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245 results on '"Calvello, M."'

4. Influence of Numerosity and Distribution of Piezometric Data on the Performance of a Warning Model for Weather-Induced Landslides in Norway

Author

Pecoraro, G., Calvello, M., di Prisco, Marco, Series Editor, Chen, Sheng-Hong, Series Editor, Vayas, Ioannis, Series Editor, Kumar Shukla, Sanjay, Series Editor, Sharma, Anuj, Series Editor, Kumar, Nagesh, Series Editor, Wang, Chien Ming, Series Editor, Calvetti, Francesco, editor, Cotecchia, Federica, editor, Galli, Andrea, editor, and Jommi, Cristina, editor

Published
2020
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8. Metaplastic breast cancer: an all-round multidisciplinary consensus

Author

Corso, G., Criscitiello, C., Nicosia, L., Pesapane, F., Vicini, E., Magnoni, F., Sibilio, A., Zanzottera, C., De Scalzi, A.M., Mannucci, S., Marabelli, M., Calvello, M., Feroce, I., Zagami, P., Porta, F.M., Toesca, A., Tarantino, P., Nicolò, E., Mazzarol, G., La Vecchia, C., Bonanni, B., Leonardi, M.C., Veronesi, P., and Fusco, N.

Subjects
Cancer Research, Oncology, Settore MED/06 - Oncologia Medica, Epidemiology, Settore MED/42 - Igiene Generale e Applicata, Public Health, Environmental and Occupational Health, Settore MED/01 - Statistica Medica
Published
2023

15. Patient-reported outcomes and patient-reported outcome measures in interstitial lung disease: where to go from here?

Author

Kalluri, M., Luppi, F., Vancheri, A., Vancheri, C., Balestro, E., Varone, F., Mogulkoc, N., Cacopardo, G., Bargagli, E., Renzoni, E., Torrisi, S., Calvello, M., Libra, A., Pavone, M., Bonella, F., Cottin, V., Valenzuela, C., Wijsenbeek, M., Bendstrup, E., 3rd International Summit for ILD (ISILD), Erice collaborators listed below: Carlo Albera, Goksel, Altinisik, Kjetil, Ask, Elisabetta, Balestro, Elena, Bargagli, Elisabeth, Bendstrup, Marialuisa, Bocchino, Francesco, Bonella, Martina, Bonifazi, Giulia, Cacopardo, Maria, Calvello, Diego, M Castillo, Nazia, Chaudhuri, Ulrich, Costabel, Vincent, Cottin, Bruno, Crestani, Manuela, Funke-Chambour, Jack, Gauldie, Peter, M George, Johannes, C Grutters, Sergio, Harari, Richard, G Jenkins, Kerri, A Johannson, Mark, G Jones, Meena, Kalluri, Michael, P Keane, Maria, A Kokosi, Michael, Kreuter, Donato, Lacedonia, Brett, Ley, Alessandro, Libra, Fabrizio, Luppi, Toby, M Maher, George, A Margaritopoulos, Fernando, J Martinez, Jelle, Miedema, Nesrin, Mogulkoc, Maria, Molina-Molina, Philip, L Molyneaux, Julie, Morisset, Stefano, Palmucci, Mauro, Pavone, Ganesh, R Raghu, Elisabetta, A Renzoni, Luca, Richeldi, Gianluca, Sambataro, Alfredo, Sebastiani, Paolo, Spagnolo, Giulia Maria Stella, Martina, Sterclova, Irina, Strambu, Tomassetti, Sara, Sebastiano, Torrisi, Jacopo, Simonetti, Haluk, Turktas, Argyrios, Tzouvelekis, Claudia, Valenzuela, Ada, Vancheri, Carlo, Vancheri, Francesco, Varone, Patrizio, Vitulo, Athol, U Wells, Marlies, S Wijsenbeek, Wim, A Wuyts, Kalluri, M, Luppi, F, Vancheri, A, Vancheri, C, Balestro, E, Varone, F, Mogulkoc, N, Cacopardo, G, Bargagli, E, Renzoni, E, Torrisi, S, Calvello, M, Libra, A, Pavone, M, Bonella, F, Cottin, V, Valenzuela, C, Wijsenbeek, M, Bendstrup, E, Kalluri, M., Luppi, F., Vancheri, A., Vancheri, C., Balestro, E., Varone, F., Mogulkoc, N., Cacopardo, G., Bargagli, E., Renzoni, E., Torrisi, S., Calvello, M., Libra, A., Pavone, M., Bonella, F., Cottin, V., Valenzuela, C., Wijsenbeek, M., Bendstrup, E., and Bocchino, M.

