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4. Platelet count does not predict bleeding in cirrhotic patients: Results from the PRO-LIVER Study

Author

Basili, S. a, Raparelli, V. b., Napoleone, L. b., Talerico, G. a., Corazza, G. R. c., Perticone, F. d., Sacerdoti, D. e., Andriulli, A. f., Licata, A. g., Pietrangelo, A., Picardi, A. i., Raimondo, G. j., Violi, F., Palasciano, G., D’Alitto, F., Palmieri, V. O., Santovito, D., Michele, Di, Croce, D., Brocco, G., Fasolato, S., Cecchetto, S., Bombonato, L., Bertoni, G., Restuccia, M., Andreozzi, T., Liguori, P., Caroleo, M. L., Perticone, B., Staltari, M., Manfredini, O., Giorgi, De, Averna, A., Giammanco, M., Granito, A., Pettinari, A., Marinelli, I., Bolondi, S., Falsetti, L., Salvi, L., Durante-Mangoni, A., Cesaro, E., Farinaro, F., Ragone, V., Morana, E., Ippolito, I., Iacobellis, A., Niro, A., Merla, G., Maimone, A., Cacciola, S., Varvara, I., Drenaggi, D., Staffolani, D., Vespasiani-Gentilucci, S., Galati, U., Gallo, G., Davì, P., Schiavone, G., Santilli, C., Tana, F., Soresi, C., Bianchi, Giovanni, Carderi, B., Pinto, I., Tuttolomondo, A., Ferrari, A., Gresele, G., Fierro, P., Morelli, T., Laffi, O., Romanelli, G., Arena, R. G., Stasi, U., Gasbarrini, A., Garcovich, M., Zocco, M. A., Riccardi, L., Ainora, M. E., Capeci, W., Martino, Giuseppe, Nobili, P., Cavallo, L., Frugiuele, M., Greco, P., Ventura, P., Cuoghi, C., Marcacci, M., Serviddio, G., Vendemiale, G., Villani, R., Gargano, R., Vidili, G., Cesare, Di, Masala, V., Delitala, M., Invernizzi, G., Vincenzo, P., Minno, Di, Tufano, G., Purrello, A., Privitera, F., Forgione, G., Curigliano, A., Senzolo, V., Rodríguez-Castro, M., Giannelli, K. I., Serra, G., Neri, C., Pignataro, S., Rizzetto, P., Debernardi, M., Svegliati, V. W., Bergamaschi, B. G., Masotti, G., Costanzo, M., Antonio, F., Angelico, F., Del, Ben, Polimeni, M., Proietti, L., Cangemi, M., Romiti, R., Toriello, G. F., Sperduti, F., Santangelo, N., Visioli, G., Todisco, G., Vestri, Anna, Farcomeni, R., Corrao, A., Gobbi, S., Corradini, E., Costantino, G., Tripepi, G., Angelico, M., Bolondi, L., D’Amico, G., Franchis, De, Gatta, R., Tassone, A., Anzaldi, E. J., Barone, M., Bazzini, M., Bianchi, C., Boari, P. I., Bracco, B., Buonauro, C., Buttà, A., Buzzetti, E., Calabria, S., Caradio, F., Carleo, P., Carrabba, Maria, Castorani, D., Cecchetto, L., Cicco, L., Cimini, S., Colombo, C., B. M., Vuono, De, Denegri, S., Del, Corso, Giosia, Di, Donnarumma, P., Giorgini, E., Grassi, P., Grembiale, D., Hijazi, A., Iamele, D., Lorusso, L., Marchese, G., Marra, Alberto, Masala, M., Miceli, M., Montebianco, G., Murgia, A. L., Naccarato, G., Padula, P., Pattoneri, D., Perego, P., Pesce, F., Petramala, P., Piano, L., Pinto, S., Pinna, D., Pignataro, M., Pretti, F. S., Pucci, V., Salinaro, G., Salzano, F., Santarossa, A., Scarpini, C., Scicali, F., Sirico, R., Suppressa, D., Talia, P., Torres, M., Traversa, D., Vazzana, M., Vecchio, Claudia, Vettore, R., Vitale, E., Basili, S., Raparelli, V., Napoleone, L., Talerico, G., Corazza, G.R., Perticone, F., Sacerdoti, D., Andriulli, A., Licata, A., Pietrangelo, A., Picardi, A., Raimondo, G., Violi, F., Palasciano, Giuseppe, D’Alitto, Felicia, Palmieri, Vincenzo Ostilio, Santovito, Daniela, Di Michele, Dario, Croce, Giuseppe, Brocco, Silvia, Fasolato, Silvano, Cecchetto, Lara, Bombonato, Giancarlo, Bertoni, Michele, Restuccia, Tea, Andreozzi, Paola, Liguori, Maria Livia, Caroleo, Benedetto, Perticone, Maria, Staltari, Orietta, Manfredini, Roberto, De Giorgi, Alfredo, Averna, Maurizio, Giammanco, Antonina, Granito, Alessandro, Pettinari, Irene, Marinelli, Sara, Bolondi, Luigi, Falsetti, Lorenzo, Salvi, Aldo, Durante-Mangoni, Emanuele, Cesaro, Flavio, Farinaro, Vincenza, Ragone, Enrico, Morana, Ignazio, Ippolito, Antonio, Iacobellis, Angelo, Niro, Grazia, Merla, Antonio, Maimone, Sergio, Cacciola, Irene, Varvara, Doriana, Drenaggi, Davide, Staffolani, Silvia, Vespasiani-Gentilucci, Umberto, Galati, Giovanni, Gallo, Paolo, Davì, Giovanni, Schiavone, Cosima, Santilli, Francesca, Tana, Claudio, Soresi, Maurizio, Bianchi Giovanni, Battista, Carderi, Isabella, Pinto, Antonio, Tuttolomondo, Antonino, Ferrari, Giovanni, Gresele, Paolo, Fierro, Tiziana, Morelli, Olivia, Laffi, Giacomo, Romanelli, Roberto Giulio, Arena, Umberto, Stasi, Cristina, Gasbarrini, Antonio, Garcovich, Matteo, Zocco, Maria Assunta, Riccardi, Laura, Ainora, Maria Elena, Capeci, William, Martino Giuseppe, Pio, Nobili, Lorenzo, Cavallo, Maurizio, Frugiuele, Pierluigi, Greco, Antonio, Ventura, Paolo, Cuoghi, Chiara, Marcacci, Matteo, Serviddio, Gaetano, Vendemiale, Gianluigi, Villani, Rosanna, Gargano, Ruggiero, Vidili, Gianpaolo, Di Cesare, Valentina, Masala, Maristella, Delitala, Giuseppe, Invernizzi, Pietro, Vincenzo, Ronca, Di Minno, Giovanni, Tufano, Antonella, Purrello, Francesco, Privitera, Graziella, Forgione, Alessandra, Curigliano, Valentina, Senzolo, Marco, Rodríguez-Castro, Kryssia Isabel, Giannelli, Gianluigi, Serra, Carla, Neri, Sergio, Pignataro, Pietro, Rizzetto, Mario, Debernardi, Venon Wilma, Svegliati, Baroni Gianluca, Bergamaschi, Gaetano, Masotti, Michela, Costanzo, Filippo, Antonio, Figliomeni, Angelico, Francesco, Del Ben, Maria, Polimeni, Licia, Proietti, Marco, Cangemi, Roberto, Romiti Giulio, Francesco, Toriello, Filippo, Sperduti, Nicolò, Santangelo, Giuseppe, Visioli, Giacomo, Todisco, Tommaso, Vestri Anna, Rita, Farcomeni, Alessio, Corrao, Salvatore, Gobbi, Paolo, Corradini, Elena, Costantino, Giorgio, Tripepi, Giovanni, Angelico, Mario, D’Amico, Gennaro, De Franchis, Roberto, Gatta, Angelo, Tassone, Eliezer Joseph, Anzaldi, Massimiliano, Barone, Milena, Bazzini, Cristina, Bianchi, Paola Ilaria, Boari, Benedetta, Bracco, Christian, Buonauro, Agostino, Buttà, Carmelo, Buzzetti, Elena, Calabria, Stefano, Caradio, Federica, Carleo, Pietro, Carrabba Maria, Domenica, Castorani, Luigi, Cicco, Sebastiano, Cimini, Claudia, Colombo, Barbara Maria, De Vuono, Stefano, Denegri, Andrea, Del Corso, Lisette, Di Giosia, Paolo, Donnarumma, Emilia, Giorgini, Paolo, Grassi, Davide, Grembiale, Alessandro, Hijazi, Daniel, Iamele, Luigi, Lorusso, Giusi, Marchese, Alessandra, Marra Alberto, Maria, Miceli, Giuseppe, Montebianco, Abenavoli Ludovico, Murgia, Giuseppe, Naccarato, Paola, Padula, Donatella, Pattoneri, Paolo, Perego, Francesca, Pesce, Paola, Petramala, Luigi, Piano, Salvatore, Pinto, Daniela, Pinna, Miriam, Pignataro, Francesca Serena, Pretti, Vincenzo, Pucci, Giacomo, Salinaro, Francesco, Salzano, Andrea, Santarossa, Claudia, Scarpini, Francesca, Scicali, Roberto, Sirico, Domenico, Suppressa, Patrizia, Talia, Michela, Torres, Daniele, Traversa, Matteo, Vazzana, Natale, Vecchio Claudia, Rita, Vettore, Elia, Vitale, Francesco, Basili, S, Raparelli, V, Napoleone, L, Talerico, G, Corazza, G, Perticone, F, Sacerdoti, D, Andriulli, A, Licata, A, Pietrangelo, A, Picardi, A, Raimondo, G, Violi, F, Palasciano, G, D'Alitto, F, Palmieri, V, Santovito, D, Di Michele, D, Croce, G, Brocco, S, Fasolato, S, Cecchetto, L, Bombonato, G, Bertoni, M, Restuccia, T, Andreozzi, P, Liguori, M, Caroleo, B, Perticone, M, Staltari, O, Manfredini, R, De Giorgi, A, Averna, M, Giammanco, A, Granito, A, Pettinari, I, Marinelli, S, Bolondi, L, Falsetti, L, Salvi, A, Durante-Mangoni, E, Cesaro, F, Farinaro, V, Ragone, E, Morana, I, Ippolito, A, Iacobellis, A, Niro, G, Merla, A, Maimone, S, Cacciola, I, Varvara, D, Drenaggi, D, Staffolani, S, Vespasiani-Gentilucci, U, Galati, G, Gallo, P, Davi, G, Schiavone, C, Santilli, F, Tana, C, Soresi, M, Bianchi Giovanni, B, Carderi, I, Pinto, A, Tuttolomondo, A, Ferrari, G, Gresele, P, Fierro, T, Morelli, O, Laffi, G, Romanelli, R, Arena, U, Stasi, C, Gasbarrini, A, Garcovich, M, Zocco, M, Riccardi, L, Ainora, M, Capeci, W, Martino