENALIDOMIDE ,STEM CELL TRANSPLANTATION ,Hematopoietic Stem Cell Transplantation ,PHASE-III TRIAL ,Hematology ,Middle Aged ,CHEMOTHERAPY ,Prognosis ,Boronic Acids ,Combined Modality Therapy ,Thalidomide ,Transplantation, Autologou ,Pyrazines ,HIGH-DOSE MELPHALAN ,INDUCTION TREATMENT ,Female ,Autologous ,Immunosuppressive Agents ,Pyrazine ,Human ,medicine.drug ,MAINTENANCE THERAPY ,medicine.medical_specialty ,DOXORUBICIN ,Antineoplastic Agents, Hormonal ,Prognosi ,Immunology ,Urology ,Antineoplastic Agents ,dexamethasone ,Transplantation, Autologous ,Disease-Free Survival ,Dexamethasone ,Humans ,Multiple Myeloma ,Cell Biology ,medicine ,Autologous transplantation ,METAANALYSIS ,Transplantation ,Antineoplastic Combined Chemotherapy Protocol ,Hormonal ,business.industry ,medicine.disease ,Surgery ,business ,Settore MED/15 - Malattie del Sangue - Abstract
In a randomized, phase 3 study, superior complete/near-complete response (CR/nCR) rates and extended progression-free survival were demonstrated with bortezomib-thalidomide-dexamethasone (VTD) versus thalidomide-dexamethasone (TD) as induction therapy before, and consolidation after, double autologous stem cell transplantation for newly diagnosed myeloma patients (intention-to-treat analysis; VTD, n = 236; TD, n = 238). This per-protocol analysis (VTD, n = 160; TD, n = 161) specifically assessed the efficacy and safety of consolidation with VTD or TD. Before starting consolidation, CR/nCR rates were not significantly different in the VTD (63.1%) and TD arms (54.7%). After consolidation, CR (60.6% vs 46.6%) and CR/nCR (73.1% vs 60.9%) rates were significantly higher for VTD-treated versus TD-treated patients. VTD consolidation significantly increased CR and CR/nCR rates, but TD did not (McNemar test). With a median follow-up of 30.4 months from start of consolidation, 3-year progression-free survival was significantly longer for the VTD group (60% vs 48% for TD). Grade 2 or 3 peripheral neuropathy (8.1% vs 2.4%) was more frequent with VTD (grade 3, 0.6%) versus TD consolidation. The superior efficacy of VTD versus TD as induction was retained despite readministration as consolidation therapy after double autologous transplantation. VTD consolidation therapy significantly contributed to improved clinical outcomes observed for patients randomly assigned to the VTD arm of the study. The study is registered at www.clinicaltrials.gov as #NCT01134484.
- Published
- 2012
19. Atypical COVID-19 dynamics in a patient with mantle cell lymphoma exposed to rituximab
- Author
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Stefania Crisci, Giuseppe Portella, Umberto Falcone, Rosaria De Filippi, Gianpaolo Marcacci, Antonio Pinto, Roberto Parrella, Giovanni Micallo, Silvia D’Ovidio, Anna Annunziata, Daniela Donnarumma, Annarosaria De Chiara, Francesco Volzone, Giuseppe Fiorentino, Marcacci, G., Fiorentino, G., Volzone, F., Falcone, U., Parrella, R., Donnarumma, D., D'Ovidio, S., Annunziata, A., Micallo, G., Portella, G., De Chiara, A., De Filippi, R., Crisci, S., and Pinto, A.
- Subjects
Cancer Research ,Epidemiology ,Population ,Short Report ,Infectious and parasitic diseases ,RC109-216 ,medicine.disease_cause ,Asymptomatic ,Virus ,Serology ,03 medical and health sciences ,0302 clinical medicine ,hemic and lymphatic diseases ,medicine ,education ,RC254-282 ,Anti-CD20 antibodies ,030304 developmental biology ,Coronavirus ,0303 health sciences ,education.field_of_study ,Anti-CD20 antibodie ,Mantle cell lymphoma ,biology ,business.industry ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,COVID-19 ,medicine.disease ,Infectious Diseases ,Oncology ,030220 oncology & carcinogenesis ,Immunology ,biology.protein ,Rituximab ,medicine.symptom ,Antibody ,business ,medicine.drug - Abstract
Patients with non-hodgkin lymphomas (NHL) represent a population of special interest during the current Coronavirus disease-19 (COVID-19) pandemics. NHLs are associated with disease- and treatment-related immunodeficiencies which may generate unusual COVID-19 dynamics and pose unique management challenges. We report the unusual clinical course of COVID-19 in a patient with mantle cell lymphoma (MCL) exposed to nine doses of Rituximab shortly before infection with severe acute respiratory syndrome corona virus 2 (SARS-CoV-2). He had a prolonged asymptomatic phase, with negative molecular and antibody testing for SARS-CoV-2, followed by a rapidly progressive evolution to severe COVID-19. Despite detection of viral RNA overlapped with first symptoms occurrence, anti-SARS-CoV-2 antibodies displayed an asynchronous pattern, with IgG first appearing two days after RNA positivity and IgM never being detected throughout the entire clinical course. While disease-associated immune derangements and/or previous treatments involving anti-CD20 antibodies might have contributed to COVID-19 dynamics in our patient, data suggests that antibody testings, without concurrent molecular assessment for SARS-CoV-2, may turn inadequate for monitoring of MCL patients, and in general NHL patients heavily exposed to anti-CD20 antibodies, during the current pandemics. Since these patients should not be denied or delayed effective treatments, we suggest that repeated molecular testing of nasopharyngeal swab should be implemented in these subjects despite a negative serology and absence of symptoms of SARS-CoV-2 infection. For the same reasons, a customized strategy needs to be developed for patients exposed to anti-CD20 antibodies, based on different features and mechanism of action of currently available SARS-CoV-2 vaccines.
- Published
- 2021
20. Dynamic behaviour of Multilamellar Vesicles under Poiseuille flow
- Author
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Dario Donnarumma, Angelo Pommella, Sergio Caserta, Stefano Guido, Matériaux, ingénierie et science [Villeurbanne] (MATEIS), Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA), Laboratoire Charles Coulomb (L2C), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Pommella, A., Donnarumma, D., Caserta, S., and Guido, S.
- Subjects
Materials science ,Chemistry (all) ,Fluid Dynamics (physics.flu-dyn) ,FOS: Physical sciences ,Video microscopy ,02 engineering and technology ,General Chemistry ,Physics - Fluid Dynamics ,021001 nanoscience & nanotechnology ,Hagen–Poiseuille equation ,Condensed Matter Physics ,01 natural sciences ,Shear rate ,Viscosity ,Rheology ,Chemical engineering ,Lamellar phase ,Phase (matter) ,0103 physical sciences ,010306 general physics ,0210 nano-technology ,Shear flow ,[PHYS.COND.CM-SCM]Physics [physics]/Condensed Matter [cond-mat]/Soft Condensed Matter [cond-mat.soft] - Abstract
Surfactant solutions exhibit multilamellar surfactant vesicles (MLVs) under flow conditions and in concentration ranges which are found in a large number of industrial applications. MLVs are typically formed from a lamellar phase and play an important role in determining the rheological properties of surfactant solutions. Despite the wide literature on the collective dynamics of flowing MLVs, investigations on the flow behavior of single MLVs are scarce. In this work, we investigate a concentrated aqueous solution of linear alkylbenzene sulfonic acid (HLAS), characterized by MLVs dispersed in an isotropic micellar phase. Rheological tests show that the HLAS solution is a shear-thinning fluid with a power law index dependent on the shear rate. Pressure-driven shear flow of the HLAS solution in glass capillaries is investigated by high-speed video microscopy and image analysis. The so obtained velocity profiles provide evidence of a power-law fluid behaviour of the HLAS solution and images show a flow-focusing effect of the lamellar phase in the central core of the capillary. The flow behavior of individual MLVs shows analogies with that of unilamellar vesicles and emulsion droplets. Deformed MLVs exhibit typical shapes of unilamellar vesicles, such as parachute and bullet-like. Furthermore, MLV velocity follows the classical Hetsroni theory for droplets provided that the power law shear dependent viscosity of the HLAS solution is taken into account. The results of this work are relevant for the processing of surfactant-based systems in which the final properties depend on flow-induced morphology, such as cosmetic formulations and food products., Comment: 11 pages, 7 figures. Accepted for publication in Soft Matter
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- 2017
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21. A phase II study of dose-dense and dose-intense ABVD (ABVDDD-DI) without consolidation radiotherapy in patients with advanced Hodgkin lymphoma
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Annamaria Bonelli, Franco Ionna, Tindaro Gatani, Elisabetta De Lutio, Cristina Becchimanzi, Gaetano Corazzelli, Gianpaolo Marcacci, Antonello Pinto, Rosaria De Filippi, Annarosaria De Chiara, Ferdinando Frigeri, Secondo Lastoria, Gaetana Capobianco, Filippo Russo, Francesco Volzone, Daniela Donnarumma, Luigi Aloj, Russo, F, Corazzelli, G, Frigeri, F, Capobianco, G, Aloj, L, Volzone, F, De Chiara, A, Bonelli, A, Gatani, T, Marcacci, G, Donnarumma, D, Becchimanzi, C, de Lutio, E, Ionna, F, DE FILIPPI, Rosaria, Lastoria, S, and Pinto, A.
