152 results on '"G Lucisano"'
Search Results
2. Arsenic metabolism and urothelial cancer risk: a systematic review and meta-analysis
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P Scampoli, Tommaso Staniscia, F Cedrone, F Meo, P Di Giovanni, G Lucisano, and G Di Martino
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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.
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- 2019
3. Investigating the ceramic processes by numerical approaches
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A. Valli, S. de Miranda, C. Fusi, G. Lucisano, Luca Patruno, Fusi C., Valli A., Lucisano G., Patruno L., and de Miranda S.
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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.
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- 2019
4. Healthcare resource use, direct and indirect costs of hypoglycemia in type 1 and type 2 diabetes, and nationwide projections. Results of the HYPOS-1 study
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C.B. Giorda, M.C. Rossi, O. Ozzello, S. Gentile, A. Aglialoro, A. Chiambretti, F. Baccetti, F.M. Gentile, F. Romeo, G. Lucisano, A. Nicolucci, R. Fornengo, A. Alessiato, A. Ozzello, L. Sciangula, N. Musacchio, G. Marelli, A. Corsi, V. Paciotti, R. Iannarelli, D. Antenucci, F. Chiaramonte, S. Leotta, V. Armentano, F. Mastinu, and D. Cucinotta
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medicine.medical_specialty ,endocrine system diseases ,Total cost ,Endocrinology, Diabetes and Metabolism ,Cost-Benefit Analysis ,Medicine (miscellaneous) ,030209 endocrinology & metabolism ,Type 2 diabetes ,Hypoglycemia ,03 medical and health sciences ,Indirect costs ,0302 clinical medicine ,Cost Savings ,Absenteeism ,medicine ,Humans ,Hypoglycemic Agents ,030212 general & internal medicine ,Hospital Costs ,Intensive care medicine ,Retrospective Studies ,Nutrition and Dietetics ,Cost–benefit analysis ,business.industry ,nutritional and metabolic diseases ,Type 2 Diabetes Mellitus ,Retrospective cohort study ,Health Care Costs ,Length of Stay ,medicine.disease ,Hospitalization ,Diabetes Mellitus, Type 1 ,Models, Economic ,Diabetes Mellitus, Type 2 ,Italy ,Emergency medicine ,Sick leave ,Health Resources ,Health Expenditures ,Sick Leave ,Cardiology and Cardiovascular Medicine ,business ,Emergency Service, Hospital ,Diabetes mellitus ,Direct and indirect costs ,Forecasting - Abstract
Background and aims To obtain an accurate picture of the total costs of hypoglycemia, including the indirect costs and comparing the differences between type 1 (T1DM) and type 2 diabetes mellitus (T2DM). Methods and results HYPOS-1 was a multicenter, retrospective cohort study which analyzed the data of 2229 consecutive patients seen at 18 diabetes clinics. Data on healthcare resource use and indirect costs by diabetes type were collected via a questionnaire. The domains of inpatient admission and hospital stay, work days lost, and third-party assistance were also explored. Resource utilization was reported as estimated incidence rates (IRs) of hypoglycemic episodes per 100 person-years and estimated costs as IRs per person-years. For every 100 patients with T1DM, 9 emergency room (ER) visits and 6 emergency medical service calls for hypoglycemia were required per year; for every 100 patients with T2DM, 3 ER visits and 1 inpatient admission were required, with over 3 nights spent in hospital. Hypoglycemia led to 58 work days per 100 person-years lost by the patient or a family member in T1DM versus 19 in T2DM. The costs in T1DM totaled €90.99 per person-year and €62.04 in T2DM. Direct and indirect costs making up the total differed by type of diabetes (60% indirect costs in T1DM versus 43% in T2DM). The total cost associated with hypoglycemia in Italy is estimated to be €107 million per year. Conclusions Indirect costs meaningfully contribute to the total costs associated with hypoglycemia. As compared with T1DM, T2DM requires fewer ER visits and incurs lower indirect costs but more frequent hospital use.
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- 2017
5. Renal histopathology
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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
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Transplantation ,Nephrology - Published
- 2013
6. Clinical nephrology - miscellaneous
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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
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Transplantation ,medicine.medical_specialty ,Nephrology ,business.industry ,medicine ,Clinical nephrology ,Intensive care medicine ,business - Published
- 2013
7. Predisctors of definite multiple sclerosis in patients with a pediatric onset first demyelinating clinical attack
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P. Iaffaldano, G. Lucisano, A. Ghezzi, G. Comi, V. Brescia Morra, F. Patti, LUGARESI, ALESSANDRA, C. Pozzilli, M. Amato, G. Salemi, E. Millefiorini, G. Lus, G. Zimatore, D. Maimone, G. Coniglio, R. Bergamaschi, M. Marrosu, G. Tedeschi, B. Ardito, G. Giuliani, C. Avolio, E. Montanari, M. Simone, L. Margari, V. Lepore, M. Trojano, P. Iaffaldano, G. Lucisano, A. Ghezzi, G. Comi, V. Brescia Morra, F. Patti, A. Lugaresi, C. Pozzilli, M. Amato, G. Salemi, E. Millefiorini, G. Lu, G. Zimatore, D. Maimone, G. Coniglio, R. Bergamaschi, M. Marrosu, G. Tedeschi, B. Ardito, G. Giuliani, C. Avolio, E. Montanari, M. Simone, L. Margari, V. Lepore, and M. Trojano
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multiple sclerosis, clinically isolated syndrome, pediatric, prognosis - Published
- 2014
8. The risk of relapse after natalizumab discontinuation could be reduced? Results from the Imedweb Registry
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P. Iaffaldano, V. Lepore, G. Lucisano, C. Pozzilli, V. Brescia Morra, A. Ghezzi, E. Millefiorini, F. Patti, LUGARESI, ALESSANDRA, G. Zimatore, M. Marrosu, M. Amato, A. Bertolotto, R. Bergamaschi, F. Granella, G. Coniglio, G. Tedeschi, D. Paolicelli, C. Tortorella, P. Sola, G. Lus, M. Ferrò, G. Iuliano, F. Corea, A. Protti, P. Cavalla, E. Montanari, G. Comi, M. Trojano, P. Iaffaldano, V. Lepore, G. Lucisano, C. Pozzilli, V. Brescia Morra, A. Ghezzi, E. Millefiorini, F. Patti, A. Lugaresi, G. Zimatore, M. Marrosu, M. Amato, A. Bertolotto, R. Bergamaschi, F. Granella, G. Coniglio, G. Tedeschi, D. Paolicelli, C. Tortorella, P. Sola, G. Lu, M. Ferrò, G. Iuliano, F. Corea, A. Protti, P. Cavalla, E. Montanari, G. Comi, and M. Trojano
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multiple sclerosis, database, natalizumab, treatment - Published
- 2014
9. Epidemiology and outcome research in CKD 5D
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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
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Transplantation ,medicine.medical_specialty ,Nephrology ,business.industry ,Epidemiology ,Medicine ,business ,Intensive care medicine ,Outcome (game theory) - Published
- 2012
10. Renal histopathology
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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
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Transplantation ,Nephrology - Published
- 2012
11. Erratum
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S. Seiler, S. M. Colbus, G. Lucisano, K. S. Rogacev, M. K. Gerhart, M. Ziegler, D. Fliser, and G. H. Heine
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Transplantation ,Nephrology - Published
- 2014
12. Clinical Activity and Safety of Anti-Programmed Death-1 (PD-1) (BMS-936558/MDX-1106/ONO-4538) in Patients (PTS) with Advanced Melanoma (MEL)
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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
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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
13. Progression & risk factors CKD 1-5 (1)
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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
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Transplantation ,medicine.medical_specialty ,Nephrology ,business.industry ,Internal medicine ,medicine ,business - Published
- 2011
14. General & clinical epidemiology CKD 1-5 (1)
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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
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Transplantation ,Nephrology - Published
- 2011
15. Acute kidney injury - Human studies
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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
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Transplantation ,Pathology ,medicine.medical_specialty ,Human studies ,Nephrology ,business.industry ,Acute kidney injury ,medicine ,medicine.disease ,business - Published
- 2011
16. Predictors of Bubble Formation and Type Obtained with Pneumatic Dissection During Deep Anterior Lamellar Keratoplasty in Keratoconus
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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
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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
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- 2020
17. Differential Activation of Signaling Pathways Involved in Cell Death, Survival and Inflammation by Radiocontrast Media in Human Renal Proximal Tubular Cells
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Michele Andreucci, Gaetano Lucisano, Mario Vitale, Giorgio Fuiano, Salvatore Salzano, Antonio Pisani, Teresa Faga, Bernardo Bertucci, Ashour Michael, Oscar Tamburrini, Massimo Sabbatini, M., Andreucci, G., Lucisano, T., Faga, B., Bertucci, O., Tamburrini, Pisani, Antonio, Sabbatini, Massimo, S., Salzano, M., Vitale, G., Fuiano, and A., Michael
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medicine.medical_specialty ,Cell Survival ,Pyridines ,Protein Kinase ,Pyridine ,p38 mitogen-activated protein kinases ,Protein Kinase Inhibitor ,Contrast Media ,Pharmacology ,Biology ,Toxicology ,Cell Line ,Proinflammatory cytokine ,Kidney Tubules, Proximal ,Internal medicine ,medicine ,Humans ,Renal cell ,Viability assay ,Phosphorylation ,Protein kinase A ,Imidazole ,Protein Kinase Inhibitors ,Protein kinase B ,Inflammation ,Toxicity ,Cell Death ,Kinase ,Imidazoles ,Endocrinology ,Signal transduction ,Protein Kinases ,Human ,Signal Transduction - Abstract
Radiocontrast media (RCM) are widely used in clinical medicine but may lead to radiocontrast-induced nephropathy (RCIN). The pathogenesis of acute renal failure secondary to RCM is not fully understood, but direct toxic effects are believed to be a major cause of RCIN. We have investigated the effect of different types of RCM on signaling pathways known to play a role in cell death, survival, and inflammation. HK-2 cells were incubated with sodium diatrizoate and iomeprol (IOM) at a concentration of 75 mg I/ml for 2 h. Both RCM caused an increase in phosphorylation of p38 mitogen-activated protein kinase (MAPK) (p38) and c-Jun N-terminal kinases (JNKs) and NF-κB (at Ser 276), with sodium diatrizoate having a more drastic effect. Although cell viability was reduced significantly by both RCM, in cells pretreated with IOM the cell viability recovered over a 22-h time period after removal of the RCM. However, viability of diatrizoate-treated cells rose at 5 h but then fell at 22 h after removal of the RCM. The decrease in cell viability in diatrizoate-treated cells corresponded with an increase in phosphorylation of JNKs, p38, and NF-κB and a decrease in phosphorylation of Akt, signal transducer and activator of transcription 3, and forkhead box O3a, as well as poly (ADP-ribose) polymerase and caspase-3 cleavage. The recovery in viability of IOM-treated cells corresponded most notably with an increase in STAT3 phosphorylation and induction of Pim-1 kinase. There was also an increase in interleukin-8 release by diatrizoate-treated cells indicating the possibility of proinflammatory effects of RCM. A knowledge of the signaling pathways by which RCM exert their cytotoxic actions may help in finding future therapies for RCIN.
