75 results on '"G. Lucisano"'
Search Results
2. Arsenic metabolism and urothelial cancer risk: a systematic review and meta-analysis
- Author
-
P Scampoli, Tommaso Staniscia, F Cedrone, F Meo, P Di Giovanni, G Lucisano, and G Di Martino
- Subjects
Oncology ,medicine.medical_specialty ,chemistry ,business.industry ,Meta-analysis ,Internal medicine ,Public Health, Environmental and Occupational Health ,medicine ,Urothelial cancer ,chemistry.chemical_element ,business ,Arsenic - Abstract
Background Arsenic is a toxic metalloid element frequently found in the environment. Chronic arsenic exposure is a critical public health issue in many countries since the identification of arsenic and its compounds as human carcinogens by the World Health Organization. After absorption, inorganic arsenic (iAs) is mainly methylated into monomethylated and dimethylated compounds (MMA, DMA), which are then excreted through the kidney together with unmethylated iAs. Whether the methylation process is to detoxify or potentiate arsenic toxicity, however, remains an ongoing debate. The purpose of this systematic review was to conduct a comprehensive meta-analysis to estimate the association between arsenic exposure and urothelial cancer. Methods 10 observational studies met the inclusion criteria and were included in the systematic review. IAs%, MMA% and DMA% were extracted from each paper. Weighted Mean Differences with 95% confidence intervals were defined according to Cases minus Controls. Pooled risk estimates from individual studies were assessed using random effects models. Meta-regression analysis was performed to estimate the extent of urothelial cancer risk as a function of iAs%, MMA% and DMA%. Results Results showed as patients with urothelial cancer presented higher level of urinary iAs% (WMD 2.70, 95%CI 0.64-4.76), MMA% (WMD 2.81, 95%CI 1.43-4.20) and DMA% (WMD-3.44, 95%CI-6.57–0.30). Conclusions These findings suggest that higher level of iAs% and MMA% and lower level of DMA% were associated with an increased risk of urothelial cancer. Additional population based studies are needed to understand the role of arsenic in cancer development. Understanding the meaning of arsenic metabolism could improve the risk assessment of arsenic toxicity and provide a potential tool for disease prediction and prevention. Key messages Higher level of iAs%, MMA% and DMA% were associated with an increased risk of urothelial cancer. Understanding the meaning of arsenic metabolism could improve the risk assessment of arsenic toxicity.
- Published
- 2019
3. Investigating the ceramic processes by numerical approaches
- Author
-
A. Valli, S. de Miranda, C. Fusi, G. Lucisano, Luca Patruno, Fusi C., Valli A., Lucisano G., Patruno L., and de Miranda S.
- Subjects
Materials science ,Mechanical Engineering ,Powder compaction ,Mechanical engineering ,Sintering ,Ceramic slab ,Discrete element method ,Finite element method ,Mechanics of Materials ,visual_art ,Finite Element Method ,visual_art.visual_art_medium ,Ceramic ,Discrete Element Method - Abstract
The considerable increase in computers performance has led in recent decades to a growing diffusion of numerical modelling as a valuable tool to support the manufacturing industry. Among the industrial sectors that may take advantage of this methodology there is the ceramic one. In fact, the production of large format ceramic slabs have introduced new technological challenges in a sector already subject to complex productdevelopment procedures, often based on a trial and error approach. For this reason, numerical simulations have become an actual and attractive method to overcome practical limitations and give a deeper insight into each phase of the production process. In this paper, advanced application of numerical modelling applied to the ceramic industry are presented, with special consideration for the production of ceramic slabs. Advantages and limitations of the adopted numerical techniques are discussed.
- Published
- 2019
4. Renal histopathology
- Author
-
E. J. Kim, J. H. Han, H. M. Koo, F. M. Doh, C. H. Kim, K. I. Ko, M. J. Lee, H. J. Oh, T.-H. Yoo, S.-W. Kang, K. H. Choi, S. H. Han, S. Assady, M. Tchirkov, R. Nasser, T. Mashiach, O. Ben Izhak, P. Housset, R. Guillemain, D. Nochy, M. Roland, C. Amrein, A. Karras, V. Boussaud, V. Pezzela, E. Thervet, S. P. Simic Ogrizovic, G. Basta Jovanovic, S. Radojevic, S. Bojic, R. Naumovic, Z. Karim, K. Cyrine, G. Rim, A. Ezzeddine, H. Hafedh, K. Hayet, B. Soumaya, O. Mondher, B. H. Fethi, E. Y. Fethi, B. A. Taieb, B. M. Hedi, B. M. Fatma, K. Adel, M. Penescu, E. Mandache, A. Zumrutdal, R. Ozelsancak, T. Canpolat, S. Barbouch, I. Mami, M. Mayara, M. Jerbi, A. Harzallah, R. Goucha, H. Ben Maiz, A. Kedher, N. Comi, P. Cianfrone, V. Piraina, R. Talarico, K. Giannakakis, G. Fuiano, G. Lucisano, K. Konat, M. Szotowska, H. Karkoszka, M. Adamczak, A. Wiecek, K. Kwiecien, O. Jercan, L. Mogoanta, I. Miller, X. Pan, J. Xu, H. Ren, W. Zhang, Y. Xu, P. Shen, X. Chen, X. Feng, and N. Chen
- Subjects
Transplantation ,Nephrology - Published
- 2013
5. Clinical nephrology - miscellaneous
- Author
-
C. Bantis, P. Heering, N.-M. Kouri, M. Siekierka-Harreis, M. Stangou, C. Schwandt, G. Efstratiadis, L.-C. Rump, K. Ivens, I. Haddiya, T. Houssaini Squalli, I. Laouad, B. Ramdani, R. Bayahia, G. G. Dimas, T. J. Tegos, S. G. Spiroglou, C. G. Pitsalidis, A. S. Sioulis, I. M. Karamouzis, C. G. Savopoulos, M. I. Karamouzis, A. G. Orologas, A. I. Hatzitolios, D. M. Grekas, D. Maixnerova, E. Jancova, I. Rychlik, R. Rysava, M. Merta, J. Reiterova, A. Kolsky, E. Honsova, J. Skibova, V. Tesar, Z. Kendi Celebi, R. Calayoglu, K. Keven, I. Kurultak, P. Mescigil, B. Erbay, O. Karatan, N. Duman, S. Erturk, G. Nergizoglu, S. Kutlay, S. Sengul, K. Ates, F. Marino, C. Martorano, M. Bellantoni, R. Tripepi, C. Zoccali, K. Ishizuka, Y. Harita, Y. Kajiho, H. Tsurumi, T. Asano, K. Nishiyama, N. Sugawara, H. Chikamoto, Y. Akioka, Y. Yamaguchi, T. Igarashi, M. Hattori, P. J. Heering, M. Sahay, D. V. Monova, S. V. Monov, Y.-y. Wang, H. Cheng, G.-q. Wang, H.-r. Dong, Y.-p. Chen, C.-j. Wang, Y.-l. Tang, E. Buti, E. Dervishi, F. Bergesio, G. Ghiandai, A. Mjeshtri, N. Paudice, A. L. Caldini, C. Nozzoli, E. E. Minetti, L. Sun, J. Feng, L. Yao, Q. Fan, J. Ma, L. Wang, T. Kirsanova, L. Merkusheva, N. Ruinihina, N. Kozlovskaya, G. Elenshleger, K. Turgutalp, U. Karabulut, T. Ozcan, I. Helvaci, A. Kiykim, A. Kaul, D. Bhadhuaria, R. sharma, N. Prasad, A. Gupta, C. Clajus, J. Schmidt, H. Haller, P. Kumpers, S. David, A. M. Sevillano, M. Molina, E. Gutierrez, E. Morales, E. Gonzalez, E. Hernandez, M. Praga, J. L. Conde Olasagasti, C. Vozmediano Poyatos, M. L. Illescas, S. Tallon, J. J. Uson Carrasco, A. Roca Munoz, F. Rivera Hernandez, G. Ismail, R. Jurubita, A. Andronesi, R. Bobeica, D. Zilisteanu, E. Rusu, C. Achim, A. Huerta, J. Caro, E. Gutierrez-Solis, A. Pasquariello, G. Pasquariello, M. Innocenti, G. Grassi, M. F. Egidi, O. Ozturk, A. Yildiz, C. B. Gul, K. Dilek, L. Tylicki, A. Jakubowska, E. Weber, S. Lizakowski, D. Swietlik, B. Rutkowski, A. Postorino, S. Costa, S. Cristadoro, G. Magazzu, G. Bellinghieri, V. Savica, M. Buemi, D. Santoro, Y. Lu, P. Shen, X. Li, Y. Xu, X. Pan, W. Wang, X. Chen, W. Zhang, H. Ren, N. Chen, B. P. Mitic, T. Cvetkovic, P. Vlahovic, R. Velickovic Radovanovic, V. Stefanovic, S. Kostic, V. Djordjevic, Q. Ao, Q. Ma, Q. Cheng, X. Wang, S. Liu, R. Zhang, S. Ozturk, S. Ozmen, D. Akin, R. Danis, M. Yilmaz, S. Hajri, S. Barbouche, H. Okpa, E. Oviasu, L. Ojogwu, N. Fotouhi, A. Ghaffari, F. Hamzavi, H. Nasri, M. Ardalan, A. Stott, A. Ullah, H. Anijeet, S. Ahmed, H. S. Kohli, R. Rajachandran, M. Rathi, V. Jha, V. Sakhuja, E. Yenigun, F. Dede, D. Turgut, E. Koc, H. Akoglu, S. Piskinpasa, R. Ozturk, A. Odabas, D. Bajcsi, G. Abraham, E. Kemeny, S. Sonkodi, P. Legrady, A. Letoha, K. Constantinou, Z. Ondrik, B. Ivanyi, G. Lucisano, N. Comi, P. Cianfrone, C. Summaria, V. Piraina, R. Talarico, C. Camastra, G. Fuiano, I. Proletov, E. Saganova, O. Galkina, E. Bogdanova, I. Zubina, V. Sipovskii, A. Smirnov, E. Bailly, D. Pierre, R. Kerdraon, O. Grezard, E. Gnappi, M. Delsante, M. Galetti, U. Maggiore, L. Manenti, M. J. Hasan, M. A. Muqueet, M. Mostafi, I. Chowdhury, W. Haque, T. Khan, Y.-J. Kang, E. J. Bae, H. S. Cho, S.-H. Chang, D. J. Park, G. Xu, H. Lin, Z. Hu, X. Yu, C. Xing, C. Mei, L. Zuo, Z. Ni, X. Ding, D. Li, Q. Zhang, X. Feng, and L. Lin
- Subjects
Transplantation ,medicine.medical_specialty ,Nephrology ,business.industry ,medicine ,Clinical nephrology ,Intensive care medicine ,business - Published
- 2013
6. Epidemiology and outcome research in CKD 5D
- Author
-
L. Coentrao, C. Ribeiro, C. Santos-Araujo, R. Neto, M. Pestana, W. Kleophas, A. Karaboyas, Y. LI, J. Bommer, R. Pisoni, B. Robinson, F. Port, G. Celik, B. Burcak Annagur, M. Yilmaz, T. Demir, F. Kara, K. Trigka, P. Dousdampanis, N. Vaitsis, S. Aggelakou-Vaitsi, K. Turkmen, I. Guney, F. Turgut, L. Altintepe, H. Z. Tonbul, E. Abdel-Rahman, P. Sclauzero, G. Galli, G. Barbati, M. Carraro, G. O. Panzetta, M. Van Diepen, M. Schroijen, O. Dekkers, F. Dekker, A. Sikole, G. Severova- Andreevska, L. Trajceska, S. Gelev, V. Amitov, S. Pavleska- Kuzmanovska, H. Rayner, R. Vanholder, M. Hecking, B. Jung, M. Leung, F. Huynh, T. Chung, S. Marchuk, M. Kiaii, L. Er, R. Werb, C. Chan-Yan, M. Beaulieu, P. Malindretos, P. Makri, G. Zagkotsis, G. Koutroumbas, G. Loukas, E. Nikolaou, M. Pavlou, E. Gourgoulianni, M. Paparizou, M. Markou, E. Syrgani, C. Syrganis, J. Raimann, L. A. Usvyat, V. Bhalani, N. W. Levin, P. Kotanko, X. Huang, P. Stenvinkel, A. R. Qureshi, U. Riserus, T. Cederholm, P. Barany, O. Heimburger, B. Lindholm, J. J. Carrero, J. H. Chang, J. Y. Sung, J. Y. Jung, H. H. Lee, W. Chung, S. Kim, J. S. Han, K. Y. Na, A. Fragoso, A. Pinho, A. Malho, A. P. Silva, E. Morgado, P. Leao Neves, N. Joki, Y. Tanaka, M. Iwasaki, S. Kubo, T. Hayashi, Y. Takahashi, K. Hirahata, Y. Imamura, H. Hase, C. Castledine, J. Gilg, C. Rogers, Y. Ben-Shlomo, F. Caskey, J. S. Sandhu, G. S. Bajwa, S. Kansal, J. Sandhu, A. Jayanti, M. Nikam, L. Ebah, A. Summers, S. Mitra, J. Agar, A. Perkins, R. Simmonds, A. Tjipto, S. Amet, V. Launay-Vacher, M. Laville, A. Tricotel, C. Frances, B. Stengel, J.-Y. Gauvrit, N. Grenier, G. Reinhardt, O. Clement, N. Janus, L. Rouillon, G. Choukroun, G. Deray, A. Bernasconi, R. Waisman, A. P. Montoya, A. A. Liste, R. Hermes, G. Muguerza, R. Heguilen, E. L. Iliescu, V. Martina, M. A. Rizzo, P. Magenta, L. Lubatti, G. Rombola, M. Gallieni, C. Loirat, H. Mellerio, M. Labeguerie, B. Andriss, E. Savoye, M. Lassale, C. Jacquelinet, C. Alberti, Y. Aggarwal, J. Baharani, S. Tabrizian, S. Ossareh, M. Zebarjadi, P. Azevedo, F. Travassos, I. Frade, M. Almeida, J. Queiros, F. Silva, A. Cabrita, R. Rodrigues, C. Couchoud, J. Kitty, S. Benedicte, C. Fergus, C. Cecile, B. Sahar, V. Emmanuel, J. Christian, E. Rene, H. Barahimi, M. Mahdavi-Mazdeh, M. Nafar, M. Petruzzi, M. De Benedittis, M. Sciancalepore, L. Gargano, P. Natale, M. C. Vecchio, V. Saglimbene, F. Pellegrini, G. Gentile, P. Stroumza, L. Frantzen, M. Leal, M. Torok, A. Bednarek, J. Dulawa, E. Celia, R. Gelfman, J. Hegbrant, C. Wollheim, S. Palmer, D. W. Johnson, P. J. Ford, J. C. Craig, G. F. Strippoli, M. Ruospo, B. El Hayek, B. Hayek, E. Baamonde, E. Bosch, J. I. Ramirez, G. Perez, A. Ramirez, A. Toledo, M. M. Lago, C. Garcia-Canton, M. D. Checa, B. Canaud, B. Lantz, A. Granger-Vallee, P. Lertdumrongluk, N. Molinari, J. Ethier, M. Jadoul, B. Gillespie, C. Bond, S. Wang, T. Alfieri, P. Braunhofer, B. Newsome, M. Wang, B. Bieber, M. Guidinger, L. Zuo, X. Yu, X. Yang, J. Qian, N. Chen, J. Albert, Y. Yan, S. Ramirez, M. Beresan, A. Lapidus, M. Canteli, A. Tong, B. Manns, J. Craig, G. Strippoli, M. Mortazavi, B. Vahdatpour, S. Shahidi, A. Ghasempour, D. Taheri, S. Dolatkhah, A. Emami Naieni, M. Ghassami, M. Khan, K. Abdulnabi, P. Pai, M. Vecchio, M. A. Muqueet, M. J. Hasan, M. A. Kashem, P. K. Dutta, F. X. Liu, L. Noe, T. Quock, N. Neil, G. Inglese, M. Motamed Najjar, B. Bahmani, A. Shafiabadi, J. Helve, M. Haapio, P.