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Adult ,Male ,medicine.medical_specialty ,Adolescent ,Dacarbazine ,Phases of clinical research ,Kaplan-Meier Estimate ,Neutropenia ,Vinblastine ,Bleomycin ,Gastroenterology ,Drug Administration Schedule ,Young Adult ,chemistry.chemical_compound ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,Neoplasm Staging ,Dose-Response Relationship, Drug ,business.industry ,Hematology ,Middle Aged ,medicine.disease ,Hodgkin Disease ,Surgery ,Regimen ,Treatment Outcome ,chemistry ,ABVD ,Doxorubicin ,Toxicity ,Female ,Radiotherapy, Adjuvant ,business ,Follow-Up Studies ,medicine.drug - Abstract
Summary We explored activity and safety of a dose-dense/dose-intense adriamycin, bleomycin, vinblastine and dacarbazine regimen (ABVDDD-DI) in 82 patients with advanced Hodgkin Lymphoma. Patients entered a two-stage Bryant-Day Phase II study to receive six cycles of ABVDDD-DI without consolidation radiotherapy. Cycles were supported with granulocyte colony-stimulating factor and delivered every 21 d; drugs were administered on days 1 and 11 at the same doses of standard ABVD except for doxorubicin (35 mg/m2; first four cycles only). Co-primary endpoints were complete response (CR) rate and severe acute cardiopulmonary toxicity; secondary endpoints were event-free (EFS) and disease-free survival (DFS). All patients received the four doxorubicin-intensified courses and 96% concluded all six cycles (82·3% within the intended 18 weeks). This translated into a 66·9% increase of received dose-intensity for doxorubicin and 31·8% for the other agents over standard ABVD. The CR rate was 95·1% (78/82) and 87·8% (72/82) achieved a metabolic CR after two cycles. Cardiopulmonary toxicity never exceeded grade 2 and affected 14·6% of patients. Most frequent toxicities were grade 4 neutropenia (10%) and anaemia (9%), grade 3 infection (17%) and grade 2 mucocutaneous changes (30%). Five-year EFS and DFS was 88·3% and 93·7%, respectively. ABVDDD-DI regimen was well-tolerated and ensured substantial CR and EFS rates without radiotherapy.
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- 2014
22. A 41-gene signature predicts complete response (CR) to Bortezomib-Thalidomide-Dexamethasone (VTD) as induction therapy prior to autologous stem-cell transplantation (ASCT) in multiple myeloma (MM)
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Carolina Terragna, Lucia Pantani, Massimo Offidani, Franco Narni, Sara Bringhen, Michele Baccarani, Sergio Cortelazzo, Daniela Donnarumma, Francesca Patriarca, Michele Cavo, Tommaso Caravita, Alfonso Zaccaria, Giuseppe Fioritoni, Giovanni Martinelli, Alessandro Rambaldi, Giorgio La Nasa, Anna Levi, Sandra Durante, Marina Martello, Luca Baldini, Daniel Remondini, Claudia Crippa, Paolo Corradini, Terragna, Carolina, Remondini, Daniel, Martello, Marina, Pezzi, Annalisa, Patriarca, Francesca, Levi, Anna, Pantani, Lucia, Donnarumma, Daniela, Montanaro, Lorenzo, Crippa, Claudia, Bringhen, Sarah, Rambaldi, Alessandro, Offidani, Massimo, Corradini, Paolo, Narni, Franco, Fioritoni, Giuseppe, Zaccaria, Alfonso, Baldini, Luca, Caravita, Tommaso, La Nasa, Giorgio, Cortellazzo, Sergio, Martinelli, Giovanni, Cavo, Michele, Terragna, C, Remondini, D, Durante, S, Martello, M, Patriarca, F, Levi, A, Pantani, L, Donnarumma, D, Crippa, C, Bringhen, S, Rambaldi, A, Offidani, M, Corradini, P, Narni, F, Fioritoni, G, Zaccaria, A, Baldini, L, Caravita, T, La Nasa, G, Cortelazzo, S, Martinelli, G, Baccarani, M, and Cavo, M
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Oncology ,medicine.medical_specialty ,education.field_of_study ,medicine.medical_treatment ,Immunology ,Population ,Phases of clinical research ,Cell Biology ,Hematology ,Gene signature ,Biology ,medicine.disease ,Bioinformatics ,Biochemistry ,Isotype ,Regimen ,Autologous stem-cell transplantation ,Internal medicine ,medicine ,education ,Multiple myeloma ,Neoadjuvant therapy - Abstract
Abstract 805FN2 Background. Achievement of CR is generally associated with improved clinical outcomes for patients (pts) with MM and represents a primary endpoint of current clinical trials. The GIMEMA Italian Myeloma Network designed a phase 3 study to demonstrate that the triplet VTD regimen was superior over a doublet such as thalidomide-dexamethasone (TD) as induction therapy prior to double ASCT for newly diagnosed MM. On an intention-to-treat basis, the rate of complete or near complete response (CR/nCR) was 31% for the 236 pts on VTD induction therapy, while it was 11% (p Methods. For this purpose, in a molecular substudy to the main clinical study we assessed the ability of gene expression profile (GEP) to predict attainment of CR/nCR in 122 pts enrolled in the VTD arm of the study. Their characteristics at baseline, including cytogenetic abnormalities, were comparable with those of the whole population of 236 pts. Highly purified CD138+ plasma cells were obtained at diagnosis from each of these pts and were profiled for gene expression using the Affymetrix U133 Plus2.0 platform. In order to build a low-dimensional signature with optimal performance, genomic data were analyzed with an original algorithm that exploits quadratic discriminant analysis with a bottom-up approach that builds N-gene signatures starting from two-dimensional signatures. Gene models were applied to test datasets to predict achievement of either CR/nCR or less than nCR, and classification performances were validated by a leave-one-out crossvalidation procedure. Results. Thirty four pts out of the 122 (28%) who were included in the present analysis achieved a CR/nCR, while the remaining 88 patients failed this objective. The molecular approach described above allowed to identify several gene signatures among which we choose a 163-gene signature that provided a predictive capability of 79% sensitivity, 87% specificity, 71% positive predictive value (PPV) and 92% negative predictive value (NPV). These expression values were used in an unsupervised hierarchical clustering to stratify the population of 122 profilated pts into 3 well defined subgroups. Seventy nine pts were included in subgroup A, while the remaining 43 pts were included in either subgroup B (n=22) or subgroup C (n=21). Notably, 19 out the 34 CR/nCR pts (56%) clustered in subgroup B, whereas the remaining 15 pts were randomly distributed within subgroup A. Analysis of demographic and disease characteristics of the pts belonging to the 3 major subgroups, revealed that in subgroup B the frequencies of pts carrying del(13q) (78%) or del(17p) (22%) or with an IgA isotype (54%) were significantly higher in comparison with the corresponding values found in subgroup A (47%, 4%, and 10%, respectively) and subgroup C (38%, 10%, and 5%, respectively). In order to obtain a more feasible set of genes predictive of CR/nCR, several smaller signatures originating from the 163-gene signature were further analyzed by means of the same algorithm described above. The best predictive capability was obtained with a 41-gene signature that provided 88% sensitivity, 97% specificity, 91% PPV and 95% NPV. A GeneGo ® network analysis of genes included in the signatures showed that the most relevant network nodes included tumour suppressor genes (FBXW7 and MAD), genes involved in inflammatory response (TREM1 and TLR4) and genes involved in B cell development (IKZF1, IL10 and NFAM1). Genes included in the signatures do not gather in specific chromosomes, thus confirming the absence of bias on selection of signatures genes, potentially due to prevalence of MM typical chromosomal aberrations. Conclusions. GEP analysis of a subgroup of pts who received VTD induction therapy allowed to provide a 41-gene signature that was able to predict attainment of CR/nCR and, conversely, failure to achieve at least nCR in 91% and 95% of cases, respectively. These favorable results might represent a first step towards the possible application of a tailored therapy based on the single patient's genetic background. Supported by: Fondazione Del Monte di Bologna e Ravenna, Ateneo RFO grants (M.C.) BolognAIL. Disclosures: Bringhen: Celgene: Honoraria; Janssen-Cilag: Honoraria; Novartis: Honoraria; Merck Sharp & Dhome: Membership on an entity's Board of Directors or advisory committees. Offidani:Janssen: Honoraria; Celgene: Honoraria.