Subjects
Pulmonary and Respiratory Medicine, medicine.medical_specialty, Concordance, Health Status, interstitial lung dieseases, MEDLINE, Medizin, Prom, 03 medical and health sciences, 0302 clinical medicine, Medicine, Humans, 030212 general & internal medicine, Patient Reported Outcome Measures, Intensive care medicine, business.industry, Minimal clinically important difference, Interstitial lung disease, respiratory system, medicine.disease, Idiopathic Pulmonary Fibrosis, female genital diseases and pregnancy complications, respiratory tract diseases, Clinical trial, patient reported outcomes, patient reported outcome measures, idiopathic pulmonary fibrosi, 030228 respiratory system, Patient-reported outcome, Computerized adaptive testing, Patient Participation, business, Lung Diseases, Interstitial
Abstract

Patient-reported outcome measures (PROMs), tools to assess patient self-report of health status, are now increasingly used in research, care and policymaking. While there are two well-developed disease-specific PROMs for interstitial lung diseases (ILD) and idiopathic pulmonary fibrosis (IPF), many unmet and urgent needs remain. In December 2019, 64 international ILD experts convened in Erice, Italy to deliberate on many topics, including PROMs in ILD. This review summarises the history of PROMs in ILD, shortcomings of the existing tools, challenges of development, validation and implementation of their use in clinical trials, and the discussion held during the meeting. Development of disease-specific PROMs for ILD including IPF with robust methodology and validation in concordance with guidance from regulatory authorities have increased user confidence in PROMs. Minimal clinically important difference for bidirectional changes may need to be developed. Cross-cultural validation and linguistic adaptations are necessary in addition to robust psychometric properties for effective PROM use in multinational clinical trials. PROM burden of use should be reduced through appropriate use of digital technologies and computerised adaptive testing. Active patient engagement in all stages from development, testing, choosing and implementation of PROMs can help improve probability of success and further growth.

Published
2021

16. Disease progression across the spectrum of idiopathic pulmonary fibrosis: A multicentre study

Author

Sgalla, G, Lo Greco, E, Calvello, M, Varone, F, Iovene, B, Cerri, S, Donatelli, P, Vancheri, A, Pavone, M, Luppi, F, Vancheri, C, Richeldi, L, Sgalla G., Lo Greco E., Calvello M., Varone F., Iovene B., Cerri S., Donatelli P., Vancheri A., Pavone M., Luppi F., Vancheri C., Richeldi L., Sgalla, G, Lo Greco, E, Calvello, M, Varone, F, Iovene, B, Cerri, S, Donatelli, P, Vancheri, A, Pavone, M, Luppi, F, Vancheri, C, Richeldi, L, Sgalla G., Lo Greco E., Calvello M., Varone F., Iovene B., Cerri S., Donatelli P., Vancheri A., Pavone M., Luppi F., Vancheri C., and Richeldi L.

Abstract

Background and objective: In clinical practice, a working diagnosis of IPF may be performed to provide effective antifibrotic treatment to patients who cannot undergo SLB. In this study, we compared the disease course across IPF diagnostic categories in a real-life clinical setting to clarify the appropriateness of a working diagnosis of IPF and treatment initiation in these patients. Methods: Longitudinal data from IPF patients receiving antifibrotic treatment (pirfenidone or nintedanib) were retrospectively collected at three tertiary centres in Italy. Univariate and multivariate analyses were performed to compare time to death and to a composite endpoint of disease progression between two diagnostic subgroups, that is, patients with UIP on HRCT and/or SLB, and patients with possible UIP and no histological confirmation. Results: A total of 249 IPF patients were included in the analysis. Among patients with a possible UIP pattern on HRCT, 41 (55%) were prescribed antifibrotic treatment (either nintedanib or pirfenidone) despite absence of histological confirmation. This group demonstrated similar mortality and disease progression as compared to patients with a definite diagnosis of IPF as per diagnostic guidelines (log-rank test P = 0.771 and P = 0.139, respectively). Such findings were confirmed on multivariate analysis (HR: 1.19, 95% CI: 0.49–2.89, P = 0.7 for death; HR: 1.42, 95% CI: 0.83–2.44, P = 0.201 for disease progression). Conclusion: In patients receiving antifibrotics following a working diagnosis of IPF, disease progression rates were similar to patients with a confident diagnosis of IPF according to consensus guidelines, supporting the rationale for treatment initiation in these patients by expert multidisciplinary teams.