-H. Groop, C. Gronhagen-Riska, P. Finne, R. Sund, M. Cai, S. Baweja, A. Clements, A. Kent, R. Reilly, N. Taylor, S. Holt, L. Mcmahon, M. Carter, F. M. Van der Sande, J. Kooman, R. Malhotra, G. Ouellet, E. L. Penne, S. Thijssen, M. Etter, A. Tashman, A. Guinsburg, A. Grassmann, C. Barth, C. Marelli, D. Marcelli, G. Von Gersdorff, I. Bayh, L. Scatizzi, M. Lam, M. Schaller, T. Toffelmire, Y. Wang, P. Sheppard, L. Neri, V. A. Andreucci, L. A. Rocca-Rey, S. V. Bertoli, D. Brancaccio, G. De Berardis, G. Lucisano, D. Johnson, A. Nicolucci, C. Bonifati, S. D. Navaneethan, V. Montinaro, M. Zsom, A. Bednarek-Skublewska, G. Graziano, J. N. Ferrari, A. Santoro, A. Zucchelli, G. Triolo, S. Maffei, S. De Cosmo, V. M. Manfreda, L. Juillard, A. Rousset, F. Butel, S. Girardot-Seguin, T. Hannedouche, M. Isnard, Y. Berland, P. Vanhille, J.-P. Ortiz, G. Janin, P. Nicoud, M. Touam, E. Bruce, B. Grace, P. Clayton, A. Cass, S. Mcdonald, Y. Furumatsu, T. Kitamura, N. Fujii, S. Ogata, H. Nakamoto, K. Iseki, Y. Tsubakihara, C.-C. Chien, J.-J. Wang, J.-C. Hwang, H.-Y. Wang, W.-C. Kan, N. Kuster, L. Patrier, A.-S. Bargnoux, M. Morena, A.-M. Dupuy, S. Badiou, J.-P. Cristol, J.-M. Desmet, V. Fernandes, F. Collart, N. Spinogatti, J.-M. Pochet, M. Dratwa, E. Goffin, J. Nortier, D. S. Zilisteanu, M. Voiculescu, E. Rusu, C. Achim, R. Bobeica, S. Balanica, T. Atasie, S. Florence, S. Anne-Marie, L. Michel, C. Cyrille, A. Strakosha, N. Pasko, S. Kodra, N. Thereska, A. Lowney, E. Lowney, R. Grant, M. Murphy, L. Casserly, T. O' Brien, W. D. Plant, J. Radic, D. Ljutic, V. Kovacic, M. Radic, K. Dodig-Curkovic, M. Sain, I. Jelicic, T. Hamano, C. Nakano, S. Yonemoto, A. Okuno, M. Katayama, Y. Isaka, M. Nordio, A. Limido, M. Postorino, M. Nichelatti, M. Khil, I. Dudar, V. Khil, I. Shifris, M. Momtaz, A. R. Soliman, M. I. El Lawindi, P. Dzekova-Vidimliski, S. Pavleska-Kuzmanovska, I. Nikolov, G. Selim, T. Shoji, R. Kakiya, N. Tatsumi-Shimomura, Y. Tsujimoto, T. Tabata, H. Shima, K. Mori, S. Fukumoto, H. Tahara, H. Koyama, M. Emoto, E. Ishimura, Y. Nishizawa, and M. Inaba
- Subjects
Transplantation ,medicine.medical_specialty ,Nephrology ,business.industry ,Epidemiology ,Medicine ,business ,Intensive care medicine ,Outcome (game theory) - Published
- 2012
7. Renal histopathology
- Author
-
F. Marie-Lucile, N. Laure-Helene, C. Yosr, M. Anne, F. Fadi, C. Levi, V. Meas-Yedid, C. Daniliuc, A. Karras, J. C. Olivo-Marin, L. Mouthon, E. Guiard, M. Roland, L. Guillevin, C. Jacquot, D. Nochy, E. Thervet, Q. Chen, C. Skerka, B. Uzonyi, S. Lindner, C. Licht, B. Hoppe, M. Riedl, M. Kirschfink, S. Habbich, G. Wolf, L. Strain, T. H. Goodship, P. F. Zipfel, H. Kfoury, A. Alsuwaida, K. Alsaad, F. Alhejaili, M. Alghonaim, J. Alwakeel, S. Husain, N. Aloudah, L. Besso, M. Tamagnone, G. Daidola, M. Burdese, L. Repetto, G. Pasquale, L. Colla, L. Biancone, P. Stratta, G. P. Segoloni, J. Bacalja, A. M. Bauer Segvic, S. Bulimbasic, A. Pacic, M. Knotek, M. Sabljar Matovinovic, K. Galesic, D. Galesic Ljubanovic, E. Zakharova, E. Stolyarevich, O. Vorobjova, H. Tamouza, J. M. Chemouny, M. Flamant, L. Raskova Kafkova, M. Demion, M. Laurent, F. Walker, B. A. Julian, E. Tissandie, M. K. Tiwari, J. Novak, N. O. Camara, M. Benhamou, F. Vrtovsnik, R. C. Monteiro, I. C. Moura, S. Samavat, P. Ahmadpoor, P. Torbati, R. Ghaderi, F. Poorrezagholi, F. Samadian, M. Nafar, A. MII, A. Shimizu, T. Kaneko, F. Yasuda, M. Fukui, Y. Masuda, Y. Iino, Y. Katayama, C. Muller, J. Markovic-Lipkovski, S. Simic-Ogrizovic, R. Naumovic, S. Cirovic, D. Mitrovic, G. Muller, A. Wozniak, M. Janicka-Jedynska, J. Zurawski, E. Kaczmarek, J. Zachwieja, S. Khilji, T. Dorman, P. O'kelly, L. Lampty, K. Leung, A. Shadivan, C. Varghese, J. Walshe, T. Saito, M. Kawano, T. Saeki, I. Mizushima, Y. Yamaguchi, N. Imai, H. Nakashima, H. Umehara, M. Shvetsov, O. Popova, N. Chebotareva, A. Ivanov, I. Bobkova, D. Cremasco, M. Ceol, L. Peruzzi, G. Mazzucco, M. Giuseppina, G. Vezzoli, R. Cristofaro, A. D'angelo, F. Anglani, D. Del Prete, G. Coppolino, N. Comi, D. Bolignano, V. Piraina, R. Talarico, A. Colombo, G. Lucisano, G. Fuiano, P. Bernich, A. Lupo, T. R. Of Renal Biopsies, M. P. Rastaldi, O. C. Jercan, P. Messa, D. Alexandru, L. Mogoanta, and V. Uribe Villegas
- Subjects
Transplantation ,Nephrology - Published
- 2012
8. Erratum
- Author
-
S. Seiler, S. M. Colbus, G. Lucisano, K. S. Rogacev, M. K. Gerhart, M. Ziegler, D. Fliser, and G. H. Heine
- Subjects
Transplantation ,Nephrology - Published
- 2014
9. Clinical Activity and Safety of Anti-Programmed Death-1 (PD-1) (BMS-936558/MDX-1106/ONO-4538) in Patients (PTS) with Advanced Melanoma (MEL)
- Author
-
Lada Mitchell, J. Pigozzo, K. Bennett, C.S.P. Lima, Silvia Park, Juan F. Medina, Antonio M. Grimaldi, David F. McDermott, Chi Hoon Maeng, R. Tanaka, L. Ridolfi, C.J.A. Punt, O.V. Korotkova, Amelia Lissia, D.M. Chen, W. Chang, J. De Vries, L. Pericleous, Ugo Marone, Corrado Caracò, Winald R. Gerritsen, E. Midena, C. Lebbé, Christian U. Blank, C. Brocia, E.F.D. Costa, R. Bassett, A. Sekulic, Tania Labiano, E. Fonsatti, D. Lawrence, Paola Queirolo, J.D. Wolchok, Stefano Mori, R. Dummer, C. Aliberti, Ruth Plummer, S. Francis, N. Vanhoutte, R. Wintherhalder, G.A.S. Nogueira, A. Amin, Jonathan D. Schwartz, M. Guida, C. Turtschi, Gerty Schreibelt, P. Mut, A. Ballesteros, S-H Lee, Anna C. Pavlick, Ester Simeone, M. Sini, K. Namikawa, R. Marconcini, Shibao Feng, Nicola Mozzillo, L. Veronese, C. Gamez, Merrick I. Ross, Donna Rowen, R. Labianca, T. Kirchhoff, M. Altomonte, Michele Maio, A. Batty, S. Yoo, James Larkin, Lev V. Demidov, Alessandro Testori, Omid Hamid, Sarvendra Kumar, Michael P. Brown, Jochen Utikal, J.A. Lopez Martin, R. Shapiro, Maria D. Lozano, N. Fischer, S. Ariad, B. Shafaeddin-Schreve, V. Chairion Sileni, M.K. Choi, Jung Yong Hong, Shreyaskumar Patel, Dimitris Bafaloukos, H. Yue, José I. Echeveste, M. Novy, M. Lebmeier, David R. Minor, F. Zambrana, M. Colombino, B. Campos, E. Muñoz, Simone M. Goldinger, D. Cumplido, P.L. Pilati, D. Lee, Giusy Gentilcore, G. Lucisano, J. Richards, Mario Sznol, F.S. Hodi, B. Merelli, Jeffrey S. Weber, M. Traversa, C. Oberkanins, Stephen M Murray, Suzanne L. Topalian, Vincent Brichard, I. Lazarev, D. Piazzalunga, F. De Galitiis, E. Wachter, C. Rubino, D. Opatt McDowell, Virginia Ferraresi, I.V. Samoylenko, M. Sereno, John A. Thompson, G. Colucci, P. Petrillo, M. Montañana, G. Di Monta, M. Maur, E. Bajetta, C. Oliveira, Kevin M. Chin, Sarah Danson, Anthony E. Oro, Igor Bondarenko, J.A. Rinck-Junior, W.J. Lesterhuis, E. Bertocci, A. Garcia Castano, T.N. Zabotina, S. Pisconti, S. Ellis, M. Hidalgo, A. Berrocal, Jeffrey A. Sosman, Sara Valpione, Miguel F. Sanmamed, Pier Francesco Ferrucci, Y. Sasajima, J. Perez, H. Linardou, F. De Rosa, J. Thompson, S. Stragliotto, Patrick Hwu, B.J. Coventry, M. Gillet, A.M. Di Giacomo, P.R. Hilfiker, L. Marchesi, Iman Osman, J. Rendleman, C. Nuzzo, G. Imberti, Edward McKenna, L. Di Guardo, Paul Nathan, I.N. Mikhaylova, Jenny Nobes, Antonio Cossu, Miguel Angel Idoate, Mario Mandalà, Giuseppe Palmieri, M. Ochoa de Olza, T. Nikoglou, M. Del Vecchio, B. Salaun, A. Cramarossa, J.M. Caminal, M. Biagioli, H. Tsuda, M.M. van Rossum, K. Harmankaya, J. Cortes, A.M. Moraes, H. Shaw, R. Danielli, S. Mosconi, John D. Hainsworth, Agop Y. Bedikian, G. Kriegshäuser, C.R. Scoggins, J. Valdivia, L. Pilla, R. Ridolfi, L.G. Campana, Christoph Rochlitz, M. Ma, V. Escrig, M.L. Cintra, I. Pesce, L. Calabrò, Karl D. Lewis, Russell S. Berman, Erik H.J.G. Aarntzen, Bart Neyns, T. Puertolas, J.A. Solomon, E. Castanon Alvarez, Georgia Kollia, F. Siannis, Katrin Conen, G.Z. Chkadua, Ana Arance, J.W. Lee, Caroline Robert, G.J. Lourenço, Jedd D. Wolchok, Lucia Benedetto, B.M. Smithers, N. Yamazaki, Axel Hauschild, A. Gupta, A. Gianatti, Luc Thomas, G. Rinaldi, A. Albano, D.P. Lawrence, F. Cognetti, A. Balogh, B. Rauscher, J.M. Wigginton, Carlo Tondini, W. Hwu, K. Baryshnikov, Y.S. Kim, A. Yakobson, J.M. Piulats, Ralf Gutzmer, Claus Garbe, R. Parrozzani, Kalijn F. Bol, M. Aglietta, V. Chiarion Sileni, Paolo A. Ascierto, M.R. Migden, P. Rojas, Nicholas E. Papadopoulos, V. De Giorgi, S. Martin Algarra, A. Tsutsumida, Ernie Marshall, S. Shang, S.V.L. Nicoletti, Joannes F M Jacobs, Anne Lynn S. Chang, J. Mayordomo, L. Cykowski, Sung Heon Kim, M. Gonzalez Cao, Sanjiv S. Agarwala, Michael S. Gordon, Carl G. Figdor, L. Alonso, Richard D. Carvajal, M.G. Bernengo, K. B. Kim, Daniela Massi, L. Dirix, O. Michielin, Nerea Gomez, Pippa Corrie, E. Ortega, Diana Giannarelli, E. Levchenko, H.R. Alexander, Alfonso Gurpide, P.M. LoRusso, Günther F.L. Hofbauer, J.D. Rinderknecht, B. Winn, L. Rivoltini, J. Hou, M. Aieta, S. Rossi, M.B. McHenry, Alejo Rodriguez-Vida, N. Eggmann, Alfred Zippelius, Y. Shao, G.J. Weiss, and Fabrizio Ayala
- Subjects
Target lesion ,medicine.medical_specialty ,business.industry ,Melanoma ,Immediate family member ,Hematology ,medicine.disease ,Clinical trial ,Oncology ,Internal medicine ,Cohort ,medicine ,Previously treated ,business ,Survival rate ,Progressive disease - Abstract
Purpose BMS-936558 is a monoclonal antibody that blocks the PD-1 co-inhibitory receptor expressed by activated T cells. This study describes its activity and safety in pts with previously treated advanced MEL. Methods BMS-936558 was administered IV q2wk to pts with various tumors at 0.1 - 10 mg/kg during dose-escalation and/or cohort expansion. Pts received up to 12 cycles (4 doses/cycle) of treatment or until unacceptable toxicity, confirmed progressive disease, or complete response. Clinical activity was assessed by RECIST v1.0. Results As of Feb 24, 2012, 104 MEL pts had received BMS-936558 at 0.1 (n = 17), 0.3 (n = 19), 1 (n = 31), 3 (n = 17), or 10 mg/kg (n = 20). ECOG performance status was 0/1/2 in 63/38/3 pts, respectively. Most pts (67/104) had received prior immunotherapy (IT); prior anti-CTLA-4, -PD-1, or -PD-L1 was not permitted. The number of prior therapies was 1 (39%), 2 (35%), or ≥3 (26%). Median therapy duration was 20 wks (range 2.0 - 121.7 wks). The incidence of grade 3 - 4 related AEs was 20% and included gastrointestinal (4%), endocrine (2%), and hepatobiliary disorders (1%). There were no drug-related deaths in MEL pts. Clinical activity (responses or prolonged stable disease) was observed at all doses (Table). Of the 26/94 (28%) evaluable responders, 19 (73%) are ongoing ranging from 1.9+ to 24.9+ months. For the 23 responders followed ≥6 months from first dose on study, 16 (70%) are progression free. ORs occurred in pts with visceral or bone metastases. Six pts (6%; 95% CI 2 - 13%) had prolonged SD (≥24 wk); 3 pts had a persistent decrease in target lesion tumor burden in the presence of new lesions and were not categorized as responders. Conclusions BMS-936558 had durable clinical benefit in pts with advanced MEL, including those who had received prior IT. Additional long-term follow-up data will be reported. Dose, (mg/kg) No. ptsa ORR, No. pts (%) [95% CI] PFSR at 24 wk (%) [95% CI] 0.1 14 4 (29) [8 - 58] 40 [13 - 66] 0.3 16 3 (19) [4 - 46] 31 [9 - 54] 1 27 8 (30) [14 - 50] 45 [26 - 65] 3 17 7 (41) [18 - 67] * 55 [30 - 80] 10 20 4 (20) [6 - 44] 30 [9 - 51] * 1 CR aResponse-evaluable pts dosed by 7/01/2011 ORR = objective response rate ([{CR + PR} ÷ n] × 100); PFSR = progression-free survival rate. Disclosure J. Sosman: Research Funding: Bristol-Myers Squibb (myself). M. Sznol: Consultant or Advisory Role: Bristol-Myers Squibb (myself, compensated). Research Funding: Bristol-Myers Squibb (myself, clinical trials funding). D.F. McDermott: Advisory Board Role: Bristol-Myers Squibb (myself). R. Carvajal: Research Funding: Bristol-Myers Squibb (myself). S.L. Topalian: Consultant or Advisory Role: Bristol-Myers Squibb (myself, immediate family member, uncompensated). Research Funding: Bristol-Myers Squibb (myself). J.M. Wigginton: Employment or Leadership Position: Bristol-Myers Squibb (myself, employment, compensated). Stock Ownership: Bristol-Myers Squibb (myself). G. Kollia: Employment or Leadership Role: Bristol-Myers Squibb (employment, myself, compensated). Stock Ownership: Bristol-Myers Squibb/BMY stocks (myself). A. Gupta: Employment or Leadership Role: Bristol-Myers Squibb (employment, myself, compensated). Stock Ownership: Bristol-Myers Squibb (myself). F.S. Hodi: Consultant or Advisory Role: Bristol-Myers Squibb (myself, uncompensated). Research Funding: Bristol-Myers Squibb (myself). All other authors have declared no conflicts of interest.