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- 2010
18. Disability trajectories by progression independent of relapse activity status differ in pediatric, adult and late-onset multiple sclerosis.
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Simone M, Lucisano G, Guerra T, Paolicelli D, Rocca MA, Brescia Morra V, Patti F, Annovazzi P, Gasperini C, De Luca G, Ferraro D, Margari L, Granella F, Pozzilli C, Romano S, Perini P, Bergamaschi R, Coniglio MG, Lus G, Vianello M, Lugaresi A, Portaccio E, Filippi M, Amato MP, and Iaffaldano P
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- Humans, Male, Female, Adult, Child, Young Adult, Adolescent, Recurrence, Middle Aged, Longitudinal Studies, Italy, Follow-Up Studies, Registries, Multiple Sclerosis, Relapsing-Remitting physiopathology, Disease Progression, Age of Onset, Disability Evaluation, Multiple Sclerosis physiopathology
- Abstract
Background: To compare Expanded Disability Status Scale (EDSS) trajectories over time between Multiple Sclerosis (MS) groups with pediatric (POMS), adult (AOMS) and late (LOMS) onset, and between patients with and without progression independent of relapse activity (PIRA)., Methods: Patients with a first visit within 1 year from onset, ≥ 5-year follow-up and ≥ 1 visit every 6 months were selected from the Italian MS Register. Adjusted disability trajectories were assessed by longitudinal models for repeated measures. Comparisons between groups and between patients with and without PIRA in subgroups were performed by evaluating the yearly differences of mean EDSS score changes versus baseline (delta-EDSS). A first CDA event was defined as a 6-months confirmed disability increase from study baseline, measured by EDSS (increase ≥ 1.5 points with baseline EDSS = 0; ≥ 1.0 with baseline EDSS score ≤ 5.0 and ≥ 0.5 point with baseline EDSS > 5.5). PIRA was defined as a CDA event occurring more than 90 days after and more than 30 days before the onset of a relapse., Results: 3777 MS patients (268 POMS, 3282 AOMS, 227 LOMS) were included. The slope of disability trajectories significantly diverged in AOMS vs POMS starting from the second year of follow-up (Year 2: delta2-EDSS 0.18 (0.05; 0.31), p = 0.0054) and then mean delta2-EDSS gradually increased up to 0.23 (0.07; 0.39, p = 0.004) at year 5. Patients with PIRA had significant (p < 0.0001) steeper increase in EDSS scores than those without PIRA in all groups, although in POMS, the disability trajectories began to diverge later and at a lesser extent with delta-EDSS score of 0.48 vs 0.83 in AOMS and 1.57 in LOMS, at 3 years after the first PIRA., Conclusions: Age is relevant in determining disability progression in MS. POMS shows a less steep increase in EDSS scores over time than older patients. The effect of PIRA in accelerating EDSS progression is less pronounced in POMS than in AOMS and LOMS., (© 2024. The Author(s).)
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- 2024
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19. Comparative outcomes of DSA positive, crossmatch negative living donor kidney transplants versus remaining on the waitlist for an HLA compatible deceased donor.
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Santos E, Lucisano G, Dor FJMF, and Willicombe M
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- Humans, Male, Female, Middle Aged, Adult, Treatment Outcome, Histocompatibility, Tissue Donors, Kidney Transplantation, Living Donors, Waiting Lists, Isoantibodies blood, Isoantibodies immunology, HLA Antigens immunology, Histocompatibility Testing, Graft Rejection immunology, Graft Survival immunology
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Introduction: The clinical relevance of preformed donor specific antibodies in the setting of a negative crossmatch (DSA + XM-) remains controversial. In this study we investigate the outcomes of patients with a DSA + XM- living donor (LDi) who proceeded with an HLA-incompatible (HLAi) transplant compared with those who waited for an HLA-compatible deceased donor (DDc)., Materials and Methods: We investigated 359 patients on the transplant waiting list who had at least one potential HLAi living donor, from which 203 DSA + XM- pairs were identified and outcomes analysed., Results: Out of 203 patients, 96 (47.3%) received a LD transplant: 52/96 (54.2%) a LDi, and 44/96 (45.8%) an alternative compatible LD. In addition, 107 patients out of 203(52.7%) waited for a DDc, of which 47(43.9%) were subsequently transplanted. Our adjusted analysis showed that the LDi transplantation did not offer a superior patient survival over waiting for a DDc transplant. For those transplanted, there was no difference in patient (p = 0.065) or death censored allograft survival (p = 0.37) between DDc and LDi recipients. However, there was a higher incidence of acute allograft rejection (p = 0.043) and antibody-mediated rejection (p = 0.005) in the LDi group. Having a high pre-transplant calculated reaction frequency and preformed DSA to both class I and class II antigens were associated with inferior outcomes in the LDi transplants., Conclusions: Given the lack of difference in allograft survival between LDi and DDc transplants, in the absence of an alternative compatible living donor, proceeding with a LDi should be supported despite a higher rejection risk, providing individual risk assessment and shared decision making is undertaken., Competing Interests: Declaration of competing interest The authors have no disclosures to declare related to this manuscript., (Copyright © 2024. Published by Elsevier B.V.)
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- 2024
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20. Prevalence and clinical determinants of rapid eGFR decline among patients with newly diagnosed type 2 diabetes.
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Russo GT, Giandalia A, Lucisano G, Rossi MC, Piscitelli P, Pontremoli R, Viazzi F, Rocca A, Manicardi V, Di Cianni G, Candido R, Nicolucci A, and De Cosmo S
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Background: Diabetic kidney disease is the most common cause of end-stage kidney disease (ESKD) in the western world. Rapid estimated glomerular filtration rate (eGFR) decline is an independent predictor of ESKD and death in the general population and in subjects with type 2 diabetes mellitus (T2D)., Aim: We investigated in a large sample of subjects with newly diagnosed T2D the prevalence and clinical determinants of fast eGFR decline, taking advantage from the dataset of the Associazione Medici Diabetologi (AMD) Annals initiative., Methods: The eGFR trajectories were evaluated by applying a linear mixed model for repeated measures (LMMRM) and rapid eGFR decline defined as an eGFR decline greater than 5 mL/min/1.73 m2 per year at 3 years., Results: Among 105,163 (57.7% M) subjects with newly diagnosed T2D, 13,587 (12.9 %) subjects showed a rapid eGFR loss. The independent significant predictors were age, female gender, HbA1c, smoking, high baseline eGFR, albuminuria and retinopathy., Conclusion: Our study demonstrates that a significant percentage of newly diagnosed T2D subjects have a rapid eGFR decline. Given the association between dynamic changes in eGFR and the risk of ESKD or death, we suggest to include this variable in the definition of CKD., (Copyright © 2024. Published by Elsevier B.V.)
