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1. Diagnostic and treatment strategies in mucopolysaccharidosis VI

Author

Vairo F, Federhen A, Baldo G, Riegel M, Burin M, Leistner-Segal S, and Giugliani R

Subjects
Medicine (General), R5-920, Genetics, QH426-470
Abstract

Filippo Vairo,1–3 Andressa Federhen,1,3,4 Guilherme Baldo,1,2,5–7 Mariluce Riegel,1,6 Maira Burin,1 Sandra Leistner-Segal,1,8 Roberto Giugliani1,5,6,81Medical Genetics Service, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil; 2Department of Genetics, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil; 3Clinical Research Group on Medical Genetics, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil; 4Post-Graduate Program in Child and Adolescent Health, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil; 5Gene Therapy Center, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil; 6Post-Graduate Program in Genetics and Molecular Biology, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil; 7Department of Physiology, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil; 8Post-Graduate Program in Medical Sciences, Universidade Federal do Rio Grande do Sul, Porto Alegre, BrazilAbstract: Mucopolysaccharidosis VI (MPS VI) is a very rare autosomal recessive disorder caused by mutations in the ARSB gene, which lead to deficient activity of the lysosomal enzyme ASB. This enzyme is important for the breakdown of the glycosaminoglycans (GAGs) dermatan sulfate and chondroitin sulfate, which accumulate in body tissues and organs of MPS VI patients. The storage of GAGs (especially dermatan sulfate) causes bone dysplasia, joint restriction, organomegaly, heart disease, and corneal clouding, among several other problems, and reduced life span. Despite the fact that most cases are severe, there is a spectrum of severity and some cases are so attenuated that diagnosis is made late in life. Although the analysis of urinary GAGs and/or the measurement of enzyme activity in dried blood spots are useful screening methods, the diagnosis is based in the demonstration of the enzyme deficiency in leucocytes or fibroblasts, and/or in the identification of pathogenic mutations in the ARSB gene. Specific treatment with enzyme replacement has been available since 2005. It is safe and effective, bringing measurable benefits and increased survival to patients. As several evidences indicate that early initiation of therapy may lead to a better outcome, newborn screening is being considered for this condition, and it is already in place in selected areas where the incidence of MPS VI is increased. However, as enzyme replacement therapy is not curative, associated therapies should be considered, and research on innovative therapies continues. The management of affected patients by a multidisciplinary team with experience in MPS diseases is highly recommended.Keywords: mucopolysaccharidosis VI, Maroteaux–Lamy syndrome, dermatan sulfate, arylsulfatase b, enzyme replacement therapy, lysosomal storage diseases

Published
2015

2. Structural Variants at the LMNB1 Locus: Deciphering Pathomechanisms in Autosomal Dominant Adult-Onset Demyelinating Leukodystrophy.

Author

Dimartino, P, Zadorozhna, M, Yumiceba, V, Basile, A, Cani, I, Melo, US, Henck, J, Breur, M, Tonon, C, Lodi, R, Brusco, A, Pippucci, T, Koufi, F-D, Boschetti, E, Ramazzotti, G, Manzoli, L, Ratti, S, Pinto E Vairo, F, Delatycki, MB, Vaula, G, Cortelli, P, Bugiani, M, Spielmann, M, Giorgio, E, Dimartino, P, Zadorozhna, M, Yumiceba, V, Basile, A, Cani, I, Melo, US, Henck, J, Breur, M, Tonon, C, Lodi, R, Brusco, A, Pippucci, T, Koufi, F-D, Boschetti, E, Ramazzotti, G, Manzoli, L, Ratti, S, Pinto E Vairo, F, Delatycki, MB, Vaula, G, Cortelli, P, Bugiani, M, Spielmann, M, and Giorgio, E

Abstract

OBJECTIVES: We aimed to elucidate the pathogenic mechanisms underlying autosomal dominant adult-onset demyelinating leukodystrophy (ADLD), and to understand the genotype/phenotype correlation of structural variants (SVs) in the LMNB1 locus. BACKGROUND: Since the discovery of 3D genome architectures and topologically associating domains (TADs), new pathomechanisms have been postulated for SVs, regardless of gene dosage changes. ADLD is a rare genetic disease associated with duplications (classical ADLD) or noncoding deletions (atypical ADLD) in the LMNB1 locus. METHODS: High-throughput chromosome conformation capture, RNA sequencing, histopathological analyses of postmortem brain tissues, and clinical and neuroradiological investigations were performed. RESULTS: We collected data from >20 families worldwide carrying SVs in the LMNB1 locus and reported strong clinical variability, even among patients carrying duplications of the entire LMNB1 gene, ranging from classical and atypical ADLD to asymptomatic carriers. We showed that patients with classic ADLD always carried intra-TAD duplications, resulting in a simple gene dose gain. Atypical ADLD was caused by LMNB1 forebrain-specific misexpression due to inter-TAD deletions or duplications. The inter-TAD duplication, which extends centromerically and crosses the 2 TAD boundaries, did not cause ADLD. Our results provide evidence that astrocytes are key players in ADLD pathology. INTERPRETATION: Our study sheds light on the 3D genome and TAD structural changes associated with SVs in the LMNB1 locus, and shows that a duplication encompassing LMNB1 is not sufficient per se to diagnose ADLD, thereby strongly affecting genetic counseling. Our study supports breaking TADs as an emerging pathogenic mechanism that should be considered when studying brain diseases. ANN NEUROL 2024.

Published
2024

6. Clinical management of imported malaria in Italy: Results from a national cross-sectional survey in 2015

Author

Lepore, L, Vairo, F, D'Abramo, A, Grilli, E, Corpolongo, A, Scorzolini, L, Nisii, C, Calleri, G, Castelli, F, Chirianni, A, Ippolito, G, Nicastri, E, Andreoni, M, Angarano, G, Anselmo, M, Ascoli Bartoli, T, Bartoloni, A, Bassi, P, Bevilacqua, N, Bisoffi, Z, Cacopardo, B, Caligaris, S, Calzetti, C, Casolari, S, Cassola, G, Chianura, L, Chiodera, A, Conforto, M, Coppola, N, De Luca, A, Feasi, M, Ferrari, C, Filippini, P, Foti, G, Francavilla, E, Fusco, F, Tekle, S, Giancola, M, Giammario, A, Giobbia, M, Giordani, M, Gobbi, F, Gori, A, Grossi, P, Iacobello, C, Iannetta, M, Libanore, M, Luzzati, R, Magnani, G, Manfrin, V, Mariano, A, Mastroianni, C, Mazzotta, F, Mecocci, L, Mondardini, V, Montineri, A, Nicolini, L, Oliva, A, Palazzolo, C, Pasquale, G, Portelli, V, Puoti, M, Quirino, T, Santantonio, T, Sarmati, L, Sciotti, M, Scotton, P, Tomasoni, L, Toscanini, F, Tunesi, S, Vanino, E, Viale, P, Vigano, P, Viscoli, C, Vullo, V, Lepore L., Vairo F., D'Abramo A., Grilli E., Corpolongo A., Scorzolini L., Nisii C., Calleri G., Castelli F., Chirianni A., Ippolito G., Nicastri E., Andreoni M., Angarano G., Anselmo M., Ascoli Bartoli T., Bartoloni A., Bassi P., Bevilacqua N., Bisoffi Z., Cacopardo B., Caligaris S., Calzetti C., Casolari S., Cassola G., Chianura L., Chiodera A., Conforto M., Coppola N., De Luca A., Feasi M., Ferrari C., Filippini P., Foti G., Francavilla E., Fusco F. M., Tekle S. G., Giancola M. L., Giammario A., Giobbia M., Giordani M. T., Gobbi F., Gori A., Grossi P., Iacobello C., Iannetta M., Libanore M., Luzzati R., Magnani G., Manfrin V., Mariano A., Mastroianni C., Mazzotta F., Mecocci L., Mondardini V., Montineri A., Nicolini L. A., Oliva A., Palazzolo C., Pasquale G., Portelli V., Puoti M., Quirino T., Santantonio T. A., Sarmati L., Sciotti M. P., Scotton P., Tomasoni L. R., Toscanini F., Tunesi S., Vanino E., Viale P., Vigano P., Viscoli C., Vullo V., Lepore, L, Vairo, F, D'Abramo, A, Grilli, E, Corpolongo, A, Scorzolini, L, Nisii, C, Calleri, G, Castelli, F, Chirianni, A, Ippolito, G, Nicastri, E, Andreoni, M, Angarano, G, Anselmo, M, Ascoli Bartoli, T, Bartoloni, A, Bassi, P, Bevilacqua, N, Bisoffi, Z, Cacopardo, B, Caligaris, S, Calzetti, C, Casolari, S, Cassola, G, Chianura, L, Chiodera, A, Conforto, M, Coppola, N, De Luca, A, Feasi, M, Ferrari, C, Filippini, P, Foti, G, Francavilla, E, Fusco, F, Tekle, S, Giancola, M, Giammario, A, Giobbia, M, Giordani, M, Gobbi, F, Gori, A, Grossi, P, Iacobello, C, Iannetta, M, Libanore, M, Luzzati, R, Magnani, G, Manfrin, V, Mariano, A, Mastroianni, C, Mazzotta, F, Mecocci, L, Mondardini, V, Montineri, A, Nicolini, L, Oliva, A, Palazzolo, C, Pasquale, G, Portelli, V, Puoti, M, Quirino, T, Santantonio, T, Sarmati, L, Sciotti, M, Scotton, P, Tomasoni, L, Toscanini, F, Tunesi, S, Vanino, E, Viale, P, Vigano, P, Viscoli, C, Vullo, V, Lepore L., Vairo F., D'Abramo A., Grilli E., Corpolongo A., Scorzolini L., Nisii C., Calleri G., Castelli F., Chirianni A., Ippolito G., Nicastri E., Andreoni M., Angarano G., Anselmo M., Ascoli Bartoli T., Bartoloni A., Bassi P., Bevilacqua N., Bisoffi Z., Cacopardo B., Caligaris S., Calzetti C., Casolari S., Cassola G., Chianura L., Chiodera A., Conforto M., Coppola N., De Luca A., Feasi M., Ferrari C., Filippini P., Foti G., Francavilla E., Fusco F. M., Tekle S. G., Giancola M. L., Giammario A., Giobbia M., Giordani M. T., Gobbi F., Gori A., Grossi P., Iacobello C., Iannetta M., Libanore M., Luzzati R., Magnani G., Manfrin V., Mariano A., Mastroianni C., Mazzotta F., Mecocci L., Mondardini V., Montineri A., Nicolini L. A., Oliva A., Palazzolo C., Pasquale G., Portelli V., Puoti M., Quirino T., Santantonio T. A., Sarmati L., Sciotti M. P., Scotton P., Tomasoni L. R., Toscanini F., Tunesi S., Vanino E., Viale P., Vigano P., Viscoli C., and Vullo V.

