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ALFONSO METELLO FRANCESCO ANDRETTA

DOCENTE A CONTRATTO presso: Dipartimento di Ingegneria "Enzo Ferrari"


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Pubblicazioni

2020 - ACE2 gene variants may underlie interindividual variability and susceptibility to COVID-19 in the Italian population [Articolo su rivista]
Benetti, E.; Tita, R.; Spiga, O.; Ciolfi, A.; Birolo, G.; Bruselles, A.; Doddato, G.; Giliberti, A.; Marconi, C.; Musacchia, F.; Pippucci, T.; Torella, A.; Trezza, A.; Valentino, F.; Baldassarri, M.; Brusco, A.; Asselta, R.; Bruttini, M.; Furini, S.; Seri, M.; Nigro, V.; Matullo, G.; Tartaglia, M.; Mari, F.; Elisa, F.; Chiara, F.; Sergio, D.; Susanna, C.; Sara, A.; Francesca, F.; Montagnani, F.; Di Sarno, L.; Tommasi, A.; Palmieri, M.; Emiliozzi, A.; Fabbiani, M.; Rossetti, B.; Zanelli, G.; Bergantini, L.; D'Alessandro, M.; Cameli, P.; Bennet, D.; Anedda, F.; Marcantonio, S.; Scolletta, S.; Franchi, F.; Mazzei, M. A.; Conticini, E.; Cantarini, L.; Frediani, B.; Tacconi, D.; Feri, M.; Scala, R.; Spargi, G.; Corridi, M.; Nencioni, C.; Caldarelli, G. P.; Spagnesi, M.; Piacentini, P.; Bandini, M.; Desanctis, E.; Canaccini, A.; Spertilli, C.; Donati, A.; Guidelli, L.; Croci, L.; Verzuri, A.; Anemoli, V.; Ognibene, A.; Vaghi, M.; D'Arminio Monforte, A.; Merlini, E.; Mondelli, M. U.; Mantovani, S.; Ludovisi, S.; Girardis, M.; Venturelli, S.; Sita, M.; Cossarizza, A.; Antinori, A.; Vergori, A.; Rusconi, S.; Siano, M.; Gabrieli, A.; Riva, A.; Francisci, D.; Schiaroli, E.; Scotton, P. G.; Andretta, F.; Panese, S.; Scaggiante, R.; Parisi, S. G.; Castelli, F.; Quiros-Roldan, M. E.; Magro, P.; Minardi, C.; Castelli, D.; Polesini, I.; Della Monica, M.; Piscopo, C.; Capasso, M.; Russo, R.; Andolfo, I.; Iolascon, A.; Carella, M.; Castori, M.; Merla, G.; Aucella, F.; Raggi, P.; Marciano, C.; Perna, R.; Bassetti, M.; Di Biagio, A.; Sanguinetti, M.; Masucci, L.; Gabbi, C.; Valente, S.; Guerrini, S.; Meloni, I.; Mencarelli, M. A.; Rizzo, C. L.; Bargagli, E.; Mandala, M.; Giorli, A.; Salerni, L.; Fiorentino, G.; Zucchi, P.; Parravicini, P.; Menatti, E.; Baratti, S.; Trotta, T.; Giannattasio, F.; Coiro, G.; Lena, F.; Coviello, D. A.; Mussini, C.; Renieri, A.; Pinto, A. M.
abstract

In December 2019, an initial cluster of interstitial bilateral pneumonia emerged in Wuhan, China. A human-to-human transmission was assumed and a previously unrecognized entity, termed coronavirus disease-19 (COVID-19) due to a novel coronavirus (SARS-CoV-2) was described. The infection has rapidly spread out all over the world and Italy has been the first European country experiencing the endemic wave with unexpected clinical severity in comparison with Asian countries. It has been shown that SARS-CoV-2 utilizes angiotensin converting enzyme 2 (ACE2) as host receptor and host proteases for cell surface binding and internalization. Thus, a predisposing genetic background can give reason for interindividual disease susceptibility and/or severity. Taking advantage of the Network of Italian Genomes (NIG), here we mined whole-exome sequencing data of 6930 Italian control individuals from five different centers looking for ACE2 variants. A number of variants with a potential impact on protein stability were identified. Among these, three more common missense changes, p.(Asn720Asp), p.(Lys26Arg), and p.(Gly211Arg) were predicted to interfere with protein structure and stabilization. Rare variants likely interfering with the internalization process, namely p.(Leu351Val) and p.(Pro389His), predicted to interfere with SARS-CoV-2 spike protein binding, were also observed. Comparison of ACE2 WES data between a cohort of 131 patients and 258 controls allowed identifying a statistically significant (P value < 0.029) higher allelic variability in controls compared with patients. These findings suggest that a predisposing genetic background may contribute to the observed interindividual clinical variability associated with COVID-19, allowing an evidence-based risk assessment leading to personalized preventive measures and therapeutic options.