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- 2024
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21. A comparison of natalizumab and ocrelizumab on disease progression in multiple sclerosis.
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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
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- 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.)
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- 2024
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22. Severe Hypertriglyceridemia in Patients with Type 2 Diabetes Mellitus Participating in the AMD Annals Initiative.
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Russo GT, Manicardi V, Rocca A, Nicolucci A, Giandalia A, Lucisano G, Rossi MC, Graziano G, Di Bartolo P, De Cosmo S, Candido R, and Di Cianni G
- Abstract
Background: Familial chylomicronemia syndrome (FCS) is a rare inherited condition due to lipoprotein lipase deficiency, characterized by hyperchylomicronemia and severe hypertriglyceridemia. Diagnosis is often delayed, thus increasing the risk of acute pancreatitis and hospitalization. Hypertriglyceridemia is a common finding in patients with type 2 diabetes (T2D), who may harbor FCS among the most severe forms. Aim of the Study: We investigated the prevalence and clinical characteristics associated with severe hypertriglyceridemia in a range indicative of FCS, in a large population of subjects with T2D. Methods: Within the large population of the AMD Annals Initiative, patients with T2D with a lipid profile suggestive of FCS [triglycerides >880 mg/dL and/or high-density lipoprotein (HDL)-cholesterol <22 mg/dL or non-HDL-cholesterol ≤70 mg/dL] and their clinical features have been identified. Results: Overall, 8592 patients had triglyceride values >880 mg/dL in a single examination, 613 in two examinations, and 34 in three or more measurements. Patients with high triglyceride levels were mostly male (80%), with a relatively young age (54 years), short duration of diabetes (6.3 years), and elevated hemoglobin A1c (HbA1c) levels (9.4%). By stratifying this group of patients according to the severity of hypertriglyceridemia, more severe hypertriglyceridemia (triglyceride levels ≥2000 mg/dL) was associated with an even younger age (52 vs. 54 years), even higher mean HbA1c values (10.0% vs. 9.4%), and significantly higher HDL-cholesterol levels (37.9 vs. 32.4 mg/dL; P < 0.0001). Patients with persistently elevated triglyceride levels ( n = 34), on three measurements, had a younger age; lower body mass index, HbA1c, and HDL-cholesterol levels; more frequent use of fibrates and insulin; and a higher prevalence of major cardiovascular events. Conclusions: Severe hypertriglyceridemia is a frequent condition in outpatients with T2D participating in the AMD Annals Initiative, and it is associated with male sex, young age, short disease duration, and a worse glycemic profile. Among patients with persistent severe hypertriglyceridemia, hidden FCS may be present.
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- 2024
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23. Temporal trends in the starting of insulin therapy in type 2 diabetes in Italy: data from the AMD Annals initiative.
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Giandalia A, Nicolucci A, Modugno M, Lucisano G, Rossi MC, Manicardi V, Rocca A, Di Cianni G, Di Bartolo P, Candido R, Cucinotta D, and Russo GT
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- Humans, Female, Male, Italy epidemiology, Middle Aged, Aged, Glycated Hemoglobin analysis, Follow-Up Studies, Time Factors, Diabetes Mellitus, Type 2 drug therapy, Diabetes Mellitus, Type 2 blood, Diabetes Mellitus, Type 2 epidemiology, Hypoglycemic Agents administration & dosage, Hypoglycemic Agents therapeutic use, Insulin administration & dosage, Insulin therapeutic use, Blood Glucose analysis, Blood Glucose metabolism, Blood Glucose drug effects
- Abstract
Aims: Opportunities and needs for starting insulin therapy in Type 2 diabetes (T2D) have changed overtime. We evaluated clinical characteristics of T2D subjects undergoing the first insulin prescription during a 15-year-observation period in the large cohort of the AMD Annals Initiative in Italy., Methods: Data on clinical and laboratory variables, complications and concomitant therapies and the effects on glucose control after 12 months were evaluated in T2D patients starting basal insulin as add-on to oral/non-insulin injectable agents, and in those starting fast-acting in add-on to basal insulin therapy in three 5-year periods (2005-2019)., Results: We evaluated data from 171.688 T2D subjects who intensified therapy with basal insulin and 137.225 T2D patients who started fast-acting insulin. Overall, intensification with insulin occurred progressively earlier over time in subjects with shorter disease duration. Moreover, the percentage of subjects with HbA1c levels > 8% at the time of basal insulin initiation progressively decreased. The same trend was observed for fast-acting formulations. Clinical characteristics of subjects starting insulin did not change in the three study-periods, although all major risk factors improved overtime. After 12 months from the starting of basal or fast-acting insulin therapy, mean HbA1c levels decreased in all the three investigated time-periods, although mean HbA1c levels remained above the recommended target., Conclusions: In this large cohort of T2D subjects, a progressively earlier start of insulin treatment was observed during a long observation period, suggesting a more proactive prescriptive approach. However, after 12 months from insulin prescription, in many patients, HbA1c levels were still out-of-target., (© 2024. The Author(s).)
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- 2024
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24. The quality of care in type 1 and type 2 diabetes - A 2023 update of the AMD Annals initiative.
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Russo G, De Cosmo S, Di Bartolo P, Lucisano G, Manicardi V, Nicolucci A, Rocca A, Rossi MC, Di Cianni G, and Candido R
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- Humans, Aged, Middle Aged, Female, Male, Italy epidemiology, Glycated Hemoglobin analysis, Glycated Hemoglobin metabolism, Adult, Aged, 80 and over, Diabetes Mellitus, Type 2 therapy, Diabetes Mellitus, Type 2 epidemiology, Diabetes Mellitus, Type 1 therapy, Diabetes Mellitus, Type 1 epidemiology, Quality of Health Care
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Aims: An initiative of continuous monitoring of the quality of diabetes care, promoted by the Association of Medical Diabetologists, is in place in Italy since 2006 (AMD Annals). The initiative was effective in improving quality of care indicators, assessed periodically through standardized measures. Here, we show the 2023 AMD Annals data on type 2 (T2D) and type 1 (T1D) diabetes., Methods: A network of over 1/3 of diabetes centers in Italy periodically extracts anonymous data from electronic medical records, using a standardized software. Process, treatment and outcome indicators, and a validated score of overall care, the Q-score, were evaluated., Results: 296 centers provided data on 573,164 T2D (mean age 69.7 ± 11.2 years) and 42,611 T1D subjects (mean age 48.6 ± 16.9 years). A HbA1c value ≤ 7.0 % was documented in 56.3 % of patients with T2D and 35.9 % of those with T1D. Only 6.6 % of T2D patients and 3.5 % of those with T1D reached the composite outcome of HbA1c ≤ 7.0 % + LDL-C < 70 mg/dl + BP < 130/80 mmHg. Notably, only 2.8 % and 3.2 % of T2D and T1D patients, respectively, showed a Q score < 15, which correlates with an 80 % higher risk of incident CVD events compared to scores > 25., Conclusions: We documented an overall good quality of care in both T1D and T2D subjects. However, the failure to achieve the targets of the main risk factors, especially if combined, in a still too large proportion of patients testify the difficulty to apply the more and more stringent indications recommended by guidelines in the everyday clinical practice., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)
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- 2024
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25. Big Multiple Sclerosis Data network: an international registry research network.
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Glaser A, Butzkueven H, van der Walt A, Gray O, Spelman T, Zhu C, Trojano M, Iaffaldano P, Battaglia MA, Lucisano G, Vukusic S, Vukusic I, Casey R, Horakova D, Drahota J, Magyari M, Joensen H, Pontieri L, Elberling F, Klyve P, Mouresan EF, Forsberg L, and Hillert J
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- Humans, Big Data, Information Dissemination, International Cooperation, Multiple Sclerosis epidemiology, Multiple Sclerosis therapy, Registries
- Abstract
Background: The Big Multiple Sclerosis Data (BMSD) network ( https://bigmsdata.org ) was initiated in 2014 and includes the national multiple sclerosis (MS) registries of the Czech Republic, Denmark, France, Italy, and Sweden as well as the international MSBase registry. BMSD has addressed the ethical, legal, technical, and governance-related challenges for data sharing and so far, published three scientific papers on pooled datasets as proof of concept for its collaborative design., Data Collection: Although BMSD registries operate independently on different platforms, similarities in variables, definitions and data structure allow joint analysis of data. Certain coordinated modifications in how the registries collect adverse event data have been implemented after BMSD consensus decisions, showing the ability to develop together., Data Management: Scientific projects can be proposed by external sponsors via the coordinating centre and each registry decides independently on participation, respecting its governance structure. Research datasets are established in a project-to-project fashion and a project-specific data model is developed, based on a unifying core data model. To overcome challenges in data sharing, BMSD has developed procedures for federated data analysis., Future Perspectives: Presently, BMSD is seeking a qualification opinion from the European Medicines Agency (EMA) to conduct post-authorization safety studies (PASS) and aims to pursue a qualification opinion also for post-authorization effectiveness studies (PAES). BMSD aspires to promote the advancement of real-world evidence research in the MS field., (© 2024. The Author(s).)