Abstract

In Italy, malaria continues to be one of the most common imported parasitoses; therefore, continuous surveillance of epidemiological data and clinical management is needed. In 2016, the National Institute for Infectious Diseases 'Lazzaro Spallanzani' in Rome promoted a retrospective questionnaire-based survey to assess the clinical management of imported malaria cases in Italy in 2015. The questionnaire was sent to 104 Tropical and/or Infectious Diseases Units in the country, and 37 of them filled out and returned the questionnaires. A total of 399 malaria cases were reported in 2015, mostly caused by Plasmodium falciparum and imported from Africa. Malaria chemoprophylaxis was correctly used by a minority of patients. Most patients presented with uncomplicated malaria and were treated orally. In severe cases, intravenous artesunate or quinine alone or in combination were administered, although one third of these severe cases received oral treatment. This retrospective survey reveals a lack of homogeneity in management of malaria-imported cases in Italy. Improvement of malaria chemoprophylaxis, standardization of clinical management of malaria cases and harmonization of oral and intravenous drug availability are needed throughout the country.

Published
2020

8. Prophylactic heparin and risk of orotracheal intubation or death in patients with mild or moderate COVID-19 pneumonia

Author

Vergori, A., Lorenzini, P., Cozzi-Lepri, A., Donno, D. R., Gualano, G., Nicastri, E., Iacomi, F., Marchioni, L., Campioni, P., Schinina, V., Cicalini, S., Agrati, C., Capobianchi, M. R., Girardi, E., Ippolito, G., Vaia, F., Petrosillo, N., Antinori, A., Taglietti, F., The ReCOVeRI Study Group: Abbonizio, M. A., Abdeddaim, A., Agostini, E., Albarello, F., Amadei, G., Amendola, A., Antonica, M. A., Antonini, M., Bartoli, T. A., Baldini, F., Barbaro, R., Bartolini, B., Bellagamba, R., Benigni, M., Bevilacqua, N., Biava, G., Bibas, M., Bordi, L., Bordoni, V., Boumis, E., Branca, M., Buonomo, R., Busso, D., Camici, M., Canichella, F., Capone, A., Caporale, C., Caraffa, E., Caravella, I., Carletti, F., Castilletti, C., Cataldo, A., Cerilli, S., Cerva, C., Chiappini, R., Chinello, P., Cianfarani, M. A., Ciaralli, C., Cimaglia, C., Cinicola, N., Ciotti, V., Colavita, F., Corpolongo, A., Cristofaro, M., Curiale, S., D'Abramo, A., Dantimi, C., De Angelis, A., De Angelis, G., De Palo, M. G., De Zottis, F., Di Bari, V., Di Lorenzo, R., Di Stefano, F., D'Offizi, G., Evangelista, F., Faraglia, F., Farina, A., Ferraro, F., Fiorentini, L., Frustaci, A., Fusetti, M., Fusto, M., Galati, V., Gagliardini, R., Galli, P., Garotto, G., Gaviano, I., Tekle, S. G., Giancola, M. L., Giansante, F., Giombini, E., Granata, G., Greci, M. C., Grilli, E., Grisetti, S., Iaconi, M., Iannicelli, G., Inversi, C., Lalle, E., Lamanna, M. E., Lanini, S., Lapa, D., Lepore, L., Libertone, R., Lionetti, R., Liuzzi, G., Loiacono, L., Lucia, A., Lufrani, F., Macchione, M., Maffongelli, G., Marani, A., Mariano, A., Marini, M. C., Maritti, M., Mastrobattista, A., Mastrorosa, I., Matusali, G., Mazzotta, V., Mencarini, P., Meschi, S., Messina, F., Micarelli, S., Mogavero, G., Mondi, A., Montalbano, M., Montaldo, C., Mosti, S., Murachelli, S., Musso, M., Nardi, M., Navarra, A., Nocioni, M., Noto, P., Noto, R., Oliva, A., Onnis, I., Ottou, S., Palazzolo, C., Pallini, E., Palmieri, F., Palombi, G., Pareo, C., Passeri, V., Pelliccioni, F., Penna, G., Petrecchia, A., Petrone, A., Pianura, E., Pinnetti, C., Pisciotta, M., Piselli, P., Pittalis, S., Pontarelli, A., Proietti, C., Puro, V., Ramazzini, P. M., Rianda, A., Rinonapoli, G., Rosati, S., Rubino, D., Rueca, M., Ruggeri, A., Sacchi, A., Sampaolesi, A., Sanasi, F., Santagata, C., Scarabello, A., Scarcia, S., Scognamiglio, P., Scorzolini, L., Stazi, G., Strano, G., Taibi, C., Taloni, G., Nardi, T., Tonnarini, R., Topino, S., Tozzi, M., Vairo, F., Valli, M. B., Vincenzi, L., Visco-Comandini, U., Vita, S., Vittozzi, P., Zaccarelli, M., Zanetti, A., Zito, S., Vergori, A., Lorenzini, P., Cozzi-Lepri, A., Donno, D. R., Gualano, G., Nicastri, E., Iacomi, F., Marchioni, L., Campioni, P., Schinina, V., Cicalini, S., Agrati, C., Capobianchi, M. R., Girardi, E., Ippolito, G., Vaia, F., Petrosillo, N., Antinori, A., Taglietti, F., Abbonizio, M. A., Abdeddaim, A., Agostini, E., Albarello, F., Amadei, G., Amendola, A., Antonica, M. A., Antonini, M., Bartoli, T. A., Baldini, F., Barbaro, R., Bartolini, B., Bellagamba, R., Benigni, M., Bevilacqua, N., Biava, G., Bibas, M., Bordi, L., Bordoni, V., Boumis, E., Branca, M., Buonomo, R., Busso, D., Camici, M., Canichella, F., Capone, A., Caporale, C., Caraffa, E., Caravella, I., Carletti, F., Castilletti, C., Cataldo, A., Cerilli, S., Cerva, C., Chiappini, R., Chinello, P., Cianfarani, M. A., Ciaralli, C., Cimaglia, C., Cinicola, N., Ciotti, V., Colavita, F., Corpolongo, A., Cristofaro, M., Curiale, S., D'Abramo, A., Dantimi, C., De Angelis, A., De Angelis, G., De Palo, M. G., De Zottis, F., Di Bari, V., Di Lorenzo, R., Di Stefano, F., D'Offizi, G., Evangelista, F., Faraglia, F., Farina, A., Ferraro, F., Fiorentini, L., Frustaci, A., Fusetti, M., Fusto, M., Galati, V., Gagliardini, R., Galli, P., Garotto, G., Gaviano, I., Tekle, S. G., Giancola, M. L., Giansante, F., Giombini, E., Granata, G., Greci, M. C., Grilli, E., Grisetti, S., Iaconi, M., Iannicelli, G., Inversi, C., Lalle, E., Lamanna, M. E., Lanini, S., Lapa, D., Lepore, L., Libertone, R., Lionetti, R., Liuzzi, G., Loiacono, L., Lucia, A., Lufrani, F., Macchione, M., Maffongelli, G., Marani, A., Mariano, A., Marini, M. C., Maritti, M., Mastrobattista, A., Mastrorosa, I., Matusali, G., Mazzotta, V., Mencarini, P., Meschi, S., Messina, F., Micarelli, S., Mogavero, G., Mondi, A., Montalbano, M., Montaldo, C., Mosti, S., Murachelli, S., Musso, M., Nardi, M., Navarra, A., Nocioni, M., Noto, P., Noto, R., Oliva, A., Onnis, I., Ottou, S., Palazzolo, C., Pallini, E., Palmieri, F., Palombi, G., Pareo, C., Passeri, V., Pelliccioni, F., Penna, G., Petrecchia, A., Petrone, A., Pianura, E., Pinnetti, C., Pisciotta, M., Piselli, P., Pittalis, S., Pontarelli, A., Proietti, C., Puro, V., Ramazzini, P. M., Rianda, A., Rinonapoli, G., Rosati, S., Rubino, D., Rueca, M., Ruggeri, A., Sacchi, A., Sampaolesi, A., Sanasi, F., Santagata, C., Scarabello, A., Scarcia, S., Scognamiglio, P., Scorzolini, L., Stazi, G., Strano, G., Taibi, C., Taloni, G., Nardi, T., Tonnarini, R., Topino, S., Tozzi, M., Vairo, F., Valli, M. B., Vincenzi, L., Visco-Comandini, U., Vita, S., Vittozzi, P., Zaccarelli, M., Zanetti, A., and Zito, S.