- Published
- 2012
10. Progression & risk factors CKD 1-5 (1)
- Author
-
D. Bolignano, L. Zanoli, S. Rastelli, C. Marcantoni, G. Coppolino, G. Lucisano, C. Tamburino, E. Battaglia, P. Castellino, P. Presta, L. Pedrelli, F. Iiadis, A. Ntemka, T. Didangelos, A. Makedou, M. Divani, E. Moralidis, K. Makedou, A. Gotzamani-Psarakou, D. Grekas, L. Selistre, V. Souza, O. Domanova, P. Cochat, B. Ranchin, A. Varennes, L. Dubourg, A. Hadj-Aissa, D. Leonardis, F. Mallamaci, G. Enia, M. Postorino, G. Tripepi, C. Zoccali, null MAURO Working Group, C. Donadio, A. Kanaki, F. Caprio, E. Donadio, D. Tognotti, L. Olivieri, S. Eloot, E. Schepers, D. Barreto, F. Barreto, S. Liabeuf, W. Van Biesen, F. Verbeke, G. Glorieux, G. Choukroun, Z. Massy, R. Vanholder, A. Chaaban, F. Torab, S. Abouchacra, B. Bernieh, Q. Hussein, M. Osman, N. Gebran, Y. Kayyal, H. Al Omary, N. Nagelkerke, M. Horio, E. Imai, Y. Yasuda, S. Takahara, T. Watanabe, S. Matsuo, A. Fujimi, S. Ueda, K. Fukami, N. Obara, S. Okuda, P. Pecchini, M. Mieth, R. Mass, F. Malberti, R. Quinn, P. Ravani, H. Fujii, K. Kono, K. Nakai, S. Goto, M. Fukagawa, S. Nishi, M. Havrda, J. Granatova, Z. Vernerova, J. Vranova, L. Hornova, J. Zabka, I. Rychlik, K. Kratka, L. De Nicola, P. Zamboli, S. Mascia, M. Calabria, M. Grimaldi, G. Conte, R. Minutolo, G. Gluhovschi, M. Modilca, A. Kaycsa, S. Velciov, C. Gluhovschi, F. Bob, L. Petrica, G. Bozdog, S. Methven, J. Traynor, C. Deighan, D. O'Reilly, M. MacGregor, M. Szotowska, J. Chudek, M. Adamczak, A. Wiecek, I. Dudar, I. Shifris, O. Loboda, N. Yanagisawa, M. Ando, K. Tsuchiya, K. Nitta, R. Heguilen, A. Liste, M. Canteli, G. Muguerza, L. Cohen, M. Ortemberg, R. Hermes, A. Bernasconi, D. Galli, N. Miani, E. Staffolani, R. Nicolais, M. S. Borzacchi, C. Tozzo, S. Manca di Villahermosa, N. Di Daniele, K. Musial, D. Zwolinska, G. Loriga, C. Carru, A. Zinellu, A. Milia, A. E. Satta, I. Frolova, A. Kuryata, L. Koppe, E. Kalabacher, C. Pelletier, A. Geloen, D. Fouque, C. Soulage, S. Feriozzi, J. Torras, M. Cybulla, K. Nicholls, G. Sunder-Plassmann, and M. West
- Subjects
Transplantation ,medicine.medical_specialty ,Nephrology ,business.industry ,Internal medicine ,medicine ,business - Published
- 2011
11. General & clinical epidemiology CKD 1-5 (1)
- Author
-
S. Seiler, B. Cremers, P. Ege, M. Fehrenz, F. Hornof, J. Jeken, S. Kersting, N. M. Rebling, C. Steimle, K. S. Rogacev, B. Scheller, M. Bohm, D. Fliser, G. H. Heine, E. V. T. Nagler, A. C. Webster, R. Vanholder, C. Zoccali, S. Chinnappa, A. Mooney, M. El Nahas, L.-B. Tan, G. Lucisano, F. Bova, P. Presta, C. Caglioti, A. Caglioti, G. Fuiano, A. Ikeda, T. Konta, S. Takasaki, Y. Mashima, I. Kubota, S. Nakamura, Y. Kokubo, H. Makino, H. Takata, T. Fujii, F. Yoshihara, T. Horio, Y. Kawano, M. Badulescu, C. Capusa, S. Stancu, V. Blaga, A. Ilyes, C. Anghel, G. Mircescu, V. Tolkacheva, S. Villevalde, E. Tyukhmenev, Z. Kobalava, Y. Shalyagin, M. Shvetsov, S. Nagaytseva, L. Lukshina, E. Shilov, M. Fusaro, G. Tripepi, G. Crepaldi, S. Maggi, A. D'Angelo, A. Naso, M. Plebani, N. Vajente, S. Giannini, L. Calo, D. Miozzo, R. Cristofaro, M. Gallieni, S. Feriozzi, J. Torras, M. Cibulla, K. Nicholls, G. Sunder-Plassmann, M. West, E. Pavlikova, V. Moiseev, C.-T. Yen, C.-H. Huang, M.-C. Wang, E. Daher, G. Silva Junior, A. P. Vieira, A. Couto Bem, A. Fiqueiredo Filho, A. Lopes Filho, A. Guedes, C. Eloy Costa, J. Holanda de Souza, A. Liborio, R. Daniel, D. Nitsch, L. Harper, null EUVAS Group, M. Little, S. M. R. Khatami, M. Mahmoodian, E. Zare, M. Pashang, F. Mc Carroll, B. Cooke, M. O'Kane, K. Moles, P. Garrett, J. Lindsay, T.-M. Yu, C.-H. Chen, M.-J. Wu, C.-H. Cheng, Y.-W. Chuang, K.-H. Shu, J. C. Cole, D. Oberdhan, R. Cheng, J. Urwongse, H. Krasa, F. Czerwiec, A. Chapman, R. Perrone, O. Moranne, C. Fafin, G. Favre, S. Mougel, A. Vido, B. Seitz, P. Dahan, L. Albano, V. Esnult, M. Rama, P. Gayathri, D. A. Leelavathi, P. A. Ravindra, V. Sundaram, P. R. Nageshwar, V. Piraina, R. Talarico, G. Esposito, A. Colombo, G. Mazza, E. Cirillo, S. Quattrone, B. Marron, N. Chen, H. Shi, X. Ma, J. Zhang, P. Mao, L. He, J. Yu, X. Ding, G. Jiang, Y. Gu, W. Zhang, N. Wang, C. Mei, Z. Ni, C. Tzanno, G. Stein, F. Nisihara, J. Rocha, P. Clesca, C. Uezima, H. Langham, M. Tomlin, E. Coyne, W. Hope, C. Bebb, C. Johnson, C. Byrne, Y. Li, H. Ren, W. Wang, X. Li, X. Chen, X. Wu, B. Canver, T. Colak, S. Can, H. Karakayali, V. Bansal, R. Davis, E. Litinas, D. Hoppensteadt, I. Thethi, and J. Fareed
- Subjects
Transplantation ,Nephrology - Published
- 2011
12. Acute kidney injury - Human studies
- Author
-
L. Locsey, I. Seres, F. Sztanek, M. Harangi, J. Padra, L. Asztalos, G. Paragh, C. A. Hutchison, A. Bevins, R. Langham, E. Mancini, O. Wirta, P. Cockwell, R. Keir, M. Vigano, A. Stella, N. Evans, M. Chappell, P. Fabbrini, M. Onuigbo, N. Onuigbo, S. Kim, J. H. Chang, J. Y. Jung, H. H. Lee, W. Chung, L. Zanoli, S. Rastelli, C. Marcantoni, C. Tamburino, P. Castellino, A. Cho, H. Choi, J. E. Lee, H. R. Jang, W. Huh, Y.-G. Kim, D. J. Kim, H. Y. Oh, N. Garcia-Fernandez, P. L. Martin-Moreno, N. Varo, J. M. Nunez-Cordoba, G. Schlieper, T. Kruger, M. Kelm, J. Floege, R. Westenfeld, A. J. Cho, S. Doganay, A. K. Oguz, I. Ergun, N. Bardachenko, O. Kuryata, L. Bardachenko, P. Ravani, F. Malberti, S. Pirelli, F. Scolari, B. Barrett, P. Presta, G. Lucisano, A. Rubino, F. Serraino, T. Amoruso, A. Renzulli, G. Fuiano, J. T. Kielstein, S. Tolk, A. Heiden, C. Kuhn, M. M. Hoeper, J. Lorenzen, M. Broll, V. Kaever, H. Burhenne, C. Hafer, H. Haller, O. Burkhardt, J. Kielstein, J. Zahalkova, N. Petejova, J. Strojil, K. Urbanek, S. Bertoli, C. Musetti, A. Cabiati, E. Assanelli, G. Lauri, I. Marana, M. De Metrio, M. Rubino, J. Campodonico, M. Grazi, M. Moltrasio, G. Marenzi, Z. Unarokov, T. Mukhoedova, P. Fidalgo, S. Coelho, B. Rodrigues, A. P. Fernandes, A. L. Papoila, F. Liano, K. Soto, J. Vanmassenhove, R. Vanholder, G. Glorieux, W. Van Biesen, R. Challiner, J. Ritchie, A. Hutchison, S. I. Zaharie, D. T. Maria, M. Zaharie, C. Vaduva, C. Grauntanu, D. Cana-Ruiu, E. Mota, M. Hayer, J. Baharani, M. Thomas, T. Eldehni, N. Selby, C. McIntyre, R. Fluck, N. Kolhe, R. M. Fagugli, F. Patera, P. R. Shah, K. K. Kaswan, V. B. Kute, A. V. Vanikar, M. R. Gumber, H. V. Patel, B. C. Munjappa, D. P. Enginner, V. V. Sainaresh, H. L. Trivedi, C. Teixeira, E. Nogueira, J. A. Lopes, E. Almeida, A. Pais de Lacerda, A. Gomes da Costa, C. Franca, F. Mariano, M. Morselli, D. Bergamo, Z. Hollo', S. Scella, M. Maio, C. Tetta, A. Dellavalle, M. Stella, G. Triolo, V. Cantaluppi, A. D. Quercia, P. Bertinetto, S. Giacalone, M. Tamagnone, E. Basso, E. Karvela, M. Gai, G. Leonardi, P. Anania, C. Guarena, C. M. Fenocchio, A. Pacitti, G. P. Segoloni, Y. O. Kim, H. G. Kim, B. S. Kim, H. C. S. Song, J.-K. Min, S. Y. Kim, W. D. Park, M. Dalboni, R. Narciso, M. Quinto, C. Grabulosa, E. Cruz, J. Monte, M. Durao, M. Cendoroglo, O. Santos, M. Batista, A. Bellasi, S. Giannone, A. Mordenti, A. Zanoni, A. Santoro, J. H. Lee, S. H. Ha, J. H. Kim, G. J. Lee, Y. C. Jung, P. Malindretos, G. Koutroumbas, A. Patrinou, G. Zagkotsis, P. Makri, I. Togousidis, C. Syrganis, G. Li Cavoli, C. Tortorici, L. Bono, A. Ferrantelli, C. Giammarresi, C. Zagarrigo, U. Rotolo, H. Kim, K. Jun, W. Choi, J.-M. Krzesinski, M.-C. Parotte, C. Vandevelde, J. Keenan, F. Dieterle, S. Sultana, M. Pinches, C. Ciorciaro, R. Schindler, V. Schmitz, J.-C. Gautier, X. Benain, J. Matchem, P. Murray, S. Adler, M. Haase, A. Haase-Fielitz, P. Devarajan, R. Bellomo, D. N. Cruz, G. Wagener, C. D. Krawczeski, J. L. Koyner, P. T. Murray, M. Zappitelli, S. Goldstein, K. Makris, C. Ronco, J. Martensson, C.-R. Martling, P. Venge, E. Siew, L. B. Ware, A. Ikizler, P. R. Mertens, A. Lacquaniti, A. Buemi, V. Donato, S. Lucisano, M. Buemi, S. Panagoutsos, P. Kriki, E. Mourvati, D. Tziakas, G. Chalikias, D. Stakos, S. Apostolakis, C. Tsigalou, T. Gioka, S. Konstantinides, V. Vargemezis, I. Torregrosa, C. Montoliu, A. Urios, C. Aguado, M. J. Puchades, M. A. Solis, I. Juan, R. Sanjuan, M. Blasco, J. Pineda, A. Carratala, C. Ramos, A. Miguel, A. Niculae, I. A. Checherita, R. Sandulovici, C. David, A. Ciocalteu, M. Espinoza, J. Hidalgo, E. Lorca, A. Santibanez, F. Arancibia, F. Gonzalez, M. Y. Park, E. J. Kim, S. J. Choi, J. K. Kim, S. D. Hwang, K.-h. Lee, S.-J. Seok, J.-O. Yang, E.-Y. Lee, S.-y. Hong, H.-w. Gil, E. Astapenko, A. Shutov, G. Savinova, V. Rechnik, M. J. Melo, M. Raimundo, A. Viegas, I. Camara, F. Antunes, M.-J. Kim, S. H. Kwon, S. W. Lee, J. H. Song, and J. W. Lee
- Subjects
Transplantation ,Pathology ,medicine.medical_specialty ,Human studies ,Nephrology ,business.industry ,Acute kidney injury ,medicine ,medicine.disease ,business - Published
- 2011
13. Predictors of Bubble Formation and Type Obtained with Pneumatic Dissection During Deep Anterior Lamellar Keratoplasty in Keratoconus
- Author
-
Cristina Bovone, James Myerscough, Vincenzo Scorcia, Giovanna Carnovale Scalzo, Gabriele Piccoli, Giuseppe Giannaccare, Mauro Soda, Andrea Lucisano, Massimo Busin, Francesco Verdoliva, Marco Pellegrini, and Scorcia V, Giannaccare G, Lucisano A, Soda M, Scalzo GC, Myerscough J, Pellegrini M, Verdoliva F, Piccoli G, Bovone C, Busin M
- Subjects
medicine.medical_specialty ,Keratoconus ,keratoconus ,Bubble ,Socio-culturale ,Astigmatism ,law.invention ,03 medical and health sciences ,0302 clinical medicine ,law ,Ectasia ,Ophthalmology ,medicine ,pneumatic dissection ,030304 developmental biology ,lamellar keratoplasty, pneumatic dissection, keratoconus ,0303 health sciences ,Keratometer ,DALK, keratoconus, bubble, predictors ,business.industry ,Retrospective cohort study ,medicine.disease ,Dissection ,030221 ophthalmology & optometry ,Liquid bubble ,lamellar keratoplasty ,business - Abstract
PURPOSE: To identify predictors of bubble formation and type during big-bubble deep anterior lamellar keratoplasty (BB-DALK) performed in keratoconus at different stages of severity. DESIGN: Retrospective Cohort Study. METHODS: Setting: University Magna Græcia (Catanzaro, Italy); Study Population: Consecutive keratoconus patients undergoing BB-DALK from September 2014 to Feb- ruary 2019; Observation Procedure: Keratometric astigmatism, mean keratometry value (K-mean), highest keratometry value (K-max), thinnest point, anterior segment Optical Coherence Tomography (AS-OCT)-based stage of ectasia. Main Outcome Measures: Rate of bubble formation and type; number and fate of micro/macro-perforation; conver- sion to mushroom keratoplasty (MK); comparison of parameters in patients with bubble formation vs failure and in type 1 vs type 2 bubble; areas under the curves (AUC) of preoperative parameters for distinguishing between bubble types. RESULTS: Pneumatic dissection succeeded in 113/155 eyes (72.9%), with 100 type 1 bubbles (88.4%), 11 type 2 (9.8%) and 2 mixed-type (1.8%). Micro-perforations were managed conservatively in type-1 bubbles; macro-perforations occurring in both types of bubbles required conversion to MK. Preoperative K-mean and K-max values were significantly higher in eyes in which bubble formation succeeded (respectively, P=0.006 and P
- Published
- 2020
14. A comparison of natalizumab and ocrelizumab on disease progression in multiple sclerosis.
- Author
-
Iaffaldano P, Lucisano G, Guerra T, Paolicelli D, Portaccio E, Inglese M, Foschi M, Patti F, Granella F, Romano S, Cavalla P, De Luca G, Gallo P, Bellantonio P, Gallo A, Montepietra S, Di Sapio A, Vianello M, Quatrale R, Spitaleri D, Clerici R, Torri Clerici V, Cocco E, Brescia Morra V, Marfia GA, Boccia VD, Filippi M, Amato MP, and Trojano M
- Subjects
- Humans, Female, Male, Adult, Middle Aged, Multiple Sclerosis drug therapy, Multiple Sclerosis, Relapsing-Remitting drug therapy, Registries, Italy, Natalizumab adverse effects, Antibodies, Monoclonal, Humanized adverse effects, Antibodies, Monoclonal, Humanized pharmacology, Antibodies, Monoclonal, Humanized administration & dosage, Disease Progression, Immunologic Factors adverse effects, Immunologic Factors pharmacology, Immunologic Factors administration & dosage
- Abstract
Objective: No direct comparisons of the effect of natalizumab and ocrelizumab on progression independent of relapse activity (PIRA) and relapse-associated worsening (RAW) events are currently available. We aimed to compare the risk of achieving first 6 months confirmed PIRA and RAW events and irreversible Expanded Disability Status Scale (EDSS) 4.0 and 6.0 in a cohort of naïve patients treated with natalizumab or ocrelizumab from the Italian Multiple Sclerosis Register., Methods: Patients with a first visit within 1 year from onset, treated with natalizumab or ocrelizumab, and ≥3 visits were extracted. Pairwise propensity score-matched analyses were performed. Risk of reaching the first PIRA, RAW, and EDSS 4.0 and 6.0 events were estimated using multivariable Cox proportional hazards models. Kaplan-Meier curves were used to show cumulative probabilities of reaching outcomes., Results: In total, 770 subjects were included (natalizumab = 568; ocrelizumab = 212) and the propensity score-matching retrieved 195 pairs. No RAW events were found in natalizumab group and only 1 was reported in ocrelizumab group. A first PIRA event was reached by 23 natalizumab and 25 ocrelizumab exposed patients; 7 natalizumab- and 10 ocrelizumab-treated patients obtained an irreversible EDSS 4.0, while 13 natalizumab- and 15 ocrelizumab-treated patients reached an irreversible EDSS 6.0. No differences between the two groups were found in the risk (HR, 95%CI) of reaching a first PIRA (1.04, 0.59-1.84; p = 0.88) event, an irreversible EDSS 4.0 (1.23, 0.57-2.66; p = 0.60) and 6.0 (0.93, 0.32-2.68; p = 0.89)., Interpretation: Both medications strongly suppress RAW events and, in the short term, the risk of achieving PIRA events, EDSS 4.0 and 6.0 milestones is not significantly different., (© 2024 The Author(s). Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)
- Published
- 2024
- Full Text
- View/download PDF
15. The legacy effect of hyperglycemia and early use of SGLT-2 inhibitors: a cohort study with newly-diagnosed people with type 2 diabetes.