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- 2024
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26. Corrigendum to "The AMD ANNALS: A continuous initiative for the improvement of type 2 diabetes care" [Diabetes Res. and Clin. Pract. 199 (2023) 110672].
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Russo G, Di Bartolo P, Candido R, Lucisano G, Manicardi V, Giandalia A, Nicolucci A, Rocca A, Rossi MC, and Di Cianni G
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- 2024
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27. Evaluation of drivers of treatment switch in relapsing multiple sclerosis: a study from the Italian MS Registry.
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Iaffaldano P, Lucisano G, Guerra T, Patti F, Cocco E, De Luca G, Brescia Morra V, Pozzilli C, Zaffaroni M, Ferraro D, Gasperini C, Salemi G, Bergamaschi R, Lus G, Inglese M, Romano S, Bellantonio P, Di Monte E, Maniscalco GT, Conte A, Lugaresi A, Vianello M, Torri Clerici VLA, Di Sapio A, Pesci I, Granella F, Totaro R, Marfia GA, Danni MC, Cavalla P, Valentino P, Aguglia U, Montepietra S, Ferraro E, Protti A, Spitaleri D, Avolio C, De Riz M, Maimone D, Cavaletti G, Gazzola P, Tedeschi G, Sessa M, Rovaris M, Di Palma F, Gatto M, Cargnelutti D, De Robertis F, Logullo FO, Rini A, Meucci G, Ardito B, Banfi P, Nasuelli D, Paolicelli D, Rocca MA, Portaccio E, Chisari CG, Fenu G, Onofrj M, Carotenuto A, Ruggieri S, Tortorella C, Ragonese P, Nica M, Amato MP, Filippi M, and Trojano M
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- Humans, Immunologic Factors therapeutic use, Cross-Sectional Studies, Recurrence, Italy epidemiology, Multiple Sclerosis drug therapy, Multiple Sclerosis, Relapsing-Remitting drug therapy, Multiple Sclerosis, Relapsing-Remitting epidemiology, Multiple Sclerosis, Relapsing-Remitting chemically induced, Multiple Sclerosis, Chronic Progressive drug therapy
- Abstract
Background: Active relapsing-remitting (RR) and secondary progressive (SP) multiple sclerosis (MS) are currently defined as "relapsing MS" (RMS). The aim of this cross-sectional study was to assess drivers of treatment switches due to clinical relapses in a population of RMS patients collected in the Italian MS and Related Disorders Register (I-MS&RD)., Methods: RRMS and SPMS patients with at least one relapse in a time window of 2 years before of data extraction were defined as RMS. Factors associated with disease-modifying therapy (DMT) switching due to clinical activity were assessed through multivariable logistic regression models in which treatment exposure was included as the last recorded DMT and the last DMT's class [moderate-efficacy (ME), high-efficacy (HE) DMTs and anti-CD20 drugs]., Results: A cohort of 4739 RMS patients (4161 RRMS, 578 SPMS) was extracted from the I-MS&RD. A total of 2694 patients switching DMTs due to relapses were identified. Switchers were significantly (p < 0.0001) younger, less disabled, more frequently affected by an RR disease course in comparison to non-switcher patients. The multivariable logistic regression models showed that Alemtuzumab (OR 0.08, 95% CI 0.02-0.37), Natalizumab (0.48, 0.30-0.76), Ocrelizumab (0.1, 0.02-0.45) and Rituximab (0.23, 0.06-0.82) exposure was a protective factor against treatment switch due to relapses. Moreover, the use of HE DMTs (0.43, 0.31-0.59), especially anti-CD20 drugs (0.14, 0.05-0.37), resulted to be a protective factor against treatment switch due to relapses in comparison with ME DMTs., Conclusions: More than 50% of RMS switched therapy due to disease activity. HE DMTs, especially anti-CD20 drugs, significantly reduce the risk of treatment switch., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)
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- 2024
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28. Delivering Person-Centered Peritoneal Dialysis.
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Corbett RW, Beckwith H, Lucisano G, and Brown EA
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- Humans, Renal Dialysis, Outcome Assessment, Health Care, Patients, Peritoneal Dialysis
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Peritoneal dialysis (PD) enables people to have a home-based therapy, permitting greater autonomy for individuals along with enhanced treatment satisfaction compared with in-center dialysis care. The burden of treatment on PD, however, remains considerable and underpins the need for person-centered care. This reflects the need to address the patient as a person with needs and preferences beyond just the medical perspective. Shared decision making is central to the recent International Society for Peritoneal Dialysis recommendations for prescribing PD, balancing the potential benefits of PD on patient well-being with the burden associated with treatment. This review considers the role of high-quality goal-directed prescribing, incremental dialysis, and remote patient monitoring in reducing the burden of dialysis, including an approach to implementing incremental PD. Although patient-related outcomes are important in assessing the response to treatment and, particularly life participation, the corollary of dialysis burden, there are no clear routes to the clinical implementation of patient-related outcome measures. Delivering person-centered care is dependent on treating people both as individuals and as equal partners in their care., (Copyright © 2023 by the American Society of Nephrology.)
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- 2024
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29. Performance of Tandem Control IQ During Outdoor Physical Activity in Children and Adolescents with Type 1 Diabetes.
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Mameli C, Rigamonti A, Felappi B, Nicolucci A, Lucisano G, Baresi S, Florini G, Macedoni M, Petitti A, Hajro A, Tortu G, Pistone C, Guerraggio LP, Zampolli M, Zuccotti G, and Bonfanti R
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- Male, Child, Humans, Adolescent, Hypoglycemic Agents therapeutic use, Blood Glucose, Insulin Infusion Systems, Blood Glucose Self-Monitoring, Insulin therapeutic use, Exercise, Diabetes Mellitus, Type 1 drug therapy, Hypoglycemia
- Abstract
Background: Few data are available in children with type 1 diabetes using automated insulin delivery systems during physical activity (PA). We evaluated the time in range (TIR) during 2-h of outdoor PA in children using t:slim X2 with Control-IQ
® technology. Materials and Methods: Caucasian children and adolescents, aged 9-18 years using t:slim X2 with Control-IQ technology were recruited during a local sporting event. Participants were divided into two groups: Group A practiced endurance activities for 60 min (1000-meter run, a jump circuit) and then power activities for 60 min (80-meter run, long jump); Group B practiced power activities for 60 min and then followed by endurance activities for 60 min. Ninety minutes before the PA, participants had lunch and self-administered a low-dose insulin, reduced by 50% compared to their regularly calculated meal dose per pump calculator. DexcomG6® data were downloaded. Results: Twenty-six children were recruited, 2 refused PA. Participants were divided as follows: 13 in Group A (7 males, median age 14.6 years) and 11 in Group B (8 males, median age 13.5 year). The mean glucose level when PA started was similar between groups ( P = 0.06). Subjects in Group B showed a higher TIR than those in Group A ([50.4%, 95% confidence interval, CI: 33.8-75] vs. 39.6% [95% CI: 26.9-58.3], respectively [ P = 0.39]). A significantly better TIR in Group B (53.8%, 95% CI: 30.2-96.1) compared to Group A (17.4%, 95% CI: 7.3-41.7, P = 0.02) was recorded during the first session. During the second session, TIR increased in both groups. There were no episodes of serious or severe hypoglycemia. Conclusions: No serious or severe hypoglycemic episodes were recorded during PA performed 90 min after lunch. Future studies using t:slim X2 with Control-IQ technology are necessary.- Published
- 2024
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30. Multiple Sclerosis Progression and Relapse Activity in Children.