Subjects
Male, medicine.medical_treatment, Rome, Kaplan-Meier Estimate, 030204 cardiovascular system & hematology, Severity of Illness Index, 0302 clinical medicine, Retrospective Studie, Coagulopathy, Clinical endpoint, Intubation, Respiratory function, 030212 general & internal medicine, Multidisciplinary, Middle Aged, Medicine, Female, Human, medicine.medical_specialty, Patients, medicine.drug_class, Science, Low molecular weight heparin, Risk Assessment, Article, NO, 03 medical and health sciences, Internal medicine, Severity of illness, medicine, Intubation, Intratracheal, Humans, Retrospective Studies, Aged, business.industry, SARS-CoV-2, COVID-19, Thrombocytopenia, Retrospective cohort study, Heparin, Low-Molecular-Weight, medicine.disease, Respiration, Artificial, COVID-19 Drug Treatment, respiratory tract diseases, Pneumonia, Viral infection, business
Abstract

Prophylactic low molecular weight heparin (pLMWH) is currently recommended in COVID-19 to reduce the risk of coagulopathy. The aim of this study was to evaluate whether the antinflammatory effects of pLMWH could translate in lower rate of clinical progression in patients with COVID-19 pneumonia. Patients admitted to a COVID-hospital in Rome with SARS-CoV-2 infection and mild/moderate pneumonia were retrospectively evaluated. The primary endpoint was the time from hospital admission to orotracheal intubation/death (OTI/death). A total of 449 patients were included: 39% female, median age 63 (IQR, 50–77) years. The estimated probability of OTI/death for patients receiving pLMWH was: 9.5% (95% CI 3.2–26.4) by day 20 in those not receiving pLMWH vs. 10.4% (6.7–15.9) in those exposed to pLMWH; p-value = 0.144. This risk associated with the use of pLMWH appeared to vary by PaO2/FiO2 ratio: aHR 1.40 (95% CI 0.51–3.79) for patients with an admission PaO2/FiO2 ≤ 300 mmHg and 0.27 (0.03–2.18) for those with PaO2/FiO2 > 300 mmHg; p-value at interaction test 0.16. pLMWH does not seem to reduce the risk of OTI/death mild/moderate COVID-19 pneumonia, especially when respiratory function had already significantly deteriorated. Data from clinical trials comparing the effect of prophylactic vs. therapeutic dosage of LMWH at various stages of COVID-19 disease are needed.

Published
2021

9. SARS-CoV-2 isolation from ocular secretions of a patient with COVID-19 in Italy with prolonged viral RNA detection

Author

Colavita F., Lapa D., Carletti F., Lalle E., Bordi L., Marsella P., Nicastri E., Bevilacqua N., Giancola M. L., Corpolongo A., Ippolito G., Capobianchi M. R., Castilletti C., Abbonizio M. A., Agrati C., Albarello F., Amadei G., Amendola A., Antonini M., Barbaro R., Bartolini B., Benigni M., Bordoni V., Branca M., Campioni P., Caporale C., Caravella I., Chiappini R., Ciaralli C., Cristofaro M., Curiale S., D'Abramo A., Dantimi C., de Angelis A., de Angelis G., Di Lorenzo R., Di Stefano F., Ferraro F., Fiorentini L., Frustaci A., Galli P., Garotto G., Giansante F., Giombini E., Greci M. C., Lanini S., Lepore L., Lucia A., Lufrani F., Macchione M., Marani A., Marchioni L., Mariano A., Marini M. C., Maritti M., Matusali G., Meschi S., Messina F., Montaldo C., Murachelli S., Noto R., Palazzolo C., Pallini E., Passeri V., Pelliccioni F., Petrecchia A., Petrone A., Petrosillo N., Pianura E., Pisciotta M., Pittalis S., Proietti C., Puro V., Rinonapoli G., Rueca M., Sacchi A., Sanasi F., Santagata C., Scarcia S., Schinina V., Scognamiglio P., Scorzolini L., Stazi G., Vaia F., Vairo F., Valli M. B., Colavita, F., Lapa, D., Carletti, F., Lalle, E., Bordi, L., Marsella, P., Nicastri, E., Bevilacqua, N., Giancola, M. L., Corpolongo, A., Ippolito, G., Capobianchi, M. R., Castilletti, C., Abbonizio, M. A., Agrati, C., Albarello, F., Amadei, G., Amendola, A., Antonini, M., Barbaro, R., Bartolini, B., Benigni, M., Bordoni, V., Branca, M., Campioni, P., Caporale, C., Caravella, I., Chiappini, R., Ciaralli, C., Cristofaro, M., Curiale, S., D'Abramo, A., Dantimi, C., de Angelis, A., de Angelis, G., Di Lorenzo, R., Di Stefano, F., Ferraro, F., Fiorentini, L., Frustaci, A., Galli, P., Garotto, G., Giansante, F., Giombini, E., Greci, M. C., Lanini, S., Lepore, L., Lucia, A., Lufrani, F., Macchione, M., Marani, A., Marchioni, L., Mariano, A., Marini, M. C., Maritti, M., Matusali, G., Meschi, S., Messina, F., Montaldo, C., Murachelli, S., Noto, R., Palazzolo, C., Pallini, E., Passeri, V., Pelliccioni, F., Petrecchia, A., Petrone, A., Petrosillo, N., Pianura, E., Pisciotta, M., Pittalis, S., Proietti, C., Puro, V., Rinonapoli, G., Rueca, M., Sacchi, A., Sanasi, F., Santagata, C., Scarcia, S., Schinina, V., Scognamiglio, P., Scorzolini, L., Stazi, G., Vaia, F., Vairo, F., and Valli, M. B.