2015 - Risk of hospitalization for heart failure in patients with type 2 diabetes newly treated with DPP-4 inhibitors or other oral glucose-lowering medications: A retrospective registry study on 127,555 patients from the Nationwide OsMed Health-DB Database [Articolo su rivista]
Fadini, G. P.; Avogaro, A.; Degli Esposti, L.; Russo, P.; Saragoni, S.; Buda, S.; Rosano, G.; Pecorelli, S.; Pani, L.; Martinetti, S.; Mero, P.; Raeli, L.; Migliazza, S.; Dellagiovanna, M.; Cerra, C.; Gambera, M.; Piccinelli, R.; Zambetti, M.; Atzeni, F.; Valsecchi, V.; Deluca, P.; Scopinaro, E.; Moltoni, D.; Pini, E.; Leoni, O.; Oria, C.; Papagni, M.; Nosetti, G.; Caldiroli, E.; Moser, V.; Roni, R.; Polverino, A.; Bovo, C.; Mezzalira, L.; Andretta, M.; Trentin, L.; Palcic, S.; Pettinelli, A.; Arbo, A.; Bertola, A.; Capparoni, G.; Cattaruzzi, C.; Marcuzzo, L.; Rosa, F. V.; Basso, B.; Saglietto, M.; Delucis, S.; Prioli, M.; Filippi, R.; Coccini, A.; Ghia, M.; Sanfelici, F.; Radici, S.; Scanavacca, P.; Campi, A.; Bianchi, S.; Verzola, A.; Morini, M.; Borsari, M.; Danielli, A.; Dal Maso, M.; Marsiglia, B.; Vujovic, B.; Pisani, M.; Bonini, P.; Lena, F.; Aletti, P.; Marcobelli, A.; Sagratella, S.; Fratini, S.; Bartolini, F.; Riccioni, G.; Meneghini, A.; Di Turi, R.; Fano, V.; Blasi, A.; Pagnozzi, E.; Quintavalle, G.; D'Avenia, P.; De Matthaeis, M. C.; Ferrante, F.; Crescenzi, S.; Marziale, L.; Venditti, P.; Bianchi, C.; Senesi, I.; Baci, R.; De Carlo, I.; Lavalle, A.; Trofa, G.; Marcello, G.; Pagliaro, C.; Troncone, C.; Farina, G.; Tari, M. G.; Motola, G.; De Luca, F.; Saltarelli, M. L.; Granieri, C.; Vulnera, M.; Palumbo, L.; La Viola, F.; Florio, L.; De Francesco, A. E.; Costantino, D.; De Francesco, A. E.; Rapisarda, F.; Lazzaro, P. L.; Pastorello, M.; Parlli, M.; Visconti, M.; Uomo, I.; Sanna, P.; Lombardo, F.
abstract

Aims Oral glucose-lowering medications are associated with excess risk of heart failure (HF). Given the absence of comparative data among drug classes, we performed a retrospective study in 32 Health Services of 16 Italian regions accounting for a population of 18 million individuals, to assess the association between HF risk and use of sulphonylureas, DPP-4i, and glitazones. Methods and results We extracted data on patients with type 2 diabetes who initiated treatment with DPP-4i, thiazolidinediones, or sulphonylureas alone or in combination with metformin during an accrual time of 2 years. The endpoint was hospitalization for HF (HHF) occurring after the first 6 months of therapy, and the observation was extended for up to 4 years. A total of 127 555 patients were included, of whom 14.3% were on DPP-4i, 72.5% on sulphonylurea, 13.2% on thiazolidinediones, with average 70.7% being on metformin as combination therapy. Patients in the three groups differed significantly for baseline characteristics: age, sex, Charlson index, concurrent medications, and previous cardiovascular events. During an average 2.6-year follow-up, after adjusting for measured confounders, use of DPP-4i was associated with a reduced risk of HHF compared with sulphonylureas [hazard ratio (HR) 0.78; 95% confidence interval (CI) 0.62-0.97; P = 0.026]. After propensity matching, the analysis was restricted to 39 465 patients, and the use of DPP-4i was still associated with a lower risk of HHF (HR 0.70; 95% CI 0.52-0.94; P = 0.018). Conclusion In a very large observational study, the use of DPP-4i was associated with a reduced risk of HHF when compared with sulphonylureas.