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- 2013
23. Study of oxidation products in aged olive oils by GC and HPLC techniques coupled to mass spectrometry to discriminate olive oil lipid substances in archaeological artifacts from ancient Taormina (Italy).
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Chiaia V, Micalizzi G, Donnarumma D, Irto A, Bretti C, Venuti M, Lando G, Mondello L, and Cardiano P
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- Italy, Chromatography, High Pressure Liquid methods, Gas Chromatography-Mass Spectrometry methods, Lipids chemistry, Lipids analysis, Fatty Acids analysis, Fatty Acids chemistry, Mass Spectrometry methods, Olive Oil chemistry, Oxidation-Reduction, Archaeology methods
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The identification of archaeological biomarkers is one of the main objectives of analytical chemistry in the archaeological field. However, no information is currently available on biomarkers able to unambiguously indicate the presence of olive oil, a cornerstone of Mediterranean ancient societies lifestyle, in an organic residue. This study aims to bridge this gap by a thorough characterization of the degradation products of extra-virgin olive oils (EVOOs) resulting from in-lab thermal oxidative treatments, with the primary goal of revealing potential archaeological biomarkers for olive oil. Thirty-three EVOOs sourced from eleven different monocultivars across five Italian regions (Sicily, Apulia, Lazio, Tuscany, and Liguria) and Spain, were analyzed before and after thermal oxidation. In addition, an identical thermal treatment was employed on pure triglyceride standards (triolein, trilinolein, and tristearin), due to the high concentration of their fatty acids in EVOO discerning their degradation patterns. A combination of analytical strategies was employed, including HPLC-MS and HPLC-ELSD for the complete evaluation of the intact lipids (triglycerides, diglycerides, and their oxidative species) in olive oils before and after oxidation, and HS-SPME-GC-MS and GC-FID for the characterization of secondary oxidation products formed by the thermal treatment. In addition, to elucidate the fatty acid distribution in the oxidized EVOOs by GC-MS and GC-FID techniques a derivatization step was performed to convert lipid compounds into trimethylsilyl (TMS) derivatives. A chemometric approach was used to thoroughly interpret the data obtained from intact and oxidized samples. This comprehensive investigation sheds light on the chemical transformations of EVOOs under thermal oxidative conditions and indicates mono-carboxylic acids such as pentanoic, hexanoic, heptanoic, octanoic, nonanoic, and decanoic acids as potential archaeological biomarkers for the presence of lipid substances coming from olive oil in archaeological organic residues. Finally, lipid contents from twenty-four real archaeological samples, grouped in amphorae (10), unguentaria (5), and lamps (9), excavated from the Roman domus of Villa San Pancrazio in Taormina (Italy), were determined. The analytical results obtained from amphorae samples revealed the presence of the selected olive oil-specific archaeological biomarkers, an information extremely interesting considering that this type of amphorae have so far been solely associated with the storage of wine., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)
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- 2024
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24. Natural Health Products for Anti-Cancer Treatment: Evidence and Controversy.
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Conti V, Polcaro G, De Bellis E, Donnarumma D, De Rosa F, Stefanelli B, Corbi G, Sabbatino F, and Filippelli A
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Natural Health Products (NHPs) have long been considered a valuable therapeutic approach for the prevention and treatment of various diseases, including cancer. However, research on this topic has led to inconclusive and often controversial results. This review aims to provide a comprehensive update of the effects and mechanisms related to the use of NHPs, to describe the results of randomized clinical trials (RCTs) on their effects in cancer patients, and to critically discuss factors influencing clinical outcomes. RCTs available in the literature, even those studying the same NHP, are very heterogeneous in terms of indications, doses, route and timing of administration, and outcomes evaluated. Silymarin, ginsenoside, and vitamin E appear to be useful in attenuating adverse events related to radiotherapy or chemotherapy, and curcumin and lycopene might provide some benefit in patients with prostate cancer. Most RCTs have not clarified whether NHP supplementation provides any real benefit, while harmful effects have been shown in some cases. Overall, the available data suggest that although there is some evidence to support the benefits of NHPs in the management of cancer patients, further clinical trials with the same design are needed before their introduction into clinical practice can be considered.
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- 2024
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25. Recurrence rate and management after endoscopic papillectomy in a tertiary referral center.
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Dioscoridi L, Donnarumma D, Forti E, Pugliese F, Cintolo M, Bonato G, Bravo M, Palermo A, and Mutignani M
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Background and Study Aims: Endoscopic papillectomy (EP) is considered a safe procedure for ampullary lesions. Few data are available on management of residual and recurrent adenomas. The aims of the present study were to evaluate long-term recurrence rate, median time-to-recurrence after EP and treatment of both residual and recurrent adenomas., Patients and Methods: Consecutive patients who underwent EP of major and minor papilla at our endoscopy center between 2011 and 2022 were enrolled. Residual adenoma was defined as the endoscopic evidence of adenomatous tissue after EP. Recurrent adenoma was defined as the presence of adenomatous tissue after the first endoscopic follow-up and complete adenoma resection., Results: 95 patients satisfied the inclusion criteria. Pathology after resection showed adenoma with low-grade dysplasia (LGD) in 52 patients, high-grade dysplasia (HGD) in 25 patients, adenocarcinoma in 6 patients, NET in 4 patients and not-neoplastic duodenal mucosa in 8 patients. Adverse events occurred in 25 % of patients. The median follow-up after EP was 22.5 months. Local residual was observed in 27 patients (28,4 %) and recurrence after the endoscopic retreatments occurred in 11 patients (11,6 %). Furthermore, recurrence occurred in 16 of 68 patients with adenoma-free after a first endoscopic follow-up and 9 patients developed at least a second recurrence. All the recurrences but one were endoscopically treated., Conclusions: EP and its ancillary treatments for residual and recurrent adenomas is an effective treatment for ampullary tumors. Long-term surveillance demonstrates that recurrences can be mainly treated endoscopically., Competing Interests: Conflict of interest The authors declare that there is no conflict of interest., (Copyright © 2024 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)
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- 2024
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26. The professional background of a referring physician predicts the diagnostic yield of small bowel capsule endoscopy in suspected small bowel bleeding.
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Compare D, Sgamato C, Rocco A, Coccoli P, Donnarumma D, Marchitto SA, Cinque S, Palmieri P, and Nardone G
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Background and study aims The diagnostic yield of small-bowel capsule endoscopy (SBCE) in suspected small bowel bleeding (SSBB) is highly variable. Different reimbursement systems and equipment costs also limit SBCE use in clinical practice. Thus, minimizing non-diagnostic procedures is advisable. This study aimed to assess the SBCE diagnostic yield and identify factors predicting diagnostic findings in a cohort of patients with SSBB. Patients and methods In this retrospective cohort study, we analyzed the medical records of patients who consecutively underwent SBCE for SSBB over 9 years. By logistic regression, we identified covariates predicting diagnostic findings at SBCE. Finally, we performed a post-hoc cost analysis based on previous gastroenterologist or endoscopist consultations versus direct SBCE ordering by other specialists. Results The final analysis included 584 patients. Most SBCEs were ordered by a gastroenterologist or endoscopist (74%). The number of SBCEs without any finding was significantly lower in the gastroenterologist/endoscopist group P <0.001). The SBCE diagnostic yield ordered by a gastroenterologist or endoscopist was significantly higher than that by other specialists (63% vs 52%, odds ratio [OR] 1.57; 95% confidence interval [CI] 1.07-2.26, P =0.019). At multivariate analysis, older age (OR 1.7, 95%CI 1.2-2.4, P =0.005), anemia (OR 4.9, 95%CI 1.9-12, P =0.001), small bowel transit time (OR 1, 95%CI 1-1.02, P =0.039), and referring physician (OR 1.8, 95%CI 1.1-2.7, P =0.003) independently predicted diagnostic findings. Implementing prior gastroenterologist or endoscopist referral vs direct SBCE ordering would reduce medical expenditures by 16%. Conclusions The professional background of referring physicians significantly improves the diagnostic yield of SBCE and contributes to controlling public health costs., Competing Interests: Conflict of Interest The authors declare that they have no conflict of interest., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)
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- 2024
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27. Human blood lipid profiles after dietary supplementation of different omega 3 ethyl esters formulations.