Subjects
Isolation (health care), Coronavirus disease 2019 (COVID-19), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Eye, NO, 03 medical and health sciences, 0302 clinical medicine, Internal Medicine, Medicine, Viral rna, 030304 developmental biology, 0303 health sciences, SARS-CoV-2, business.industry, COVID-19, RNA, Pneumonia, General Medicine, Conjunctivitis, medicine.disease, Letters: Observations, Virology, 3. Good health, Viral replication, 030221 ophthalmology & optometry, business, Viral load, COVID-19, Conjunctivitis, Eye, Pneumonia, SARS-CoV-2
Abstract

Background: Coronavirus disease 2019 (COVID-19), the disease caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that originated in China in December 2019, was recently recognized as pandemic threat by the World Health Organization, with the potential of rapidly overloading health care systems and causing substantial mortality worldwide (www.who.int/dg/speeches/detail/who-director-general -s-opening-remarks-at-the-media-briefing-on-covid-19 —11-march -2020). Human-to-human transmission occurs mainly through respiratory droplets, but other routes are under investigation, because SARS-CoV-2 has been detected in several body fluids (1). So far, few data are available on ocular samples from patients with COVID-19, although conjunctivitis has been occasionally reported among COVID-19 symptoms, similar to infections caused by other human coronaviruses (2, 3). During the SARS epidemic, eye exposure to infectious fluids was associated with an increased risk for SARS-CoV transmission to health care workers (3, 4). Although SARS-CoV RNA was occasionally found in ocular specimens during the early phase of illness, its infectivity is unknown (2, 3). With regard to COVID-19, unprotected ocular exposure was thought to be responsible for infections that occurred in the Wuhan Fever Clinic in January 2020 (3, 4); in addition, SARS-CoV-2 RNA was detected in conjunctival secretions collected from the only patient with conjunctivitis out of 30 patients with COVID-19 from a hospital in China (5). However, further studies are needed to evaluate the infectious potential of the SARS-CoV-2 RNA detected in the ocular specimens and to determine whether transmission may occur through ocular secretions (3, 4). Objective: To present the early detection of infectious SARS-CoV-2 in ocular fluids from a patient with the first confirmed case of COVID-19 in Italy, who had been hospitalized at the National Institute for Infectious Diseases “L. Spallanzani” (INMI) in Rome. Methods and Findings: The patient, a 65-year-old woman, travelled from Wuhan, China, to Italy on 23 January 2020 and was admitted on 29 January 2020, 1 day after symptom onset. At admission to the high isolation unit at INMI, she presented with nonproductive cough, sore throat, coryza, and bilateral conjunctivitis. She had no fever until day 4, when fever (38 °C), nausea, and vomiting began. Infection with SARS-CoV-2 was confirmed by performing real-time reverse transcription polymerase chain reaction (RT-PCR) assay on sputum samples (cycle threshold value [Ct], 16.1) on the admission day, followed by viral M gene sequencing (GenBank accession number MT008022), and virus isolation on Vero E6 cell line (2019-nCoV/Italy-INMI1). The full genome sequence was obtained from either clinical sample or culture isolate (GISAID accession numbers EPI_ISL_410545 and EPI_ISL_410546). At admission, no other respiratory infections were detected (QIAstat-Dx Respiratory Panel; Qiagen).

Published
2020

11. Active site variants in STT3A cause a dominant type I congenital disorder of glycosylation with neuromusculoskeletal findings

Author

Wilson, M., Garanto, A., Vairo, F., Ng, Bobby G., Ranatunga, Wasantha K., Ventouratou, Marina, Barenfanger, M., Huijben, Karin, Ashikov, A.M., Janssen, M.C.H., Morava, E., Lefeber, D.J., Wilson, M., Garanto, A., Vairo, F., Ng, Bobby G., Ranatunga, Wasantha K., Ventouratou, Marina, Barenfanger, M., Huijben, Karin, Ashikov, A.M., Janssen, M.C.H., Morava, E., and Lefeber, D.J.

Abstract

Item does not contain fulltext

Published
2021

12. Clinical and Functional Consequences of C-Terminal Variants in MCT8: A Case Series

Author

Geest, F.S. van, Meima, M.E., Stuurman, K.E., Wolf, N.I., Knaap, M.S. van der, Lorea, C.F., Poswar, F.O., Vairo, F., Brunetti-Pierri, N., Cappuccio, G., Bakhtiani, P., Munnik, S.A. de, Peeters, R.P., Visser, W.E., Groeneweg, S., Geest, F.S. van, Meima, M.E., Stuurman, K.E., Wolf, N.I., Knaap, M.S. van der, Lorea, C.F., Poswar, F.O., Vairo, F., Brunetti-Pierri, N., Cappuccio, G., Bakhtiani, P., Munnik, S.A. de, Peeters, R.P., Visser, W.E., and Groeneweg, S.

Abstract

Contains fulltext : 231654.pdf (Publisher’s version ) (Open Access)

Published
2021

13. Clinical and Functional Consequences of C-Terminal Variants in MCT8: A Case Series

Author

Geest, F.S. (Ferdy) van, Meima, M.E. (Marcel), Stuurman, K.E. (Kyra), Wolf, N.I. (Nicole I.), van der Knaap, M.S. (Marjo S.), Lorea, C.F. (Cláudia F), Poswar, F.O. (Fabiano O.), Vairo, F. (Filippo), Brunetti-Pierri, N. (Nicola), Cappuccio, G. (Gerarda), Bakhtiani, P. (Priyanka), Munnik, S.A. (Sonja) de, Peeters, R.P. (Robin), Visser, W.E. (Edward), Groeneweg, S. (Stefan), Geest, F.S. (Ferdy) van, Meima, M.E. (Marcel), Stuurman, K.E. (Kyra), Wolf, N.I. (Nicole I.), van der Knaap, M.S. (Marjo S.), Lorea, C.F. (Cláudia F), Poswar, F.O. (Fabiano O.), Vairo, F. (Filippo), Brunetti-Pierri, N. (Nicola), Cappuccio, G. (Gerarda), Bakhtiani, P. (Priyanka), Munnik, S.A. (Sonja) de, Peeters, R.P. (Robin), Visser, W.E. (Edward), and Groeneweg, S. (Stefan)

Abstract

CONTEXT: Genetic variants in SLC16A2, encoding the thyroid hormone transporter MCT8, can cause intellectual and motor disability and abnormal serum thyroid function tests, known as MCT8 deficiency. The C-terminal domain of MCT8 is poorly conserved, which complicates prediction of the deleteriousness of variants in this region. We studied the functional consequences of 5 novel variants within this domain and their relation to the clinical phenotypes. METHODS: We enrolled male subjects with intellectual disability in whom genetic variants were identified in exon 6 of SLC16A2. The impact of identified variants was evaluated in transiently transfected cell lines and patient-derived fibroblasts. RESULTS: Seven individuals from 5 families harbored potentially deleterious variants affecting the C-terminal domain of MCT8. Two boys with clinical features considered atypical for MCT8 deficiency had a missense variant [c.1724A>G;p.(His575Arg) or c.1796A>G;p.(Asn599Ser)] that did not affect MCT8 function in transfected cells or patient-derived fibroblasts, challenging a causal relationship. Two brothers with classical MCT8 deficiency had a truncating c.1695delT;p.(Val566*) variant that completely inactivated MCT8 in vitro. The 3 other boys had relatively less-severe clinical features and harbored frameshift variants that elongate the MCT8 protein [c.1805delT;p.(Leu602HisfsTer680) and c.del1826-1835;p.(Pro609GlnfsTer676)] and retained ~50% residual activity. Additional truncating variants within transmembrane domain 12 were fully inactivating, whereas those within the intracellular C-terminal tail were tolerated. CONCLUSIONS: Variants affecting the intracellular C-terminal tail of MCT8 are likely benign unless they cause frameshifts that elongate the MCT8 protein. These findings provide clinical guidance in the assessment of the pathogenicity of variants within the C-terminal domain of MCT8.