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Iaffaldano P, Portaccio E, Lucisano G, Simone M, Manni A, Guerra T, Paolicelli D, Betti M, De Meo E, Pastò L, Razzolini L, Rocca MA, Ferrè L, Brescia Morra V, Patti F, Zaffaroni M, Gasperini C, De Luca G, Ferraro D, Granella F, Pozzilli C, Romano S, Gallo P, Bergamaschi R, Coniglio MG, Lus G, Vianello M, Banfi P, Lugaresi A, Totaro R, Spitaleri D, Cocco E, Di Palma F, Maimone D, Valentino P, Torri Clerici V, Protti A, Maniscalco GT, Salemi G, Pesci I, Aguglia U, Lepore V, Filippi M, Trojano M, and Amato MP
- Subjects
- Adult, Child, Humans, Female, Male, Cohort Studies, Disease Progression, Chronic Disease, Recurrence, Multiple Sclerosis diagnostic imaging, Multiple Sclerosis epidemiology, Multiple Sclerosis, Relapsing-Remitting diagnostic imaging, Multiple Sclerosis, Relapsing-Remitting drug therapy, Multiple Sclerosis, Relapsing-Remitting epidemiology
- Abstract
Importance: Although up to 20% of patients with multiple sclerosis (MS) experience onset before 18 years of age, it has been suggested that people with pediatric-onset MS (POMS) are protected against disability because of greater capacity for repair., Objective: To assess the incidence of and factors associated with progression independent of relapse activity (PIRA) and relapse-associated worsening (RAW) in POMS compared with typical adult-onset MS (AOMS) and late-onset MS (LOMS)., Design, Setting, and Participants: This cohort study on prospectively acquired data from the Italian MS Register was performed from June 1, 2000, to September 30, 2021. At the time of data extraction, longitudinal data from 73 564 patients from 120 MS centers were available in the register., Main Outcomes and Measures: The main outcomes included age-related cumulative incidence and adjusted hazard ratios (HRs) for PIRA and RAW and associated factors., Exposures: Clinical and magnetic resonance imaging features, time receiving disease-modifying therapy (DMT), and time to first DMT., Results: After applying the inclusion and exclusion criteria, the study assessed 16 130 patients with MS (median [IQR] age at onset, 28.7 [22.8-36.2 years]; 68.3% female). Compared with AOMS and LOMS, patients with POMS had less disability, exhibited more active disease, and were exposed to DMT for a longer period. A first 48-week-confirmed PIRA occurred in 7176 patients (44.5%): 558 patients with POMS (40.4%), 6258 patients with AOMS (44.3%), and 360 patients with LOMS (56.8%) (P < .001). Factors associated with PIRA were older age at onset (AOMS vs POMS HR, 1.42; 95% CI, 1.30-1.55; LOMS vs POMS HR, 2.98; 95% CI, 2.60-3.41; P < .001), longer disease duration (HR, 1.04; 95% CI, 1.04-1.05; P < .001), and shorter DMT exposure (HR, 0.69; 95% CI, 0.64-0.74; P < .001). The incidence of PIRA was 1.3% at 20 years of age, but it rapidly increased approximately 7 times between 21 and 30 years of age (9.0%) and nearly doubled for each age decade from 40 to 70 years (21.6% at 40 years, 39.0% at 50 years, 61.0% at 60 years, and 78.7% at 70 years). The cumulative incidence of RAW events followed a similar trend from 20 to 60 years (0.5% at 20 years, 3.5% at 30 years, 7.8% at 40 years, 14.4% at 50 years, and 24.1% at 60 years); no further increase was found at 70 years (27.7%). Delayed DMT initiation was associated with higher risk of PIRA (HR, 1.16; 95% CI, 1.00-1.34; P = .04) and RAW (HR, 1.75; 95% CI, 1.28-2.39; P = .001)., Conclusions and Relevance: PIRA can occur at any age, and although pediatric onset is not fully protective against progression, this study's findings suggest that patients with pediatric onset are less likely to exhibit PIRA over a decade of follow-up. However, these data also reinforce the benefit for DMT initiation in patients with POMS, as treatment was associated with reduced occurrence of both PIRA and RAW regardless of age at onset.
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- 2024
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31. ANGPTL3 Deficiency and Risk of Hepatic Steatosis.
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D'Erasmo L, Di Martino M, Neufeld T, Fraum TJ, Kang CJ, Burks KH, Di Costanzo A, Minicocci I, Bini S, Maranghi M, Pigna G, Labbadia G, Zheng J, Fierro D, Montali A, Ceci F, Catalano C, Davidson NO, Lucisano G, Nicolucci A, Arca M, and Stitziel NO
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- Humans, Angiopoietin-like Proteins genetics, Triglycerides, Cholesterol, LDL, Angiopoietin-Like Protein 3
- Abstract
Background: ANGPTL3 (angiopoietin-like 3) is a therapeutic target for reducing plasma levels of triglycerides and low-density lipoprotein cholesterol. A recent trial with vupanorsen, an antisense oligonucleotide targeting hepatic production of ANGPTL3, reported a dose-dependent increase in hepatic fat. It is unclear whether this adverse effect is due to an on-target effect of inhibiting hepatic ANGPTL3., Methods: We recruited participants with ANGPTL3 deficiency related to ANGPTL3 loss-of-function (LoF) mutations, along with wild-type (WT) participants from 2 previously characterized cohorts located in Campodimele, Italy, and St. Louis, MO. Magnetic resonance spectroscopy and magnetic resonance proton density fat fraction were performed to measure hepatic fat fraction and the distribution of extrahepatic fat. To estimate the causal relationship between ANGPTL3 and hepatic fat, we generated a genetic instrument of plasma ANGPTL3 levels as a surrogate for hepatic protein synthesis and performed Mendelian randomization analyses with hepatic fat in the UK Biobank study., Results: We recruited participants with complete (n=6) or partial (n=32) ANGPTL3 deficiency related to ANGPTL3 LoF mutations, as well as WT participants (n=92) without LoF mutations. Participants with ANGPTL3 deficiency exhibited significantly lower total cholesterol (complete deficiency, 78.5 mg/dL; partial deficiency, 172 mg/dL; WT, 188 mg/dL; P <0.05 for both deficiency groups compared with WT), along with plasma triglycerides (complete deficiency, 26 mg/dL; partial deficiency, 79 mg/dL; WT, 88 mg/dL; P <0.05 for both deficiency groups compared with WT) without any significant difference in hepatic fat (complete deficiency, 9.8%; partial deficiency, 10.1%; WT, 9.9%; P >0.05 for both deficiency groups compared with WT) or severity of hepatic steatosis as assessed by magnetic resonance imaging. In addition, ANGPTL3 deficiency did not alter the distribution of extrahepatic fat. Results from Mendelian randomization analyses in 36 703 participants from the UK Biobank demonstrated that genetically determined ANGPTL3 plasma protein levels were causally associated with low-density lipoprotein cholesterol ( P =1.7×10
-17 ) and triglycerides ( P =3.2×10-18 ) but not with hepatic fat ( P =0.22)., Conclusions: ANGPTL3 deficiency related to LoF mutations in ANGPTL3 , as well as genetically determined reduction of plasma ANGPTL3 levels, is not associated with hepatic steatosis. Therapeutic approaches to inhibit ANGPTL3 production in hepatocytes are not necessarily expected to result in the increased risk for hepatic steatosis that was observed with vupanorsen., Competing Interests: Disclosures Dr Stitziel has received investigator-initiated research funding from Regeneron Pharmaceuticals related to ANGPTL3 (angiopoietin-like 3). Dr Arca has received research grant support from Amryt Pharmaceutical, Amgen, IONIS, Akcea Therapeutics, Daichi-Sankio, Novartis, Pfizer, and Sanofi; has served as a consultant for Amgen, Akcea Therapeutics, Daichi-Sankio, Novartis, Pfizer, Sanofi, and Alfasigma, and has received lecturing fees from Amgen, Amryth Pharmaceutical, Daichi-Sankio, Regeneron, Sanofi, and AlfaSigma. Dr D’Erasmo has received personal fees for public speaking or consultancy or grant support from Amryt Pharmaceuticals, Akcea Therapeutics, Pfizer, SOBI, Amgen, and Sanofi.- Published
- 2023
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32. The Burden of Obesity in Type 1 Diabetic Subjects: A Sex-specific Analysis From the AMD Annals Initiative.
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Giandalia A, Russo GT, Ruggeri P, Giancaterini A, Brun E, Cristofaro M, Bogazzi A, Rossi MC, Lucisano G, Rocca A, Manicardi V, Bartolo PD, Cianni GD, Giuliani C, and Napoli A
- Subjects
- Adult, Humans, Female, Male, Middle Aged, Aged, Obesity complications, Obesity epidemiology, Risk Factors, Body Mass Index, Prevalence, Diabetes Mellitus, Type 1 complications, Diabetes Mellitus, Type 1 epidemiology, Diabetes Mellitus, Type 1 drug therapy, Diabetes Mellitus, Type 2, Cardiovascular Diseases etiology, Cardiovascular Diseases complications, Obesity, Morbid complications
- Abstract
Objective: Obesity is a growing emergency in type 1 diabetes (T1D). Sex differences in obesity prevalence and its clinical consequences in adult T1D subjects have been poorly investigated. The aim of this study was to investigate the prevalence of obesity and severe obesity, clinical correlates, and potential sex differences in a large cohort of T1D subjects participating to the AMD (Associazione Medici Diabetologi) Annals Initiative in Italy., Research Design and Methods: The prevalence of obesity [body mass index(BMI) ≥30 kg/m2] and severe obesity (BMI ≥ 35 kg/m2) according to sex and age, as well as obesity-associated clinical variables, long-term diabetes complications, pharmacological treatment, process indicators and outcomes, and overall quality of care (Q-score) were evaluated in 37 436 T1D subjects (45.3% women) attending 282 Italian diabetes clinics during 2019., Results: Overall, the prevalence of obesity was similar in the 2 sexes (13.0% in men and 13.9% in women; mean age 50 years), and it increased with age, affecting 1 out of 6 subjects ages >65 years. Only severe obesity (BMI >35 kg/m2) was more prevalent among women, who showed a 45% higher risk of severe obesity, compared with men at multivariate analysis. Cardiovascular disease risk factors (lipid profile, glucose, and blood pressure control), and the overall quality of diabetes care were worse in obese subjects, with no major sex-related differences. Also, micro- and macrovascular complications were more frequent among obese than nonobese T1D men and women., Conclusions: Obesity is a frequent finding in T1D adult subjects, and it is associated with a higher burden of cardiovascular disease risk factors, micro- and macrovascular complications, and a lower quality of care, with no major sex differences. T1D women are at higher risk of severe obesity., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society.)