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Donnarumma D, Di Salle A, Micalizzi G, Vento F, La Tella R, Iannotta P, Trovato E, Melone MAB, Rigano F, Donato P, Mondello L, and Peluso G
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- Animals, Humans, Gas Chromatography-Mass Spectrometry, Eicosapentaenoic Acid, Fatty Acids, Dietary Supplements, Esters, Fatty Acids, Omega-3
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The validity of omega 3 fatty acids (ω3 FAs), mainly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), as dietary supplements has been widely proved. It's well known in fact, that they protect against cardiovascular diseases, reduce the levels of triacylglycerides (TAGs) and cholesteryl esters (CEs) in blood, and have anti-inflammatory activity. For these reasons, in the last few years the production of dietary supplement containing ω3 has increased significantly. In this context, the possibility to obtain ω3 and other high value molecules from alternative sources as fish waste, in accordance with the principles of circular economy, becomes an enormous attractive. In addition, the opportunity of creating new products, with greater health benefits, represents an interesting challenge. The current study was focused on the extraction of ω3 fatty acids and peptides from tuna waste industry, to realize a new dietary supplement. To this purpose, a supercritical fluid extraction (SFE) method was developed to separate, isolate, and enrich the different fractions subsequently used to produce an innovative formulate. The obtained supplement was characterized in terms of fatty acids esterified ester (FAEE) composition by gas chromatography (GC) coupled to both flame ionization detection (FID) and mass spectrometry (MS), and content of heavy metals by inductively coupled plasma-mass spectrometry (ICP-MS). The effects of ω3 supplementation on metabolism and circulating lipid profiles was tested on 12 volunteers and assessed by GC-FID analysis of whole blood collected on paper support (Dried Blood Spot, DBS) at the beginning of the study and after thirty days. The results of plasma fatty acids levels after 30 days showed a significant decrease in the ω6/ω3 ratio, as well as the saturated/polyunsaturated fatty acids (SFA/PUFA) ratio, compared to subjects who took the ω3 ethyl esters unformulated. The novel formulated supplements proved to be extremely interesting and promising products, due to a significant increase in bioavailability, that makes it highly competitive in the current panorama of the nutraceutical industry., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)
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- 2023
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28. Blunt traumatic isolated duodenal perforation treated by multimodal endoscopic approach.
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Donnarumma D, Ksissa O, Dioscoridi L, Forti E, Chiara O, Raparelli L, and Mutignani M
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- Humans, Duodenum surgery, Duodenal Ulcer, Peptic Ulcer Perforation, Intestinal Perforation diagnostic imaging, Intestinal Perforation etiology, Intestinal Perforation surgery
- Abstract
Competing Interests: The authors declare that they have no conflict of interest.
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- 2023
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29. A miniaturized comprehensive approach for total lipidome analysis and vitamin D metabolite quantification in human serum.
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Donnarumma D, Arena A, Trovato E, Rigano F, Zoccali M, and Mondello L
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- Humans, Vitamins, Calcifediol, Chromatography, High Pressure Liquid methods, Lipidomics, Vitamin D
- Abstract
The balance between the different lipid molecules present in biological fluids accurately reflects the health state of the organism and can be used by medical personnel to finely tune therapy to a single patient, a process known as precision medicine. In this work, we developed a miniaturized workflow for the analysis of different lipid classes at the intact level, as well as their fatty acid constituents, starting from human serum. Fatty acids were identified by using flow-modulated comprehensive gas chromatography coupled to mass spectrometry (FM-GC × GC-MS), and their relative amount as well as the ratio of specific FA classes was determined by using FM-GC × GC with a flame ionization detector. Ultra-high-performance liquid chromatography coupled to tandem mass spectrometry was used for the simultaneous quantification of vitamin D metabolites and assessment of different intact lipid classes. An MRM method was developed for the quantification of five vitamin D metabolites (vitamin D2, vitamin D3, 25-hydroxyvitamin D2, 25-hydroxyvitamin D3, 24R,25-dihydroxyvitamin D3), and validated in terms of LoD, LoQ, accuracy, and precision, also using a certified reference material. At the same time, a combination of SCAN, precursor ion scan, and neutral loss scan, in both positive and negative modes, was used for the identification of 81 intact lipid species, such as phospholipids, cholesteryl esters, and triacylglycerols, in less than 25 min. In order to easily monitor the lipid composition and speed up the identification process, a two-dimensional map of the lipidome was generated, by plotting the molecular weight of the identified molecules versus their retention time. Moreover, a relative quantification was performed within each lipid class identified. The combination of untargeted and targeted data could provide useful information about the pathophysiological condition of the organism and evaluate, in a tailored manner, an efficient action., (© 2023. Springer-Verlag GmbH Germany, part of Springer Nature.)
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- 2023
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30. Anti-PD1 Consolidation in Patients with Hodgkin Lymphoma at High Risk of Relapse after Autologous Stem Cell Transplantation: A Multicenter Real-Life Study.
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De Filippi R, Marcacci G, Derenzini E, Musso M, Donnarumma D, Morelli E, Patti C, Maraglino AME, Scalone R, Simeone L, Becchimanzi C, Mele S, Crisci S, Morabito F, and Pinto A
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(1) Background: Consolidation therapy is an emerging strategy for patients with relapsed/refractory (RR) Hodgkin Lymphoma (HL) at high risk of failing salvage autologous stem cell transplantation (ASCT). (2) Objectives: To assess the safety and effectiveness of PD1-blockade consolidation for these high-risk patients. (3) Design: Multi-center retrospective analysis. (4) Methods: We identified 26 patients given anti-PD1 consolidation, from June 2016 to May 2020. (5) Results: Patients displayed the following risk factors: refractory disease (69%), relapse < 12 months from upfront therapy (15%), ≥2 lines of salvage therapy (73%), extranodal disease (65%). Nineteen patients (73%) had ≥3 of these factors. In addition, 16 patients (61%) also displayed PET-positive (Deauville ≥ 4) disease before ASCT. Treatment-related adverse events (TRAEs), never graded > 3, occurred in 12 patients (46.15%) and mainly included skin rashes (41.7%), transaminitis (33.3%), and thyroid hypofunction (25%). Patients completed a median of 13 courses (range 6−30). At a median follow-up of 25.8 months post-ASCT, the median progression-free (PFS) was 42.6 months, with a 2-year PFS and overall survival rates of 79% and 87%, respectively. (6) Conclusions: Post-ASCT consolidation with anti-PD1 is feasible and effective. Further studies are warranted to define the optimal treatment length and patients’ subsets more likely to benefit from this approach.
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- 2022
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31. FHUSPA2/10 is a bactericidal monoclonal antibody targeting multiple repeated sequences of Moraxella catarrhalis UspA2.
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Donnarumma D, Giusti F, Ysebaert C, Hermand P, Devos N, Ferlenghi I, Margarit I, Rossi Paccani S, Scarselli M, and Norais N
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- Adult, Humans, Amino Acids metabolism, Bacterial Outer Membrane Proteins immunology, Epitopes metabolism, Extracellular Matrix Proteins metabolism, Type V Secretion Systems metabolism, Antibodies, Monoclonal pharmacology, Moraxella catarrhalis, Anti-Bacterial Agents pharmacology
- Abstract
Moraxella catarrhalis is an important and common respiratory pathogen that can cause Otitis Media, Community Acquired Pneumonia, and has been associated with an increased risk of exacerbations in chronic obstructive pulmonary disease in adults, leading to morbidity and mortality. Its ubiquitous surface protein A2 (UspA2) has been shown to interact with host structures and extracellular matrix proteins, suggesting a role at an early stage of infection and a contribution to bacterial serum resistance. The UspA proteins are homo-trimeric autotransporters that appear as a lollipop-shaped structure in electron micrographs. They are composed of an N-terminal head with adhesive properties, followed by a stalk, which ends by an amphipathic helix and a C-terminal membrane domain. The three family members UspA1, UspA2 and UspA2H, present different amino acid signatures both at the head and membrane-spanning regions. By combining electron microscopy, hydrogen deuterium exchange mass spectrometry and protein modeling, we identified a shared and repeated epitope recognized by FHUSPA2/10, a potent cross-bactericidal monoclonal antibody raised by UspA2 and deduced key amino acids involved in the binding. The finding strengthens the potential of UspA2 to be incorporated in a vaccine formulation against M. catarrhalis., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)
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- 2022
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32. Mucus from human bronchial epithelial cultures: rheology and adhesion across length scales.