- Author
-
Ceriello A, Lucisano G, Prattichizzo F, La Grotta R, Frigé C, De Cosmo S, Di Bartolo P, Di Cianni G, Fioretto P, Giorda CB, Pontremoli R, Russo G, Viazzi F, and Nicolucci A
- Abstract
Background: A delay in reaching HbA1c targets in patients with newly-diagnosed type 2 diabetes (T2D) is associated with an increased long-term risk of developing cardiovascular diseases (CVD), a phenomenon referred to as legacy effect. Whether an early introduction of glucose-lowering drugs with proven benefit on CVD can attenuate this phenomenon is unknown., Methods: Using data derived from a large Italian clinical registry, i.e . the AMD Annals, we identified 251,339 subjects with newly-diagnosed T2D and without CVD at baseline. Through Cox regressions adjusted for multiple risk factors, we examined the association between having a mean HbA1c between 7.1 and 8% or >8%, compared with ≤7%, for various periods of early exposure (0-1, 0-2, 0-3 years) and the development of later (mean subsequent follow-up 4.6 ± 2.9 years) CVD, evaluated as a composite of myocardial infarction, stroke, coronary or peripheral revascularization, and coronary or peripheral bypass. We performed this analysis in the overall cohort and then splitting the population in two groups of patients: those that introduced sodium-glucose transport protein 2 inhibitors (SGLT-2i) during the exposure phase and those not treated with these drugs., Findings: Considering the whole cohort, subjects with both a mean HbA1c between 7.1 and 8% and >8%, compared with patients attaining a mean HbA1c ≤ 7%, showed an increased risk of developing the outcome in all the three early exposure periods assessed, with the highest risk observed in patients with mean HbA1c > 8% in the 3 years exposure period (hazard ratio [HR]1.33; 95% confidence interval [CI] 1.063-1.365). The introduction of SGLT-2i during the exposure periods of 0-1 and 0-2 years eliminated the association between poor glycemic control and the outcome (p for interaction 0.006 and 0.003, respectively, vs. patients with the same degree of glycemic control but not treated with these drugs)., Interpretation: Among patients with newly diagnosed T2D and free of CVD at baseline, a poor glycemic control in the first three years after diagnosis is associated with an increased subsequent risk of CVD. This association is no longer evident when SGLT-2i are introduced in the first two years, suggesting that these drugs attenuate the phenomenon of legacy effect. An early treatment with these drugs might thus promote a long-lasting benefit in patients not attaining proper glycemic control after T2D diagnosis., Funding: This work was supported, in part, by the Italian Ministry of Health (Ricerca Corrente) to IRCCS MultiMedica., Competing Interests: AC is on the advisory board and does consultancy and lectures for AstraZeneca, BERLIN-CHEMIE, Eli Lilly, Novo Nordisk, Mitsubishi, Roche Diagnostics, and Theras Lifetech. FP is a lecturer for BERLIN-CHEMIE. AN has received honoraria from AstraZeneca, Eli Lilly, Novo Nordisk, and research support from Alfasigma, Novo Nordisk, Sanofi, Shionogi, SOBI. GR is on the advisory board and does consultancy and lectures for Novo Nordisk, Astra Zeneca, Sanofi, Boehringer, Lilly, Mundipharma, and Sanchio. SDC received honoraria for lectures from Eli Lilly, Boehringer, Astra-Zeneca, MundiPharma, MSD, Sanofi, Novo-Nordisk, Daiichi Sankyo, and Bayer. RP received honoraria for lectures from Lilly, Boehringer, AstraZeneca, Novartis, Menarini, MSD, Sanofi, Novo-Nordisk, Vifor, Alfa-Sigma, and Bayer. P.F. reports receiving personal fees from Astra Zeneca, Lilly, Boehringer Ingelheim, Bayer, and Novo Nordisk. The remaining authors declare no conflict of interests., (© 2023 The Author(s).)
- Published
- 2023
- Full Text
- View/download PDF
16. Serum Neurofilament Light Chain and Glial Fibrillary Acidic Protein as Potential Diagnostic Biomarkers in Autism Spectrum Disorders: A Preliminary Study.
- Author
-
Simone M, De Giacomo A, Palumbi R, Palazzo C, Lucisano G, Pompamea F, Micella S, Pascali M, Gabellone A, Marzulli L, Giordano P, Gargano CD, Margari L, Frigeri A, and Ruggieri M
- Subjects
- Child, Humans, Glial Fibrillary Acidic Protein, Intermediate Filaments, Neuroinflammatory Diseases, Neurofilament Proteins, Biomarkers, Autism Spectrum Disorder diagnosis
- Abstract
Autism spectrum disorder (ASD) is one of the most common neurodevelopment disorders, characterized by a multifactorial etiology based on the interaction of genetic and environmental factors. Recent evidence supports the neurobiological hypothesis based on neuroinflammation theory. To date, there are no sufficiently validated diagnostic and prognostic biomarkers for ASD. Therefore, we decided to investigate the potential diagnostic role for ASD of two biomarkers well known for other neurological inflammatory conditions: the glial fibrillary acidic protein (GFAP) and the neurofilament (Nfl). Nfl and GFAP serum levels were analyzed using SiMoA technology in a group of ASD patients and in a healthy control group (CTRS), age- and gender-matched. Then we investigated the distribution, frequency, and correlation between serum Nfl and GFAP levels and clinical data among the ASD group. The comparison of Nfl and GFAP serum levels between ASD children and the control group showed a mean value of these two markers significantly higher in the ASD group (sNfL mean value ASD pt 6.86 pg/mL median value ASD pt 5.7 pg/mL; mean value CTRS 3.55 pg/mL; median value CTRS 3.1 pg; GFAP mean value ASD pt 205.7 pg/mL median value ASD pt 155.4 pg/mL; mean value CTRS 77.12 pg/mL; median value CTRS 63.94 pg/mL). Interestingly, we also found a statistically significant positive correlation between GFAP levels and hyperactivity symptoms ( p -value <0.001). Further investigations using larger groups are necessary to confirm our data and to verify in more depth the potential correlation between these biomarkers and ASD clinical features, such as the severity of the core symptoms, the presence of associated symptoms, and/or the evaluation of a therapeutic intervention. However, these data not only might shed a light on the neurobiology of ASD, supporting the neuroinflammation and neurodegeneration hypothesis, but they also might support the use of these biomarkers in the early diagnosis of ASD, to longitudinally monitor the disease activity, and even more as future prognostic biomarkers.
- Published
- 2023
- Full Text
- View/download PDF
17. HbA1c variability predicts cardiovascular complications in type 2 diabetes regardless of being at glycemic target.
- Author
-
Ceriello A, Lucisano G, Prattichizzo F, La Grotta R, Franzén S, Svensson AM, Eliasson B, and Nicolucci A
- Subjects
- Aged, Biomarkers blood, Blood Glucose metabolism, Cardiovascular Diseases diagnosis, Cardiovascular Diseases mortality, Databases, Factual, Diabetes Mellitus, Type 2 blood, Diabetes Mellitus, Type 2 diagnosis, Diabetes Mellitus, Type 2 mortality, Female, Humans, Male, Middle Aged, Predictive Value of Tests, Prevalence, Registries, Risk Assessment, Risk Factors, Sweden epidemiology, Time Factors, Treatment Outcome, Blood Glucose drug effects, Cardiovascular Diseases epidemiology, Diabetes Mellitus, Type 2 drug therapy, Glycated Hemoglobin metabolism, Glycemic Control, Hypoglycemic Agents therapeutic use
- Abstract
Background: HbA1c variability has emerged as risk factor for cardiovascular diseases in diabetes. However, the impact of HbA1c variability on cardiovascular diseases in subjects within the recommended HbA1c target has been relatively unexplored., Methods: Using data from a large database, we studied 101,533 people with type 2 diabetes without cardiovascular diseases. HbA1c variability was expressed as quartiles of the standard deviation of HbA1c during three years (exposure phase). The primary composite outcome included non-fatal myocardial infarction, non-fatal stroke, all-cause mortality and was assessed during five years following the first three years of exposure to HbA1c variability (longitudinal phase). An expanded composite outcome including non-fatal myocardial infarction, non-fatal stroke, coronary revascularization/reperfusion procedures, peripheral revascularization procedures, and all-cause mortality was also considered, as well as a series of specific cardiovascular complications. Cox models were adjusted for a large range of risk factors and results were expressed as adjusted hazard ratios., Results: An association between HbA1c variability and all the outcomes considered was found. The correlation between HbA1c variability and cardiovascular complications development was confirmed in both the subgroups of subjects with a mean HbA1c ≤ 53 mmol/mol (recommended HbA1c target) or > 53 mmol/mol during the exposure phase. The risk related to HbA1c variability was higher in people with mean HbA1c ≤ 53 mmol/mol for the primary outcome (p for interaction 0.004), for the expanded secondary outcome (p for interaction 0.001) and for the stroke (p for interaction 0.001), even though HbA1c remained at the target during the follow-up., Conclusions: These findings suggest that HbA1c variability may provide additional information for an optimized management of diabetes, particularly in people within the target of HbA1c., (© 2022. The Author(s).)
- Published
- 2022
- Full Text
- View/download PDF
18. Risk of Getting COVID-19 in People With Multiple Sclerosis: A Case-Control Study.
- Author
-
Iaffaldano P, Lucisano G, Manni A, Paolicelli D, Patti F, Capobianco M, Brescia Morra V, Sola P, Pesci I, Lus G, De Luca G, Lugaresi A, Cavalla P, Montepietra S, Maniscalco GT, Granella F, Ragonese P, Vianello M, Brambilla L, Totaro R, Toscano S, Malucchi S, Petracca M, Moiola L, Ferraro D, Lepore V, Mosconi P, Ponzio M, Tedeschi G, Comi G, Battaglia MA, Filippi M, Amato MP, and Trojano M
- Subjects
- Adult, Age Factors, Case-Control Studies, Dimethyl Fumarate therapeutic use, Female, Fingolimod Hydrochloride therapeutic use, Glatiramer Acetate therapeutic use, Humans, Interferon-beta therapeutic use, Italy epidemiology, Male, Middle Aged, Multiple Sclerosis drug therapy, Multiple Sclerosis, Chronic Progressive drug therapy, Multiple Sclerosis, Chronic Progressive epidemiology, Multiple Sclerosis, Relapsing-Remitting drug therapy, Multiple Sclerosis, Relapsing-Remitting epidemiology, Natalizumab therapeutic use, Odds Ratio, Risk Factors, SARS-CoV-2, Severity of Illness Index, Sex Factors, Time Factors, COVID-19 epidemiology, Immunosuppressive Agents therapeutic use, Multiple Sclerosis epidemiology
- Abstract
Background and Objectives: Several studies have assessed risk factors associated with the severity of COVID-19 outcomes in people with multiple sclerosis (PwMS). The potential role of disease-modifying therapies (DMTs) and demographic and clinical factors on the risk of acquiring SARS-CoV-2 infection has not been evaluated so far. The objective of this study was to assess risk factors of contracting SARS-CoV-2 infection in PwMS by using data collected in the Italian MS Register (IMSR)., Methods: A case-control (1:2) study was set up. Cases included PwMS with a confirmed diagnosis of COVID-19, and controls included PwMS without a confirmed diagnosis of COVID-19. Both groups were propensity score-matched by the date of COVID-19 diagnosis, the date of last visit, and the region of residence. No healthy controls were included in this study. COVID-19 risk was estimated by multivariable logistic regression models including demographic and clinical covariates. The impact of DMTs was assessed in 3 independent logistic regression models including one of the following covariates: last administered DMT, previous DMT sequences, or the place where the last treatment was administered., Results: A total of 779 PwMS with confirmed COVID-19 (cases) were matched to 1,558 PwMS without COVID-19 (controls). In all 3 models, comorbidities, female sex, and a younger age were significantly associated ( p < 0.02) with a higher risk of contracting COVID-19. Patients receiving natalizumab as last DMT (OR [95% CI]: 2.38 [1.66-3.42], p < 0.0001) and those who underwent an escalation treatment strategy (1.57 [1.16-2.13], p = 0.003) were at significantly higher COVID-19 risk. Moreover, PwMS receiving their last DMT requiring hospital access (1.65 [1.34-2.04], p < 0.0001) showed a significant higher risk than those taking self-administered DMTs at home., Discussion: This case-control study embedded in the IMSR showed that PwMS at higher COVID-19 risk are younger, more frequently female individuals, and with comorbidities. Long-lasting escalation approach and last therapies that expose patients to the hospital environment seem to significantly increase the risk of SARS-CoV2 infection in PwMS., Classification of Evidence: This study provides Class III evidence that among patients with MS, younger age, being female individuals, having more comorbidities, receiving natalizumab, undergoing an escalating treatment strategy, or receiving treatment at a hospital were associated with being infected with COVID-19. Among patients with MS who were infected with COVID-19, a severe course was associated with increasing age and having a progressive form of MS, whereas not being on treatment or receiving an interferon beta agent was protective., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)
- Published
- 2022
- Full Text
- View/download PDF
19. Variability in body weight and the risk of cardiovascular complications in type 2 diabetes: results from the Swedish National Diabetes Register.
- Author
-
Ceriello A, Lucisano G, Prattichizzo F, Eliasson B, Franzén S, Svensson AM, and Nicolucci A
- Subjects
- Aged, Cardiovascular Diseases diagnosis, Cardiovascular Diseases mortality, Cardiovascular Diseases therapy, Diabetes Mellitus, Type 2 diagnosis, Female, Humans, Male, Middle Aged, Obesity diagnosis, Obesity physiopathology, Prognosis, Registries, Risk Assessment, Risk Factors, Sweden epidemiology, Time Factors, Body Weight, Cardiovascular Diseases epidemiology, Diabetes Mellitus, Type 2 epidemiology, Obesity epidemiology
- Abstract
Background: There is a high incidence of cardiovascular disease in diabetes. Weight variability has been reported as independent risk factor for cardiovascular disease in the general population and preliminarily also in people with type 2 diabetes., Methods: Using data from the Swedish National Diabetes Register the possible link between visit-to-visit body weight variability and the risk of cardiovascular complications among people with type 2 diabetes and without prevalent cardiovascular diseases at baseline has been evaluated. Overall, 100,576 people with type 2 diabetes, with at least five measurements of body weight taken over three consecutive years, were included. Variability was expressed as quartiles of the standard deviation of the measures during the three years. The primary composite outcome included non-fatal myocardial infarction, non-fatal stroke, and all-cause mortality and was assessed during five years following the first 3 years of exposure to weight variability., Results: After adjusting for known cardiovascular risk factors, the risk of the primary composite outcome significantly increased with increasing body weight variability [upper quartile HR = 1.45; 95% confidence interval 1.39-1.52]. Furthermore, elevated body weight variability was associated with almost all the other cardiovascular complications considered (non-fatal myocardial infarction, non-fatal stroke, all-cause mortality, peripheral arterial disease, peripheral vascular angioplasty, hospitalization for heart failure, foot ulcer, and all-cause mortality)., Conclusions: High body weight variability predicts the development of cardiovascular complications in type 2 diabetes. These data suggest that any strategy to reduce the body weight in these subjects should be aimed at maintaining the reduction in the long-term, avoiding oscillations., (© 2021. The Author(s).)
- Published
- 2021
- Full Text
- View/download PDF
20. Long-term disability trajectories in relapsing multiple sclerosis patients treated with early intensive or escalation treatment strategies.