Giuseppe, P, Nobili, L, Cavallo, M, Frugiuele, P, Greco, A, Ventura, P, Cuoghi, C, Marcacci, M, Serviddio, G, Vendemiale, G, Villani, R, Gargano, R, Vidili, G, Di Cesare, V, Masala, M, Delitala, G, Invernizzi, P, Vincenzo, R, Di Minno, G, Tufano, A, Purrello, F, Privitera, G, Forgione, A, Curigliano, V, Senzolo, M, Rodriguez-Castro, K, Giannelli, G, Serra, C, Neri, S, Pignataro, P, Rizzetto, M, Debernardi, V, Svegliati, B, Bergamaschi, G, Masotti, M, Costanzo, F, Antonio, F, Angelico, F, Del Ben, M, Polimeni, L, Proietti, M, Cangemi, R, Romiti, G, Toriello, F, Sperduti, N, Santangelo, G, Visioli, G, Todisco, T, Vestri Anna, R, Farcomeni, A, Corrao, S, Gobbi, P, Corradini, E, Costantino, G, Tripepi, G, Angelico, M, D'Amico, G, De Franchis, R, Gatta, A, Tassone, E, Anzaldi, M, Barone, M, Bazzini, C, Bianchi, P, Boari, B, Bracco, C, Buonauro, A, Butta, C, Buzzetti, E, Calabria, S, Caradio, F, Carleo, P, Carrabba Maria, D, Castorani, L, Cicco, S, Cimini, C, Colombo, B, De Vuono, S, Denegri, A, Del Corso, L, Di Giosia, P, Donnarumma, E, Giorgini, P, Grassi, D, Grembiale, A, Hijazi, D, Iamele, L, Lorusso, G, Marchese, A, Marra, A, Miceli, G, Montebianco, A, Murgia, G, Naccarato, P, Padula, D, Pattoneri, P, Perego, F, Pesce, P, Petramala, L, Piano, S, Pinto, D, Pinna, M, Pignataro, F, Pretti, V, Pucci, G, Salinaro, F, Salzano, A, Santarossa, C, Scarpini, F, Scicali, R, Sirico, D, Suppressa, P, Talia, M, Torres, D, Traversa, M, Vazzana, N, Vecchio Claudia, R, Vettore, E, Vitale, F, S Basili, V Raparelli, L Napoleone, G Talerico, G Corazza, F Perticone, D Sacerdoti, A Andriulli, A Licata, A Pietrangelo, A Picardi, G Raimondo, F Violi, MD on behalf of PRO-LIVER Collaborator, Palasciano Giuseppe, D’Alitto Felicia, Palmieri Vincenzo Ostilio, Santovito Daniela, Di Michele Dario, Croce Giuseppe, Brocco Silvia, Fasolato Silvano, Cecchetto Lara, Bombonato Giancarlo, Bertoni Michele, Restuccia Tea, Andreozzi Paola, Liguori Maria Livia, Caroleo Benedetto, Perticone Maria, Staltari Orietta, Manfredini Roberto, De Giorgi Alfredo, Averna Maurizio, Giammanco Antonina, Granito Alessandro, Pettinari Irene, Marinelli Sara, Bolondi Luigi, Falsetti Lorenzo, Salvi Aldo, Durante-Mangoni Emanuele, Cesaro Flavio, Farinaro Vincenza, Ragone Enrico, Morana Ignazio, Ippolito Antonio, Iacobellis Angelo, Niro Grazia, Merla Antonio, Maimone Sergio, Cacciola Irene, Varvara Doriana, Drenaggi Davide, Staffolani Silvia, Vespasiani-Gentilucci Umberto, Galati Giovanni, Gallo Paolo, Davi Giovanni, Schiavone Cosima, Santilli Francesca, Tana Claudio, Soresi Maurizio, Bianchi Giovanni Battista, Carderi Isabella, Pinto Antonio, Tuttolomondo Antonino, Ferrari Giovanni, Gresele Paolo, Fierro Tiziana, Morelli Olivia, Laffi Giacomo, Romanelli Roberto Giulio, Arena Umberto, Stasi Cristina, Gasbarrini Antonio, Garcovich Matteo, Zocco Maria Assunta, Riccardi Laura, Ainora Maria Elena, Capeci William, Martino Giuseppe Pio, Nobili Lorenzo, Cavallo Maurizio, Frugiuele Pierluigi, Greco Antonio, Ventura Paolo, Cuoghi Chiara, Marcacci Matteo, Serviddio Gaetano, Vendemiale Gianluigi, Villani Rosanna, Gargano Ruggiero, Vidili Gianpaolo, Di Cesare Valentina, Masala Maristella, Delitala Giuseppe, Invernizzi Pietro, Vincenzo Ronca, Di Minno Giovanni, Tufano Antonella, Purrello Francesco, Privitera Graziella, Forgione Alessandra, Curigliano Valentina, Senzolo Marco, Rodríguez-Castro Kryssia Isabel, Giannelli Gianluigi, Serra Carla, Neri Sergio, Pignataro Pietro, Rizzetto Mario, Debernardi Venon Wilma, Svegliati Baroni Gianluca, Bergamaschi Gaetano, Masotti Michela, Costanzo Filippo, Antonio Figliomeni, Angelico Francesco, Del Ben Maria, Polimeni Licia, Proietti Marco, Cangemi Roberto, Romiti Giulio Francesco, Toriello Filippo, Sperduti Nicolò, Santangelo Giuseppe, Visioli Giacomo, Todisco Tommaso, Vestri Anna Rita, Farcomeni Alessio, Corrao Salvatore, Gobbi Paolo, Corradini Elena, Costantino Giorgio, Tripepi Giovanni, Angelico Mario, D’Amico Gennaro, de Franchis Roberto, Gatta Angelo, Tassone Eliezer Joseph, Anzaldi Massimiliano, Barone Milena, Bazzini Cristina, Bianchi Paola Ilaria, Boari Benedetta, Bracco Christian, Buonauro Agostino, Buttà Carmelo, Buzzetti Elena, Calabria Stefano, Caradio Federica, Carleo Pietro, Carrabba Maria Domenica, Castorani Luigi, Cicco Sebastiano, Cimini Claudia, Colombo Barbara Maria, De Vuono Stefano, Denegri Andrea, Del Corso Lisette, Di Giosia Paolo, Donnarumma Emilia, Giorgini Paolo, Grassi Davide, Grembiale Alessandro, Hijazi Daniel, Iamele Luigi, Lorusso Giusi, Marchese Alessandra, Marra Alberto Maria, Miceli Giuseppe, Montebianco Abenavoli Ludovico, Murgia Giuseppe, Naccarato Paola, Padula Donatella, Pattoneri Paolo, Perego Francesca, Pesce Paola, Petramala Luigi, Piano Salvatore, Pinto Daniela, Pinna Miriam, Pignataro Francesca Serena, Pretti Vincenzo, Pucci Giacomo, Salinaro Francesco, Salzano Andrea, Santarossa Claudia, Scarpini Francesca, Scicali Roberto, Sirico Domenico, Suppressa Patrizia, Talia Michela, Torres Daniele, Traversa Matteo, Vazzana Natale, Vecchio Claudia Rita, Vettore Elia, Vitale Francesco, Corazza, G. R., Guidacci, Raimondo, Palasciano, G., D'Alitto, F., Palmieri, V. O., Santovito, D., Di Michele, D., Croce, G., Brocco, S., Fasolato, S., Cecchetto, L., Bombonato, G., Bertoni, M., Restuccia, T., Andreozzi, P., Liguori, M. L., Caroleo, B., Perticone, M., Staltari, O., Manfredini, R., De Giorgi, A., Averna, M., Giammanco, A., Granito, A., Pettinari, I., Marinelli, S., Bolondi, L., Falsetti, L., Salvi, A., Durante-Mangoni, E., Cesaro, F., Farinaro, V., Ragone, E., Morana, I., Ippolito, A., Iacobellis, A., Niro, G., Merla, A., Maimone, S., Cacciola, I., Varvara, D., Drenaggi, D., Staffolani, S., Vespasiani-Gentilucci, U., Galati, G., Gallo, P., Davi, G., Schiavone, C., Santilli, F., Tana, C., Soresi, M., Bianchi Giovanni, B., Carderi, I., Pinto, A., Tuttolomondo, A., Ferrari, G., Gresele, P., Fierro, T., Morelli, O., Laffi, G., Romanelli, R. G., Arena, U., Stasi, C., Gasbarrini, A., Garcovich, M., Zocco, M. A., Riccardi, L., Ainora, M. E., Capeci, W., Martino Giuseppe, P., Nobili, L., Cavallo, M., Frugiuele, P., Greco, A., Ventura, P., Cuoghi, C., Marcacci, M., Serviddio, G., Vendemiale, G., Villani, R., Gargano, R., Vidili, G., Di Cesare, V., Masala, M., Delitala, G., Invernizzi, P., Vincenzo, R., Di Minno, G., Tufano, A., Purrello, F., Privitera, G., Forgione, A., Curigliano, V., Senzolo, M., Rodriguez-Castro, K. I., Giannelli, G., Serra, C., Neri, S., Pignataro, P., Rizzetto, M., Debernardi, V. W., Svegliati, B. G., Bergamaschi, G., Masotti, M., Costanzo, F., Antonio, F., Angelico, F., Del Ben, M., Polimeni, L., Proietti, M., Cangemi, R., Romiti, G. F., Toriello, F., Sperduti, N., Santangelo, G., Visioli, G., Todisco, T., Vestri Anna, R., Farcomeni, A., Corrao, S., Gobbi, P., Corradini, E., Costantino, G., Tripepi, G., Angelico, M., D'Amico, G., De Franchis, R., Gatta, A., Tassone, E. J., Anzaldi, M., Barone, M., Bazzini, C., Bianchi, P. I., Boari, B., Bracco, C., Buonauro, A., Butta, C., Buzzetti, E., Calabria, S., Caradio, F., Carleo, P., Carrabba Maria, D., Castorani, L., Cicco, S., Cimini, C., Colombo, B. M., De Vuono, S., Denegri, A., Del Corso, L., Di Giosia, P., Donnarumma, E., Giorgini, P., Grassi, D., Grembiale, A., Hijazi, D., Iamele, L., Lorusso, G., Marchese, A., Marra, A. M., Miceli, G., Montebianco, A. L., Murgia, G., Naccarato, P., Padula, D., Pattoneri, P., Perego, F., Pesce, P., Petramala, L., Piano, S., Pinto, D., Pinna, M., Pignataro, F. S., Pretti, V., Pucci, G., Salinaro, F., Salzano, A., Santarossa, C., Scarpini, F., Scicali, R., Sirico, D., Suppressa, P., Talia, M., Torres, D., Traversa, M., Vazzana, N., Vecchio Claudia, R., Vettore, E., and Vitale, F.