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Jory M, Donnarumma D, Blanc C, Bellouma K, Fort A, Vachier I, Casanellas L, Bourdin A, and Massiera G
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Mucus is a viscoelastic aqueous fluid that participates in the protective barrier of many mammals' epithelia. In the airways, together with cilia beating, mucus rheological properties are crucial for lung mucociliary function, and, when impaired, potentially participate in the onset and progression of chronic obstructive pulmonary disease (COPD). Samples of human mucus collected in vivo are inherently contaminated and are thus poorly characterized. Human bronchial epithelium (HBE) cultures, differentiated from primary cells at an air-liquid interface, are highly reliable models to assess non-contaminated mucus. In this paper, the viscoelastic properties of HBE mucus derived from healthy subjects, patients with COPD and from smokers are measured. Hallmarks of shear-thinning and elasticity are obtained at the macroscale, whereas at the microscale mucus appears as a heterogeneous medium showing an almost Newtonian behaviour in some extended regions and an elastic behaviour close to boundaries. In addition, we developed an original method to probe mucus adhesion at the microscopic scale using optical tweezers. The measured adhesion forces and the comparison with mucus-simulants rheology as well as mucus imaging collectively support a structure composed of a network of elastic adhesive filaments with a large mesh size, embedded in a very soft gel., (© 2022 The Author(s).)
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- 2022
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33. Endoscopic and Surgical Removal of Gastrointestinal Foreign Bodies in Dogs: An Analysis of 72 Cases.
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Di Palma C, Pasolini MP, Navas L, Campanile A, Lamagna F, Fatone G, Micieli F, Esposito C, Donnarumma D, Uccello V, and Lamagna B
- Abstract
In emergency veterinary practice, gastrointestinal foreign body (GFB) removal is a common procedure that is performed with different techniques, such as endoscopy or surgery. The aims of this retrospective, multicentre, clinical study were to report the common locations and types of objects recovered and to investigate clinical factors and outcomes in dogs after surgical or endoscopic treatment for GFB removal. Records of dogs with a GFB diagnosis referred to the Teaching Veterinary Hospital or treated in three different veterinary hospitals from September 2017 to September 2019 were examined. The data obtained from each case included breed, age, clinical signs at presentation, duration of clinical signs, type and location of the GFB, treatment, length of hospitalisation and outcome. Seventy-two dogs were enrolled in the study. There were 42 males (58%) and 30 females (42%). The median age was 36 months (range: 3 months to 8 years). Endoscopic retrieval was performed in 56% of GFBs (located in the stomach or duodenum), whereas 44% of dogs underwent surgery. The type of FB detected varied greatly: kid toy (14%), metallic object/coin (13%), cloth (13%), sock (8%), ball (8%), plastic material (8%), peach stone (7%), fishhook (6%), sewing needle (4%), hair tie (4%), pacifier (3%), plant materials (3%) and others (9%). Moreover, the FBs were classified as sharp (13%, n = 9), pointed (33%, n = 24), blunt (26%, n = 19), or linear (28%, n = 20). In this study, 68% of FBs were localised in the stomach, 25% in the intestinal tract (50% duodenum, 28% jejunum, and 22% ileum), and 7% in both the stomach and small intestine. The type of GFB was not significantly associated with age, site or breed. There was a significant association between the type of GFB and sex: if the dog was male, there was a 38% probability of ingesting linear GFBs. The dog survival rate was 100% in cases treated by gastric endoscopic or surgical removal, 94% in cases treated with enterotomy and 33% in cases in which enterectomy was necessary. Enterectomy and multiple surgical sites were associated with a poor outcome. The presence of vomiting for more than 24 h was significantly associated with death.
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- 2022
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34. Listeria monocytogenes exposed to antimicrobial peptides displays differential regulation of lipids and proteins associated to stress response.
- Author
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Stincone P, Fonseca Veras F, Micalizzi G, Donnarumma D, Vitale Celano G, Petras D, de Angelis M, Mondello L, and Brandelli A
- Subjects
- Antimicrobial Peptides, Lipids, Bacteriocins, Listeria monocytogenes physiology, Nisin pharmacology
- Abstract
With the onset of Listeria monocytogenes resistance to the bacteriocin nisin, the search for alternative antimicrobial treatments is of fundamental importance. In this work, we set out to investigate proteins and lipids involved in the resistance mechanisms of L. monocytogenes against the antimicrobial peptides (AMPs) nisin and fengycin. The effect of sub-lethal concentrations of nisin and lipopeptide fengycin secreted by Bacillus velezensis P34 on L. monocytogenes was investigated by mass spectrometry-based lipidomics and proteomics. Both AMPs caused a differential regulation of biofilm formation, confirming the promotion of cell attachment and biofilm assembling after treatment with nisin, whereas growth inhibition was observed after fengycin treatment. Anteiso branched-chain fatty acids were detected in higher amounts in fengycin-treated samples (46.6%) as compared to nisin-treated and control samples (39.4% and 43.4%, respectively). In addition, a higher relative abundance of 30:0, 31:0 and 32:0 phosphatidylglycerol species was detected in fengycin-treated samples. The lipidomics data suggest the inhibition of biofilm formation by the fengycin treatment, while the proteomics data revealed downregulation of important cell wall proteins involved in the building of biofilms, such as the lipoteichoic acid backbone synthesis (Lmo0927) and the flagella-related (Lmo0718) proteins among others. Together, these results provide new insights into the modification of lipid and protein profiles and biofilm formation in L. monocytogenes upon exposure to antimicrobial peptides., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)
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- 2022
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35. Overcoming the lack of reliability associated to monodimensional gas chromatography coupled to isotopic ratio mass spectrometry data by heart-cut two-dimensional gas chromatography.
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Cucinotta L, De Grazia G, Salerno TMG, Donnarumma D, Donato P, Sciarrone D, and Mondello L
- Subjects
- Carbon Isotopes, Mass Spectrometry, Reproducibility of Results, Gas Chromatography-Mass Spectrometry
- Abstract
The use of IRMS as a GC detector has a history going back decades, however the critical issue of wrong δ
13 C measurements resulting from impure peaks has been often underestimated. To this regard, multidimensional separation techniques are effective tools to improve the reliability of the data, with respect to those obtained after monodimensional analysis. The present research aims to draw attention to one critical issue, related to the reliability of the δ13 C data obtained by means of monodimensional GC-C-IRMS. Although already known from the literature, such aspect has been greatly overlooked, as is reflected in the few papers reporting the use of MDGC, among the plethora of published research dealing with GC-C-IRMS applications. Hereby, a set of natural samples of complex composition were analysed to investigate the presence of minor or even undetected coelutions, and to which extent it affected the isotope ratio determination. Apart from chromatographic effects, and issues related to analytes conversion to CO2 prior to IRMS measurement, unpredictable co-elutions with compounds, either resulting from oxidation or intentionally added in fraudulent practices, could also contribute to a shift of the δ13 C data, up to 10‰ and higher. Last, the influence of column bleed was investigated, as affecting the determination of the δ13 C data for compounds that were eluted at high temperatures. It was finally demonstrated by the selected key studies that implementation of MDGC separation is mandatory to prevent the aforementioned issues, aiming to guarantee accurate results. In the light of the above conclusions, and considering the level of automation of heart-cut devices nowadays available, routine practice of MDGC results highly recommendable in any IRMS applications., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021. Published by Elsevier B.V.)- Published
- 2021
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36. Atypical COVID-19 dynamics in a patient with mantle cell lymphoma exposed to rituximab.