- Author
-
Iaffaldano P, Lucisano G, Caputo F, Paolicelli D, Patti F, Zaffaroni M, Brescia Morra V, Pozzilli C, De Luca G, Inglese M, Salemi G, Maniscalco GT, Cocco E, Sola P, Lus G, Conte A, Amato MP, Granella F, Gasperini C, Bellantonio P, Totaro R, Rovaris M, Salvetti M, Torri Clerici VLA, Bergamaschi R, Maimone D, Scarpini E, Capobianco M, Comi G, Filippi M, and Trojano M
- Abstract
Background and Aims: No consensus exists on how aggressively to treat relapsing-remitting multiple sclerosis (RRMS) nor on the timing of the treatment. The objective of this study was to evaluate disability trajectories in RRMS patients treated with an early intensive treatment (EIT) or with a moderate-efficacy treatment followed by escalation to higher-efficacy disease modifying therapy (ESC)., Methods: RRMS patients with ⩾5-year follow-up and ⩾3 visits after disease modifying therapy (DMT) start were selected from the Italian MS Registry. EIT group included patients who received as first DMT fingolimod, natalizumab, mitoxantrone, alemtuzumab, ocrelizumab, cladribine. ESC group patients received the high efficacy DMT after ⩾1 year of glatiramer acetate, interferons, azathioprine, teriflunomide or dimethylfumarate treatment. Patients were 1:1 propensity score (PS) matched for characteristics at the first DMT. The disability trajectories were evaluated by applying a longitudinal model for repeated measures. The effect of early versus late start of high-efficacy DMT was assessed by the mean annual Expanded Disability Status Scale (EDSS) changes compared with baseline values (delta-EDSS) in EIT and ESC groups., Results: The study cohort included 2702 RRMS patients. The PS matching procedure produced 363 pairs, followed for a median (interquartile range) of 8.5 (6.5-11.7) years. Mean annual delta-EDSS values were all significantly ( p < 0.02) higher in the ESC group compared with the EIT group. In particular, the mean delta-EDSS differences between the two groups tended to increase from 0.1 (0.01-0.19, p = 0.03) at 1 year to 0.30 (0.07-0.53, p = 0.009) at 5 years and to 0.67 (0.31-1.03, p = 0.0003) at 10 years., Conclusion: Our results indicate that EIT strategy is more effective than ESC strategy in controlling disability progression over time., Competing Interests: Conflict of interest statement: All the authors report no competing interest related to this specific project. The authors report no conflicts of interest with respect to the contents of the current study, but note that the patients in the study were treated with a number of disease modifying drugs and that authors Pietro Iaffaldano, Giuseppe Lucisano, Francesca Caputo, Damiano Paolicelli, Francesco Patti, Mauro Zaffaroni, Vincenzo Brescia Morra, Carlo Pozzilli, Giovanna De Luca, Matilde Inglese, Giuseppe Salemi, Giorgia Teresa Maniscalco, Eleonora Cocco, Patrizia Sola, Giacomo Lus, Antonella Conte, Maria Pia Amato, Franco Granella, Claudio Gasperini, Paolo Bellantonio, Rocco Totaro, Marco Rovaris, Marco Salvetti, Valentina Liliana Adriana Torri Clerici, Roberto Bergamaschi, Davide Maimone, Elio Scarpini, Marco Capobianco, Giancarlo Comi, Massimo Filippi and Maria Trojano report having received advisory board membership, speaker’s honoraria, travel support, research grants, consulting fees, or clinical trial support from the manufacturers of those drugs, including Actelion, Allergan, Almirall, Bayer Schering, Biogen, Celgene, Excemed, Genzyme, Forward Pharma, Ipsen, Medday, Merck, Merz, Mylan, Novartis, Sanofi, Roche, Teva, and their local affiliates., (© The Author(s), 2021.)
- Published
- 2021
- Full Text
- View/download PDF
21. Informing the Risk of Kidney Transplantation Versus Remaining on the Waitlist in the Coronavirus Disease 2019 Era.
- Author
-
Clarke C, Lucisano G, Prendecki M, Gleeson S, Martin P, Ali M, McAdoo SP, Lightstone L, Ashby D, Charif R, Griffith M, McLean A, Dor F, and Willicombe M
- Abstract
Introduction: There are limited data pertaining to comparative outcomes of remaining on dialysis versus kidney transplantation as the threat of coronavirus disease 2019 (COVID-19) remains. In this study we delineate the differential risks involved using serologic methods to help define exposure rates., Methods: From a cohort of 1433 patients with end-stage kidney disease (ESKD), we analyzed COVID-19 infection rates and outcomes in 299 waitlist patients compared with 237 transplant recipients within their first year post-transplant. Patients were followed over a 68-day period from the time our transplant program closed due to COVID-19., Results: The overall mortality rates in waitlist and transplant populations were equivalent ( P = 0.69). However, COVID-19 infection was more commonly diagnosed in the waitlist patients ( P = 0.001), who were more likely to be tested by reverse transcriptase polymerase chain reaction ( P = 0.0004). Once infection was confirmed, mortality risk was higher in the transplant patients ( P = 0.015). The seroprevalence in dialysis and transplant patients with undetected infection was 18.3% and 4.6%, respectively ( P = 0.0001). After adjusting for potential screening bias, the relative risk of death after a diagnosis of COVID-19 remained higher in transplant recipients (hazard ratio = 3.36 [95% confidence interval = 1.19-9.50], P = 0.022)., Conclusions: Although COVID-19 infection was more common in the waitlist patients, a higher COVID-19‒associated mortality rate was seen in the transplant recipients, resulting in comparable overall mortality rates., (© 2020 Published by Elsevier, Inc., on behalf of the International Society of Nephrology.)
- Published
- 2021
- Full Text
- View/download PDF
22. Disease-modifying drugs can reduce disability progression in relapsing multiple sclerosis.
- Author
-
Amato MP, Fonderico M, Portaccio E, Pastò L, Razzolini L, Prestipino E, Bellinvia A, Tudisco L, Fratangelo R, Comi G, Patti F, De Luca G, Brescia Morra V, Cocco E, Pozzilli C, Sola P, Bergamaschi R, Salemi G, Inglese M, Millefiorini E, Galgani S, Zaffaroni M, Ghezzi A, Salvetti M, Lus G, Florio C, Totaro R, Granella F, Vianello M, Gatto M, Di Battista G, Aguglia U, Logullo FO, Simone M, Lucisano G, Iaffaldano P, and Trojano M
- Subjects
- Adult, Cohort Studies, Female, Follow-Up Studies, Humans, Italy epidemiology, Male, Middle Aged, Multiple Sclerosis, Relapsing-Remitting diagnosis, Prospective Studies, Retrospective Studies, Antirheumatic Agents therapeutic use, Disabled Persons, Disease Progression, Multiple Sclerosis, Relapsing-Remitting drug therapy, Multiple Sclerosis, Relapsing-Remitting epidemiology
- Abstract
An ever-expanding number of disease-modifying drugs for multiple sclerosis have become available in recent years, after demonstrating efficacy in clinical trials. In the real-world setting, however, disease-modifying drugs are prescribed in patient populations that differ from those included in pivotal studies, where extreme age patients are usually excluded or under-represented. In this multicentre, observational, retrospective Italian cohort study, we evaluated treatment exposure in three cohorts of patients with relapsing-remitting multiple sclerosis defined by age at onset: paediatric-onset (≤18 years), adult-onset (18-49 years) and late-onset multiple sclerosis (≥50 years). We included patients with a relapsing-remitting phenotype, ≥5 years follow-up, ≥3 Expanded Disability Status Scale (EDSS) evaluations and a first neurological evaluation within 3 years from the first demyelinating event. Multivariate Cox regression models (adjusted hazard ratio with 95% confidence intervals) were used to assess the risk of reaching a first 12-month confirmed disability worsening and the risk of reaching a sustained EDSS of 4.0. The effect of disease-modifying drugs was assessed as quartiles of time exposure. We found that disease-modifying drugs reduced the risk of 12-month confirmed disability worsening, with a progressive risk reduction in different quartiles of exposure in paediatric-onset and adult-onset patients [adjusted hazard ratios in non-exposed versus exposed >62% of the follow-up time: 8.0 (3.5-17.9) for paediatric-onset and 6.3 (4.9-8.0) for adult-onset, P < 0.0001] showing a trend in late-onset patients [adjusted hazard ratio = 1.9 (0.9-4.1), P = 0.07]. These results were confirmed for a sustained EDSS score of 4.0. We also found that relapses were a risk factor for 12-month confirmed disability worsening in all three cohorts, and female sex exerted a protective role in the late-onset cohort. This study provides evidence that sustained exposure to disease-modifying drugs decreases the risk of disability accumulation, seemingly in a dose-dependent manner. It confirms that the effectiveness of disease-modifying drugs is lower in late-onset patients, although still detectable., (© The Author(s) (2020). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For permissions, please email: journals.permissions@oup.com.)
- Published
- 2020
- Full Text
- View/download PDF
23. Clinical Outcomes of Switching to Insulin Glargine 300 U/ml from Other Basal Insulins in People with Type 2 Diabetes in Italy: A Real-World Study.
- Author
-
Ragonese M, Larosa M, Angotti S, Annese S, Cruciani L, Dainelli M, Lucisano G, Prosperini G, Sacco M, Salomone E, Saponara C, Semprini R, Rossi MC, and Nicolucci A
- Abstract
Introduction: Primary aim was to provide real-world evidence of the outcomes after the switch to glargine 300 U/ml (Gla-300) from other basal insulins (first or second generation) in Italy., Methods: Multicenter, observational, retrospective study based on electronic medical records., Results: Overall, 953 T2DM insulin ± OAD treated people switched to Gla-300 or Gla-100 from January 2015 to July 2018. Three clinically relevant cohorts were identified: patients switching to Gla-300 from first-generation basal insulin (cohort 1), patients switching to Gla-300 from degludec-100 (Deg-100) (cohort 2), and those switching to Gla-100 from any basal insulin (cohort 3). The three cohorts differed in terms of age, diabetes duration, and metabolic control. HbA1c changes after 6 months from the switch were - 0.27% (95% CI - 0.38; - 0.16), - 0.06% (95% CI - 0.31; 0.19), and - 0.30% (95% CI - 0.51; - 0.09) in the three cohorts, respectively. FPG significantly decreased in cohort 1 (- 14.07 mg/dl, 95% CI - 20.25; - 7.89), while body weight significantly decreased in cohort 2 (- 1.47 kg, 95% CI - 2.55; - 0.39). Doses of insulin marginally changed during the follow-up (+ 0.89 U in basal insulin daily dose in cohort 1 and + 2.07 U in short-acting insulin daily dose in cohort 2)., Conclusions: Switching to Gla-300 from first-generation basal insulin in the real world is associated with improvements in metabolic control despite a suboptimal titration of both basal and short-acting insulins. Inertia in insulin titration documented in the Gla-100 cohort is also observed with the second-generation basal insulin. The switch to Gla-300 from Deg-100 was associated with a decrease in body weight of - 1.47 kg despite a slight increase in short-acting insulin daily doses of about + 2 U.
- Published
- 2020
- Full Text
- View/download PDF
24. Oral potassium binders: increasing flexibility in times of crisis.
- Author
-
Dattani R, Hill P, Medjeral-Thomas N, Griffith ME, Ashby D, McAdoo S, Corbett RW, Lucisano G, Beadle J, McCafferty K, Frankel A, and Thomas D
- Published
- 2020
- Full Text
- View/download PDF
25. Osteopathic Manipulative Treatment in Neonatal Intensive Care Units.
- Author
-
Cicchitti L, Di Lelio A, Barlafante G, Cozzolino V, Di Valerio S, Fusilli P, Lucisano G, Renzetti C, Verzella M, and Rossi MC
- Abstract
The aim of this study was to assess the impact of osteopathic manipulative treatment (OMT) on newborn babies admitted at a neonatal intensive care unit (NICU). This was an observational, longitudinal, retrospective study. All consecutive admitted babies were analyzed by treatment (OMT vs. usual care). Treatment group was randomly assigned. Between-group differences in weekly weight change and length of stay (LOS) were evaluated in the overall and preterm populations. Among 1249 babies (48.9% preterm) recorded, 652 received usual care and 597 received OMT. Weight increase was more marked in the OMT group than in the control group (weekly change: +83 g vs. +35 g; p < 0.001). Similar trends were found in the subgroup of preterm babies. A shorter LOS was found in the OMT group vs. the usual care group both in overall population (average mean difference: -7.9 days, p = 0.15) and in preterm babies (-12.3 days; p = 0.04). In severe preterm babies, mean LOS was more than halved as compared to the control group. OMT was associated with a more marked weekly weight increase and, especially in preterm babies, to a relevant LOS reduction: OMT may represent an efficient support to usual care in newborn babies admitted at a NICU.
- Published
- 2020
- Full Text
- View/download PDF
26. Arsenic Exposure and Risk of Urothelial Cancer: Systematic Review and Meta-Analysis.
- Author
-
Di Giovanni P, Di Martino G, Scampoli P, Cedrone F, Meo F, Lucisano G, Romano F, and Staniscia T
- Subjects
- Environmental Exposure adverse effects, Humans, Observational Studies as Topic, Arsenic analysis, Arsenic toxicity, Arsenicals analysis, Carcinoma, Transitional Cell chemically induced, Carcinoma, Transitional Cell epidemiology, Urologic Neoplasms chemically induced, Urologic Neoplasms epidemiology
- Abstract
Background : Arsenic is a toxic metalloid element widely distributed throughout the environment. Arsenic contaminated water has become an ongoing public health issue affecting hundred million people worldwide. The aim of this paper was to summarize the evidence in the association between arsenic metabolites and urinary tract cancer risk. Methods : A systematic review was conducted searching for observational studies that evaluated the association of arsenic metabolites and urinary tract cancer. Risk estimates from individual studies were pooled by using random effects models. Results : All the metabolites considered in this study resulted to be significantly associated to urothelial cancer, respectively: IA% 3.51 (1.21-5.82) ( p = 0.003), MMA with WMD = 2.77 (1.67-3.87) ( p < 0.001) and DMA with WMD = -4.56 (-7.91-1.22) ( p = 0.008). Conclusions : Arsenic metabolites are significantly associated to urothelial cancer. Future studies will help to verify the independent association(s) between arsenic metabolites and urothelial cancer.
- Published
- 2020
- Full Text
- View/download PDF
27. Response to Letter to the Editor: "Cardiovascular Effects of Pioglitazone or Sulfonylureas According to Pretreatment Risk: Moving Toward Personalized Care".
- Author
-
Vaccaro O, Nicolucci A, Lucisano G, Masulli M, and Riccardi G
- Subjects
- Humans, Hypoglycemic Agents adverse effects, Pioglitazone, Sulfonylurea Compounds adverse effects
- Published
- 2020
- Full Text
- View/download PDF
28. Erratum. Overall Quality of Care Predicts the Variability of Key Risk Factors for Complications in Type 2 Diabetes: An Observational, Longitudinal Retrospective Study. Diabetes Care 2019;42:514-519.
- Author
-
Ceriello A, Rossi MC, De Cosmo S, Lucisano G, Pontremoli R, Fioretto P, Giorda C, Pacilli A, Viazzi F, Russo G, and Nicolucci A
- Published
- 2020
- Full Text
- View/download PDF
29. Donor-specific antibodies detected by single antigen beads alone can help risk stratify patients undergoing retransplantation across a repeat HLA mismatch.
- Author
-
Lucisano G, Thiruvengadam S, Hassan S, Gueret-Wardle A, Brookes P, Santos-Nunez E, and Willicombe M
- Subjects
- Adult, Aged, Biomarkers blood, Female, Follow-Up Studies, Graft Rejection diagnosis, Graft Rejection prevention & control, Histocompatibility Testing instrumentation, Humans, Isoantibodies immunology, Male, Middle Aged, Multivariate Analysis, Proportional Hazards Models, Risk Assessment, Graft Rejection immunology, HLA Antigens immunology, Histocompatibility Testing methods, Isoantibodies blood, Kidney Transplantation, Reoperation
- Abstract
Whether reexposure to mismatched HLA antigens (RMM) in the setting of a negative crossmatch is associated with increased immunological risk remains an area of uncertainty. This is due to evidence derived predominantly from registry data, which lacks comprehensive information on alloantibody and rejection. In this study, we analyze the impact of low-level preformed donor-specific antibodies (DSA) against an RMM on transplant outcomes. From 1988 consecutive renal transplant recipients, we analyzed 179 patients undergoing retransplantation, of whom 55 had a RMM. All patients were crossmatch negative and preformed DSA were detected by single antigen beads alone. Multivariate analysis revealed that patients with preformed DSA against an RMM were independently at risk of antibody-mediated rejection (HR 8.70 [3.42-22.10], P < .0001) and death-censored allograft loss (HR 3.08 [1.17-8.14], P = .023). In addition, prior transplant nephrectomy (HR 2.04 [1.00-4.17], P = .0495) was also associated with allograft failure, whereas receiving a retransplant that was matched at HLA class II was associated with a favorable outcome (HR 0.37 [0.14-0.99], P = .047). In the absence of preformed DSA, an RMM was not associated with de novo DSA development, rejection, or allograft loss. In conclusion, an RMM portends increased immunological risk only in the presence of a preformed DSA in patients undergoing retransplantation., (© 2019 The American Society of Transplantation and the American Society of Transplant Surgeons.)
- Published
- 2020
- Full Text
- View/download PDF
30. Switching Patients with Type 1 Diabetes to Insulin Degludec from Other Basal Insulins: Real-World Data of Effectiveness and Safety.
- Author
-
Ponzani P, Berra C, Di Lelio A, Del Sindaco P, Di Loreto C, Reggiani F, Lucisano G, and Rossi MC
- Abstract
Introduction: Real-world evidence on the effectiveness and safety of insulin degludec (IDeg) in patients with diabetes is a priority. We have therefore evaluated the effectiveness and safety of IDeg, including impact on metabolic control, glycemic variability, weight gain and hypoglycemia, in patients with type 1 diabetes under routine clinical practice conditions., Methods: This was an observational longitudinal multicenter study. A retrospective chart review of all patients with type 1 diabetes who were switched from basal insulin to IDeg was performed, and temporal trends in clinical outcomes were assessed., Results: Data obtained from 195 patients, with a median age of 42.8 [interquartile range (IQR) 24.6-56.4] years and a median diabetes duration of 16 (IQR 10.0-28) years, were analyzed. Median follow-up was 9.5 (IQR 7.7-11.3) months. Improvements were found in glycated hemoglobin (- 0.34%; p < 0.0001), fasting blood glucose (- 24.82 mg/dL; p < 0.0001), post-prandial glucose (- 17.23 mg/dL; p = 0.0009), glycemic variability as indicated by standard deviation of blood glucose (- 5.67 mg/dL; p < 0.0001) and high blood glucose index (- 3.77; p < 0.0001). Body weight and body mass index remained substantially stable during the follow-up (- 0.18 kg; p = 0.56 and - 0.12; p = 0.42, respectively). Risk of nocturnal hypoglycemia decreased by 52% [incidence rate ratio 0.48; 95% confidence interval (CI) 0.29-0.77] and risk of total hypoglycemic episodes by 41% (incidence ratio 0.59; 95% CI 0.45-0.83). Basal and short-acting insulin doses decreased by - 1.4 and - 3.1 IU, respectively., Conclusion: Switching patients with type 1 diabetes to IDeg from other basal insulins was associated with relevant improvements in metabolic control and glycemic variability without weight gain; the risk of hypoglycemic episodes also significantly declined., Funding: Novo Nordisk S.p.A. unconditional grant.