Subjects
Liver Cirrhosis, Male, Settore MED/09 - Medicina Interna, 030204 cardiovascular system & hematology, Gastroenterology, Severity of Illness Index, cjirrhosis, ACTIVATION, 0302 clinical medicine, Risk Factors, Medicine, Platelet, Prospective Studies, Prospective cohort study, RISK, Aged, 80 and over, medicine.diagnostic_test, PRO-LIVER, Platelet, cirrhosis, gastrointestinal bleeding, ASSOCIATION, Middle Aged, Prognosis, Italy, 030211 gastroenterology & hepatology, Female, Gastrointestinal Hemorrhage, Human, Adult, Platelets, medicine.medical_specialty, Prognosi, Liver Cirrhosi, MEDLINE, COAGULATION, gastrointestinal bleeding, Socio-culturale, Hemorrhage, Hepatology, Follow-Up Studie, 03 medical and health sciences, Text mining, Internal medicine, Severity of illness, ENDOTOXEMIA, Pro-Liver Study, Humans, HEMOSTASIS, International Normalized Ratio, Aged, Proportional Hazards Models, Prothrombin time, Cirrhosi, Platelet Count, Bleeding, Liver Cirrhosis, business.industry, Proportional hazards model, Platelet Count, Risk Factor, cirrhosis, bleeding, Thrombocytopenia, Prospective Studie, THROMBOSIS, Platelets, cjirrhosis, bleeding, PRO-LIVER, Proportional Hazards Model, Prothrombin Time, business, DECOMPENSATED CIRRHOSIS, Follow-Up Studies
Abstract

OBJECTIVES: Thrombocytopenia is a hallmark for patients with cirrhosis and it is perceived as a risk factor for bleeding events. However, the relationship between platelet count and bleeding is still unclear. METHODS: We investigated the relationship between platelet count and major or clinical relevant nonmajor bleedings during a follow-up of ∼4 years. RESULTS: A total of 280 cirrhotic patients with different degrees of liver disease (67% males; age 64±37 years; 47% Child–Pugh B and C) were followed up for a median of 1,129 (interquartile range: 800–1,498) days yielding 953.12 patient-year of observation. The annual rate of any significant bleeding was 5.45%/year (3.57%/year and 1.89%/year for major and minor bleeding, respectively). Fifty-two (18.6%) patients experienced a major (n=34) or minor (n=18) bleeding event, predominantly from gastrointestinal origin. Platelet counts progressively decreased with the worsening of liver disease and were similar in patients with or without major or minor bleeding: a platelet count ≤50×103/μl was detected in 3 (6%) patients with and in 20 (9%) patients without any bleeding event. Conversely, prothrombin time-international normalized ratio was slightly higher in patients with overall or major bleeding. On Cox proportional hazard analysis, only a previous gastrointestinal bleeding (hazard ratio (HR): 1.96; 95% confidence interval: 1.11–3.47; P=0.020) and encephalopathy (HR: 2.05; 95% confidence interval: 1.16–3.62; P=0.013) independently predicted overall bleeding events. CONCLUSIONS: Platelet count does not predict unprovoked major or minor bleeding in cirrhotic patients.

Published
2018

7. Addition of Either Lonidamine or Granulocyte Colony-Stimulating Factor Does Not Improve Survival in Early Breast Cancer Patients Treated With High-Dose Epirubicin and Cyclophosphamide