Published
2020

17. Fatigue in Covid-19 survivors: The potential impact of a nutritional supplement on muscle strength and function

Author

Galluzzo, Vincenzo, Zazzara, Maria Beatrice, Ciciarello, Francesca, Savera, Giulia, Pais, C., Calvani, Riccardo, Picca, A., Marzetti, Emanuele, Landi, Francesco, Tosato, Matteo, Steering, Committee, Gremese, Elisa, Coordination, Bernabei, Roberto, Fantoni, Massimo, Gasbarrini, Antonio, Field, Investigator, Gastroenterology, Team, Porcari, Serena, Settanni, Carlo Romano, Geriatric, Team, Benvenuto, F., Bramato, Giulia, Brandi, Vincenzo, Carfi, A., Fabrizi, Sofia, Lo Monaco, Maria Rita, Martone, Anna Maria, Napolitano, C., Pagano, Francesco Cosimo, Rocchi, Sara, Rota, E., Salerno, Andrea Maria, Tritto, M., Catalano, Lucio, Damiano, Francesco Paolo, Rocconi, Alessandra, Galliani, Alessandro, Spaziani, G., Tupputi, Salvatore, Cocchi, Camilla, Pirone, Flavia, D'Ignazio, F., Cacciatore, Stefano, Infectious disease, Team, Cauda, Roberto, Tamburrini, Enrica, Borghetti, Alberto, Di Gianbenedetto, S., Murri, Rita, Cingolani, Antonella, Ventura, Giulio, Taddei, E., Moschese, D., Ciccullo, A., Dusina, A., Internal Medicine, Team, Stella, L., Addolorato, Giovanni, Franceschi, Francesco, Mingrone, Geltrude, Zocco, Maria Assunta, Microbiology, Team, Sanguinetti, Maurizio, Cattani Franchi, Paola, Marchetti, Simona, Posteraro, Brunella, Sali, M., Neurology, Team, Bizzarro, Alessandra, Lauria, Alessandra, Ophthalmology, Team, Rizzo, Stanislao, Savastano, Maria Cristina, Gambini, Gloria, Cozzupoli, G. M., Culiersi, Carola, Otolaryngology, Team, Passali, Giulio Cesare, Paludetti, Gaetano, Galli, Jacopo, Crudo, F., Di Cintio, G., Longobardi, Ylenia, Tricarico, Laura, Santantonio, M., Pediatric, Team, Buonsenso, Danilo, Valentini, Piero, Pata, D., Sinatti, Dario, De Rose, Cristina, Pneumology, Team, Richeldi, Luca, Lombardi, F., Calabrese, Anna Chiara, Leone, Paolo Maria, Calvello, M. R., Intini, Enrica, Montemurro, G., Psychiatric, Team, Sani, Gabriele, Janiri, Delfina, Simonetti, Alessio, Giuseppin, G., Molinaro, M., Odica, M., Radiology, Team, Natale, Luigi, Larici, Anna Rita, Marano, Riccardo, Rheumatology, Team, Paglionico, A., Petricca, Luca, Gigante, Lavinia, Natalello, G., Fedele, Anna Laura, Lizzio, Marco Maria, Tolusso, Barbara, Di Mario, Clara, Alivernini, Stefano, Vascular, Team, Santoliquido, Angelo, Santoro, L., Di Giorgio, A., Nesci, A., Popolla, Valentina, Galluzzo V., Zazzara M. B., Ciciarello F., Savera G., Calvani R. (ORCID:0000-0001-5472-2365), Marzetti E. (ORCID:0000-0001-9567-6983), Landi F. (ORCID:0000-0002-3472-1389), Tosato M., Gremese E. (ORCID:0000-0002-2248-1058), Bernabei R. (ORCID:0000-0002-9197-004X), Fantoni M. (ORCID:0000-0001-6913-8460), Gasbarrini A. (ORCID:0000-0002-7278-4823), Porcari S., Settanni C. R., Bramato G., Brandi V., Fabrizi S., Lo Monaco M. R. (ORCID:0000-0002-1457-7981), Martone A. M., Pagano F. C., Rocchi S., Salerno A., Catalano L., Damiano F. P., Rocconi A., Galliani A., Tupputi S., Cocchi C., Pirone F., Cacciatore S., Cauda R. (ORCID:0000-0002-1498-4229), Tamburrini E. (ORCID:0000-0003-4930-426X), Borghetti A., Murri R. (ORCID:0000-0003-4263-7854), Cingolani A. (ORCID:0000-0002-3793-2755), Ventura G. (ORCID:0000-0002-0304-7264), Addolorato G. (ORCID:0000-0002-1522-9946), Franceschi F. (ORCID:0000-0001-6266-445X), Mingrone G. (ORCID:0000-0003-2021-528X), Zocco M. A. (ORCID:0000-0002-0814-9542), Sanguinetti M. (ORCID:0000-0002-9780-7059), Cattani P. (ORCID:0000-0003-4678-4763), Marchetti S., Posteraro B. (ORCID:0000-0002-1663-7546), Bizzarro A., Lauria A., Rizzo S. (ORCID:0000-0001-6302-063X), Savastano M. C. (ORCID:0000-0003-1397-4333), Gambini G., Culiersi C., Passali G. C. (ORCID:0000-0002-8176-0962), Paludetti G. (ORCID:0000-0003-2480-1243), Galli J. (ORCID:0000-0001-6353-6249), Longobardi Y., Tricarico L., Buonsenso D., Valentini P. (ORCID:0000-0001-6095-9510), Sinatti D., De Rose C., Richeldi L. (ORCID:0000-0001-8594-1448), Calabrese A., Leone P. M., Intini E., Sani G. (ORCID:0000-0002-9767-8752), Janiri D., Simonetti A., Natale L. (ORCID:0000-0002-7949-5119), Larici A. R. (ORCID:0000-0002-1882-6244), Marano R. (ORCID:0000-0003-2710-2093), Petricca L., Gigante L., Fedele A. L., Lizzio M. M., Tolusso B. (ORCID:0000-0002-9108-6609), Di Mario C., Alivernini