- Published
- 2020
- Full Text
- View/download PDF
31. Weekend-Based Parent-Group Intervention to Reduce Stress in Parents of Children and Adolescents with Type 1 Diabetes: A Pilot Study.
- Author
-
Ferrito L, Predieri B, Pjetraj D, Alessandrelli MC, Pagnini M, Iannilli A, Marino M, Tombolini S, Pintaudi B, Lucisano G, Zani F, Iughetti L, Nicolucci A, and Cherubini V
- Subjects
- Adolescent, Adolescent Behavior, Adult, Age Factors, Breathing Exercises, Child, Child Behavior, Child, Preschool, Diabetes Mellitus, Type 1 diagnosis, Diabetes Mellitus, Type 1 psychology, Emotions, Feasibility Studies, Female, Health Knowledge, Attitudes, Practice, Humans, Imagery, Psychotherapy, Male, Middle Aged, Parents psychology, Pilot Projects, Relaxation Therapy, Social Behavior, Stress, Psychological diagnosis, Stress, Psychological psychology, Time Factors, Treatment Outcome, Adaptation, Psychological, Cost of Illness, Diabetes Mellitus, Type 1 therapy, Parents education, Psychotherapy, Group, Stress, Psychological prevention & control
- Abstract
Diagnosis of type 1 diabetes (T1D) in a child is often associated with anger, denial, fear, and depression from the parents. The aim of the study was to improve parents' adaptation to the diagnosis of diabetes of their child. Sixty-two parents (29 mothers, 33 fathers) of 36 children with type 1 diabetes (mean age = 11.3-3.3 years; diabetes duration > 1 year; HbA1c = 57 ± 11 mmol/mol) participated in a three-day educational working group pilot intervention study. Intervention was based on the reexamination of the traumatic event of diagnosis of T1D through spatial and time-line anchorage, retracing of the future, emotional awareness, and interactive discussion. Relaxing technique, diaphragmatic breathing, and guided visualization were used by 2 psychologists and 1 pediatric endocrinologist. The study was approved by EC and participants filled a consent form. At baseline and after intervention, parents filled in a questionnaire including Diabetes-Related Distress (DRD), Parent Health Locus of Control Scale (PHLOC), Parent Stress Index Short Form (PSI-SF), Hypoglycemia Fear Survey-Parents (HFS-P) and Hypoglycemia Fear Survey-Parents of Young Children (HFS-P-YC), and Health Survey Short Form-36 (SF-36). Three months after the intervention, both parents reported a reduction in the "difficult child" subscale of the PSI-SF ( p < 0.05) and increased scores of social functioning of the SF-36 ( p < 0.05). DRD score was significantly reduced in mothers ( p = 0.03), while the "parental distress" subscale of the PSI-SF was significantly improved in fathers ( p = 0.03). This weekend-based parent group intervention seems to reduce stress and improve social functioning of parents of children and adolescents with type 1 diabetes., Competing Interests: The authors declare that there is no conflict of interest regarding the publication of this article., (Copyright © 2019 Lucia Ferrito et al.)
- Published
- 2019
- Full Text
- View/download PDF
32. Allosensitization after transplant failure: the role of graft nephrectomy and immunosuppression - a retrospective study.
- Author
-
Lucisano G, Brookes P, Santos-Nunez E, Firmin N, Gunby N, Hassan S, Gueret-Wardle A, Herbert P, Papalois V, Willicombe M, and Taube D
- Subjects
- Adult, Aged, Female, Histocompatibility Antigens Class I immunology, Histocompatibility Antigens Class II immunology, Humans, Immunosuppressive Agents administration & dosage, Kidney Failure, Chronic surgery, Male, Middle Aged, Postoperative Complications surgery, Retrospective Studies, Tacrolimus administration & dosage, Immunosuppression Therapy, Kidney Failure, Chronic immunology, Nephrectomy adverse effects, Postoperative Complications immunology, Transplantation Immunology
- Abstract
There are conflicting data about the role of transplant nephrectomy and immunosuppression withdrawal on the development of allosensitization and the impact on re-transplantation. We divided 109 first graft recipients into two groups according to whether they underwent nephrectomy (NX+, n = 61) or their graft was left in situ (NX-, n = 48). Sera were assessed for HLA-A/B/Cw/DR/DQ antibodies at the time of NX/transplant failure and after 3, 6, 12, 24 months. The NX+ group showed a higher rate of donor specific antibody (DSA) and non-DSA human leukocyte antigen (HLA) antibody production at all the time points. Multivariable analysis showed that nephrectomy was a strong, independent risk factor for the development of DSAs after 12 and 24 months (P = 0.005 and 0.008). In the NX- group, low tacrolimus levels correlated with DSA formation (AUC 0.817, P = 0.002; best cut-off level 2.9 ng/ml). Analysis with a standardized pool of UK donors showed a more difficult grade of HLA matchability following nephrectomy compared with the NX- group. Nephrectomy is followed by the long-term production of DSA and non-DSA HLA antibodies and negatively impacts on the chances of finding a HLA-compatible kidney. Tacrolimus levels ≥3 ng/ml are protective against the development of allosensitization and could facilitate re-transplantation in the NX- group., (© 2019 Steunstichting ESOT.)
- Published
- 2019
- Full Text
- View/download PDF
33. Cardiovascular Effects of Pioglitazone or Sulfonylureas According to Pretreatment Risk: Moving Toward Personalized Care.
- Author
-
Vaccaro O, Lucisano G, Masulli M, Bonora E, Del Prato S, Rivellese AA, Giorda CB, Mocarelli P, Squatrito S, Maggioni AP, Riccardi G, and Nicolucci A
- Subjects
- Aged, Cardiovascular Diseases etiology, Cardiovascular System drug effects, Diabetes Mellitus, Type 2 complications, Diabetes Mellitus, Type 2 drug therapy, Female, Humans, Male, Middle Aged, Randomized Controlled Trials as Topic, Risk Assessment, Cardiovascular Diseases prevention & control, Diabetes Mellitus, Type 2 physiopathology, Hypoglycemic Agents pharmacology, Pioglitazone pharmacology, Sulfonylurea Compounds pharmacology
- Abstract
Context: Hypoglycemic drugs with proven cardiovascular (CV) benefits are recommended for patients with type 2 diabetes and CV disease. Whether the beneficial effects extend to those at lower risk remains unclear., Aim: We investigated the long-term CV effects of pioglitazone or sulfonylureas (SUs) across the spectrum of pretreatment CV risk., Methods: Among 2820 participants of the TOSCA.IT trial, four subgroups with different risk of outcome-a composite of all-cause death, nonfatal myocardial infarction, nonfatal stroke, urgent coronary revascularization-were identified by the RECursive Partitioning and AMalgamation (RECPAM) method. Within each group, the effect of SUs or pioglitazone on the outcome was evaluated., Results: Sex was the first splitting variable, followed by urinary albumin-to-creatinine ratio (UACR) (>9 mg/g or ≤9 mg/g) and body mass index (BMI) (>28.7 or ≤28.7 kg/m2). Female patients had the lowest risk (reference); male patients with UACR >9 mg/g and BMI >28.7 kg/m2 had the highest risk [hazard ratio (HR), 5.58; 95% CI, 3.32 to 9.69]. Patients in this group present a cluster of conditions suggestive of marked insulin resistance (higher BMI, waist circumference, triglycerides, blood pressure, and UACR and lower high-density lipoprotein cholesterol) than the other groups. Treatment with pioglitazone in this group was associated with a significantly lower occurrence of the outcome than SUs (HR, 0.48; 95% CI, 0.25 to 0.76). No significant difference between study treatments was observed in the other RECPAM classes., Conclusions: It is possible to identify patients with type 2 diabetes early in the stage of their disease and who are largely free from evident CV disease in whom add-on pioglitazone to metformin confers CV protection as compared with SUs., (Copyright © 2019 Endocrine Society.)
- Published
- 2019
- Full Text
- View/download PDF
34. Control of Gram-negative multi-drug resistant microorganisms in an Italian ICU: Rapid decline as a result of a multifaceted intervention, including conservative use of antibiotics.
- Author
-
Frattari A, Savini V, Polilli E, Di Marco G, Lucisano G, Corridoni S, Spina T, Costantini A, Nicolucci A, Fazii P, Viale P, and Parruti G
- Subjects
- Aged, Drug Resistance, Multiple, Bacterial, Female, Gram-Negative Bacteria drug effects, Humans, Male, Microbial Sensitivity Tests, Middle Aged, Retrospective Studies, Anti-Bacterial Agents therapeutic use, Gram-Negative Bacteria isolation & purification, Intensive Care Units
- Abstract
Background: Gram-negative Multi-Drug-Resistant Organisms (GNMDROs) cause an increasing burden of disease in Intensive Care Units (ICUs). We deployed a multifaceted intervention to control selection and transmission of GNMDROs and to estimate at which rate GNMDROs would decline with our interventional bundle., Methods: Interventions implemented in 2015: in-ward Antimicrobial-Stewardship-Program for appropriate management of antimicrobial prescription; infection monitoring with nasal/rectal swabs and repeated procalcitonin assays; 24 h microbiological support (since 2016); prevention of catheter-related infections, VAPs and in-ward GNMDROs transmission; education of ICU personnel. In May 2017, epidemiological, clinical and microbiological data were collected and retrospectively analyzed. Rates of resistance in Klebsiella pneumoniae, Pseudomonas aeruginosa and Acinetobacter baumannii, as well as percentages of resistance among all Gram-negative bacteria were compared during the study period., Results: Of 668 patients, at least one isolate was obtained from 399 patients. The proportions of patients with infection and with Gram-negative isolates were even across the 5 semesters (p = 0.8). For Klebsiella pneumoniae, the number of strains resistant to carbapenems fell from 94% to 6% (p < 0.001). Significant drops were also observed for Pseudomonas aeruginosa and Acinetobacter baumannii. Percentages of resistance for all Gram-negative isolates fell from 91% to 13% (p < 0.0001). The reduction in antibiotic prescription translated in a considerable reduction of pharmacy costs. Multivariate models confirmed that the hospitalization semester was the most relevant independent predictor of resistance among Gram-negative bacteria., Conclusions: Our experience provides further evidence that a multi-faceted intervention, aimed to reduce selection and transmission of GNMDROs with efficient microbiological support, may yield remarkable results in a short time interval., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)
- Published
- 2019
- Full Text
- View/download PDF
35. Lymphocyte Count and Body Mass Index as Biomarkers of Early Treatment Response in a Multiple Sclerosis Dimethyl Fumarate-Treated Cohort.
- Author
-
Manni A, Iaffaldano A, Lucisano G, D'Onghia M, Mezzapesa DM, Felica V, Iaffaldano P, Trojano M, and Paolicelli D
- Subjects
- Adult, Biomarkers, Pharmacological, Body Mass Index, Cohort Studies, Dermatologic Agents therapeutic use, Dimethyl Fumarate therapeutic use, Female, Follow-Up Studies, Humans, Lymphocyte Count, Male, Middle Aged, Multiple Sclerosis drug therapy, Retrospective Studies, Treatment Outcome, Multiple Sclerosis diagnosis
- Abstract
Introduction: In relapsing Multiple Sclerosis (RMS) patients treated with disease modifying drugs (DMDs), few data are available regarding the biomarkers of treatment response. We aimed to assess the predictive value of lymphocyte count (LC) and Body Mass Index (BMI) for treatment response in a real life setting of dimethyl fumarate (DMF) treated patients. Materials and Methods: We included in our observational analysis 338 patients who were prescribed DMF in an Italian MS Center. We collected clinical and demographic data at the beginning of DMF (T0), and assessed White Blood Cells (WBC) and LC at T0 and at 3 (T3), 6 (T6), 9 (T9), and 12 (T12) months. Gadolinium enhancing (Gd+), new T2 lesions and relapses within the first year of treatment (T12) were recorded in order to evaluate clinical activity at 12 months. Analysis of correlation was performed to correlate WBC, LC and BMI with clinical and radiological responses. We evaluated whether BMI or LC can predict treatment response by using multivariate logistic regression models at each follow-up. Results: Our cohort was followed up for a mean period of 19.8 ± 6.8 months. The mean BMI at baseline was 24.19 ± 4.48. The multivariate models gave as predictive factors for Gd+ lesions at T12, LC at T3 (OR = 1.003, 95% CI = 1.00-1.07; p = 0.046) and baseline BMI (OR = 0.71, 95% CI = 0.52-0.98; p = 0.037). Predictive factors for new T2 lesions at T12 were LC at T3 (OR = 1.01 95%CI = 1.00-1.95; p = 0.005) and baseline BMI (OR = 0.99, 95% CI = 0.98-1.00; p = 0.026). Conclusions: In our real life-experience, BMI and LC may be early biomarkers to predict treatment response during DMF.
- Published
- 2019
- Full Text
- View/download PDF
36. Overall Quality of Care Predicts the Variability of Key Risk Factors for Complications in Type 2 Diabetes: An Observational, Longitudinal Retrospective Study.
- Author
-
Ceriello A, Rossi MC, De Cosmo S, Lucisano G, Pontremoli R, Fioretto P, Giorda C, Pacilli A, Viazzi F, Russo G, and Nicolucci A
- Subjects
- Aged, Blood Pressure physiology, Cholesterol blood, Diabetes Complications epidemiology, Diabetes Mellitus, Type 2 epidemiology, Female, Glycated Hemoglobin analysis, Humans, Italy epidemiology, Longitudinal Studies, Male, Middle Aged, Prognosis, Retrospective Studies, Risk Factors, Treatment Outcome, Uric Acid blood, Diabetes Complications diagnosis, Diabetes Mellitus, Type 2 complications, Diabetes Mellitus, Type 2 diagnosis, Diabetes Mellitus, Type 2 therapy, Quality of Health Care standards, Quality of Health Care statistics & numerical data
- Abstract
Objective: An association between variability in clinical parameters (HbA
1c , blood pressure, cholesterol, and uric acid) and risk of complications in type 2 diabetes has been reported. In this analysis, we investigated to what extent such variability is associated with overall quality of care., Research Design and Methods: The quality of care summary score (Q-score) represents a validated, overall quality of care indicator ranging between 0 and 40; the higher the score, the better the quality of care provided by the diabetes center. We identified patients with five or more measurements of clinical parameters after the assessment of the Q-score. Multiple linear regression analyses assessed the role of the Q-score in predicting the variability of the different parameters., Results: Overall, 273,888 patients were analyzed. The variability of all the parameters systematically increased with decreasing Q-score values. At multivariate linear regression analysis, compared with a Q-score >25, a score <15 was associated with a significantly larger variation in HbA1c , blood pressure, uric acid, total cholesterol, and LDL cholesterol and a lower variation in HDL cholesterol. The analysis of standardized β coefficients show that the Q-score has a larger impact on the variability of HbA1c (0.34; P < 0.0001), systolic blood pressure (0.21; P < 0.0001), total cholesterol (0.21; P < 0.0001), and LDL cholesterol (0.20; P < 0.0001)., Conclusions: The variability of risk factors for diabetic complications is associated with quality of care. Quality of care improvement initiatives should be targeted to increase the achievement of the recommended target while reducing such variability., (© 2019 by the American Diabetes Association.)- Published
- 2019
- Full Text
- View/download PDF
37. Impact of Insulin Degludec in Type 2 Diabetes: Real-World Data on Effectiveness and Safety.
- Author
-
Ponzani P, Berra C, Di Lelio A, Del Sindaco P, Di Loreto C, Reggiani F, Lucisano G, and Rossi MC
- Abstract
Introduction: Real-world evidence on effectiveness and safety of insulin degludec (IDeg) in patients with diabetes is a priority. The aim of the study was to evaluate patterns of use and the long-term effectiveness and safety of IDeg in routine clinical practice., Methods: This was an observational longitudinal study. A retrospective chart review of all patients with type 2 diabetes treated with IDeg was performed and temporal trends in clinical outcomes were assessed. All data was stratified by treatment modality: the switch group consisted of patients already treated with another basal insulin before initiating IDeg; the add-on group consisted of basal insulin-naïve patients., Results: Overall, 247 patients were analyzed (55 in the add-on group and 192 in the switch group), mean age 67.0 ± 10.9 years ,and diabetes duration 16.3 ± 8.9 years. Median (interquartile range) follow-up was 9.7 (8.0-11.9) months. In the add-on group, improvements were found in glycated hemoglobin (HbA1c) (- 1.68%; p < 0.0001), fasting blood glucose (FBG) (- 64.7 mg/dL; p < 0.0001), post-prandial glucose (PPG) (- 81.1 mg/dl; p < 0.0001), and glycemic variability (i.e., standard deviation of blood glucose) (- 11.6 mg/dl; p = 0.04). Even in the switch group, improvements were found in HbA1c (- 0.57%; p < 0.0001), FBG (- 28.1 mg/dL; p < 0.0001), and PPG (- 22.6 mg/dl; p = 0.001). Body weight increase during the follow-up was not statistically significant vs. baseline in both groups. Benefits on overall, nocturnal, and severe hypoglycemia were found in the switch group., Conclusion: These real-world data documented that initiating IDeg or switching to IDeg from other basal insulins in type 2 diabetes was associated with significant improvement in metabolic control without significant weight gain; a decrease in the risk of hypoglycemia was observed when switching to IDeg from another basal insulin.