Author

Papaldo, P., Lopez, M., Cortesi, Enrico, Cammilluzzi, E., Antimi, M., Terzoli, E., Lepidini, G., Vici, P., Barone, C., Ferretti, G., Di Cosimo, S., Nistico, C., Carlini, P., Conti, F., Di Lauro, L., Botti, C., Vitucci, C., Fabi, A., Giannarelli, D., Marolla, P., Di Maio, M., Perrone, F., Gallo, C., Iaffaioli, R. V., Manzione, L., Piantedosi, F. V., Cigolari, S., Illiano, A., Barbera, S., Robbiati, S. F., Piazza, E., Ianniello, G. P., Frontini, L., Veltri, E., Castiglione, F., Rosetti, F., De Maio, E., Maione, P., Gridelli, C., Rossi, A., Barletta, E., Barzelloni, M. L., Signoriello, G., Bilancia, D., Dinota, A., Rosati, G., Germano, D., Lamberti, A., Pontillo, V., Brancacio, L., Crispino, C., Esposito, M., Battiloro, C., Tufano, G., Cioffi, A., Guardasole, V., Angelini, V., Guidetti, G., Renda, F., Romano, F., Volpintesta, A., Sannicolo, M., Filipazzi, V., Esani, G., Gambaro, A., Ferrario, S., Tinessa, V., Caprio, M. G., Zonato, S., Cabiddu, M., Raina, A., D'Aprile, M., Pistillucci, G., Porcile, G., Ostellino, O., Vinante, O., Azzarello, G., Gebbia, V., Borsellino, N., Testa, A., Gasparini, G., Morabito, A., Gattuso, D., Romito, S., Carrozza, F., Fava, S., Calcagno, A., Grimi, E., Bertetto, O., Ciuffreda, L., Parello, G., Maiorino, L., Santoro, A., Santoro, M., Failla, G., Aiello, R. A., Bearz, A., Sorio, R., Scalone, S., Clerici, M., Bollina, R., Belloni, P., Sacco, C., Sibau, A., Adamo, V., Altavilla, G., Scimone, A., Spatafora, M., Bellia, V., Hopps, M. R., Monfardini, S., Favaretto, A., Stefani, M., Corradini, G. M., Pavia, G., Scagliotti, G., Novello, S., Selvaggi, G., Tonato, M., Darwish, S., Michetti, G., Belometti, M. O., Labianca, R., Quadri, A., De Marinis, F., Migliorino, M. R., Martelli, O., Colucci, G., Galetta, D., Giotta, F., Isa, L., Candido, P., Rossi, N., Calandriello, A., Ferrau, F., Malaponte, E., Barni, S., Cazzaniga, M., Gebbia, N., Valerio, Mr, Belli, M., Colantuoni, G., Capuano, M. A., Angiolillo, M., Sollitto, F., Ardizzoia, A., Luporini, G., Locatelli, M. C., Pari, F., Aitini, E., Pedicini, T., Febbraro, A., Zollo, C., Di Costanzo, F., Bartolucci, R., Gasperoni, S., Gaion, F., Palazzolo, G., Galligioni, E., Caffo, O., Cortesi, E., D'Auria, G., Curcio, C., Vasta, M., Bumma, C., Celano, A., Bretti, S., Nettis, G., Anselmo, A., Mattioli, R., Aschelter, A., and Foa, P.

Subjects
Adult, Cancer Research, medicine.medical_specialty, Indazoles, Filgrastim, Cyclophosphamide, medicine.medical_treatment, Breast Neoplasms, Gastroenterology, Disease-Free Survival, chemistry.chemical_compound, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, Granulocyte Colony-Stimulating Factor, medicine, Humans, Survival rate, Aged, Epirubicin, Chemotherapy, business.industry, Lonidamine, Middle Aged, medicine.disease, Metastatic breast cancer, Recombinant Proteins, Granulocyte colony-stimulating factor, Surgery, Survival Rate, Oncology, chemistry, Female, business, Follow-Up Studies, medicine.drug
Abstract

Purpose: Lonidamine (LND) can enhance the activity of anthracyclines in patients with metastatic breast cancer. A multicenter, prospective, randomized trial was designed to determine whether the association of LND with high-dose epirubicin plus cyclophosphamide (EC) could improve disease-free survival (DFS) in patients with early breast cancer (BC) compared with EC alone. Granulocyte colony-stimulating factor (G-CSF) was added to maintain the EC dose-intensity. Patients and Methods: From October 1991 to April 1994, 506 patients with stage I/II BC were randomly assigned to four groups: (A) epirubicin 120 mg/m2 and cyclophosphamide 600 mg/m2 administered intravenously on day 1 every 21 days for four cycles (124 patients); (B) EC plus LND 450 mg/d administered orally (125 patients); (C) EC plus G-CSF administered subcutaneously (129 patients); (D) EC plus LND plus G-CSF (128 patients). Results: Median follow-up was 55 months. Five-year DFS rate was similar for LND (B+D groups; 69.6%) versus non-LND arms (A+C groups; 70.3%) and G-CSF (C+D groups; 67.2%) versus non–G-CSF arms (A+B groups; 72.9%). Five-year overall survival (OS) was comparable in LND (79.1%) versus non-LND arms (81.3%) and in G-CSF (80.6%) versus non–G-CSF arms (79.6%). DFS and OS distributions in LND and G-CSF arms did not change according to tumor size, node, receptor, and menopausal status. G-CSF dramatically reduced hematologic toxicity without having a significant impact on dose-intensity (98.1% v 95.5% for C+D and A+B groups, respectively). Conclusion: EC is active and well tolerated in patients with early breast cancer. The addition of LND or G-CSF does not improve DFS or OS.

Published
2003

15. Supportive care in patients with advanced non-small-cell lung cancer

Author

DI MAIO, Massimo, Perrone, F, Gallo, C, Iaffaioli, Rv, Manzione, L, Piantedosi, Fv, Cigolari, S, Illiano, A, Barbera, S, Robbiati, Sf, Piazza, E, Ianniello, Gp, Frontini, L, Veltri, E, Castiglione, F, Rosetti, F, De Maio, E, Maione, P, Gridelli, C, Rossi, A, Barletta, E, Barzelloni, Ml, Signoriello, G, Bilancia, D, Dinota, A, Rosati, G, Germano, D, Lamberti, A, Pontillo, V, Brancacio, L, Crispino, C, Esposito, M, Battiloro, C, Tufano, G, Cioffi, A, Guardasole, V, Angelini, V, Guidetti, G, Renda, F, Romano, F, Volpintesta, A, Sannicolò, M, Filipazzi, V, Esani, G, Gambaro, A, Ferrario, S, Tinessa, V, Caprio, Mg, Zonato, S, Cabiddu, M, Raina, A, D'Aprile, M, Pistillucci, G, Porcile, G, Ostellino, O, Vinante, O, Azzarello, G, Gebbia, V, Borsellino, N, Testa, A, Gasparini, G, Morabito, A, Gattuso, D, Romito, S, Carrozza, F, Fava, S, Calcagno, A, Grimi, E, Bertetto, O, Ciuffreda, L, Parello, G, Maiorino, L, Santoro, A, Santoro, M, Failla, G, Aiello, Ra, Bearz, A, Sorio, R, Scalone, S, Clerici, M, Bollina, R, Belloni, P, Sacco, C, Sibau, A, Adamo, V, Altavilla, G, Scimone, A, Spatafora, M, Bellia, V, Hopps, Mr, Monfardini, S, Favaretto, A, Stefani, M, Corradini, Gm, Pavia, G, Scagliotti, Giorgio Vittorio, Novello, Silvia, Selvaggi, G, Tonato, M, Darwish, S, Michetti, G, Belometti, Mo, Labianca, R, Quadri, A, De Marinis, F, Migliorino, Mr, Martelli, O, Colucci, G, Galetta, D, Giotta, F, Isa, L, Candido, P, Rossi, N, Calandriello, A, Ferraù, F, Malaponte, E, Barni, S, Cazzaniga, M, Gebbia, N, Valerio, Mr, Belli, M, Colantuoni, G, Capuano, Ma, Angiolillo, M, Sollitto, F, Ardizzoia, A, Luporini, G, Locatelli, Mc, Pari, F, Aitini, E, Pedicini, T, Febbraro, A, Zollo, C, Di Costanzo, F, Bartolucci, R, Gasperoni, S, Gaion, F, Palazzolo, G, Galligioni, E, Caffo, O, Cortesi, E, D'Auria, G, Curcio, C, Vasta, M, Bumma, C, Celano, A, Bretti, S, Nettis, G, Anselmo, A, Mattioli, R, Nisticò, C, Aschelter, A, Foa, P., DI MAIO, M, Perrone, F, Gallo, Ciro, Iaffaioli, Rv, Manzione, L, Piantedosi, Fv, Cigolari, S, Illiano, A, Barbera, S, Robbiati, Sf, Piazza, E, Ianniello, Gp, Frontini, L, Veltri, E, Castiglione, F, Rosetti, F, DE MAIO, E, Maione, P, and Gridelli, C.

Subjects
Adult, Male, concomitant drugs, Cancer Research, medicine.medical_specialty, Aging, Palliative care, Lung Neoplasms, medicine.medical_treatment, Vinorelbine, Vinblastine, Deoxycytidine, Clinical, Quality of life, Internal medicine, Carcinoma, Non-Small-Cell Lung, Antineoplastic Combined Chemotherapy Protocols, polypharmacotherapy, medicine, Humans, Lung cancer, Survival rate, Aged, Randomized Controlled Trials as Topic, Aged, 80 and over, Chemotherapy, Performance status, business.industry, Palliative Care, Middle Aged, medicine.disease, Gemcitabine, Surgery, Survival Rate, supportive care, lung cancer, Oncology, Concomitant, Quality of Life, Antiemetics, Female, Cisplatin, business, medicine.drug
Abstract

The present study describes supportive care (SC) in patients with advanced non-small-cell lung cancer (NSCLC), evaluating whether it is affected by concomitant chemotherapy, patient's performance status (PS) and age. Data of patients enrolled in three randomised trials of first-line chemotherapy, conducted between 1996 and 2001, were pooled. The analysis was limited to the first three cycles of treatment. Supportive care data were available for 1185 out of 1312 (90%) enrolled patients. Gastrointestinal drugs (45.7%), corticosteroids (33.4%) and analgesics (23.8%) were the most frequently observed categories. The mean number of drugs per patient was 2.43; 538 patients (45.4%) assumed three or more supportive drugs. Vinorelbine does not produce substantial variations in the SC pattern, while cisplatin-based treatment requires an overall higher number of supportive drugs, with higher use of antiemetics (41 vs 27%) and antianaemics (10 vs 4%). Patients with worse PS are more exposed to corticosteroids (42 vs 30%). Elderly patients require drugs against concomitant diseases significantly more than adults (20 vs 7%) and are less frequently exposed to antiemetics (12 vs 27%). In conclusion, polypharmacotherapy is a relevant issue in patients with advanced NSCLC. Chemotherapy does not remarkably affect the pattern of SC, except for some drugs against side effects. Elderly patients assume more drugs for concomitant diseases and receive less antiemetics than adults.