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Marcacci G, Fiorentino G, Volzone F, Falcone U, Parrella R, Donnarumma D, D'Ovidio S, Annunziata A, Micallo G, Portella G, De Chiara A, De Filippi R, Crisci S, and Pinto A
- Abstract
Patients with non-hodgkin lymphomas (NHL) represent a population of special interest during the current Coronavirus disease-19 (COVID-19) pandemics. NHLs are associated with disease- and treatment-related immunodeficiencies which may generate unusual COVID-19 dynamics and pose unique management challenges. We report the unusual clinical course of COVID-19 in a patient with mantle cell lymphoma (MCL) exposed to nine doses of Rituximab shortly before infection with severe acute respiratory syndrome corona virus 2 (SARS-CoV-2). He had a prolonged asymptomatic phase, with negative molecular and antibody testing for SARS-CoV-2, followed by a rapidly progressive evolution to severe COVID-19. Despite detection of viral RNA overlapped with first symptoms occurrence, anti-SARS-CoV-2 antibodies displayed an asynchronous pattern, with IgG first appearing 2 days after RNA positivity and IgM never being detected throughout the entire clinical course. While disease-associated immune derangements and/or previous treatments involving anti-CD20 antibodies might have contributed to COVID-19 dynamics in our patient, data suggests that antibody testings, without concurrent molecular assessment for SARS-CoV-2, may turn inadequate for monitoring of MCL patients, and in general NHL patients heavily exposed to anti-CD20 antibodies, during the current pandemics. We suggest that repeated molecular testing of nasopharyngeal swab should be implemented in these subjects despite a negative serology and absence of symptoms of SARS-CoV-2 infection. For the same reasons, a customized strategy needs to be developed for patients exposed to anti-CD20 antibodies, based on different features and mechanism of action of available SARS-CoV-2 vaccines and novel vaccinomics developments.
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- 2021
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37. Reversed phase versus hydrophilic interaction liquid chromatography as first dimension of comprehensive two-dimensional liquid chromatography systems for the elucidation of the polyphenolic content of food and natural products.
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Cacciola F, Arena K, Mandolfino F, Donnarumma D, Dugo P, and Mondello L
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- Hydrophobic and Hydrophilic Interactions, Mass Spectrometry, Biological Products chemistry, Chromatography, Liquid methods, Food Analysis methods, Polyphenols analysis
- Abstract
Comprehensive two-dimensional liquid chromatography is a well-established method for the unraveling of very complex real-world samples. With regard to food and natural products such a technique turned out to be a very promising approach due to its high resolving power and improved identification capability, especially in combination with mass spectrometry. In this context, polyphenols comprise a particular complex class of bioactive compounds, due to their nature and content in commonly consumed foodstuffs, making their analysis challenging. The present contribution shows an overview of the two commonly employed approaches used for polyphenol analysis, viz. RP-LC × RP-LC and HILIC × RP-LC. Furthermore, the latest implementations as well as limitations and future perspectives are critically reported., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021. Published by Elsevier B.V.)
- Published
- 2021
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38. Identification of high-value generating molecules from the wastes of tuna fishery industry by liquid chromatography and gas chromatography hyphenated techniques with automated sample preparation.
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Rigano F, Arena P, Mangraviti D, Donnarumma D, Dugo P, Donato P, Mondello L, and Micalizzi G
- Subjects
- Animals, Chromatography, Gas, Chromatography, High Pressure Liquid, Fisheries, Industry, Tuna, Automation, Lipids analysis, Proteins analysis, Waste Products analysis
- Abstract
The present work aims to a promising re-utilization of the massive waste derived from the tuna fishing industry, for which by-products can represent more than 50% of the original material. Due to the considerable content in polyunsaturated fatty acids and noble proteins, such wastes can be used as primary source of functional ingredients in the production of nutraceuticals. The composition of the lipid and protein tuna fractions was investigated by means of gas chromatography-mass spectrometry and high-performance liquid chromatography-tandem mass spectrometry methods (in wastes and edible parts), and a preliminary characterization of potential bioactive peptides was achieved. Automated sample preparation allowed speeding up the analytical workflow, while allowing for highly sensitive and selective lipid characterization. The ω3 fatty acid content was found higher in waste products compared to the muscle, in terms of fatty acids as well as complex lipids. As for peptides, extraction by isoelectric solubilization/precipitation was performed, followed by enzymatic digestion and high-performance liquid chromatography-tandem mass spectrometry analysis. Furthermore, the use of bioinformatics tools highlighted the presence of potential antimicrobial peptides in the samples investigated., (© 2021 Wiley-VCH GmbH.)
- Published
- 2021
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39. Cannabis Sativa L.: a comprehensive review on the analytical methodologies for cannabinoids and terpenes characterization.
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Micalizzi G, Vento F, Alibrando F, Donnarumma D, Dugo P, and Mondello L
- Subjects
- Cannabinoids chemistry, Chromatography, High Pressure Liquid, Gas Chromatography-Mass Spectrometry, Plant Extracts chemistry, Terpenes chemistry, Cannabinoids analysis, Cannabis chemistry, Terpenes analysis
- Abstract
The global Cannabis Sativa market, including essential oils, foods, personal-care products, and medical formulations has gained much attention over the last years due to the favorable regulatory framework. Undoubtedly, the enormous interest about cannabis cultivation mainly derives from the well-known pharmacological properties of cannabinoids and terpenes biosynthesized by the plants. In this review, the most recently used analytical methodologies for detecting both cannabinoids and terpenes are described. Well-established and innovative extraction protocols, and chromatographic separations, such as GC and HPLC, are reviewed highlighting their respective advantages and drawbacks. Lastly, GC × GC techniques are also reported for accurate identification and quantification of terpenes in complex cannabis matrices., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020. Published by Elsevier B.V.)
- Published
- 2021
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40. Structural basis for cooperativity of human monoclonal antibodies to meningococcal factor H-binding protein.
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Peschiera I, Giuliani M, Giusti F, Melero R, Paccagnini E, Donnarumma D, Pansegrau W, Carazo JM, Sorzano COS, Scarselli M, Masignani V, Liljeroos LJ, and Ferlenghi I
- Subjects
- Antibodies, Monoclonal immunology, Blood Bactericidal Activity, Complement Factor H metabolism, Epitope Mapping, Humans, Meningococcal Vaccines immunology, Microscopy, Electron, Transmission, Surface Plasmon Resonance, Antibodies, Monoclonal chemistry, Antigens, Bacterial immunology, Bacterial Proteins immunology
- Abstract
Monoclonal antibody (mAb) cooperativity is a phenomenon triggered when mAbs couples promote increased bactericidal killing compared to individual partners. Cooperativity has been deeply investigated among mAbs elicited by factor H-binding protein (fHbp), a Neisseria meningitidis surface-exposed lipoprotein and one of the key antigens included in both serogroup B meningococcus vaccine Bexsero and Trumenba. Here we report the structural and functional characterization of two cooperative mAbs pairs isolated from Bexsero vaccines. The 3D electron microscopy structures of the human mAb-fHbp-mAb cooperative complexes indicate that the angle formed between the antigen binding fragments (fAbs) assume regular angle and that fHbp is able to bind simultaneously and stably the cooperative mAbs pairs and human factor H (fH) in vitro. These findings shed light on molecular basis of the antibody-based mechanism of protection driven by simultaneous recognition of the different epitopes of the fHbp and underline that cooperativity is crucial in vaccine efficacy., Competing Interests: Competing interestsAll authors have declared no competing financial interest but the following competing nonfinancial interests: I.F., M.G., F.G., D.D., W.P., M.S., and V.M. are employees of GSK group of companies. L.J.L. was an employee of GSK group of companies when the experiments were performed. L.J.L. reports a grant from the European Union FP7 Framework Programme (FP7-PEOPLE-2013-IEF, grant number 623168) during the conduct of the study. I.P. held a Novartis Academy Ph.D. fellowship at the University of Bologna. The other authors report no financial conflict of interest.
- Published
- 2019
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41. The Streptococcus agalactiae complement interfering protein combines multiple complement-inhibitory mechanisms by interacting with both C4 and C3 ligands.