- Published
- 2023
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33. The legacy effect of hyperglycemia and early use of SGLT-2 inhibitors: a cohort study with newly-diagnosed people with type 2 diabetes.
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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).)
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- 2023
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34. Risk factor variability and cardiovascular risk among patients with diabetes: a nationwide observational study.
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Ceriello A, Lucisano G, Prattichizzo F, La Grotta R, Franzén S, Gudbjörnsdottir S, Eliasson B, and Nicolucci A
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- Humans, Risk Factors, Glycated Hemoglobin, Heart Disease Risk Factors, Cholesterol, Body Weight, Diabetes Mellitus, Type 2 diagnosis, Diabetes Mellitus, Type 2 epidemiology, Cardiovascular Diseases diagnosis, Cardiovascular Diseases epidemiology
- Abstract
Aims: Cardiovascular risk factor control fluctuates, tends to change over time, and is potentially impacted by multifactorial interactions. Currently, the presence of risk factors, rather than their variability or interplay with one another, is taken into account to define the population at risk. The association between variability of risk factors and cardiovascular morbidity and mortality risk among patients with Type 2 diabetes mellitus (T2DM) remains debatable., Methods and Results: Using registry-derived data, we identified 29 471 people with T2DM, without cardiovascular disease (CVD) at baseline, and with at least five measurements of risk factors. Variability for each variable was expressed as quartiles of the standard deviation during 3 years (exposure). The incidence of myocardial infarction, stroke, and all-cause mortality was assessed during 4.80 (2.40-6.70) years following the exposure phase. The association between the measures of variability and the risk of developing the outcome was investigated through multivariable Cox proportional-hazards regression analysis with stepwise variable selection. Then, the recursive partitioning and amalgamation (RECPAM) algorithm was used to explore the interaction among the variability of risk factors associated with the outcome. An association between the variability of HbA1c, body weight, systolic blood pressure, and total cholesterol with the outcome considered was found. Among the six classes of risk identified by RECPAM, patients with a high variability of both body weight and blood pressure had the highest risk [Class 6, hazard ratio (HR) = 1.81; 95% confidence interval (CI) 1.61-2.05] compared with patients with low variability of both body weight and total cholesterol (Class 1, reference), despite a progressive reduction in the mean level of risk factors during successive visits. Individuals with high weight variability but low-moderate systolic blood pressure variability (Class 5, HR = 1.57; 95% CI 1.28-1.68), patients with moderate/high weight variability associated with high/very high HbA1c variability (Class 4, HR = 1.33; 95% CI 1.20-1.49), subjects with moderate/high weight variability and with low/moderate HbA1c variability (Class 3, HR = 1.12; 95% CI 1.00-1.25), as well as those with low weight variability associated with high/very high total cholesterol variability (Class 2, HR = 1.14; 95% CI 1.00-1.30) also showed a significant increase in the risk of an event., Conclusion: Combined high variability of two risk factors, particularly body weight and blood pressure, is associated with cardiovascular risk among patients with T2DM. These findings highlight the importance of continuous balancing of multiple risk factors., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
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- 2023
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35. The AMD ANNALS: A continuous initiative for the improvement of type 2 diabetes care.
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Russo G, Di Bartolo P, Candido R, Lucisano G, Manicardi V, Giandalia A, Nicolucci A, Rocca A, Rossi MC, and Di Cianni G
- Subjects
- Humans, Sodium-Glucose Transporter 2 therapeutic use, Glycated Hemoglobin, Risk Factors, Diabetes Mellitus, Type 2 drug therapy, Cardiovascular Diseases
- Abstract
Aims: Since 2006, the Italian AMD (Associations of Medical Diabetologists) Annals Initiative promoted a continuous monitoring of the quality of diabetes care, that was effective in improving process, treatment and outcome indicators through a periodic assessment of standardized measures. Here, we show the 2022 AMD Annals data on type 2 diabetes (T2D)., Methods: A network involving ∼1/3 of diabetes centers in Italy periodically extracts anonymous data from electronic clinical records, by a standardized software. Process, treatment and outcome indicators, and a validated score of overall care, the Q-score, were evaluated., Results: 295 centers provided the annual sample of 502,747 T2D patients. Overall, HbA1c value ≤7.0% was documented in 54.6% of patients, blood pressure <130/80 mmHg in 23.0%, and LDL-cholesterol levels <70 mg/dl in 34.3%, but only 5.2% were at- target for all the risk factors. As for innovative drugs, 29.0% of patients were on SGLT2-i, and 27.5% on GLP1-RAs. In particular, 59.7% were treated with either GLP1-RAs or SGLT2-i among those with established cardiovascular disease (CVD), 26.6% and 49.3% with SGLT2-i among those with impaired renal function and heart failure, respectively. Notably, only 3.2% of T2D patients showed a Q score <15, which correlates with a 80% higher risk of incident CVD events compared to scores >25., Conclusions: The 2022 AMD Annals data show an improvement in the use of innovative drugs and in the overall quality of T2D care in everyday clinical practice. However, additional efforts are needed to reach the recommended targets for HbA1c and major CVD risk factors., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)
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- 2023
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36. Serum Neurofilament Light Chain and Glial Fibrillary Acidic Protein as Potential Diagnostic Biomarkers in Autism Spectrum Disorders: A Preliminary Study.
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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
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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.
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- 2023
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37. Towards a validated definition of the clinical transition to secondary progressive multiple sclerosis: A study from the Italian MS Register.
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Iaffaldano P, Lucisano G, Guerra T, Patti F, Onofrj M, Brescia Morra V, Zaffaroni M, Pozzilli C, Cocco E, Sola P, Salemi G, Inglese M, Bergamaschi R, Gasperini C, Conte A, Salvetti M, Lus G, Maniscalco GT, Totaro R, Vianello M, Granella F, Ferraro E, Aguglia U, Gatto M, Sangalli F, Chisari CG, De Luca G, Carotenuto A, Baroncini D, Colombo D, Nica M, Paolicelli D, Comi G, Filippi M, Amato MP, and Trojano M
- Subjects
- Humans, Area Under Curve, Multiple Sclerosis, Multiple Sclerosis, Chronic Progressive diagnosis, Multiple Sclerosis, Relapsing-Remitting diagnosis
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Background: Definitions for reliable identification of transition from relapsing-remitting multiple sclerosis (MS) to secondary progressive (SP)MS in clinical cohorts are not available., Objectives: To compare diagnostic performances of two different data-driven SPMS definitions., Methods: Data-driven SPMS definitions based on a version of Lorscheider's algorithm (DDA) and on the EXPAND trial inclusion criteria were compared, using the neurologist's definition (ND) as gold standard, in terms of sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), Akaike information criterion (AIC) and area under the curve (AUC)., Results: A cohort of 10,240 MS patients with ⩾5 years of follow-up was extracted from the Italian MS Registry; 880 (8.5%) patients were classified as SPMS according to the neurologist definition, 1806 (17.6%) applying the DDA and 1134 (11.0%) with the EXPAND definition. The DDA showed greater discrimination power (AUC: 0.8 vs 0.6) and a higher sensitivity (77.1% vs 38.0%) than the EXPAND definition, with similar specificity (88.0% vs 91.5%). PPV and NPV were higher using the DDA than considering EXPAND definition (37.5% vs 29.5%; 97.6% vs 94.0%)., Conclusion: Data-driven definitions demonstrated greater ability to capture SP transition than neurologist's definition and the global accuracy of DDA seems to be higher than the EXPAND definition.
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- 2022
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38. Role of telemedicine during COVID-19 pandemic in type 2 diabetes outpatients: The AMD annals initiative.
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Russo GT, Andreozzi F, Calabrese M, Di Bartolo P, Di Cianni G, Bruno Giorda C, Lapice E, Manicardi E, Giandalia A, Lucisano G, Nicolucci A, Rocca A, Rossi MC, Spreafico E, Vespasiani G, and Manicardi V
- Subjects
- Humans, Pandemics, Outpatients, COVID-19 epidemiology, Diabetes Mellitus, Type 2 complications, Diabetes Mellitus, Type 2 epidemiology, Diabetes Mellitus, Type 2 therapy, Telemedicine
- Abstract
Aims: Telemedicine is advocated as a fundamental tool in modern clinical management. However, data on the effects of telemedicine vs face-to-face consultation on clinical outcomes in type 2 diabetes (T2DM) are still uncertain. This paper describes the use of telemedicine during the 2020 COVID-19 emergency and compares volume activity and quality indicators of diabetes care between face-to-face vs telemedicine counseling in the large cohort of T2DM patients from the AMD Annals Initiative., Methods: Demographic and clinical characteristics, including laboratory parameters, rate of the screening of long-term complications, current therapies and the Q-score, a validated score that measures the overall quality of care, were compared between 364,898 patients attending face-to-face consultation and 46,424 on telemedicine, during the COVID-19 pandemic., Results: Patients on telemedicine showed lower HbA1c levels (7.1 ± 1.2 % vs 7.3 ± 1.3 %, p < 0.0001), and they were less frequently treated with metformin, GLP1-RAs and SGLT2i and more frequently with DPP4i. The telemedicine group showed reduced monitoring of the various parameters considered as process indicators, especially, eye and foot examination. The proportion of patients with a good quality of care (Q score > 25) was higher among those receiving face-to-face consultation. Moreover, in the telemedicine group, all major clinical outcomes remained stable when further compared to those collected in the year 2019, when the same patients underwent a regular face-to-face consultation, suggesting that the care provided through telemedicine did not negatively affect the most important parameters., Conclusions: During the COVID-19 pandemic, telemedicine provided an acceptable quality of diabetes care, comparable to that of patients attending face-to-face consultation, although a less frequent screening of complications seems to have occurred in subjects consulted by telemedicine., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)
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- 2022
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39. A prediction model to assess the risk of egfr loss in patients with type 2 diabetes and preserved kidney function: The amd annals initiative.