- Published
- 2018
- Full Text
- View/download PDF
38. The Long-Term Impact of Renin-Angiotensin System (RAS) Inhibition on Cardiorenal Outcomes (LIRICO): A Randomized, Controlled Trial.
- Author
-
Saglimbene V, Palmer SC, Ruospo M, Natale P, Maione A, Nicolucci A, Vecchio M, Tognoni G, Craig JC, Pellegrini F, Lucisano G, Hegbrant J, Ariano R, Lamacchia O, Sasso A, Morano S, Filardi T, De Cosmo S, Pugliese G, Procaccini DA, Gesualdo L, Palasciano G, Johnson DW, Tonelli M, and Strippoli GFM
- Subjects
- Aged, Angiotensin Receptor Antagonists administration & dosage, Angiotensin Receptor Antagonists adverse effects, Angiotensin-Converting Enzyme Inhibitors administration & dosage, Angiotensin-Converting Enzyme Inhibitors adverse effects, Cardiovascular Diseases drug therapy, Cardiovascular Diseases mortality, Drug Therapy, Combination, Female, Humans, Hypertension drug therapy, Male, Middle Aged, Renin-Angiotensin System drug effects, Risk Factors, Treatment Outcome, Albuminuria drug therapy, Angiotensin Receptor Antagonists therapeutic use, Angiotensin-Converting Enzyme Inhibitors therapeutic use, Diabetes Mellitus drug therapy
- Abstract
Background: The comparative effectiveness of treatment with angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), or their combination in people with albuminuria and cardiovascular risk factors is unclear., Methods: In a multicenter, randomized, open label, blinded end point trial, we evaluated the effectiveness on cardiovascular events of ACE or ARB monotherapy or combination therapy, targeting BP<130/80 in patients with moderate or severe albuminuria and diabetes or other cardiovascular risk factors. End points included a primary composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, and hospitalization for cardiovascular causes and a revised end point of all-cause mortality. Additional end points included ESRD, doubling of serum creatinine, albuminuria, eGFR, BP, and adverse events., Results: Because of slow enrollment, the trial was modified and stopped 41% short of targeted enrollment of 2100 participants, corresponding to 35% power to detect a 25% reduced risk in the primary outcome. Our analysis included 1243 adults, with median follow-up of 2.7 years. Efficacy outcomes were similar between groups (ACE inhibitor versus ARB, ACE inhibitor versus combination, ARB versus combination) as were rates of serious adverse events. The rate of permanent discontinuation for ARB monotherapy (6.3%) was significantly lower than for ACE inhibitor monotherapy (15.7%) or combined therapy (18.3%)., Conclusions: Patients may tolerate ARB monotherapy better than ACE inhibitor monotherapy. However, data from this trial and similar trials, although as yet inconclusive, show no trend suggesting differences in mortality and renal outcomes with ACE inhibitors or ARBs as dual or monotherapy in patients with albuminuria and diabetes or other cardiovascular risk factors., (Copyright © 2018 by the American Society of Nephrology.)
- Published
- 2018
- Full Text
- View/download PDF
39. Treatment with insulin is associated with worse outcome in patients with chronic heart failure and diabetes.
- Author
-
Cosmi F, Shen L, Magnoli M, Abraham WT, Anand IS, Cleland JG, Cohn JN, Cosmi D, De Berardis G, Dickstein K, Franzosi MG, Gullestad L, Jhund PS, Kjekshus J, Køber L, Lepore V, Lucisano G, Maggioni AP, Masson S, McMurray JJV, Nicolucci A, Petrarolo V, Robusto F, Staszewsky L, Tavazzi L, Teli R, Tognoni G, Wikstrand J, and Latini R
- Subjects
- Aged, Cause of Death trends, Comorbidity, Diabetes Mellitus, Type 2 epidemiology, Double-Blind Method, Female, Heart Failure diagnosis, Heart Failure physiopathology, Humans, Hypoglycemic Agents therapeutic use, Italy epidemiology, Male, Prognosis, Propensity Score, Risk Factors, Survival Rate trends, Diabetes Mellitus, Type 2 drug therapy, Heart Failure epidemiology, Insulin therapeutic use, Registries
- Abstract
Aims: Up to one-third of patients with diabetes mellitus and heart failure (HF) are treated with insulin. As insulin causes sodium retention and hypoglycaemia, its use might be associated with worse outcomes., Methods and Results: We examined two datasets: 24 012 patients with HF from four large randomized trials and an administrative database of 4 million individuals, 103 857 of whom with HF. In the former, survival was examined using Cox proportional hazards models adjusted for baseline variables and separately for propensity scores. Fine-Gray competing risk regression models were used to assess the risk of hospitalization for HF. For the latter, a case-control nested within a population-based cohort study was conducted with propensity score. Prevalence of diabetes mellitus at study entry ranged from 25.5% to 29.5% across trials. Insulin alone or in combination with oral hypoglycaemic drugs was prescribed at randomization to 24.4% to 34.5% of the patients with diabetes. The rates of death from any cause and hospitalization for HF were higher in patients with vs. without diabetes, and highest of all in patients prescribed insulin [propensity score pooled hazard ratio for all-cause mortality 1.27 (1.16-1.38), for HF hospitalization 1.23 (1.13-1.33)]. In the administrative registry, insulin prescription was associated with a higher risk of all-cause death [odds ratio (OR) 2.02, 95% confidence interval (CI) 1.87-2.19] and rehospitalization for HF (OR 1.42, 95% CI 1.32-1.53)., Conclusions: Whether insulin use is associated with poor outcomes in HF should be investigated further with controlled trials, as should the possibility that there may be safer alternative glucose-lowering treatments for patients with HF and type 2 diabetes mellitus., (© 2018 The Authors. European Journal of Heart Failure © 2018 European Society of Cardiology.)
- Published
- 2018
- Full Text
- View/download PDF
40. 8th edition of the AJCC/TNM staging system of thyroid cancer: what to expect (ITCO#2).
- Author
-
Lamartina L, Grani G, Arvat E, Nervo A, Zatelli MC, Rossi R, Puxeddu E, Morelli S, Torlontano M, Massa M, Bellantone R, Pontecorvi A, Montesano T, Pagano L, Daniele L, Fugazzola L, Ceresini G, Bruno R, Rossetto R, Tumino S, Centanni M, Meringolo D, Castagna MG, Salvatore D, Nicolucci A, Lucisano G, Filetti S, and Durante C
- Subjects
- Humans, Neoplasm Staging, Thyroid Neoplasms pathology
- Published
- 2018
- Full Text
- View/download PDF
41. Factors associated with circulating concentrations of irisin in the general population cohort of the ABCD study.
- Author
-
Buscemi S, Corleo D, Vasto S, Buscemi C, Massenti MF, Nuzzo D, Lucisano G, Barile AM, Rosafio G, Maniaci V, and Giordano C
- Subjects
- Adult, Cohort Studies, Female, Humans, Italy epidemiology, Male, Middle Aged, Exercise physiology, Fibronectins blood
- Abstract
Objective: Animal studies have shown that irisin is a myokine secreted following physical exercise, and that it induces the remodeling of white adipose tissue toward brown adipose tissue. Therefore, a protective role of irisin against obesity, diabetes, and other metabolic and cardiovascular conditions has been hypothesized. However, data in humans are contradictory and few data are available concerning the general population., Design: We aimed to evaluate the association between serum irisin concentrations and habitual physical activity, as well as other metabolic and cardiovascular factors in a general population in a Mediterranean area., Methods: We considered 858 consecutive individuals included in the ABCD (Alimentazione, Benessere Cardiovascolare e Diabete) study (ISRCTN15840340), a longitudinal observational single-center study of a cohort representative of the general population of Palermo, Sicily. Irisin serum concentrations (Phoenix Europe, Germany), habitual physical activity (HPA) level, and other blood and clinical variables were measured., Results: The irisin serum concentrations were not normally distributed in the cohort (Shapiro-Wilk test=0.94; P<0.001). A significant association between irisin concentrations and HPA was observed (P<0.001). Irisin concentrations were higher in women than in men (P<0.01), and significantly correlated with serum concentrations of HDL-cholesterol (P<0.05) and hs-C-reactive protein (hs-CRP; P<0.05). Binary logistic regression analysis demonstrated that high (⩾ median value) irisin serum concentrations were significantly associated with female gender (OR=1.63; 95% CI=1.16-2.28), high serum hs-CRP concentrations (OR=1.61; 95% CI=1.02-2.54) and the HPA level (OR=1.42; 95% CI=1.02-1.96)., Conclusions: Our study confirms, in a cohort of a general population, that irisin concentrations gradually increase with the usual level of habitual physical activity.
- Published
- 2018
- Full Text
- View/download PDF
42. The prevalence and correlates of low sexual functioning in women on hemodialysis: A multinational, cross-sectional study.
- Author
-
Saglimbene V, Natale P, Palmer S, Scardapane M, Craig JC, Ruospo M, Gargano L, Lucisano G, Török M, Celia E, Gelfman R, Bednarek-Skublewska A, Dulawa J, Stroumza P, Leal M, Del Castillo D, Murgo AM, Schon S, Wollheim C, Hegbrant J, and Strippoli GFM
- Subjects
- Aged, Arousal, Cross-Sectional Studies, Depression complications, Female, Humans, Linear Models, Lubrication, Middle Aged, Orgasm, Prevalence, Renal Dialysis, Sexual Behavior, Sexual Dysfunction, Physiological complications, Surveys and Questionnaires, Kidney Failure, Chronic complications, Sexual Dysfunction, Physiological epidemiology
- Abstract
Sexual dysfunction may affect 80% of women in hemodialysis. However the specific patterns and clinical correlates of sexual functioning remain poorly described. The aim of this study was to assess prevalence and correlates of the individual domains of sexual functioning in women treated with hemodialysis. We recruited, into this multinational cross-sectional study, women treated with long-term hemodialysis (Collaborative Working Group on Depression and Sexual dysfunction in Hemodialysis study). Self-reported domains of sexual functioning were assessed by the Female Sexual Function Index, which is routinely administered within the network of dialysis patients followed by the working group. Lower scores represented lower sexual functioning. Socio-demographic and clinical correlates of each domain of sexual functioning were identified by stepwise multivariable linear regression. Sensitivity analyses were restricted to women who reported being sexually active. We found that of 1309 enrolled women, 659 (50.3%) provided complete responses to FSFI survey questions and 232 (35%) reported being sexually active. Overall, most respondents reported either no sexual activity or low sexual functioning in all measured domains (orgasm 75.1%; arousal 64.0%; lubrication 63.3%; pain 60.7%; satisfaction 60.1%; sexual desire 58.0%). Respondents who were waitlisted for a kidney transplant reported scores with higher sexual functioning, while older respondents reported scores with lower functioning. The presence of depression was associated with worse lubrication and pain scores [mean difference for depressed versus non-depressed women (95% CI) -0.42 (-0.73 to -0.11), -0.53 (-0.89 to -0.16), respectively] while women who had experienced a previous cardiovascular event reported higher pain scores [-0.77 (-1.40- to -0.13)]. In conclusion, women in hemodialysis reported scores consistent with marked low sexual functioning across a range of domains; the low functioning appeared to be associated with comorbidity.
- Published
- 2017
- Full Text
- View/download PDF
43. Exercise in Patients on Dialysis: A Multicenter, Randomized Clinical Trial.
- Author
-
Manfredini F, Mallamaci F, D'Arrigo G, Baggetta R, Bolignano D, Torino C, Lamberti N, Bertoli S, Ciurlino D, Rocca-Rey L, Barillà A, Battaglia Y, Rapanà RM, Zuccalà A, Bonanno G, Fatuzzo P, Rapisarda F, Rastelli S, Fabrizi F, Messa P, De Paola L, Lombardi L, Cupisti A, Fuiano G, Lucisano G, Summaria C, Felisatti M, Pozzato E, Malagoni AM, Castellino P, Aucella F, Abd ElHafeez S, Provenzano PF, Tripepi G, Catizone L, and Zoccali C
- Subjects
- Combined Modality Therapy, Female, Humans, Male, Middle Aged, Exercise Therapy, Physical Fitness, Quality of Life, Renal Dialysis, Renal Insufficiency, Chronic therapy, Walking
- Abstract
Previous studies have suggested the benefits of physical exercise for patients on dialysis. We conducted the Exercise Introduction to Enhance Performance in Dialysis trial, a 6-month randomized, multicenter trial to test whether a simple, personalized walking exercise program at home, managed by dialysis staff, improves functional status in adult patients on dialysis. The main study outcomes included change in physical performance at 6 months, assessed by the 6-minute walking test and the five times sit-to-stand test, and in quality of life, assessed by the Kidney Disease Quality of Life Short Form (KDQOL-SF) questionnaire. We randomized 296 patients to normal physical activity (control; n =145) or walking exercise ( n =151); 227 patients (exercise n =104; control n =123) repeated the 6-month evaluations. The distance covered during the 6-minute walking test improved in the exercise group (mean distance±SD: baseline, 328±96 m; 6 months, 367±113 m) but not in the control group (baseline, 321±107 m; 6 months, 324±116 m; P <0.001 between groups). Similarly, the five times sit-to-stand test time improved in the exercise group (mean time±SD: baseline, 20.5±6.0 seconds; 6 months, 18.2±5.7 seconds) but not in the control group (baseline, 20.9±5.8 seconds; 6 months, 20.2±6.4 seconds; P =0.001 between groups). The cognitive function score ( P =0.04) and quality of social interaction score ( P =0.01) in the kidney disease component of the KDQOL-SF improved significantly in the exercise arm compared with the control arm. Hence, a simple, personalized, home-based, low-intensity exercise program managed by dialysis staff may improve physical performance and quality of life in patients on dialysis., (Copyright © 2017 by the American Society of Nephrology.)
- Published
- 2017
- Full Text
- View/download PDF
44. Low versus high dose erythropoiesis-stimulating agents in hemodialysis patients with anemia: A randomized clinical trial.
- Author
-
Saglimbene V, Palmer SC, Craig JC, Ruospo M, Nicolucci A, Tonelli M, Johnson D, Lucisano G, Williams G, Valentini M, D'Alonzo D, Pellegrini F, Strippoli P, Salomone M, Santoro A, Maffei S, Hegbrant J, Tognoni G, and Strippoli GF
- Subjects
- Aged, Cardiovascular Diseases blood, Cardiovascular Diseases chemically induced, Cardiovascular Diseases mortality, Dose-Response Relationship, Drug, Double-Blind Method, Female, Follow-Up Studies, Hematinics adverse effects, Hemoglobins metabolism, Humans, Male, Middle Aged, Anemia blood, Anemia drug therapy, Anemia etiology, Anemia mortality, Hematinics administration & dosage, Quality of Life, Renal Dialysis adverse effects
- Abstract
The increased risks of death and adverse events with erythropoiesis-stimulating agent (ESA) therapy targeting a higher hemoglobin level are established. It is uncertain whether the adverse effects of ESA therapy are related to dose and are mitigated when a fixed low ESA dose is used. We conducted a multicenter, prospective randomized open-label, blinded-endpoint (PROBE) trial to evaluate fixed low versus high dose ESA therapy on patient outcomes. We intended to recruit 2104 hemodialysis patients >18 years with anemia or receiving ESA treated at dialysis clinics in Italy. The intervention was fixed low (4000 IU epoetin alfa equivalent weekly) or high (18,000 IU epoetin alfa equivalent weekly) dose ESA for 12 months. Primary outcomes were serum transferrin, ferritin, albumin, C-reactive protein and ESA dose. Secondary outcomes were the composite of death or cardiovascular event, all-cause mortality, cardiovascular mortality, myocardial infarction, stroke, cardiovascular hospitalization, and quality of life. Study recruitment was terminated after inclusion of 656 participants with convergence of ESA dose between groups during follow up. Fixed low dose ESA had uncertain effects on serum ferritin (delta of delta (DD) 3.9 ng/ml, 95% CI -85.0 to 92.8), transferrin (9.2 mg/dl, -6.3 to 24.8), transferrin saturation (3.7%, -5.0 to 12.3), serum albumin (-0.03 g/dl, -0.2 to 0.1), or C-reactive protein (-0.6 mg/l, -3.3 to 2.1). In addition, fixed dose therapy had inconclusive effects on the composite endpoint of mortality and cardiovascular events (hazard ratio [HR] 0.95, 95% CI 0.66 to 1.37), death (0.98, 0.64 to 1.52), nonfatal myocardial infarction (0.52, 0.18 to 1.52), nonfatal stroke (no events), hospital admission for cardiovascular causes (0.93, 0.50 to 1.72) or health-related quality of life. A fixed low ESA dose in hemodialysis patients has uncertain effects on serum parameters, mortality, cardiovascular events, and quality of life. Hemoglobin targets may be so entrenched in nephrology practice that a trial of ESA dose is no longer possible.