Published
2004

16. Supportive care in patients with advanced non small cell lung cancer

Author

DI MAIO, M, Perrone, F, Gallo, C, Iaffaioli, Rv, Manzione, L, Piantedosi, Fv, Cigolari, S, Illiano, A, Barbera, S, Robbiati, Sf, Piazza, E, Ianniello, Gp, Frontini, L, Veltri, E, Castiglione, F, Rosetti, F, DE MAIO, E, Maione, P, Gridelli, C, Rossi, A, Barletta, E, Barzelloni, Ml, Signoriello, G, Bilancia, D, Dinota, A, Rosati, G, Germano, D, Lamberti, A, Pontillo, V, Brancacio, L, Crispino, C, Esposito, M, Battiloro, C, Tufano, G, Cioffi, A, Guardasole, V, Angelini, V, Guidetti, G, Renda, F, Romano, F, Volpintesta, A, Sannicolo, M, Filipazzi, V, Esani, G, Gambaro, A, Ferrario, S, Tinessa, V, Caprio, Mg, Zonato, S, Cabiddu, M, Raina, A, D'Aprile, M, Pistillucci, G, Porcile, G, Ostellino, O, Vinante, O, Azzarello, G, Gebbia, V, Borsellino, N, Testa, A, Gasparini, G, Morabito, A, Gattuso, D, Romito, S, Carrozza, F, Fava, S, Calcagno, A, Grimi, E, Bertetto, O, Ciuffreda, L, Parello, G, Maiorino, L, Santoro, A, Santoro, M, Failla, G, Aiello, Ra, Bearz, A, Sorio, R, Scalone, S, Clerici, M, Bollina, R, Belloni, P, Sacco, C, Sibau, A, Adamo, Vincenzo, Altavilla, Giuseppe, Scimone, A, Spatafora, M, Bellia, V, Hopps, Mr, Monfardini, S, Favaretto, A, Stefani, M, Corradini, Gm, Pavia, G, Scagliotti, G, Novello, S, Selvaggi, G, Tonato, M, Darwish, S, Michetti, G, Belometti, Mo, Labianca, R, Quadri, A, DE MARINIS, F, Migliorino, Mr, Martelli, O, Colucci, G, Galetta, D, Giotta, F, Isa, L, Candido, P, Rossi, N, Calandriello, A, Ferrau, F, Malaponte, E, Barni, S, Cazzaniga, M, Gebbia, N, Valerio, Mr, Belli, M, Colantuoni, G, Capuano, Ma, Angiolillo, M, Sollitto, F, Ardizzoia, A, Luporini, G, Locatelli, Mc, Pari, F, Aitini, E, Pedicini, T, Febbraro, A, Zollo, C, DI COSTANZO, F, Bartolucci, R, Gasperoni, S, Gaion, F, Palazzolo, G, Galligioni, E, Caffo, O, Cortesi, E, D'Auria, G, Curcio, C, Vasta, M, Bumma, C, Celano, A, Bretti, S, Nettis, G, Anselmo, A, Mattioli, R, Nistico, C, Aschelter, A, and Foa, P.

Published
2003

20. Ottimizzazione della ricerca di anticorpi anti-HLA su panel cellulare

Author

Meschini L, Pellegrini P, Bonavia VM, and Tufano G

Subjects
panel cellulare, Elaboratore elettronico
Abstract

Il nostro package è stato ideato con lo scopo di rendere più agevole e precisa la lettura i Panel cellulari riguardanti gli anticopri anti-HLA nei pazienti in attesa di trapioanto di renale

Published
1983

21. Nephrotoxicity and CyA/Metabolites

Author

Cortini, C., Iacona, A., De Paolis, P., Utzeri, G., Pisani, Francesco, Tufano, G., Rossetti, A., Adorno, D., and Casciani, C. U.

Published
1989

22. Pulmonary sarcoidosis during interferon therapy: A rare or underestimated event?

Author

Salvio, A., Mormile, M., Giannattasio, F., Varriale, M., D Errico, T., Balzano, B., Pierluigi Carratù, Tufano, G., Visconti, M., A., Salvio, Mormile, Mauro, F., Giannattasio, M., Varriale, T., D'Errico, B., Balzano, P., Carratù, G., Tufano, and M., Visconti

Abstract

Interferon (IFN)-alpha with or without ribavirin is the treatment of choice for patients with chronic HCV-related hepatitis. Cough and dyspnea during IFN therapy are often regarded as a side effect and not as a possible sign of the onset of a pulmonary interstitial disease. It may therefore be claimed that the likelihood that patients treated with IFN develop sarcoidosis is being underestimated. Although they are not conventionally classified as etiopathologic agents of sarcoidosis, the IFNs have been proven to be capable of triggering macrophages and of promoting the expression of class II HLA antigens. It is therefore possible that IFN-a treatment could trigger macrophages and promote the polarization of the immune response towards Th1 in the presence of particular susceptibility conditions, thus starting the series of events that lead to the onset of sarcoidosis. We describe a case of pulmonary sarcoidosis in a 33-year-old patient treated with IFN- a2b and ribavirin for chronic HCV-related hepatitis after 6 months of therapy. The case we report here brings forth the issue of a possible underestimation of the real incidence of sarcoidosis during IFN therapy and highlights the need for more attention to and a more careful evaluation of respiratory symptoms manifesting in treated patients.

23. A new HLA-DRB1 allele: DRB1*1152

Author

Ozzella, G., Monaco, Pi, Iacona, A., Calcagni, E., Cortini, C., Piancatelli, D., Anna Aureli, Tufano, G., Piazza, A., and Adorno, D.

Subjects
new HLA alleles

24. A computed tomography-based comparative cephalometric analysis of the Italian craniofacial pattern through 2,700 years

Author

Letizia Perillo, Salvatore Cappabianca, T. G. Thanassoulas, Francesco Iaselli, V. Esposito, Roberto Grassi, G. Tufano, M. Montemarano, Antonio Rotondo, Cappabianca, Salvatore, Perillo, Letizia, Esposito, V, Iaselli, F, Tufano, G, Thanassoulas, Tg, Montemarano, M, Grassi, Roberto, and Rotondo, Antonio

Subjects
Male, Cephalometric analysis, Basicranium, Cephalometry, Population, Dentistry, Splanchnocranium, Humans, Medicine, Radiology, Nuclear Medicine and imaging, Craniofacial, education, Computed tomography, Human evolution, Orthodontics, education.field_of_study, Craniometry, Occlusion, business.industry, Skull, Neurocranium, Paleontology, General Medicine, Sagittal plane, medicine.anatomical_structure, Italy, Data Interpretation, Statistical, Female, Tomography, X-Ray Computed, business
Abstract