Published
2021
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14. Clinical and Functional Consequences of C-Terminal Variants in MCT8: A Case Series

Author

van Geest, Ferdy, Meima, Marcel, Stuurman, Kyra, Wolf, NI, van der Knaap, MS, Lorea, CF, Poswar, FO, Vairo, F, Brunetti-Pierri, N, Cappuccio, G, Bakhtiani, P, de Munnik, SA, Peeters, Robin, Visser, Edward, Groeneweg, Stefan, van Geest, Ferdy, Meima, Marcel, Stuurman, Kyra, Wolf, NI, van der Knaap, MS, Lorea, CF, Poswar, FO, Vairo, F, Brunetti-Pierri, N, Cappuccio, G, Bakhtiani, P, de Munnik, SA, Peeters, Robin, Visser, Edward, and Groeneweg, Stefan

Abstract

Context: Genetic variants in SLC16A2, encoding the thyroid hormone transporter MCT8, can cause intellectual and motor disability and abnormal serum thyroid function tests, known as MCT8 deficiency. The C-terminal domain of MCT8 is poorly conserved, which complicates prediction of the deleteriousness of variants in this region. We studied the functional consequences of 5 novel variants within this domain and their relation to the clinical phenotypes. Methods: We enrolled male subjects with intellectual disability in whom genetic variants were identified in exon 6 of SLC16A2. The impact of identified variants was evaluated in transiently transfected cell lines and patient-derived fibroblasts. Results: Seven individuals from 5 families harbored potentially deleterious variants affecting the C-terminal domain of MCT8. Two boys with clinical features considered atypical for MCT8 deficiency had a missense variant [c.1724A>G;p.(His575Arg) or c.1796A>G;p.(Asn599Ser)] that did not affect MCT8 function in transfected cells or patient-derived fibroblasts, challenging a causal relationship. Two brothers with classical MCT8 deficiency had a truncating c.1695delT;p.(Val566∗) variant that completely inactivated MCT8 in vitro. The 3 other boys had relatively less-severe clinical features and harbored frameshift variants that elongate the MCT8 protein [c.1805delT;p.(Leu602HisfsTer680) and c.del1826-1835;p.(Pro609GlnfsTer676)] and retained ~50% residual activity. Additional truncating variants within transmembrane domain 12 were fully inactivating, whereas those within the intracellular C-terminal tail were tolerated. Conclusions: Variants affecting the intracellular C-terminal tail of MCT8 are likely benign unless they cause frameshifts that elongate the MCT8 protein. These findings provide clinical guidance in the assessment of the pathogenicity of variants within the C-terminal domain of MCT8.

Published
2021

17. Lessons from the COVID-19 Pandemic—Unique Opportunities for Unifying, Revamping and Reshaping Epidemic Preparedness of Europe's Public Health Systems

Author

Ippolito, G., Lauria, F. N., Locatelli, Franco, Magrini, N., Montaldo, C., Sadun, R., Maeurer, M., Strada, G., Vairo, F., Curiale, S., Lafont, A., di Caro, A., Capobianchi, M. R., Meilicke, R., Petersen, E., Zumla, A., Pletschette, M., Locatelli F. (ORCID:0000-0002-7976-3654), Ippolito, G., Lauria, F. N., Locatelli, Franco, Magrini, N., Montaldo, C., Sadun, R., Maeurer, M., Strada, G., Vairo, F., Curiale, S., Lafont, A., di Caro, A., Capobianchi, M. R., Meilicke, R., Petersen, E., Zumla, A., Pletschette, M., and Locatelli F. (ORCID:0000-0002-7976-3654)

Abstract

NO ABSTRACT

Published
2020

18. COVID-19 disease - Temporal analyses of complete blood count parameters over course of illness, and relationship to patient demographics and management outcomes in survivors and non-survivors: A longitudinal descriptive cohort study

Author

Lanini, S., Montaldo, C., Nicastri, E., Vairo, F., Agrati, C., Petrosillo, N., Scognamiglio, P., Antinori, A., Puro, V., Di Caro, A., De Carli, G., Navarra, A., Agresta, A., Cimaglia, C., Palmieri, F., D'Offizi, G., Marchioni, L., Kobinger, G. P., Maeurer, M., Girardi, E., Capobianchi, M. R., Zumla, A., Locatelli, Franco, Ippolito, G., Locatelli F. (ORCID:0000-0002-7976-3654), Lanini, S., Montaldo, C., Nicastri, E., Vairo, F., Agrati, C., Petrosillo, N., Scognamiglio, P., Antinori, A., Puro, V., Di Caro, A., De Carli, G., Navarra, A., Agresta, A., Cimaglia, C., Palmieri, F., D'Offizi, G., Marchioni, L., Kobinger, G. P., Maeurer, M., Girardi, E., Capobianchi, M. R., Zumla, A., Locatelli, Franco, Ippolito, G., and Locatelli F. (ORCID:0000-0002-7976-3654)

Abstract

Background Detailed temporal analyses of complete (full) blood count (CBC) parameters, their evolution and relationship to patient age, gender, co-morbidities and management outcomes in survivors and non-survivors with COVID-19 disease, could identify prognostic clinical biomarkers. Methods From 29 January 2020 until 28 March 2020, we performed a longitudinal cohort study of COVID-19 inpatients at the Italian National Institute for Infectious Diseases, Rome, Italy. 9 CBC parameters were studied as continuous variables [neutrophils, lymphocytes, monocytes, platelets, mean platelet volume, red blood cell count, haemoglobin concentration, mean red blood cell volume and red blood cell distribution width (RDW %)]. Model-based punctual estimates, as average of all patients' values, and differences between survivors and non-survivors, overall, and by co-morbidities, at specific times after symptoms, with relative 95% CI and P-values, were obtained by marginal prediction and ANOVA- style joint tests. All analyses were carried out by STATA 15 statistical package. Main findings 379 COVID-19 patients [273 (72% were male; mean age was 61.67 (SD 15.60)] were enrolled and 1,805 measures per parameter were analysed. Neutrophils' counts were on average significantly higher in non-survivors than in survivors (P<0.001) and lymphocytes were on average higher in survivors (P<0.001). These differences were time dependent. Average platelets' counts (P<0.001) and median platelets' volume (P<0.001) were significantly different in survivors and non-survivors. The differences were time dependent and consistent with acute inflammation followed either by recovery or by death. Anaemia with anisocytosis was observed in the later phase of COVID-19 disease in non-survivors only. Mortality was significantly higher in patients with diabetes (OR = 3.28; 95%CI 1.51-7.13; p = 0.005), obesity (OR = 3.89; 95%CI 1.51-10.04; p = 0.010), chronic renal failure (OR = 9.23; 95%CI 3.49-24.36; p = 0.

Published
2020

19. COVID-19: Viral-host interactome analyzed by network based-approach model to study pathogenesis of SARS-CoV-2 infection

Author

Messina, F., Giombini, E., Agrati, C., Vairo, F., Ascoli Bartoli, T., Al Moghazi, S., Piacentini, M., Locatelli, Franco, Kobinger, G., Maeurer, M., Zumla, A., Capobianchi, M. R., Lauria, F. N., Ippolito, G., Locatelli F. (ORCID:0000-0002-7976-3654), Messina, F., Giombini, E., Agrati, C., Vairo, F., Ascoli Bartoli, T., Al Moghazi, S., Piacentini, M., Locatelli, Franco, Kobinger, G., Maeurer, M., Zumla, A., Capobianchi, M. R., Lauria, F. N., Ippolito, G., and Locatelli F. (ORCID:0000-0002-7976-3654)

Abstract

Background: Epidemiological, virological and pathogenetic characteristics of SARS-CoV-2 infection are under evaluation. A better understanding of the pathophysiology associated with COVID-19 is crucial to improve treatment modalities and to develop effective prevention strategies. Transcriptomic and proteomic data on the host response against SARS-CoV-2 still have anecdotic character; currently available data from other coronavirus infections are therefore a key source of information. Methods: We investigated selected molecular aspects of three human coronavirus (HCoV) infections, namely SARS-CoV, MERS-CoV and HCoV-229E, through a network based-approach. A functional analysis of HCoV-host interactome was carried out in order to provide a theoretic host-pathogen interaction model for HCoV infections and in order to translate the results in prediction for SARS-CoV-2 pathogenesis. The 3D model of S-glycoprotein of SARS-CoV-2 was compared to the structure of the corresponding SARS-CoV, HCoV-229E and MERS-CoV S-glycoprotein. SARS-CoV, MERS-CoV, HCoV-229E and the host interactome were inferred through published protein-protein interactions (PPI) as well as gene co-expression, triggered by HCoV S-glycoprotein in host cells. Results: Although the amino acid sequences of the S-glycoprotein were found to be different between the various HCoV, the structures showed high similarity, but the best 3D structural overlap shared by SARS-CoV and SARS-CoV-2, consistent with the shared ACE2 predicted receptor. The host interactome, linked to the S-glycoprotein of SARS-CoV and MERS-CoV, mainly highlighted innate immunity pathway components, such as Toll Like receptors, cytokines and chemokines. Conclusions: In this paper, we developed a network-based model with the aim to define molecular aspects of pathogenic phenotypes in HCoV infections. The resulting pattern may facilitate the process of structure-guided pharmaceutical and diagnostic research with the prospect to identify potential

Published
2020

21. Comprehensive germline mutation analysis and clinical profile in a large cohort of Brazilian xeroderma pigmentosum patients