- Published
- 2017
- Full Text
- View/download PDF
45. The complex interplay between clinical and person-centered diabetes outcomes in the two genders.
- Author
-
Rossi MC, Lucisano G, Pintaudi B, Bulotta A, Gentile S, Scardapane M, Skovlund SE, Vespasiani G, and Nicolucci A
- Subjects
- Adult, Aged, Aged, 80 and over, Female, Health Surveys, Humans, Male, Middle Aged, Sex Factors, Social Support, Surveys and Questionnaires, Adaptation, Psychological, Chronic Disease psychology, Diabetes Mellitus, Type 2 complications, Diabetes Mellitus, Type 2 psychology, Quality of Life psychology, Self Care psychology
- Abstract
Background: New approaches to cope with clinical and psychosocial aspects of type 2 diabetes (T2DM) are needed; gender influences the complex interplay between clinical and non-clinical factors. We used data from the BENCH-D study to assess gender-differences in terms of clinical and person-centered measures in T2DM., Methods: Clinical quality of care indicators relative to control of HbA1c, lipid profile, blood pressure, and BMI were derived from electronic medical records. Ten self-administered validated questionnaires (SF-12 Health Survey; WHO-5 well-being index; Problem Areas in Diabetes (PAID) 5, Health Care Climate Questionnaire, Patients Assessment of Chronic Illness Care, Diabetes Empowerment Scale, Diabetes Self-care Activities, Global Satisfaction for Diabetes Treatment, Barriers to Taking Medications, Perceived Social Support) were adopted as person-centered outcomes indicators., Results: Overall, 26 diabetes clinics enrolled 2,335 people (men: 59.7%; women: 40.3%). Lower percentages of women reached HbA1c levels < =7.0% (23.2% vs. 27.8%; p = 0.03), LDL-cholesterol < 100 mg/dl (48.3 vs. 57.8%; p = 0.0005), and BMI <27 Kg/m2 (27.2 vs. 31.6%; p = 0.04) than men. Women had statistically significant poorer scores for physical functioning, psychological well-being, self-care activities dedicated to physical activities, empowerment, diabetes-related distress, satisfaction with treatment, barriers to medication taking, satisfaction with access to chronic care and healthcare communication, and perceived social support than men; 24.8% of women and 8.8% of men had WHO-5 < =28 (likely depression) (p < 0.0001); 67.7% of women and 55.1% of men had PAID-5 > 40 (high levels of diabetes-related distress) (p < 0.0001). At multivariate analysis, factors associated with an increased likelihood of having elevated HbA1c levels (≥8.0%) were different in men and women, e.g. having PAID-5 levels >40 was associated with a higher likelihood of HbA1c ≥8.0% in women (OR = 1.15; 95%CI 1.05-1.25) but not in men (OR = 1.00; 95%CI 0.93-1.08)., Conclusions: In T2DM, women show poorer clinical and person-centered outcomes indicators than men. Diabetes-related distress plays a role as a correlate of metabolic control in women but not in men. The study provides new information about the interplay between clinical and person-centered indicators in men and women which may guide further improvements in diabetes education and support programs.
- Published
- 2017
- Full Text
- View/download PDF
46. Gender-Disparities in Adults with Type 1 Diabetes: More Than a Quality of Care Issue. A Cross-Sectional Observational Study from the AMD Annals Initiative.
- Author
-
Manicardi V, Russo G, Napoli A, Torlone E, Li Volsi P, Giorda CB, Musacchio N, Nicolucci A, Suraci C, Lucisano G, and Rossi MC
- Subjects
- Adult, Body Mass Index, Cross-Sectional Studies, Female, Glomerular Filtration Rate, Glycated Hemoglobin analysis, Humans, Male, Middle Aged, Quality Indicators, Health Care, Sex Factors, Treatment Outcome, Diabetes Mellitus, Type 1 therapy, Healthcare Disparities statistics & numerical data, Quality of Health Care statistics & numerical data
- Abstract
We evaluated gender-differences in quality of type 1 diabetes (T1DM) care. Starting from electronic medical records of 300 centers, 5 process indicators, 3 favorable and 6 unfavorable intermediate outcomes, 6 treatment intensity/appropriateness measures and an overall quality score were measured. The likelihood of women vs. men (reference class) to be monitored, to reach outcomes, or to be treated has been investigated through multilevel logistic regression analyses; results are expressed as Odd Ratios (ORs) and 95% confidence intervals (95%CIs). The inter-center variability in the achievement of the unfavorable outcomes was also investigated. Overall, 28,802 subjects were analyzed (45.5% women). Women and men had similar age (44.5±16.0 vs. 45.0±17.0 years) and diabetes duration (18.3±13.0 vs. 18.8±13.0 years). No between-gender differences were found in process indicators. As for intermediate outcomes, women showed 33% higher likelihood of having HbA1c ≥8.0% (OR = 1.33; 95%CI: 1.25-1.43), 29% lower risk of blood pressure ≥140/90 mmHg (OR = 0.71; 95%CI: 0.65-0.77) and 27% lower risk of micro/macroalbuminuria (OR = 0.73; 95%CI: 0.65-0.81) than men, while BMI, LDL-c and GFR did not significantly differ; treatment intensity/appropriateness was not systematically different between genders; overall quality score was similar in men and women. Consistently across centers a larger proportion of women than men had HbA1c ≥8.0%, while a smaller proportion had BP ≥140/90 mmHg. No gender-disparities were found in process measures and improvements are required in both genders. The systematic worse metabolic control in women and worse blood pressure in men suggest that pathophysiologic differences rather than the care provided might explain these differences., Competing Interests: We have the following interests: We received non conditional funding from a commercial source, i.e. EliLilly-Italy. Antonio Nicolucci, Giuseppe Lucisano and Maria Chiara Rossi are employed by CORESEARCH srl. CORESEARCH srl is a Clinical Research Organization which has been commissioned by AMD to plan and perform data analysis and to prepare the manuscript in collaboration with AMD. AMD Annals data are available in aggregated form upon request. There are no patents, products in development or marketed products to declare. This does not alter our adherence to all the PLOS ONE policies on sharing data and materials, as detailed online in the guide for authors.
- Published
- 2016
- Full Text
- View/download PDF
47. The Drug Derived Complexity Index (DDCI) Predicts Mortality, Unplanned Hospitalization and Hospital Readmissions at the Population Level.
- Author
-
Robusto F, Lepore V, D'Ettorre A, Lucisano G, De Berardis G, Bisceglia L, Tognoni G, and Nicolucci A
- Subjects
- Adult, Aged, Cohort Studies, Comorbidity, Databases, Factual, Female, Humans, Incidence, Italy, Kaplan-Meier Estimate, Male, Middle Aged, Mortality, Proportional Hazards Models, Registries, Risk Factors, Drug Prescriptions, Hospitalization, Models, Statistical, Patient Readmission, Population Surveillance
- Abstract
Objective: to develop and validate the Drug Derived Complexity Index (DDCI), a predictive model derived from drug prescriptions able to stratify the general population according to the risk of death, unplanned hospital admission, and readmission, and to compare the new predictive index with the Charlson Comorbidity Index (CCI)., Design: Population-based cohort study, using a record-linkage analysis of prescription databases, hospital discharge records, and the civil registry. The predictive model was developed based on prescription patterns indicative of chronic diseases, using a random sample of 50% of the population. Multivariate Cox proportional hazards regression was used to assess weights of different prescription patterns and drug classes. The predictive properties of the DDCI were confirmed in the validation cohort, represented by the other half of the population. The performance of DDCI was compared to the CCI in terms of calibration, discrimination and reclassification., Setting: 6 local health authorities with 2.0 million citizens aged 40 years or above., Results: One year and overall mortality rates, unplanned hospitalization rates and hospital readmission rates progressively increased with increasing DDCI score. In the overall population, the model including age, gender and DDCI showed a high performance. DDCI predicted 1-year mortality, overall mortality and unplanned hospitalization with an accuracy of 0.851, 0.835, and 0.584, respectively. If compared to CCI, DDCI showed discrimination and reclassification properties very similar to the CCI, and improved prediction when used in combination with the CCI., Conclusions and Relevance: DDCI is a reliable prognostic index, able to stratify the entire population into homogeneous risk groups. DDCI can represent an useful tool for risk-adjustment, policy planning, and the identification of patients needing a focused approach in everyday practice.
- Published
- 2016
- Full Text
- View/download PDF
48. Clobetasol and Halcinonide Act as Smoothened Agonists to Promote Myelin Gene Expression and RxRγ Receptor Activation.
- Author
-
Porcu G, Serone E, De Nardis V, Di Giandomenico D, Lucisano G, Scardapane M, Poma A, and Ragnini-Wilson A
- Subjects
- Animals, Anti-Inflammatory Agents pharmacology, Cell Line, Cytoskeletal Proteins agonists, Drug Repositioning, Gene Expression drug effects, Immunoblotting, Mice, Microscopy, Fluorescence, Muscle Proteins agonists, Myelin Basic Protein metabolism, Oligodendroglia drug effects, Oligodendroglia metabolism, Retinoid X Receptor gamma genetics, Reverse Transcriptase Polymerase Chain Reaction, Transcription Factors genetics, Clobetasol pharmacology, Cytoskeletal Proteins metabolism, Halcinonide pharmacology, Muscle Proteins metabolism, Myelin Sheath metabolism, Retinoid X Receptor gamma metabolism
- Abstract
One of the causes of permanent disability in chronic multiple sclerosis patients is the inability of oligodendrocyte progenitor cells (OPCs) to terminate their maturation program at lesions. To identify key regulators of myelin gene expression acting at the last stages of OPC maturation we developed a drug repositioning strategy based on the mouse immortalized oligodendrocyte (OL) cell line Oli-neu brought to the premyelination stage by stably expressing a key factor regulating the last stages of OL maturation. The Prestwick Chemical Library of 1,200 FDA-approved compound(s) was repositioned at three dosages based on the induction of Myelin Basic Protein (MBP) expression. Drug hits were further validated using dosage-dependent reproducibility tests and biochemical assays. The glucocorticoid class of compounds was the most highly represented and we found that they can be divided in three groups according to their efficacy on MBP up-regulation. Since target identification is crucial before bringing compounds to the clinic, we searched for common targets of the primary screen hits based on their known chemical-target interactomes, and the pathways predicted by top ranking compounds were validated using specific inhibitors. Two of the top ranking compounds, Halcinonide and Clobetasol, act as Smoothened (Smo) agonists to up-regulate myelin gene expression in the Oli-neuM cell line. Further, RxRγ activation is required for MBP expression upon Halcinonide and Clobetasol treatment. These data indicate Clobetasol and Halcinonide as potential promyelinating drugs and also provide a mechanistic understanding of their mode of action in the pathway leading to myelination in OPCs. Furthermore, our classification of glucocorticoids with respect to MBP expression provides important novel insights into their effects in the CNS and a rational criteria for their choice in combinatorial therapies in de-myelinating diseases.
- Published
- 2015
- Full Text
- View/download PDF
49. Fingolimod versus interferon beta/glatiramer acetate after natalizumab suspension in multiple sclerosis.
- Author
-
Iaffaldano P, Lucisano G, Pozzilli C, Brescia Morra V, Ghezzi A, Millefiorini E, Patti F, Lugaresi A, Zimatore GB, Marrosu MG, Amato MP, Bertolotto A, Bergamaschi R, Granella F, Coniglio G, Tedeschi G, Sola P, Lus G, Ferrò MT, Iuliano G, Corea F, Protti A, Cavalla P, Guareschi A, Rodegher M, Paolicelli D, Tortorella C, Lepore V, Prosperini L, Saccà F, Baroncini D, Comi G, and Trojano M
- Subjects
- Adult, Cohort Studies, Drug Substitution, Drug Therapy, Combination, Female, Humans, Italy, Male, Middle Aged, Poisson Distribution, Prospective Studies, Regression Analysis, Treatment Outcome, Fingolimod Hydrochloride therapeutic use, Glatiramer Acetate therapeutic use, Immunologic Factors therapeutic use, Immunosuppressive Agents therapeutic use, Interferon-beta therapeutic use, Multiple Sclerosis, Relapsing-Remitting drug therapy, Natalizumab therapeutic use, Registries
- Abstract
The comparative effectiveness of fingolimod versus interferon beta/glatiramer acetate was assessed in a multicentre, observational, prospectively acquired cohort study including 613 patients with relapsing multiple sclerosis discontinuing natalizumab in the Italian iMedWeb registry. First, after natalizumab suspension, the relapse risk during the untreated wash-out period and during the course of switch therapies was estimated through Poisson regression analyses in separated models. During the wash-out period an increased risk of relapses was found in patients with a higher number of relapses before natalizumab treatment (incidence rate ratio = 1.31, P = 0.0014) and in patients discontinuing natalizumab due to lack of efficacy (incidence rate ratio = 2.33, P = 0.0288), patient's choice (incidence rate ratio = 2.18, P = 0.0064) and adverse events (incidence rate ratio = 2.09, P = 0.0084). The strongest independent factors influencing the relapse risk after the start of switch therapies were a wash-out duration longer than 3 months (incidence rate ratio = 1.78, P < 0.0001), the number of relapses experienced during and before natalizumab treatment (incidence rate ratio = 1.61, P < 0.0001; incidence rate ratio = 1.13, P = 0.0118, respectively) and the presence of comorbidities (incidence rate ratio = 1.4, P = 0.0097). Switching to fingolimod was associated with a 64% reduction of the adjusted-risk for relapse in comparison with switching to interferon beta/glatiramer acetate (incidence rate ratio = 0.36, P < 0.0001). Secondly, patients who switched to fingolimod or to interferon beta/glatiramer acetate were propensity score-matched on a 1-to-1 basis at the switching date. In the propensity score-matched sample a Poisson model showed a significant lower incidence of relapses in patients treated with fingolimod in comparison with those treated with interferon beta/glatiramer acetate (incidence rate ratio = 0.52, P = 0.0003) during a 12-month follow-up. The cumulative probability of a first relapse after the treatment switch was significantly lower in patients receiving fingolimod than in those receiving interferon beta/glatiramer acetate (P = 0.028). The robustness of this result was also confirmed by sensitivity analyses in subgroups with different wash-out durations (less or more than 3 months). Time to 3-month confirmed disability progression was not significantly different between the two groups (Hazard ratio = 0.58; P = 0.1931). Our results indicate a superiority of fingolimod in comparison to interferon beta/glatiramer acetate in controlling disease reactivation after natalizumab discontinuation in the real life setting., (© The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)
- Published
- 2015
- Full Text
- View/download PDF
50. The long-term effects of stillbirth on women with and without gestational diabetes: a population-based cohort study.
- Author
-
Pintaudi B, Lucisano G, Pellegrini F, D'Ettorre A, Lepore V, De Berardis G, Scardapane M, Di Vieste G, Rossi MC, Sacco M, Tognoni G, and Nicolucci A
- Subjects
- Adult, Cardiovascular Diseases therapy, Case-Control Studies, Cohort Studies, Female, Follow-Up Studies, Hospitalization statistics & numerical data, Humans, Infant, Newborn, Pregnancy, Time Factors, Cardiovascular Diseases epidemiology, Diabetes Mellitus, Type 2 epidemiology, Diabetes, Gestational epidemiology, Stillbirth epidemiology
- Abstract
Aims/hypothesis: The aim of this study was to estimate the incidence of type 2 diabetes (primary objective) and hospitalisation for cardiovascular events (secondary objective) in women with previous gestational diabetes mellitus (GDM) and in those with normal glucose tolerance (NGT) in pregnancy, and to evaluate the role of stillbirth in differentiating the risks., Methods: This was a population-based cohort study using administrative data and involving 12 local health authorities. Women with GDM (n = 3,851) during the index period from 2002 to 2010 were propensity matched with women with NGT (n = 11,553). Information was collected on type 2 diabetes development and hospitalisation for cardiovascular events., Results: During a median follow-up of 5.4 years, the incidence rate per 1,000 person-years of type 2 diabetes was 2.1 (95% CI 1.8, 2.5) in women without GDM and 54.0 (95% CI 50.2, 58.0) among women with GDM and pregnancy at term (incidence rate ratio [IRR] 26.9; 95% CI 22.1, 32.7 compared with NGT and pregnancy at term). A history of stillbirth increased the risk of type 2 diabetes development by about twofold, irrespective of GDM status. No significant interaction between stillbirth and GDM on type 2 diabetes risk was found. GDM was associated with a significantly higher risk of cardiovascular events compared with NGT (IRR 2.4; 95% CI 1.5, 3.8)., Conclusions/interpretation: Pregnancy complicated by GDM and ending in stillbirth represents an important contributory factor in determining type 2 diabetes development. Women with GDM are at a high risk of future cardiovascular events. Women with pregnancy complicated by GDM and stillbirth deserve careful follow-up.
- Published
- 2015
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.