The aim of our study was to define the changes in morphovolumetric features of neurocranium, basicranium and splanchnocranium in the population of Campania, southern Italy, over the last 2,700 years. This was a very intense period for this region from both historical and evolutionary perspectives and was marked by the succession of colonisations, dominations and invasions by several European and non-European peoples, events that profoundly influenced the original genetic heritage, which subsequently became more complex. Unlike most previous authors, we based our craniometric comparative analysis on multidetector computed tomography (MDCT) studies of contemporary and ancient series dating to between the seventh and fifth centuries B.C. of skulls found in the Etruscan necropolis of Pompei and Pontecagnano. MDCT is extremely reliable in identifying landmarks and measuring linear and angular indices through the use of multiplanar and tridimensional reformations. While highlighting a remarkable stability of 22/32 of the indices considered, as an effect of the role of the genetic heritage in preserving morphovolumetric features in a given population, statistical analysis showed some interesting results: the main changes concerned the splanchnocranium and the occlusion, indicating a higher sensitivity of these districts to environmental factors, mainly related to diet. Conversely, neurobasicranial complex morphovolumetric features remained amazingly intact. In particular, the neurocranium increased in overall capacity in response to the growing brain and changed shape with a progressive shift to a dolichocranic, flattened frontal pattern; the basicranium shape was preserved, as indicated by the stability of the cranial base (NSBa) angle over time. The splanchnocranium, on the contrary, has undergone a dramatic involution, even conditioning gnathic structures with changes in palatal shape (more acute) and in the relationship between the jaws on the sagittal plane, resulting in increased prevalence of Angle's class I and III malocclusions. © 2012 Springer-Verlag Italia. The aim of our study was to define the changes in morphovolumetric features of neurocranium, basicranium and splanchnocranium in the population of Campania, southern Italy, over the last 2,700 years. This was a very intense period for this region from both historical and evolutionary perspectives and was marked by the succession of colonisations, dominations and invasions by several European and non-European peoples, events that profoundly influenced the original genetic heritage, which subsequently became more complex. Unlike most previous authors, we based our craniometric comparative analysis on multidetector computed tomography (MDCT) studies of contemporary and ancient series dating to between the seventh and fifth centuries B.C. of skulls found in the Etruscan necropolis of Pompei and Pontecagnano. MDCT is extremely reliable in identifying landmarks and measuring linear and angular indices through the use of multiplanar and tridimensional reformations. While highlighting a remarkable stability of 22/32 of the indices considered, as an effect of the role of the genetic heritage in preserving morphovolumetric features in a given population, statistical analysis showed some interesting results: the main changes concerned the splanchnocranium and the occlusion, indicating a higher sensitivity of these districts to environmental factors, mainly related to diet. Conversely, neurobasicranial complex morphovolumetric features remained amazingly intact. In particular, the neurocranium increased in overall capacity in response to the growing brain and changed shape with a progressive shift to a dolichocranic, flattened frontal pattern; the basicranium shape was preserved, as indicated by the stability of the cranial base (NSBa) angle over time. The splanchnocranium, on the contrary, has undergone a dramatic involution, even conditioning gnathic structures with changes in palatal shape (more acute) and in the relationship between the jaws on the sagittal plane, resulting in increased prevalence of Angle's class I and III malocclusions.

Published
2012

25. Orthodeoxia without Platypnea from Interatrial Defect Associated with Persistent Left Superior Vena cava in the Absence of Pulmonary Hypertension

Author

Matteo Sofia, Mauro Maniscalco, Giovanni Tufano, Annamaria Romano, Giovanni Dialetto, Maniscalco, M, Dialetto, G, Tufano, G, Romano, A, and Sofia, Matteo

Subjects
Adult, Male, Pulmonary and Respiratory Medicine, medicine.medical_specialty, Vena Cava, Superior, Posture, Foramen secundum, Heart Septal Defects, Atrial, Persistent fetal circulation, Hypoxemia, medicine, Humans, Persistent left superior vena cava, Ultrasonography, Doppler, Color, Hypoxia, Platypnea, Coronary sinus, business.industry, Prostheses and Implants, medicine.disease, Pulmonary hypertension, Surgery, Military Personnel, Heart catheterization, medicine.symptom, business
Abstract

Orthodeoxia-platypnea is a rare but increasingly recognized syndrome of upright hypoxemia usually associated to breathlessness relieved by recumbency. We report the case of isolated orthodeoxia discovered in a military recruit who referred only fatigability as the clinical symptom after a forced march. Transesophageal echocardiography demonstrated the presence of interatrial defect ostium secundum type with the persistence of left superior vena cava draining into coronary sinus. Right-to-left shunt was visualized by peripheral saline contrast infusion, despite normal right hemodynamics at heart catheterization. Hypoxemia recovered after the percutaneous closure of the interatrial defect. Orthodeoxia and platypnea could occur as separate disease manifestations, the latter probably being a rarer acute event, whereas orthodeoxia was underestimated and potentially earlier screenable.

Published
2003

26. Mesorectum, is it an appropiate term?

Author

G. del Genio, Gianluca Rossetti, C. Di Stazio, G. Tufano, A. Del Genio, Luigi Brusciano, M. Grillo, A. Tufano, Tufano, A, Tufano, G, Brusciano, L, DEL GENIO, Gianmattia, Rossetti, G, Di Stazio, C, Grillo, M, and del Genio, A.

Subjects
medicine.medical_specialty, Rectal Neoplasms, business.industry, Internal medicine, General surgery, Rectum, Gastroenterology, Humans, Medicine, Mesorectum, Hepatology, business, Term (time)
Published
2007

27. TFEB controls syncytiotrophoblast formation and hormone production in placenta.

Author

Cesana M, Tufano G, Panariello F, Zampelli N, Soldati C, Mutarelli M, Montefusco S, Grieco G, Sepe LV, Rossi B, Nusco E, Rossignoli G, Panebianco G, Merciai F, Salviati E, Sommella EM, Campiglia P, Martello G, Cacchiarelli D, Medina DL, and Ballabio A

Abstract

TFEB, a bHLH-leucine zipper transcription factor belonging to the MiT/TFE family, globally modulates cell metabolism by regulating autophagy and lysosomal functions. Remarkably, loss of TFEB in mice causes embryonic lethality due to severe defects in placentation associated with aberrant vascularization and resulting hypoxia. However, the molecular mechanism underlying this phenotype has remained elusive. By integrating in vivo analyses with multi-omics approaches and functional assays, we have uncovered an unprecedented function for TFEB in promoting the formation of a functional syncytiotrophoblast in the placenta. Our findings demonstrate that constitutive loss of TFEB in knock-out mice is associated with defective formation of the syncytiotrophoblast layer. Indeed, using in vitro models of syncytialization, we demonstrated that TFEB translocates into the nucleus during syncytiotrophoblast formation and binds to the promoters of crucial placental genes, including genes encoding fusogenic proteins (Syncytin-1 and Syncytin-2) and enzymes involved in steroidogenic pathways, such as CYP19A1, the rate-limiting enzyme for the synthesis of 17β-Estradiol (E2). Conversely, TFEB depletion impairs both syncytial fusion and endocrine properties of syncytiotrophoblast, as demonstrated by a significant decrease in the secretion of placental hormones and E2 production. Notably, restoration of TFEB expression resets syncytiotrophoblast identity. Our findings identify that TFEB controls placental development and function by orchestrating both the transcriptional program underlying trophoblast fusion and the acquisition of endocrine function, which are crucial for the bioenergetic requirements of embryonic development., (© 2024. The Author(s).)

Published
2024
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28. TFEB and TFE3 control glucose homeostasis by regulating insulin gene expression.

Author

Pasquier A, Pastore N, D'Orsi L, Colonna R, Esposito A, Maffia V, De Cegli R, Mutarelli M, Ambrosio S, Tufano G, Grimaldi A, Cesana M, Cacchiarelli D, Delalleau N, Napolitano G, and Ballabio A

Subjects
Animals, Mice, Autophagy genetics, Gene Expression, Glucose, Lysosomes metabolism, Basic Helix-Loop-Helix Leucine Zipper Transcription Factors genetics, Basic Helix-Loop-Helix Leucine Zipper Transcription Factors metabolism, Insulin
Abstract

To fulfill their function, pancreatic beta cells require precise nutrient-sensing mechanisms that control insulin production. Transcription factor EB (TFEB) and its homolog TFE3 have emerged as crucial regulators of the adaptive response of cell metabolism to environmental cues. Here, we show that TFEB and TFE3 regulate beta-cell function and insulin gene expression in response to variations in nutrient availability. We found that nutrient deprivation in beta cells promoted TFEB/TFE3 activation, which resulted in suppression of insulin gene expression. TFEB overexpression was sufficient to inhibit insulin transcription, whereas beta cells depleted of both TFEB and TFE3 failed to suppress insulin gene expression in response to amino acid deprivation. Interestingly, ChIP-seq analysis showed binding of TFEB to super-enhancer regions that regulate insulin transcription. Conditional, beta-cell-specific, Tfeb-overexpressing, and Tfeb/Tfe3 double-KO mice showed severe alteration of insulin transcription, secretion, and glucose tolerance, indicating that TFEB and TFE3 are important physiological mediators of pancreatic function. Our findings reveal a nutrient-controlled transcriptional mechanism that regulates insulin production, thus playing a key role in glucose homeostasis at both cellular and organismal levels., (© 2023 The Authors. Published under the terms of the CC BY 4.0 license.)

Published
2023
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29. EGR1 drives cell proliferation by directly stimulating TFEB transcription in response to starvation.