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Russo GT, Giandalia A, Ceriello A, Di Bartolo P, Di Cianni G, Fioretto P, Giorda CB, Manicardi V, Pontremoli R, Viazzi F, Lucisano G, Nicolucci A, and De Cosmo S
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- Humans, Glomerular Filtration Rate, Kidney, Risk Factors, Cohort Studies, Diabetes Mellitus, Type 2 complications
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Objective: To develop and validate a model for predicting 5-year eGFR-loss in type 2 diabetes mellitus (T2DM) patients with preserved renal function at baseline., Research Design and Methods: A cohort of 504.532 T2DM outpatients participating to the Medical Associations of Diabetologists (AMD) Annals Initiative was splitted into the Learning and Validation cohorts, in which the predictive model was respectively developed and validated. A multivariate Cox proportional hazard regression model including all baseline characteristics was performed to identify predictors of eGFR-loss. A weight derived from regression coefficients was assigned to each variable and the overall sum of weights determined the 0 to 8-risk score., Results: A set of demographic, clinical and laboratory parameters entered the final model. The eGFR-loss score showed a good performance in the Validation cohort. Increasing score values progressively identified a higher risk of GFR loss: a score ≥ 8 was associated with a HR of 13.48 (12.96-14.01) in the Learning and a HR of 13.45 (12.93-13.99) in the Validation cohort. The 5 years-probability of developing the study outcome was 55.9% higher in subjects with a score ≥ 8., Conclusions: In the large AMD Annals Initiative cohort, we developed and validated an eGFR-loss prediction model to identify T2DM patients at risk of developing clinically meaningful renal complications within a 5-years time frame., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. The Association of Medical Diabetologists (AMD) founded this research., (Copyright © 2022. Published by Elsevier B.V.)
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- 2022
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40. Disease-Modifying Treatments and Time to Loss of Ambulatory Function in Patients With Primary Progressive Multiple Sclerosis.
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Portaccio E, Fonderico M, Iaffaldano P, Pastò L, Razzolini L, Bellinvia A, De Luca G, Ragonese P, Patti F, Brescia Morra V, Cocco E, Sola P, Inglese M, Lus G, Pozzilli C, Maimone D, Lugaresi A, Gazzola P, Comi G, Pesci I, Spitaleri D, Rezzonico M, Vianello M, Avolio C, Logullo FO, Granella F, Salvetti M, Zaffaroni M, Lucisano G, Filippi M, Trojano M, and Amato MP
- Subjects
- Adult, Disease Progression, Female, Humans, Recurrence, Retrospective Studies, Multiple Sclerosis, Multiple Sclerosis, Chronic Progressive drug therapy, Multiple Sclerosis, Relapsing-Remitting
- Abstract
Importance: Except for ocrelizumab, treatment options in primary progressive multiple sclerosis (PPMS) are lacking., Objective: To investigate the effectiveness of DMTs on the risk of becoming wheelchair dependent in a real-world population of patients with PPMS., Design, Setting, and Participants: This was a multicenter, observational, retrospective, comparative effectiveness research study. Data were extracted on November 28, 2018, from the Italian multiple sclerosis register and analyzed from June to December 2021. Mean study follow-up was 11 years. Included in the study cohort were patients with a diagnosis of PPMS and at least 3 years of Expanded Disability Status Scale (EDSS) evaluations and 3 years of follow-up., Main Outcomes and Measures: The risk of reaching an EDSS score of 7.0 was assessed through multivariable Cox regression models., Exposures: Patients who received DMT before the outcome were considered treated. DMT was assessed as a time-dependent variable and by class of DMT (moderately and highly effective)., Results: From a total of 3298 patients with PPMS, 2633 were excluded because they did not meet the entry criteria for the phase 3, multicenter, randomized, parallel-group, double-blind, placebo-controlled study to evaluate the efficacy and safety of ocrelizumab in adults with PPMS (ORATORIO) trial. Among the remaining 665 patients (mean [SD] age, 43.0 [10.7] years; 366 female patients [55.0%]), 409 were further selected for propensity score matching (288 treated and 121 untreated patients). In the matched cohort, during the study follow-up, 37% of patients (152 of 409) reached an EDSS score of 7.0 after a mean (SD) follow-up of 10.6 (5.6) years. A higher EDSS score at baseline (adjusted hazard ratio [aHR], 1.32; 95% CI, 1.13-1.55; P < .001), superimposed relapses (aHR, 2.37; 95% CI, 1.24-4.54; P = .009), and DMT exposure (aHR, 1.75; 95% CI, 1.04-2.94; P = .03) were associated with a higher risk of an EDSS score of 7.0, whereas the interaction term between DMT and superimposed relapses was associated with a reduced risk of EDSS score of 7.0 (aHR, 0.33; 95% CI, 0.16-0.71; P = .004). Similar findings were obtained when treatment according to DMT class was considered and when DMT was included as a time-dependent covariate. These results were confirmed in the subgroup of patients with available magnetic resonance imaging data., Conclusions and Relevance: Results of this comparative effectiveness research study suggest that inflammation also occurs in patients with PPMS, may contribute to long-term disability, and may be associated with a reduced risk of becoming wheelchair dependent by current licensed DMTs.
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- 2022
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41. Effect of a Behavioural Intervention for Adoption and Maintenance of a Physically Active Lifestyle on Psychological Well-Being and Quality of Life in Patients with Type 2 Diabetes: The IDES_2 Randomized Clinical Trial.
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Nicolucci A, Haxhi J, D'Errico V, Sacchetti M, Orlando G, Cardelli P, Vitale M, Bollanti L, Conti F, Zanuso S, Lucisano G, Balducci S, and Pugliese G
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- Exercise, Humans, Life Style, Sedentary Behavior, Diabetes Mellitus, Type 2 therapy, Quality of Life
- Abstract
Background: Psychological well-being and quality of life (QoL) are important outcomes of lifestyle interventions, as a positive impact may favour long-term maintenance of behaviour change., Objective: This study investigated the effect of a behavioural intervention for adopting and maintaining an active lifestyle on psychological well-being and health-related QoL in individuals with type 2 diabetes., Methods: Three hundred physically inactive and sedentary patients were randomized 1:1 to receive 1 month's theoretical and practical counselling once a year (intervention group, INT) or standard care (control group, CON) for 3 years. Psychological well-being and QoL, assessed using the World Health Organization (WHO)-5 and the 36-Item Short Form (SF-36) questionnaire, respectively, were pre-specified secondary endpoints. The primary endpoint was sustained behaviour change, as assessed by accelerometer-based measurement of physical activity (PA) and sedentary time., Results: WHO-5 and SF-36 physical and mental component summary (PCS and MCS) scores increased progressively in the INT group and decreased in the CON group, resulting in significant between-group differences (WHO-5: mean difference 7.35 (95% confidence interval (CI) 3.15-11.55), P = 0.0007; PCS 4.20 (95% CI 2.25-6.15), P < 0.0001; MCS 3.04 (95% CI 1.09-4.99), P = 0.0025). Percentage of participants with likely depression decreased in the INT group and increased in the CON group. PA volume changes were independently associated with WHO-5 changes, which were significantly higher in participants who accumulated > 150 min·wk
-1 of moderate-to-vigorous intensity PA versus those who did not (13.06 (95% CI 7.51-18.61), P < 0.0001), whereas no relationship was detected for QoL., Conclusion: A counselling intervention that was effective in promoting a sustained change in PA and sedentary behaviour significantly improved psychological well-being and QoL., Trial Registration: ClinicalTrials.gov; NCT01600937; 10 October 2012., (© 2021. The Author(s).)- Published
- 2022
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42. A few clinical features improve the prediction of mortality and cardiovascular outcomes in patients with type 2 diabetes.