Author

Santiago, K.M., primary, Castro, L.P., additional, Neto, J.P.D., additional, de Nóbrega, A.F., additional, Pinto, C.A.L., additional, Ashton‐Prolla, P., additional, Pinto e Vairo, F., additional, de Medeiros, P.F.V., additional, Ribeiro, E.M., additional, Ribeiro, B.F.R., additional, do Valle, F.F., additional, Doriqui, M.J.R., additional, Leite, C.H.B., additional, Rocha, R.M., additional, Moura, L.M.S., additional, Munford, V., additional, Galante, P.A.F., additional, Menck, C.F.M., additional, Rogatto, S.R., additional, and Achatz, M.I., additional

Published
2020
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25. Imported severe malaria and risk factors for intensive care: A single-centre retrospective analysis

Author

D'Abramo, A, Lepore, L, Iannetta, M, Tekle, Sg, Corpolongo, A, Scorzolini, L, Bevilacqua, N, Mariano, A, Giancola, Ml, Vulcano, A, Maritti, M, Agresta, A, Antonini, M, D'Alessandro, U, Nicastri, E, Bartoli, Ta, Calo, F, Di Caro, A, Fabbri, G, Marchioni, L, Navarra, A, Nisii, C, Paglia, Mg, Palazzolo, C, Scognamiglio, P, and Vairo, F

Subjects
Male, Plasmodium, Multivariate analysis, Rome, Aminotransferases, Comorbidity, Biochemistry, Severity of Illness Index, 0302 clinical medicine, Mathematical and Statistical Techniques, 030202 anesthesiology, Communicable Diseases, Imported, Risk Factors, Medicine and Health Sciences, 030212 general & internal medicine, Coma, Protozoans, Multidisciplinary, Statistics, Malarial Parasites, Eukaryota, Middle Aged, Hospitals, Enzymes, Hospitalization, Intensive Care Units, Neurology, Physical Sciences, Medicine, Female, Research Article, Adult, medicine.medical_specialty, Critical Care, Science, MEDLINE, macromolecular substances, Research and Analysis Methods, Communicable Diseases, 03 medical and health sciences, Transferases, Intensive care, Internal medicine, Humans, Malaria, Retrospective Studies, Severity of illness, Parasite Groups, medicine, Parasitic Diseases, Severe Malaria, Statistical Methods, business.industry, Organisms, Biology and Life Sciences, Proteins, Retrospective cohort study, medicine.disease, Tropical Diseases, Settore MED/17, Parasitic Protozoans, Health Care, Imported, Health Care Facilities, Multivariate Analysis, Enzymology, Parasitology, business, Apicomplexa, Mathematics
Abstract

Objectives This study aims to identify the risk factors for intensive care (IC) in severe malaria patients admitted to the "Lazzaro Spallanzani" National Institute for Infectious Diseases, Rome, Italy. Methods All patients with confirmed severe malaria and hospitalized between 2007 and 2015 were included in the analysis and stratified into two groups: those requiring IC and those who did not. Five prognostic malaria scores were estimated; clinical severity at IC unit admission was assessed using the Sequential Organ Failure Assessment and the quick-Sequential Organ Failure Assessment scores. Univariate and multivariate analysis were performed to assess factors independently associated to IC. Results A total of 98 severe malaria patients were included; 10 of them required IC. There were no deaths or sequelae. Patients requiring IC had higher severity scores. At the multivariate analysis, only the number of World Health Organization criteria and the aspartate aminotransferase value were independently associated with the need of IC. Conclusions An early and accurate assessment of the severity score is essential for the management of severe malaria patients.

Published
2019

27. Clinical, epidemiological and virological features of acute hepatitis B in Italy

Author

Zuccaro O, Romanò L, Mele A, Mariano A, Clementi M, Tosti ME, Taliani G, Galli C, Zanetti AR, Spada E, Raise E, Eseme FE, Maio G, Rummo G, Maio P, Di Giuli C, Bellissima P, Bonfante S, Chiriacò P, Cacopardo B, Blanc P, Palattella S, Santantonio T, Guastadisegni A, Amoroso P, Fabris P, Giordani MT, Vullo V, Giuberti T, Schivazzappa S, Trezzi M, Biagetti C, Pocaterra D, Sagnelli E, Messina V, Antonucci G, Spallanzani L, Vairo F, Marinelli M, Paladini S, Tagliacarne C., VERUCCHI, GABRIELLA, Zuccaro O, Romanò L, Mele A, Mariano A, Clementi M, Tosti ME, Taliani G, Galli C, Zanetti AR, Spada E, Raise E, Eseme FE, Maio G, Rummo G, Maio P, Di Giuli C, Bellissima P, Bonfante S, Chiriacò P, Cacopardo B, Blanc P, Palattella S, Santantonio T, Guastadisegni A, Amoroso P, Fabris P, Giordani MT, Vullo V, Giuberti T, Schivazzappa S, Trezzi M, Verucchi G, Biagetti C, Pocaterra D, Sagnelli E, Messina V, Antonucci G, Spallanzani L, Vairo F, Marinelli M, Paladini S, Tagliacarne C, Zuccaro, O., Romano, L., Mele, A., Mariano, A., Clementi, M., Tosti, M. E., Taliani, G., Galli, C., Zanetti, A. R., and Spada, E.

Subjects
Adult, Male, Microbiology (medical), Hepatitis B virus, medicine.medical_specialty, Adolescent, Genotype, Epidemiology, Genotypes, Gene mutation, medicine.disease_cause, Cohort Studies, Young Adult, Basal (phylogenetics), 80 and over, medicine, Humans, Hepatitis B Vaccines, Prospective Studies, Acute infection, Hepatitis B, Mutations, Risk factors, Aged, Acute Disease, Aged, 80 and over, Female, Follow-Up Studies, Hepatitis B Core Antigens, Italy, Middle Aged, Infectious Diseases, business.industry, Promoter, General Medicine, medicine.disease, Virology, Mutation, Immunology, Acute hepatitis B, business
Abstract

Purpose: To evaluate the association of hepatitis B virus (HBV) genotypes, basal core promoter (BCP)/precore (PC) and S gene mutations with the clinical-epidemiological characteristics of acute hepatitis B (AHB) in Italy. Methods: During July 2005–January 2007, 103 symptomatic AHB patients were enrolled and prospectively followed up at 15 national hospitals. HBV genotypes, BCP/PC and S gene variants were determined by nested-PCR and direct sequence analysis. Results: Genotype D, A and F were detected in 49, 45 and 6% of patients, respectively. BCP, PC, and BCP plus PC variants were found in 3.1, 11.3 and 7.2% of patients, respectively. At enrollment, 68.3% of patients were hepatitis B e antigen (HBeAg)-positive and 31.7% HBeAg-negative. BCP/PC mutations were more common in HBeAg-negative than in HBeAg-positive patients (p&nbsp

Published
2015

29. Overproduction of IL-6 and Type I IFN in a lethal case of Chikungunya virus infection in an elderly man during the 2017 Italian outbreak

Author

Colavita, F., primary, Vita, S., additional, Lalle, E., additional, Bordi, L., additional, Carletti, F., additional, Pozzetto, I., additional, Aiuti, M., additional, Vincenti, D., additional, Cimini, E., additional, Vairo, F., additional, Capobianchi, M.R., additional, Lichtner, M., additional, and Castilletti, C., additional

Published
2019
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30. De Novo Pathogenic Variants in CACNA1E Cause Developmental and Epileptic Encephalopathy with Contractures, Macrocephaly, and Dyskinesias