S. (ORCID:0000-0002-7383-4212), Santoliquido A. (ORCID:0000-0003-1539-4017), Popolla V., Galluzzo, Vincenzo, Zazzara, Maria Beatrice, Ciciarello, Francesca, Savera, Giulia, Pais, C., Calvani, Riccardo, Picca, A., Marzetti, Emanuele, Landi, Francesco, Tosato, Matteo, Steering, Committee, Gremese, Elisa, Coordination, Bernabei, Roberto, Fantoni, Massimo, Gasbarrini, Antonio, Field, Investigator, Gastroenterology, Team, Porcari, Serena, Settanni, Carlo Romano, Geriatric, Team, Benvenuto, F., Bramato, Giulia, Brandi, Vincenzo, Carfi, A., Fabrizi, Sofia, Lo Monaco, Maria Rita, Martone, Anna Maria, Napolitano, C., Pagano, Francesco Cosimo, Rocchi, Sara, Rota, E., Salerno, Andrea Maria, Tritto, M., Catalano, Lucio, Damiano, Francesco Paolo, Rocconi, Alessandra, Galliani, Alessandro, Spaziani, G., Tupputi, Salvatore, Cocchi, Camilla, Pirone, Flavia, D'Ignazio, F., Cacciatore, Stefano, Infectious disease, Team, Cauda, Roberto, Tamburrini, Enrica, Borghetti, Alberto, Di Gianbenedetto, S., Murri, Rita, Cingolani, Antonella, Ventura, Giulio, Taddei, E., Moschese, D., Ciccullo, A., Dusina, A., Internal Medicine, Team, Stella, L., Addolorato, Giovanni, Franceschi, Francesco, Mingrone, Geltrude, Zocco, Maria Assunta, Microbiology, Team, Sanguinetti, Maurizio, Cattani Franchi, Paola, Marchetti, Simona, Posteraro, Brunella, Sali, M., Neurology, Team, Bizzarro, Alessandra, Lauria, Alessandra, Ophthalmology, Team, Rizzo, Stanislao, Savastano, Maria Cristina, Gambini, Gloria, Cozzupoli, G. M., Culiersi, Carola, Otolaryngology, Team, Passali, Giulio Cesare, Paludetti, Gaetano, Galli, Jacopo, Crudo, F., Di Cintio, G., Longobardi, Ylenia, Tricarico, Laura, Santantonio, M., Pediatric, Team, Buonsenso, Danilo, Valentini, Piero, Pata, D., Sinatti, Dario, De Rose, Cristina, Pneumology, Team, Richeldi, Luca, Lombardi, F., Calabrese, Anna Chiara, Leone, Paolo Maria, Calvello, M. R., Intini, Enrica, Montemurro, G., Psychiatric, Team, Sani, Gabriele, Janiri, Delfina, Simonetti, Alessio, Giuseppin, G., Molinaro, M., Odica, M., Radiology, Team, Natale, Luigi, Larici, Anna Rita, Marano, Riccardo, Rheumatology, Team, Paglionico, A., Petricca, Luca, Gigante, Lavinia, Natalello, G., Fedele, Anna Laura, Lizzio, Marco Maria, Tolusso, Barbara, Di Mario, Clara, Alivernini, Stefano, Vascular, Team, Santoliquido, Angelo, Santoro, L., Di Giorgio, A., Nesci, A., Popolla, Valentina, Galluzzo V., Zazzara M. B., Ciciarello F., Savera G., Calvani R. (ORCID:0000-0001-5472-2365), Marzetti E. (ORCID:0000-0001-9567-6983), Landi F. (ORCID:0000-0002-3472-1389), Tosato M., Gremese E. (ORCID:0000-0002-2248-1058), Bernabei R. (ORCID:0000-0002-9197-004X), Fantoni M. (ORCID:0000-0001-6913-8460), Gasbarrini A. (ORCID:0000-0002-7278-4823), Porcari S., Settanni C. R., Bramato G., Brandi V., Fabrizi S., Lo Monaco M. R. (ORCID:0000-0002-1457-7981), Martone A. M., Pagano F. C., Rocchi S., Salerno A., Catalano L., Damiano F. P., Rocconi A., Galliani A., Tupputi S., Cocchi C., Pirone F., Cacciatore S., Cauda R. (ORCID:0000-0002-1498-4229), Tamburrini E. (ORCID:0000-0003-4930-426X), Borghetti A., Murri R. (ORCID:0000-0003-4263-7854), Cingolani A. (ORCID:0000-0002-3793-2755), Ventura G. (ORCID:0000-0002-0304-7264), Addolorato G. (ORCID:0000-0002-1522-9946), Franceschi F. (ORCID:0000-0001-6266-445X), Mingrone G. (ORCID:0000-0003-2021-528X), Zocco M. A. (ORCID:0000-0002-0814-9542), Sanguinetti M. (ORCID:0000-0002-9780-7059), Cattani P. (ORCID:0000-0003-4678-4763), Marchetti S., Posteraro B. (ORCID:0000-0002-1663-7546), Bizzarro A., Lauria A., Rizzo S. (ORCID:0000-0001-6302-063X), Savastano M. C. (ORCID:0000-0003-1397-4333), Gambini G., Culiersi C., Passali G. C. (ORCID:0000-0002-8176-0962), Paludetti G. (ORCID:0000-0003-2480-1243), Galli J. (ORCID:0000-0001-6353-6249), Longobardi Y., Tricarico L., Buonsenso D., Valentini P. (ORCID:0000-0001-6095-9510), Sinatti D., De Rose C., Richeldi L. (ORCID:0000-0001-8594-1448), Calabrese A., Leone P. M., Intini E., Sani G. (ORCID:0000-0002-9767-8752), Janiri D., Simonetti A., Natale L. (ORCID:0000-0002-7949-5119), Larici A. R. (ORCID:0000-0002-1882-6244), Marano R. (ORCID:0000-0003-2710-2093), Petricca L., Gigante L., Fedele A. L., Lizzio M. M., Tolusso B. (ORCID:0000-0002-9108-6609), Di Mario C., Alivernini S. (ORCID:0000-0002-7383-4212), Santoliquido A. (ORCID:0000-0003-1539-4017), and Popolla V.