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Masulli M, Lucisano G, Bonora E, Del Prato S, Rivellese AA, Signorini S, Mocarelli P, Riccardi G, Vaccaro O, and Nicolucci A
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- Humans, Risk Factors, Cardiovascular Diseases diagnosis, Cardiovascular System, Diabetes Mellitus, Type 2 complications, Diabetes Mellitus, Type 2 diagnosis
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- 2022
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43. HbA1c variability predicts cardiovascular complications in type 2 diabetes regardless of being at glycemic target.
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Ceriello A, Lucisano G, Prattichizzo F, La Grotta R, Franzén S, Svensson AM, Eliasson B, and Nicolucci A
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- 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).)
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- 2022
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44. Risk of Getting COVID-19 in People With Multiple Sclerosis: A Case-Control Study.
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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.)
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- 2022
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45. Temporal trends in intensification of glucose-lowering therapy for type 2 diabetes in Italy: Data from the AMD Annals initiative and their impact on clinical inertia.
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Cucinotta D, Nicolucci A, Giandalia A, Lucisano G, Manicardi V, Mannino D, Rossi MC, Russo GT, and Di Bartolo P
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- Glucose, Glycated Hemoglobin analysis, Humans, Hypoglycemic Agents therapeutic use, Italy epidemiology, Retrospective Studies, Diabetes Mellitus, Type 2 drug therapy, Diabetes Mellitus, Type 2 epidemiology, Metformin therapeutic use
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Aims: Clinical inertia negatively affects type 2 diabetes (T2DM) management. We evaluated changes in prescription patterns of hypoglycemic drugs during a 15 year-observation period in a large population of T2DM outpatients and their effect on metabolic control., Methods: Data on all T2DM patients attending 258 Italian diabetes clinics between 2005 and 2019 were collected and analyzed for three 5-years periods. The addition of a second drug to metformin and the addition of a third agent to dual therapy were evaluated., Results: During the observation period, 437.179 patients added a second drug to metformin. The intensification occurred earlier over time: patients had a shorter duration of disease and a better cardiovascular risk profile in the last five years, compared to previous periods. During the same period, 208.767 patients added a third agent to dual therapy. Duration of diabetes at the time of intensification decreased, and cardiovascular risk profile improved over time. Also HbA1c levels at the time of intensification decreased over time., Conclusions: in this large cohort of T2MD subjects during a long observation period an earlier treatment intensification and a better metabolic control were observed, suggesting an improved approach to clinical inertia., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)
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- 2021
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46. Early treatment delays long-term disability accrual in RRMS: Results from the BMSD network.
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Iaffaldano P, Lucisano G, Butzkueven H, Hillert J, Hyde R, Koch-Henriksen N, Magyari M, Pellegrini F, Spelman T, Sørensen PS, Vukusic S, and Trojano M
- Subjects
- Cohort Studies, Disease Progression, Humans, Time-to-Treatment, Disabled Persons, Multiple Sclerosis
- Abstract
Background: The optimal timing of treatment starts for achieving the best control on the long-term disability accumulation in multiple sclerosis (MS) is still to be defined., Objective: The aim of this study was to estimate the optimal time to start disease-modifying therapies (DMTs) to prevent the long-term disability accumulation in MS, using a pooled dataset from the Big Multiple Sclerosis Data (BMSD) network., Methods: Multivariable Cox regression models adjusted for the time to first treatment start from disease onset (in quintiles) were used. To mitigate the impact of potential biases, a set of pairwise propensity score (PS)-matched analyses were performed. The first quintile, including patients treated within 1.2 years from onset, was used as reference., Results: A cohort of 11,871 patients (median follow-up after treatment start: 13.2 years) was analyzed. A 3- and 12-month confirmed disability worsening event and irreversible Expanded Disability Status Scale (EDSS) 4.0 and 6.0 scores were reached by 7062 (59.5%), 4138 (34.9%), 3209 (31.1%), and 1909 (16.5%) patients, respectively. The risk of reaching all the disability outcomes was significantly lower ( p < 0.0004) for the first quintile patients' group., Conclusion: Real-world data from the BMSD demonstrate that DMTs should be commenced within 1.2 years from the disease onset to reduce the risk of disability accumulation over the long term.
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- 2021
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47. Effects of weight loss medications on mortality and cardiovascular events: A systematic review of randomized controlled trials in adults with overweight and obesity.
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Capristo E, Maione A, Lucisano G, Russo MF, Mingrone G, and Nicolucci A
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- Anti-Obesity Agents adverse effects, Cardiovascular Diseases diagnosis, Cardiovascular Diseases mortality, Cardiovascular Diseases physiopathology, Female, Heart Disease Risk Factors, Humans, Male, Obesity diagnosis, Obesity mortality, Obesity physiopathology, Randomized Controlled Trials as Topic, Risk Assessment, Time Factors, Treatment Outcome, Anti-Obesity Agents therapeutic use, Cardiovascular Diseases prevention & control, Obesity drug therapy, Weight Loss drug effects
- Abstract
Aims: Adults affected by obesity are at higher risk of premature mortality. Medications can help to lose weight and to maintain weight loss. Aim of this meta-analysis was to assess whether anti-obesity medications affect all-cause mortality, mortality due to cardiovascular events, cardiovascular risk factors and body weight., Data Synthesis: A Medline search was performed to identify randomized controlled trials (RCTs) of anti-obesity medications in adults with overweight or obesity reporting data on all-cause mortality, cardiovascular mortality or non-fatal cardiovascular events, with a follow-up of at least 6 months. We identified 28 RCTs with 50,106 participants. The median follow-up was 52 weeks. Evidence did not show superiority of anti-obesity medications over placebo in reducing all-cause mortality (risk ratio 1.03, 95%Confidence Interval [CI] 0.87 to 1.21) or cardiovascular mortality (risk ratio 0.92, 95%CI 0.72 to 1.18). All-cause mortality rate was positively associated with weight loss (β = 0.0007; p = 0.045); hence, for each kg of body weight lost there was a 0.07% decrease of all-cause mortality. The pharmacological treatment reduced total-cholesterol (7.15 mg/dl; 95%CI 1.46-12.85), LDL-cholesterol (5.06 mg/dl; 95%CI 1.12-9.00), and triglycerides levels (9.88 mg/dl; 95%CI 5.02-14.75), while it increased HDL-cholesterol (1.37 mg/dl; 95%CI 0.17-2.57). Systolic blood pressure decreased (0.90 mmHg; 95%CI 0.15-1.64)., Conclusions: Although we were unable to demonstrate a superiority of anti-obesity medications over placebo on mortality, metaregression showed that even a small weight reduction tends to reduce all-cause mortality in obesity. Our data support public health measures to reduce the obesity burden by including the use of anti-obesity medications., Registration Number (prospero): CRD42020210329., (Copyright © 2021 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)
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- 2021
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48. Variability in body weight and the risk of cardiovascular complications in type 2 diabetes: results from the Swedish National Diabetes Register.
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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).)
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- 2021
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49. Long-term disability trajectories in relapsing multiple sclerosis patients treated with early intensive or escalation treatment strategies.
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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.)
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- 2021
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50. Transition to secondary progression in relapsing-onset multiple sclerosis: Definitions and risk factors.
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Iaffaldano P, Lucisano G, Patti F, Brescia Morra V, De Luca G, Lugaresi A, Zaffaroni M, Inglese M, Salemi G, Cocco E, Conte A, Ferraro D, Galgani S, Bergamaschi R, Pozzilli C, Salvetti M, Lus G, Rovaris M, Maniscalco GT, Logullo FO, Paolicelli D, Achille M, Marrazzo G, Lovato V, Comi G, Filippi M, Amato MP, and Trojano M
- Subjects
- Disease Progression, Humans, Recurrence, Risk Factors, Multiple Sclerosis, Multiple Sclerosis, Chronic Progressive epidemiology, Multiple Sclerosis, Relapsing-Remitting epidemiology
- Abstract
Background: No uniform criteria for a sensitive identification of the transition from relapsing-remitting multiple sclerosis (MS) to secondary-progressive multiple sclerosis (SPMS) are available., Objective: To compare risk factors of SPMS using two definitions: one based on the neurologist judgment (ND) and an objective data-driven algorithm (DDA)., Methods: Relapsing-onset MS patients ( n = 19,318) were extracted from the Italian MS Registry. Risk factors for SPMS and for reaching irreversible Expanded Disability Status Scale (EDSS) 6.0, after SP transition, were estimated using multivariable Cox regression models., Results: SPMS identified by the DDA ( n = 2343, 12.1%) were older, more disabled and with a faster progression to severe disability ( p < 0.0001), than those identified by the ND ( n = 3868, 20.0%). In both groups, the most consistent risk factors ( p < 0.05) for SPMS were a multifocal onset, an age at onset >40 years, higher baseline EDSS score and a higher number of relapses; the most consistent protective factor was the disease-modifying therapy (DMT) exposure. DMT exposure during SP did not impact the risk of reaching irreversible EDSS 6.0., Conclusion: A DDA definition of SPMS identifies more aggressive progressive patients. DMT exposure reduces the risk of SPMS conversion, but it does not prevent the disability accumulation after the SP transition.
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- 2021
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