Author

Helbig, K.L., Lauerer, R.J., Bahr, J.C., Souza, I.A., Myers, C.T., Uysal, B., Schwarz, N., Gandini, M.A., Huang, S., Keren, B., Mignot, C., Afenjar, A., Villemeur, T. Billette de, Heron, D., Nava, C., Valence, S., Buratti, J., Fagerberg, C.R., Soerensen, K.P., Kibaek, M., Kamsteeg, E.J., Koolen, D.A., Gunning, B., Schelhaas, H.J., Kruer, M.C., Fox, J., Bakhtiari, S., Jarrar, R., Padilla-Lopez, S., Lindstrom, K., Jin, S.C., Zeng, X., Bilguvar, K., Papavasileiou, A., Xin, Q., Zhu, C., Boysen, K., Vairo, F., Lanpher, B.C., Klee, E.W., Tillema, J.M., Payne, E.T., Cousin, M.A., Kruisselbrink, T.M., Wick, M.J., Baker, J., Haan, E., Smith, N., Corbett, M.A., MacLennan, A.H., Gecz, J., Biskup, S., Goldmann, E., Rodan, L.H., Kichula, E., Segal, E., Jackson, K.E., Asamoah, A., Dimmock, D., McCarrier, J., Botto, L.D., Filloux, F., Tvrdik, T., Cascino, G.D., Klingerman, S., Neumann, C., Wang, R., Jacobsen, J.C., Nolan, M.A., Snell, R.G., Lehnert, K., Sadleir, L.G., Anderlid, B.M., Kvarnung, M., Guerrini, R., Friez, M.J., Lyons, M.J., Leonhard, J., Kringlen, G., Casas, K., Achkar, C.M. El, Smith, L.A., Rotenberg, A., Poduri, A., Sanchis-Juan, A., Carss, K.J., Rankin, J., Zeman, A., Raymond, F.L., Blyth, M., Kerr, B., Ruiz, K., Urquhart, J., Hughes, I., Banka, S., Hedrich, U.B.S., Scheffer, I.E., Helbig, I., Zamponi, G.W., Lerche, H., et al., Helbig, K.L., Lauerer, R.J., Bahr, J.C., Souza, I.A., Myers, C.T., Uysal, B., Schwarz, N., Gandini, M.A., Huang, S., Keren, B., Mignot, C., Afenjar, A., Villemeur, T. Billette de, Heron, D., Nava, C., Valence, S., Buratti, J., Fagerberg, C.R., Soerensen, K.P., Kibaek, M., Kamsteeg, E.J., Koolen, D.A., Gunning, B., Schelhaas, H.J., Kruer, M.C., Fox, J., Bakhtiari, S., Jarrar, R., Padilla-Lopez, S., Lindstrom, K., Jin, S.C., Zeng, X., Bilguvar, K., Papavasileiou, A., Xin, Q., Zhu, C., Boysen, K., Vairo, F., Lanpher, B.C., Klee, E.W., Tillema, J.M., Payne, E.T., Cousin, M.A., Kruisselbrink, T.M., Wick, M.J., Baker, J., Haan, E., Smith, N., Corbett, M.A., MacLennan, A.H., Gecz, J., Biskup, S., Goldmann, E., Rodan, L.H., Kichula, E., Segal, E., Jackson, K.E., Asamoah, A., Dimmock, D., McCarrier, J., Botto, L.D., Filloux, F., Tvrdik, T., Cascino, G.D., Klingerman, S., Neumann, C., Wang, R., Jacobsen, J.C., Nolan, M.A., Snell, R.G., Lehnert, K., Sadleir, L.G., Anderlid, B.M., Kvarnung, M., Guerrini, R., Friez, M.J., Lyons, M.J., Leonhard, J., Kringlen, G., Casas, K., Achkar, C.M. El, Smith, L.A., Rotenberg, A., Poduri, A., Sanchis-Juan, A., Carss, K.J., Rankin, J., Zeman, A., Raymond, F.L., Blyth, M., Kerr, B., Ruiz, K., Urquhart, J., Hughes, I., Banka, S., Hedrich, U.B.S., Scheffer, I.E., Helbig, I., Zamponi, G.W., and Lerche, H., et al.

Abstract

Item does not contain fulltext, Developmental and epileptic encephalopathies (DEEs) are severe neurodevelopmental disorders often beginning in infancy or early childhood that are characterized by intractable seizures, abundant epileptiform activity on EEG, and developmental impairment or regression. CACNA1E is highly expressed in the central nervous system and encodes the alpha1-subunit of the voltage-gated CaV2.3 channel, which conducts high voltage-activated R-type calcium currents that initiate synaptic transmission. Using next-generation sequencing techniques, we identified de novo CACNA1E variants in 30 individuals with DEE, characterized by refractory infantile-onset seizures, severe hypotonia, and profound developmental impairment, often with congenital contractures, macrocephaly, hyperkinetic movement disorders, and early death. Most of the 14, partially recurring, variants cluster within the cytoplasmic ends of all four S6 segments, which form the presumed CaV2.3 channel activation gate. Functional analysis of several S6 variants revealed consistent gain-of-function effects comprising facilitated voltage-dependent activation and slowed inactivation. Another variant located in the domain II S4-S5 linker results in facilitated activation and increased current density. Five participants achieved seizure freedom on the anti-epileptic drug topiramate, which blocks R-type calcium channels. We establish pathogenic variants in CACNA1E as a cause of DEEs and suggest facilitated R-type calcium currents as a disease mechanism for human epilepsy and developmental disorders.

Published
2018

31. A CACNA1D mutation in a patient with persistent hyperinsulinaemic hypoglycaemia, heart defects, and severe hypotonia

Author

Flanagan, SE, Vairo, F, Johnson, MB, Caswell, R, Laver, TW, Lango Allen, H, Hussain, K, Ellard, S, Flanagan, SE [0000-0002-8670-6340], and Apollo - University of Cambridge Repository

Subjects
Heart Defects, Congenital, Calcium Channels, L-Type, Developmental Disabilities, Aortic Valve Insufficiency, DNA Mutational Analysis, Infant, Newborn, Case Report, hyperinsulinism, Neuromuscular Diseases, Hypoglycemia, Fetal Macrosomia, CACNA1D, Amino Acid Substitution, Mutation, Humans, Muscle Hypotonia, calcium channel, Female, exome sequencing, hypoglycaemia
Abstract

Congenital hyperinsulinaemic hypoglycaemia (HH) can occur in isolation or it may present as part of a wider syndrome. For approximately 40%-50% of individuals with this condition, sequence analysis of the known HH genes identifies a causative mutation. Identifying the underlying genetic aetiology in the remaining cases is important as a genetic diagnosis will inform on recurrence risk, may guide medical management and will provide valuable insights into β-cell physiology. We sequenced the exome of a child with persistent diazoxide-responsive HH, mild aortic insufficiency, severe hypotonia, and developmental delay as well as the unaffected parents. This analysis identified a de novo mutation, p.G403D, in the proband's CACNA1D gene. CACNA1D encodes the main L-type voltage-gated calcium channel in the pancreatic β-cell, a key component of the insulin secretion pathway. The p.G403D mutation had been reported previously as an activating mutation in an individual with primary hyper-aldosteronism, neuromuscular abnormalities, and transient hypoglycaemia. Sequence analysis of the CACNA1D gene in 60 further cases with HH did not identify a pathogenic mutation. Identification of an activating CACNA1D mutation in a second patient with congenital HH confirms the aetiological role of CACNA1D mutations in this disorder. A genetic diagnosis is important as treatment with a calcium channel blocker may be an option for the medical management of this patient.

Published
2017

33. Genetic profile of Brazilian patients with dystrophinopathies

Author

de Almeida, P.A.D., primary, Machado-Costa, M.C., additional, Manzoli, G.N., additional, Ferreira, L.S., additional, Rodrigues, M.C.S., additional, Bueno, L.S.M., additional, Saute, J.A.M., additional, Pinto Vairo, F., additional, Matte, U.S., additional, Siebert, M., additional, Cossio, S.L., additional, Macedo, G.S., additional, Winckler, P.B., additional, Becker, M.M., additional, Magalhães, L.V.B., additional, Gonçalves, M.V.M., additional, Marrone, C.D., additional, Nucci, A., additional, and França, M.C., additional

Published
2017
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34. Preparedness and response during Mass-gatherings: The ongoing experience of the Regional Plan for surveillance and response to infectious diseases emergencies during the extraordinary Jubilee 2015-16

Author

Vairo, F., primary, Schepisi, M. Sane, additional, Perrelli, F., additional, Di Bari, V., additional, Pisapia, R., additional, Nicastri, E., additional, Lauria, F.N., additional, Ippolito, G., additional, Scognamiglio, P., additional, and Puro, V., additional

Published
2016
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36. Molecular signature of the Ebola virus associated with the fishermen community outbreak in Aberdeen, Sierra Leone, in February 2015

Author

Capobianchi, M, Gruber, C, Carletti, F, Meschi, S, Castilletti, C, Vairo, F, Biava, M, Minosse, C, Strada, G, Portella, G, Miccio, R, Minardi, V, Rolla, L, Kamara, A, Chillemi, G, Desideri, A, Di Caro, A, Ippolito, G, Cannas, A, Venditti, C, Zaccaro, P, Colavita, F, Mazzarelli, A, Vulcano, A, Chiappini, R, Valli, M, Grassi, G, Lapa, D, Quartu, S, and Coen, S

Subjects
Ebola virus, Settore BIO/11, Outbreak, Subclade, Biology, Disease cluster, Bioinformatics, medicine.disease_cause, Virology, 3. Good health, Sierra leone, Viruses, Genetics, medicine, Molecular Biology, Health worker
Abstract

We report the complete genome sequence of Ebola virus from a health worker linked to a cluster of cases occurring in the fishing community of Aberdeen, Sierra Leone (February 2015), which were characterized by unusually severe presentation. The sequence, clustering in the SL subclade 3.2.4, harbors mutations potentially relevant for pathogenesis.