Author

Cesana M, Tufano G, Panariello F, Zampelli N, Ambrosio S, De Cegli R, Mutarelli M, Vaccaro L, Ziller MJ, Cacchiarelli D, Medina DL, and Ballabio A

Subjects
Humans, Mechanistic Target of Rapamycin Complex 1 genetics, Mechanistic Target of Rapamycin Complex 1 metabolism, Cell Proliferation genetics, Early Growth Response Protein 1 genetics, Early Growth Response Protein 1 metabolism, Basic Helix-Loop-Helix Leucine Zipper Transcription Factors genetics, Basic Helix-Loop-Helix Leucine Zipper Transcription Factors metabolism, Autophagy genetics, Lysosomes metabolism
Abstract

The stress-responsive transcription factor EB (TFEB) is a master controller of lysosomal biogenesis and autophagy and plays a major role in several cancer-associated diseases. TFEB is regulated at the posttranslational level by the nutrient-sensitive kinase complex mTORC1. However, little is known about the regulation of TFEB transcription. Here, through integrative genomic approaches, we identify the immediate-early gene EGR1 as a positive transcriptional regulator of TFEB expression in human cells and demonstrate that, in the absence of EGR1, TFEB-mediated transcriptional response to starvation is impaired. Remarkably, both genetic and pharmacological inhibition of EGR1, using the MEK1/2 inhibitor Trametinib, significantly reduced the proliferation of 2D and 3D cultures of cells displaying constitutive activation of TFEB, including those from a patient with Birt-Hogg-Dubé (BHD) syndrome, a TFEB-driven inherited cancer condition. Overall, we uncover an additional layer of TFEB regulation consisting in modulating its transcription via EGR1 and propose that interfering with the EGR1-TFEB axis may represent a therapeutic strategy to counteract constitutive TFEB activation in cancer-associated conditions., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: A.B. is a cofounder of Casma Therapeutics and an advisory board member of Next Generation Diagnostic srl, Avilar Therapeutics and Coave Therapeutics. Davide Cacchiarelli is Co-Founder, Shareholder and Consultant of Next Generation Diagnostic srl., (Copyright: © 2023 Cesana et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Published
2023
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30. Preoperative assessment of simple and complex anorectal fistulas: Tridimensional endoanal ultrasound? Magnetic resonance? Both?

Author

Brillantino A, Iacobellis F, Reginelli A, Monaco L, Sodano B, Tufano G, Tufano A, Maglio M, De Palma M, Di Martino N, Renzi A, and Grassi R

Subjects
Adult, Female, Humans, Hydrogen Peroxide, Image Enhancement methods, Male, Prospective Studies, Rectal Fistula surgery, Sensitivity and Specificity, Severity of Illness Index, Endosonography, Imaging, Three-Dimensional, Magnetic Resonance Imaging, Rectal Fistula diagnostic imaging
Abstract

Purpose: The purpose of the study is to evaluate the diagnostic value of tridimensional endoanal ultrasound (3D-EAUS) and magnetic resonance (MR) in the preoperative assessment of both simple and complex anorectal fistulas., Methods: All the patients referred for the treatment of anal fistulas were enrolled in this study and underwent, as preoperative assessment, anamnestic evaluation, clinical examination, and unenhanced and H2O2-enhanced 3D-EAUS and MR. The results of imaging evaluation were compared with surgical findings, considered as reference standard., Results: During the study period, 124 patients operated on for anal fistulas underwent complete preoperative imaging assessment. Perfect agreement between 3D-EAUS and surgery in the anal fistulas' severity grading was found (K = 1). The fistulas were classified as simple in 68/126 (53.9%) and complex in 58/126 (46.03%) cases, according to fistulas' Parks' classification and the most recent American Guidelines. In both simple and complex anal fistulas, 3D-EAUS did not show a significantly higher accuracy in the evaluation of internal openings, if compared with MR (P = 0.47; McNemar's Chi-square test). In the complex anal fistulas, MR showed a significantly higher accuracy in the evaluation of secondary extensions if compared with 3D-EAUS (P = 0.041; McNemar's Chi-square test), whereas in the simple anal fistulas, no significant difference was found., Conclusion: In the preoperative work-up of patients with anorectal fistulas, 3D-EAUS may represent the first-line diagnostic tool. In cases of fistulas classified as complex by 3D-EAUS, MR may be indicated as adjunctive diagnostic imaging examination, to more carefully describe the fistulas' complete anatomy.

Published
2019
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31. Sphincter-saving surgery in low rectal cancer.

Author

Guerriero O, Tufano G, Pennetti L, D'Amore E, Sarnella G, and Sodano B

Subjects
Adult, Aged, Anal Canal, Digestive System Surgical Procedures methods, Female, Humans, Male, Middle Aged, Postoperative Complications epidemiology, Retrospective Studies, Rectal Neoplasms surgery
Abstract

A correct surgical approach to rectal cancer today has to make due allowance for both improved overall survival with local control of disease and preservation of the sphincter and urinary and genital functions. Increased understanding of the natural history, the importance of preoperative accurate staging and new surgical techniques may influence future treatment strategies. The aim of this study was to review and make a reappraisal of the role of sphincter-preserving surgery in the treatment of carcinomas of the lower third of the rectum. From January 1999 to June 2004, 63 consecutive total rectal resections were performed at our surgical department. Thirty-five of these patients, who underwent surgery for a primary adenocarcinoma of the distal rectum (3.5 to 8 cm from the anal verge), were reviewed retrospectively. The preoperative clinical assessment was based largely on T staging, tumor size, fixation and distance from the anal verge. Patient stratification, based on the definitive pathological report, was 3 Dukes' stage A (T1 N0), 21 stage B (T2 N0) and 11 stage C (T2-3-4 N+). The distance from the anal verge was > 5 cm in 30 patients and < 5 cm in 5. Sphincter-saving procedures were performed in 28/35 patients (80%); 7 (20%) had abdominoperineal resections of the rectum for very distal, locally extensive tumours or local recurrence (2 patients). The overall recurrence rate was 11.4%. Postoperative morbidity related to the procedures was low: anastomotic leakage occurred in 10.7% (3/28). Perfect continence was documented in 86.3%. The minimum follow-up time is 12 months. Our data, in agreement with the findings of other Authors, appear to bear out the validity of sphincter-saving procedures in the treatment of cancer of the lower third of the rectum. This approach is possible for the majority of patients. Functional results are good, using an accurate nerve-sparing technique, and may be improved by employing a colonic reservoir in selected cases.

Published
2006

32. Pulmonary sarcoidosis during interferon therapy: a rare or underestimated event?

Author

Salvio A, Mormile M, Giannattasio F, Varriale M, d'Errico T, Balzano B, Carratù P, Tufano G, and Visconti M

Subjects
Adult, Cough etiology, Drug Therapy, Combination, Dyspnea etiology, Gallium Radioisotopes, Hepatitis C, Chronic complications, Humans, Immunosuppressive Agents therapeutic use, Interferon alpha-2, Interferon-alpha administration & dosage, Interferon-alpha therapeutic use, Macrophage Activation, Male, Prednisone therapeutic use, RNA, Viral blood, Radiopharmaceuticals, Recombinant Proteins, Ribavirin administration & dosage, Ribavirin adverse effects, Ribavirin therapeutic use, Sarcoidosis, Pulmonary complications, Sarcoidosis, Pulmonary diagnosis, Sarcoidosis, Pulmonary drug therapy, Sarcoidosis, Pulmonary epidemiology, Viremia complications, Viremia drug therapy, Hepatitis C, Chronic drug therapy, Interferon-alpha adverse effects, Sarcoidosis, Pulmonary chemically induced
Abstract

Interferon (IFN)-alpha with or without ribavirin is the treatment of choice for patients with chronic HCV-related hepatitis. Cough and dyspnea during IFN therapy are often regarded as a side effect and not as a possible sign of the onset of a pulmonary interstitial disease. It may therefore be claimed that the likelihood that patients treated with IFN develop sarcoidosis is being underestimated. Although they are not conventionally classified as etiopathologic agents of sarcoidosis, the IFNs have been proven to be capable of triggering macrophages and of promoting the expression of class II HLA antigens. It is therefore possible that IFN-alpha treatment could trigger macrophages and promote the polarization of the immune response towards Th1 in the presence of particular susceptibility conditions, thus starting the series of events that lead to the onset of sarcoidosis. We describe a case of pulmonary sarcoidosis in a 33-year-old patient treated with IFN-alpha2b and ribavirin for chronic HCV-related hepatitis after 6 months of therapy. The case we report here brings forth the issue of a possible underestimation of the real incidence of sarcoidosis during IFN therapy and highlights the need for more attention to and a more careful evaluation of respiratory symptoms manifesting in treated patients.