- Author
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Giussani S, Pietrocola G, Donnarumma D, Norais N, Speziale P, Fabbrini M, and Margarit I
- Subjects
- Amino Acid Sequence, B-Lymphocytes drug effects, B-Lymphocytes immunology, Bacterial Proteins pharmacology, Binding Sites, Calcium Signaling, Cell Line, Tumor, Complement C3b antagonists & inhibitors, Complement C3b metabolism, Complement C3d metabolism, Enzyme-Linked Immunosorbent Assay, Humans, Lymphocyte Activation drug effects, Mass Spectrometry, Protein Binding, Protein Interaction Mapping, Receptors, Complement 3d metabolism, Sequence Alignment, Sequence Homology, Amino Acid, Streptococcus agalactiae immunology, Streptococcus agalactiae metabolism, Surface Plasmon Resonance, Virulence, Virulence Factors pharmacology, Bacterial Proteins metabolism, Complement C3d antagonists & inhibitors, Complement C4 antagonists & inhibitors, Streptococcus agalactiae pathogenicity, Virulence Factors metabolism
- Abstract
Group B Streptococcus (GBS) colonizes the human lower intestinal and genital tracts and constitutes a major threat to neonates from pregnant carrier mothers and to adults with underlying morbidity. The pathogen expresses cell-surface virulence factors that enable cell adhesion and penetration and that counteract innate and adaptive immune responses. Among these, the complement interfering protein (CIP) was recently described for its capacity to interact with the human C4b ligand and to interfere with the classical- and lectin-complement pathways. In the present study, we provide evidence that CIP can also interact with C3, C3b, and C3d. Immunoassay-based competition experiments showed that binding of CIP to C3d interferes with the interaction between C3d and the complement receptor 2/cluster of differentiation 21 (CR2/CD21) receptor on B cells. By B-cell intracellular signaling assays, CIP was confirmed to down-regulate CR2/CD21-dependent B-cell activation. The CIP domain involved in C3d binding was mapped via hydrogen deuterium exchange-mass spectrometry. The data obtained reveal a new role for this GBS polypeptide at the interface between the innate and adaptive immune responses, adding a new member to the growing list of virulence factors secreted by gram-positive pathogens that incorporate multiple immunomodulatory functions.-Giussani, S., Pietrocola, G., Donnarumma, D., Norais, N., Speziale, P., Fabbrini, M., Margarit, I. The Streptococcus agalactiae complement interfering protein combines multiple complement-inhibitory mechanisms by interacting with both C4 and C3 ligands.
- Published
- 2019
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42. High-speed quantitative 3D imaging by dual-illumination holographic microscopy.
- Author
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Donnarumma D, Rawat N, and Brodoline A
- Subjects
- Animals, Equipment Design, Erythrocytes chemistry, Erythrocytes cytology, Larva chemistry, Larva physiology, Zebrafish embryology, Zebrafish physiology, Holography methods, Imaging, Three-Dimensional methods, Microscopy methods, Zebrafish blood
- Abstract
A new blood flow imaging (BFI) technique using digital holography with double illumination of the sample is proposed. We imaged the moving red blood cells (RBCs) using a two microscope objective lenses setup. The setup consists in a larger angle of separation (90 °) between the two illumination beams, allowing a wider angular rotation at good z resolution. Moreover, the setup geometry allows an easier displacement of the sample in all directions. Results show that this technique is able to perform phase-shifting reconstruction for the two beams at the same time which is more suitable for the future implementation of live 3D holography. Experimental results are carried out for the verification of the effectiveness of the proposed technique on a zebrafish larvae sample. RESEARCH HIGHLIGHTS: Blood flow imaging techniques are often invasive and image analysis is time consuming. To alleviate this issue an imaging technique based on dual illumination in holographic domain is proposed. This method has been validated on zebrafish embryos., (© 2018 Wiley Periodicals, Inc.)
- Published
- 2018
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43. Native State Organization of Outer Membrane Porins Unraveled by HDx-MS.
- Author
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Donnarumma D, Maestri C, Giammarinaro PI, Capriotti L, Bartolini E, Veggi D, Petracca R, Scarselli M, and Norais N
- Subjects
- Bacterial Outer Membrane Proteins chemistry, Escherichia coli Proteins chemistry, Kinetics, Protein Conformation, Bacterial Proteins chemistry, Deuterium Exchange Measurement methods, Mass Spectrometry methods, Porins chemistry
- Abstract
Hydrogen-deuterium exchange (HDx) associated with mass spectrometry (MS) is emerging as a powerful tool to provide conformational information about membrane proteins. Unfortunately, as for X-ray diffraction and NMR, HDx performed on reconstituted in vitro systems might not always reflect the in vivo environment. Outer-membrane vesicles naturally released by Escherichia coli were used to carry out analysis of native OmpF through HDx-MS. A new protocol compatible with HDx analysis that avoids hindrance from the lipid contents was setup. The extent of deuterium incorporation was in good agreement with the X-ray diffraction data of OmpF as the buried β-barrels incorporated a low amount of deuterium, whereas the internal loop L3 and the external loops incorporated a higher amount of deuterium. Moreover, the kinetics of incorporation clearly highlights that peptides segregate well in two distinct groups based exclusively on a trimeric organization of OmpF in the membrane: peptides presenting fast kinetics of labeling are facing the complex surrounding environment, whereas those presenting slow kinetics are located in the buried core of the trimer. The data show that HDx-MS applied to a complex biological system is able to reveal solvent accessibility and spatial arrangement of an integral outer-membrane protein complex.
- Published
- 2018
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44. Blood flow imaging in zebrafish by laser doppler digital holography.
- Author
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Donnarumma D, Brodoline A, Alexandre D, and Gross M
- Subjects
- Animals, Blood Physiological Phenomena, Laser-Doppler Flowmetry methods, Zebrafish blood, Zebrafish embryology, Holography methods, Microvessels diagnostic imaging, Zebrafish anatomy & histology
- Abstract
Microvessel blood flow imaging techniques are widely used in biomedical research and clinical diagnostics where many diseases have a vascular etiology or involvement. For testing purposes, zebrafish embryo provides an ideal animal model to achieve high-resolution imaging of superficial and deeply localized vessels. Moreover, the study of the formation of a closed circulatory system in vertebrates is a topic of recent interest in biophysics. However, most of the existing techniques are invasive due to the use of a contrast agent for imaging purposes. Recent developments in Digital Holography and Laser Doppler Holography techniques can be considered to alleviate this issue. Laser Doppler holography and transmission microscopy can be coupled to analyze blood flow in fish embryos by adapting a laser Doppler holographic setup to a standard bio-microscope: the two beams of the holographic interferometer (illumination of the object and reference), whose frequency offset is controlled, were addressed to the microscope by optical fibers. Multimodal acquisition and analysis of the data is made by acting on the frequency offset of the two beams, and on the location of the Fourier space filtered zone. In this work, we show that it is possible to select the signal of moving scatterers, and to image Red Blood Cells (RBCs) and blood vessels. Individual RBCs are imaged, and movies showing the RBC motion are obtained. Microsc. Res. Tech. 81:153-161, 2018. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)
- Published
- 2018
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45. Structural basis for potent antibody-mediated neutralization of human cytomegalovirus.
- Author
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Chandramouli S, Malito E, Nguyen T, Luisi K, Donnarumma D, Xing Y, Norais N, Yu D, and Carfi A
- Abstract
Human cytomegalovirus (HCMV) is the leading viral cause of birth defects and organ transplant rejection. The HCMV gH/gL/UL128/UL130/UL131A complex (Pentamer) is the main target of humoral responses and thus a key vaccine candidate. We report two structures of Pentamer bound to human neutralizing antibodies, 8I21 and 9I6, at 3.0 and 5.9 Å resolution, respectively. The HCMV gH/gL architecture is similar to that of Epstein-Barr virus (EBV) except for amino-terminal extensions on both subunits. The extension of gL forms a subdomain composed of a three-helix bundle and a β hairpin that acts as a docking site for UL128/UL130/UL131A. Structural analysis reveals that Pentamer is a flexible molecule, and suggests sites for engineering stabilizing mutations. We also identify immunogenic surfaces important for cellular interactions by epitope mapping and functional assays. These results can guide the development of effective vaccines and immunotherapeutics against HCMV., (Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)
- Published
- 2017
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46. 4D holographic microscopy of zebrafish larvae microcirculation.
- Author
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Donnarumma D, Brodoline A, Alexandre D, and Gross M
- Subjects
- Algorithms, Animals, Imaging, Three-Dimensional methods, Larva, Lighting, Zebrafish, Erythrocytes, Holography methods, Microcirculation, Microscopy methods
- Abstract
An original technique that combines digital holography, dual illumination of the sample and cleaning algorithm 3D reconstruction is proposed. It uses a standard transmission microscopy setup coupled with a digital holography detection. The technique is 4D, since it allows to determine, at each time step, the 3D locations (x,y,z) of many moving objects that scatter the dual illumination beam. The technique has been validated by imaging the microcirculation of blood in a fish larvae sample (the moving objects are thus red blood cells RBCs). Videos showing in 4D the moving RBCs superimposed with the perfused blood vessels are obtained.