Published
2015

43. Antiretroviral strategies for the treatment of pregnant HIV+ women and prevention of perinatal HIV transmission in Dodoma, Tanzania: AMANI Study

Author

Liuzzi, G, Vairo, F, Chaula, Z, Nguhuni, B, Nicastri, E, Bevilacqua, N, Cannas, A, Paglia, Mg, and Ippolito, G

Subjects
Pregnant women -- Drug therapy, HIV infection -- Drug therapy -- Prevention, Health
Abstract

7‐11 November 2010, Tenth International Congress on Drug Therapy in HIV Infection, Glasgow, UK, Background The use of HAART during lactation has also been discussed as an approach to reduce postnatal HIV‐1 transmission. The benefits and safety of HAART used solely for prevention of [...]

Published
2010
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44. Maple syrup urine disease: mechanisms and management

Author

Blackburn PR, Gass JM, Vairo FP, Farnham KM, Atwal HK, Macklin S, Klee EW, and Atwal PS

Subjects
Maple Syrup Urine Disease, BCKDHA, BCKDHB, DBT, newborn screening, alloisoleucine, branched-chain amino acids, Medicine (General), R5-920, Genetics, QH426-470
Abstract

Patrick R Blackburn,1,2,* Jennifer M Gass,1,* Filippo Pinto e Vairo,3,4,* Kristen M Farnham,5 Herjot K Atwal,6 Sarah Macklin,5 Eric W Klee,3,4,7,8 Paldeep S Atwal1,5 1Center for Individualized Medicine, 2Department of Health Sciences Research, Mayo Clinic, Jacksonville, FL, 3Center for Individualized Medicine, 4Department of Health Sciences Research, Mayo Clinic, Rochester, MN, 5Department of Clinical Genomics, Mayo Clinic, Jacksonville, FL, 6Department of Pharmacy, Mayo Clinic, Rochester, MN, 7Department of Clinical Genomics, Mayo Clinic, Jacksonville, FL, 8Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA *These authors contributed equally to this work Abstract: Maple syrup urine disease (MSUD) is an inborn error of metabolism caused by defects in the branched-chain α-ketoacid dehydrogenase complex, which results in elevations of the branched-chain amino acids (BCAAs) in plasma, α-ketoacids in urine, and production of the pathognomonic disease marker, alloisoleucine. The disorder varies in severity and the clinical spectrum is quite broad with five recognized clinical variants that have no known association with genotype. The classic presentation occurs in the neonatal period with developmental delay, failure to thrive, feeding difficulties, and maple syrup odor in the cerumen and urine, and can lead to irreversible neurological complications, including stereotypical movements, metabolic decompensation, and death if left untreated. Treatment consists of dietary restriction of BCAAs and close metabolic monitoring. Clinical outcomes are generally good in patients where treatment is initiated early. Newborn screening for MSUD is now commonplace in the United States and is included on the Recommended Uniform Screening Panel (RUSP). We review this disorder including its presentation, screening and clinical diagnosis, treatment, and other relevant aspects pertaining to the care of patients. Keywords: maple syrup urine disease, BCKDHA, BCKDHB, DBT, newborn screening, alloisoleucine, branched-chain amino acids

Published
2017

45. Clinical management of imported malaria in Italy: Results from a national cross-sectional survey in 2015

Author

Lepore, L., Vairo, F., D Abramo, A., Grilli, E., Corpolongo, A., Scorzolini, L., Nisii, C., Calleri, G., Castelli, F., Chirianni, A., Ippolito, G., Nicastri, E., Andreoni, M., Angarano, G., Anselmo, M., Ascoli Bartoli, T., Bartoloni, A., Bassi, P., Bevilacqua, N., Bisoffi, Z., Cacopardo, B., Caligaris, S., Calzetti, C., Casolari, S., Cassola, G., Chianura, L., Chiodera, A., Conforto, M., Coppola, N., Luca, A., Feasi, M., Ferrari, C., Filippini, P., Foti, G., Francavilla, E., Fusco, F. M., Tekle, S. G., Giancola, M. L., Giammario, A., Giobbia, M., Giordani, M. T., Gobbi, F., Gori, A., Grossi, P., Iacobello, C., Iannetta, M., Libanore, M., Luzzati, R., Magnani, G., Manfrin, V., Mariano, A., Mastroianni, C., Mazzotta, F., Mecocci, L., Mondardini, V., Montineri, A., Nicolini, L. A., Oliva, A., Palazzolo, C., Pasquale, G., Portelli, V., Puoti, M., Quirino, T., Santantonio, T. A., Sarmati, L., Sciotti, M. P., Scotton, P., Tomasoni, L. R., Toscanini, F., Tunesi, S., Elisa Vanino, Viale, P., Viganò, P., Viscoli, C., Vullo, V., Lepore, L., Vairo, F., D'Abramo, A., Grilli, E., Corpolongo, A., Scorzolini, L., Nisii, C., Calleri, G., Castelli, F., Chirianni, A., Ippolito, G., Nicastri, E., Andreoni, M., Angarano, G., Anselmo, M., Ascoli Bartoli, T., Bartoloni, A., Bassi, P., Bevilacqua, N., Bisoffi, Z., Cacopardo, B., Caligaris, S., Calzetti, C., Casolari, S., Cassola, G., Chianura, L., Chiodera, A., Conforto, M., Coppola, N., De Luca, A., Feasi, M., Ferrari, C., Filippini, P., Foti, G., Francavilla, E., Fusco, F. M., Tekle, S. G., Giancola, M. L., Giammario, A., Giobbia, M., Giordani, M. T., Gobbi, F., Gori, A., Grossi, P., Iacobello, C., Iannetta, M., Libanore, M., Luzzati, R., Magnani, G., Manfrin, V., Mariano, A., Mastroianni, C., Mazzotta, F., Mecocci, L., Mondardini, V., Montineri, A., Nicolini, L. A., Oliva, A., Palazzolo, C., Pasquale, G., Portelli, V., Puoti, M., Quirino, T., Santantonio, T. A., Sarmati, L., Sciotti, M. P., Scotton, P., Tomasoni, L. R., Toscanini, F., Tunesi, S., Vanino, E., Viale, P., Vigano, P., Viscoli, C., and Vullo, V.

Subjects
Plasmodium, Travel, Clinical Management, Imported Malaria, Italian National Survey, Plasmodium falciparum, Malaria, Antimalarials, Cross-Sectional Studies, Humans, Italy, Retrospective Studies, Surveys and Questionnaires
Abstract

In Italy, malaria continues to be one of the most common imported parasitoses; therefore, continuous surveillance of epidemiological data and clinical management is needed. In 2016, the National Institute for Infectious Diseases 'Lazzaro Spallanzani' in Rome promoted a retrospective questionnaire-based survey to assess the clinical management of imported malaria cases in Italy in 2015. The questionnaire was sent to 104 Tropical and/or Infectious Diseases Units in the country, and 37 of them filled out and returned the questionnaires. A total of 399 malaria cases were reported in 2015, mostly caused by Plasmodium falciparum and imported from Africa. Malaria chemoprophylaxis was correctly used by a minority of patients. Most patients presented with uncomplicated malaria and were treated orally. In severe cases, intravenous artesunate or quinine alone or in combination were administered, although one third of these severe cases received oral treatment. This retrospective survey reveals a lack of homogeneity in management of malaria-imported cases in Italy. Improvement of malaria chemoprophylaxis, standardization of clinical management of malaria cases and harmonization of oral and intravenous drug availability are needed throughout the country.

47. Short-term economic impact of the Zika virus outbreak

Author

Macciocchi D, Lanini S, Vairo F, Zumla A, Lt, Figueiredo, Fn, Lauria, Strada G, Brouqui P, Puro V, Krishna S, Kremsner P, Scognamiglio P, Köhler C, Nicastri E, Di Caro A, Rm, Cieri, Jp, Ioannidis, Kobinger G, Mn, Burattini, and Giuseppe Ippolito

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