Published
2004

33. Supportive care in patients with advanced non-small-cell lung cancer.

Author

Di Maio M, Perrone F, Gallo C, Iaffaioli RV, Manzione L, Piantedosi FV, Cigolari S, Illiano A, Barbera S, Robbiati SF, Piazza E, Ianniello GP, Frontini L, Veltri E, Castiglione F, Rosetti F, De Maio E, Maione P, Gridelli C, Rossi A, Barletta E, Barzelloni ML, Signoriello G, Bilancia D, Dinota A, Rosati G, Germano D, Lamberti A, Pontillo V, Brancacio L, Crispino C, Esposito M, Battiloro C, Tufano G, Cioffi A, Guardasole V, Angelini V, Guidetti G, Barbera S, Renda F, Romano F, Volpintesta A, Robbiati SF, Sannicolò M, Filipazzi V, Esani G, Gambaro A, Ferrario S, Tinessa V, Caprio MG, Zonato S, Cabiddu M, Raina A, Veltri E, D'Aprile M, Pistillucci G, Porcile G, Ostellino O, Vinante O, Azzarello G, Gebbia V, Borsellino N, Testa A, Gasparini G, Morabito A, Gattuso D, Romito S, Carrozza F, Fava S, Calcagno A, Grimi E, Bertetto O, Ciuffreda L, Parello G, Maiorino L, Santoro A, Santoro M, Failla G, Aiello RA, Bearz A, Sorio R, Scalone S, Clerici M, Bollina R, Belloni P, Sacco C, Sibau A, Adamo V, Altavilla G, Scimone A, Spatafora M, Bellia V, Hopps MR, Monfardini S, Favaretto A, Stefani M, Corradini GM, Pavia G, Scagliotti G, Novello S, Selvaggi G, Tonato M, Darwish S, Michetti G, Belometti MO, Labianca R, Quadri A, De Marinis F, Migliorino MR, Martelli O, Colucci G, Galetta D, Giotta F, Isa L, Candido P, Rossi N, Calandriello A, Ferraù F, Malaponte E, Barni S, Cazzaniga M, Gebbia N, Valerio MR, Belli M, Colantuoni G, Capuano MA, Angiolillo M, Sollitto F, Ardizzoia A, Luporini G, Locatelli MC, Pari F, Aitini E, Pedicini T, Febbraro A, Zollo C, Di Costanzo F, Bartolucci R, Gasperoni S, Gaion F, Palazzolo G, Galligioni E, Caffo O, Cortesi E, D'Auria G, Curcio C, Vasta M, Bumma C, Celano A, Bretti S, Nettis G, Anselmo A, Mattioli R, Nisticò C, Aschelter A, and Foa P

Subjects
Adult, Aged, Aged, 80 and over, Aging, Antiemetics therapeutic use, Antineoplastic Combined Chemotherapy Protocols adverse effects, Carcinoma, Non-Small-Cell Lung pathology, Carcinoma, Non-Small-Cell Lung secondary, Cisplatin administration & dosage, Deoxycytidine administration & dosage, Female, Humans, Lung Neoplasms pathology, Lung Neoplasms secondary, Male, Middle Aged, Palliative Care, Quality of Life, Randomized Controlled Trials as Topic, Survival Rate, Vinblastine administration & dosage, Vinorelbine, Gemcitabine, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Carcinoma, Non-Small-Cell Lung drug therapy, Deoxycytidine analogs & derivatives, Lung Neoplasms drug therapy, Vinblastine analogs & derivatives
Abstract

The present study describes supportive care (SC) in patients with advanced non-small-cell lung cancer (NSCLC), evaluating whether it is affected by concomitant chemotherapy, patient's performance status (PS) and age. Data of patients enrolled in three randomised trials of first-line chemotherapy, conducted between 1996 and 2001, were pooled. The analysis was limited to the first three cycles of treatment. Supportive care data were available for 1185 out of 1312 (90%) enrolled patients. Gastrointestinal drugs (45.7%), corticosteroids (33.4%) and analgesics (23.8%) were the most frequently observed categories. The mean number of drugs per patient was 2.43; 538 patients (45.4%) assumed three or more supportive drugs. Vinorelbine does not produce substantial variations in the SC pattern, while cisplatin-based treatment requires an overall higher number of supportive drugs, with higher use of antiemetics (41 vs 27%) and antianaemics (10 vs 4%). Patients with worse PS are more exposed to corticosteroids (42 vs 30%). Elderly patients require drugs against concomitant diseases significantly more than adults (20 vs 7%) and are less frequently exposed to antiemetics (12 vs 27%). In conclusion, polypharmacotherapy is a relevant issue in patients with advanced NSCLC. Chemotherapy does not remarkably affect the pattern of SC, except for some drugs against side effects. Elderly patients assume more drugs for concomitant diseases and receive less antiemetics than adults.

Published
2003
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34. [Small intestinal polyposis in Peutz-Jeghers syndrome: combined treatment with surgery and intra-operative endoscopy].

Author

Guerriero O, Tufano G, Pennetti L, D'Amore E, and Sarnella G

Subjects
Adult, Humans, Intestinal Polyps etiology, Intraoperative Period, Jejunal Neoplasms etiology, Male, Treatment Outcome, Digestive System Surgical Procedures methods, Endoscopy, Gastrointestinal methods, Intestinal Polyps surgery, Jejunal Neoplasms surgery, Peutz-Jeghers Syndrome complications
Abstract

Polyps occur throughout the gastrointestinal tract in Peutz-Jeghers syndrome, but the most serious problems are encountered in the management of small bowel polyposis. We report here on a case of Peutz-Jeghers syndrome admitted to hospital for intestinal obstruction and anaemia. The patient was submitted to colonoscopy, oesophagogastro-duodenoscopy and small bowel enema. At laparotomy, multiple intussusceptions were found and we conducted a combined surgical-endoscopic approach. Most of the polyps were identified and removed endoscopically (snare polypectomy). Five enterotomies were performed to remove 18 very large polyps (> 3 cm). Finally, a limited portion of the jejunal tract (20 cm) was resected owing to the presence of multiple, large, obstructive polyps. None of the polyps showed cancerous transformation. The shortcomings of the traditional surgical approach include repeated small bowel resections and often early reoperation to manage complications caused by polyps missed at the time of previous surgery. If surgical intervention is required, intraoperative endoscopy is always indicated. Conservative surgical management, the role of intraoperative endoscopy, planned medical follow-up and the need for a national registration system are stressed.

Published
2003

35. Orthodeoxia without platypnea from interatrial defect associated with persistent left superior vena cava in the absence of pulmonary hypertension.

Author

Maniscalco M, Dialetto G, Tufano G, Romano A, and Sofia M

Subjects
Adult, Heart Septal Defects, Atrial diagnostic imaging, Heart Septal Defects, Atrial therapy, Humans, Male, Military Personnel, Prostheses and Implants, Ultrasonography, Doppler, Color, Heart Septal Defects, Atrial complications, Hypoxia etiology, Posture, Vena Cava, Superior abnormalities
Abstract

Orthodeoxia-platypnea is a rare but increasingly recognized syndrome of upright hypoxemia usually associated to breathlessness relieved by recumbency. We report the case of isolated orthodeoxia discovered in a military recruit who referred only fatigability as the clinical symptom after a forced march. Transesophageal echocardiography demonstrated the presence of interatrial defect ostium secundum type with the persistence of left superior vena cava draining into coronary sinus. Right-to-left shunt was visualized by peripheral saline contrast infusion, despite normal right hemodynamics at heart catheterization. Hypoxemia recovered after the percutaneous closure of the interatrial defect. Orthodeoxia and platypnea could occur as separate disease manifestations, the latter probably being a rarer acute event, whereas orthodeoxia was underestimated and potentially earlier screenable., (Copyright 2003 S. Karger AG, Basel)

Published
2003
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36. [Spigelian hernia: our experience during a decade].

Author

Ammaturo C, Tufano G, Bruzzese E, Carotenuto S, and Romano C

Subjects
Aged, Diagnosis, Differential, Female, Hernia, Ventral diagnosis, Humans, Male, Middle Aged, Hernia, Ventral surgery
Abstract

The Authors report a small series (three cases) of Spigelian hernias and underline the rarity of this pathology (0.2% in their series of hernias of the abdominal wall). They determine the anatomical features of the region, recall clinical features and discuss the most interesting points differential diagnosis and therapy.

Published
1991

37. [Primary mucinous carcinoid of the ovary].

Author

Ammaturo C, Gerardi G, Giardiello C, Tufano G, Romano C, and De Angelis P

Subjects
Female, Humans, Middle Aged, Ovary pathology, Carcinoid Tumor pathology, Carcinoid Tumor surgery, Ovarian Neoplasms pathology, Ovarian Neoplasms surgery
Abstract

A case of primary mucinous carcinoid of the ovary observed in a 52-year-old woman is reported after some remarks on the various histogenetic theories. The observation of this extremely rare cancer was fortuitous during surgery carried out for benign pathology in the contralateral organ. Careful postoperative controls absolutely excluded the possibility of a metastatic tumour. The patient was treated by combining surgery with chemotherapy and eight months after operation is apparently free of cancer.

Published
1990

38. [Porto-systemic shunts and hepatic coma].

Author

Tufano R, Porcellini M, Zotti GC, Tufano G, and Santangelo ML

Subjects
Hepatic Encephalopathy drug therapy, Humans, Levodopa administration & dosage, Levodopa therapeutic use, Hepatic Encephalopathy etiology, Hypertension, Portal surgery, Portacaval Shunt, Surgical adverse effects
Published
1978

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