- Published
- 2016
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47. Epitope Mapping of a Monoclonal Antibody Directed against Neisserial Heparin Binding Antigen Using Next Generation Sequencing of Antigen-Specific Libraries.
- Author
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Domina M, Lanza Cariccio V, Benfatto S, Venza M, Venza I, Donnarumma D, Bartolini E, Borgogni E, Bruttini M, Santini L, Midiri A, Galbo R, Romeo L, Patanè F, Biondo C, Norais N, Masignani V, Teti G, Felici F, and Beninati C
- Subjects
- Animals, Bacterial Outer Membrane Proteins genetics, Carrier Proteins genetics, Cross Reactions, High-Throughput Nucleotide Sequencing, Mass Spectrometry methods, Mice, Neisseria meningitidis, Serogroup B immunology, Recombinant Proteins genetics, Recombinant Proteins immunology, Antibodies, Monoclonal immunology, Bacterial Outer Membrane Proteins immunology, Carrier Proteins immunology, Epitope Mapping methods, Peptide Library
- Abstract
We explore here the potential of a newly described technology, which is named PROFILER and is based on next generation sequencing of gene-specific lambda phage-displayed libraries, to rapidly and accurately map monoclonal antibody (mAb) epitopes. For this purpose, we used a novel mAb (designated 31E10/E7) directed against Neisserial Heparin-Binding Antigen (NHBA), a component of the anti-group B meningococcus Bexsero® vaccine. An NHBA phage-displayed library was affinity-selected with mAb 31E10/E7, followed by massive sequencing of the inserts present in antibody-selected phage pools. Insert analysis identified an amino acid stretch (D91-A128) in the N-terminal domain, which was shared by all of the mAb-enriched fragments. Moreover, a recombinant fragment encompassing this sequence could recapitulate the immunoreactivity of the entire NHBA molecule against mAb 31E10/E7. These results were confirmed using a panel of overlapping recombinant fragments derived from the NHBA vaccine variant and a set of chemically synthetized peptides covering the 10 most frequent antigenic variants. Furthermore, hydrogen-deuterium exchange mass-spectrometry analysis of the NHBA-mAb 31E10/E7 complex was also compatible with mapping of the epitope to the D91-A128 region. Collectively, these results indicate that the PROFILER technology can reliably identify epitope-containing antigenic fragments and requires considerably less work, time and reagents than other epitope mapping methods.
- Published
- 2016
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48. Identification of a Monoclonal Antibody Against Pneumococcal Pilus 1 Ancillary Protein Impairing Bacterial Adhesion to Human Epithelial Cells.
- Author
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Amerighi F, Valeri M, Donnarumma D, Maccari S, Moschioni M, Taddei A, Lapazio L, Pansegrau W, Buccato S, De Angelis G, Ruggiero P, Masignani V, Soriani M, and Pezzicoli A
- Subjects
- Cell Line, Epitope Mapping, Humans, Virulence Factors immunology, Antibodies, Bacterial immunology, Antibodies, Monoclonal immunology, Bacterial Adhesion drug effects, Epithelial Cells microbiology, Fimbriae Proteins immunology, Fimbriae, Bacterial immunology, Streptococcus pneumoniae immunology
- Abstract
The adhesion of Streptococcus pneumoniae is a key step during colonization of human respiratory tract mucosae. Here we demonstrate that pneumococcal type I pilus significantly increases the adhesiveness of poorly adhering highly capsulated strains in vitro. Interestingly, preincubation of bacteria with antibodies against the major pilus backbone subunit (RrgB) or the adhesin component (RrgA) impaired pneumococcal association to human epithelial cells. Screening for anti-RrgA monoclonal antibodies specifically affecting the adhesive capacity of S. pneumoniae led to the identification of the monoclonal 11B9/61 antibody, which greatly reduced pilus-dependent cell contact. Proteomic-based epitope mapping of 11B9/61 monoclonal antibody revealed a well-exposed epitope on the D2 domain of RrgA as the target of this functional antibody. The data presented here confirm the importance of pilus I for S. pneumoniae pathogenesis and the potential use of antipilus antibodies to prevent bacterial colonization., (© The Author 2015. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.)
- Published
- 2016
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49. The role of structural proteomics in vaccine development: recent advances and future prospects.
- Author
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Donnarumma D, Faleri A, Costantino P, Rappuoli R, and Norais N
- Subjects
- Animals, Antigens chemistry, Antigens immunology, Antigens isolation & purification, Deuterium Exchange Measurement, Epitope Mapping, Humans, Mass Spectrometry, Protein Conformation, Vaccines immunology, Vaccines isolation & purification, Proteomics methods, Vaccines chemistry
- Abstract
Vaccines are the most effective way to fight infectious diseases saving countless lives since their introduction. Their evolution during the last century made use of the best technologies available to continuously increase their efficacy and safety. Mass spectrometry (MS) and proteomics are already playing a central role in the identification and characterization of novel antigens. Over the last years, we have been witnessing the emergence of structural proteomics in vaccinology, as a major tool for vaccine candidate discovery, antigen design and life cycle management of existing products. In this review, we describe the MS techniques associated to structural proteomics and we illustrate the contribution of structural proteomics to vaccinology discussing potential applications.
- Published
- 2016
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50. Improved outcome of patients with relapsed/refractory Hodgkin lymphoma with a new fotemustine-based high-dose chemotherapy regimen.
- Author
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Musso M, Messina G, Di Renzo N, Di Carlo P, Vitolo U, Scalone R, Marcacci G, Scalzulli PR, Moscato T, Matera R, Crescimanno A, Santarone S, Orciuolo E, Merenda A, Pavone V, Pastore D, Donnarumma D, Carella AM, Ciochetto C, Cascavilla N, Mele A, Lanza F, Di Nicola M, Bonizzoni E, and Pinto A
- Subjects
- Adolescent, Adult, Aged, Antineoplastic Combined Chemotherapy Protocols administration & dosage, Antineoplastic Combined Chemotherapy Protocols adverse effects, Child, Cytarabine administration & dosage, Cytarabine adverse effects, Drug Evaluation methods, Etoposide administration & dosage, Etoposide adverse effects, Female, Graft Survival, Hematopoietic Stem Cell Transplantation methods, Hodgkin Disease diagnostic imaging, Hodgkin Disease therapy, Humans, Kaplan-Meier Estimate, Male, Melphalan administration & dosage, Melphalan adverse effects, Middle Aged, Nitrosourea Compounds administration & dosage, Nitrosourea Compounds adverse effects, Organophosphorus Compounds administration & dosage, Organophosphorus Compounds adverse effects, Positron-Emission Tomography, Prospective Studies, Registries, Salvage Therapy adverse effects, Salvage Therapy methods, Transplantation Conditioning methods, Treatment Outcome, Young Adult, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Hodgkin Disease drug therapy
- Abstract
High-dose chemotherapy (HDT) with autologous stem cell transplantation is the standard of care for relapsed/refractory (RR) Hodgkin lymphoma (HL). Given that HDT may cure a sizeable proportion of patients refractory to first salvage, development of newer conditioning regimens remains a priority. We present the results of a novel HDT regimen in which carmustine was substituted by a third-generation chloroethylnitrosourea, fotemustine, with improved pharmacokinetics and safety (FEAM; fotemustine, etoposide, cytarabine, melphalan) in 122 patients with RR-HL accrued into a prospective registry-based study. Application of FEAM resulted in a 2-year progression-free survival (PFS) of 73·8% [95% confidence interval (CI), 0·64-0·81] with median PFS, overall survival and time to progression yet to be reached. The 2-year risk of progression adjusted for the competitive risk of death was 19·4% (95% CI, 0·12-0·27) for the entire patient population. Most previously established independent risk factors, except for fluorodeoxyglucose ((18) (F) FDG)-uptake, were unable to predict for disease progression and survival after FEAM. Although 32% of patients had (18) (F) FDG-positrin emission tomography-positive lesions before HDT, the 2-year risk of progression adjusted for competitive risk of death was 19·4% (95% CI; 0·12-0·27). No unusual acute toxicities or early/late pulmonary adverse events were registered. FEAM emerges as an ideal HDT regimen for RR-HL patients typically pre-exposed to lung-damaging treatments., (© 2015 John Wiley & Sons Ltd.)
- Published
- 2016
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