Abstract

Background: Fatigue with reduced tolerance to exercise is a common persistent long-lasting feature amongst COVID-19 survivors. The assessment of muscle function in this category of patients is often neglected.Aim.: To evaluate the potential impact of a daily supplementation based on amino acids, minerals, vi-tamins, and plant extracts (Apportal (R)) on muscle function, body composition, laboratory parameters and self-rated health in a small group of COVID-19 survivors affected by fatigue.Methods: Thirty participants were enrolled among patients affected by physical fatigue during or after acute COVID-19 and admitted to the post-COVID-19 outpatient service at Fondazione Policlinico Gemelli in Rome between 1st March 2021 and 30th April 2021. All participants were evaluated at first visit (t0) and at control visit (t1), after taking a daily sachet of Apportal (R) for 28 days. Muscle function was analyzed using hand grip strength test, exhaustion strength time and the number of repetitions at one -minute chair stand test. Body composition was assessed with bioelectrical impedance analysis (BIA). Laboratory parameters, including standard blood biochemistry and ferritin levels, were evaluated at the first visit and during the control visit. A quick evaluation of self-rated health, before COVID-19, at t0 and t1, was obtained through a visual analogue scale (VAS). Results: Participants aged 60 years and older were 13 (43%). Females represented the 70% of the study sample. Participants hospitalized for COVID-19 with low -flow oxygen supplementation represented the 43.3% of the study sample while 3.3% received noninvasive ventilation (NIV) or invasive ventilation. Hand grip strength improved from 26.3 Kg to 28.9 Kg (p < 0.05) at t1 as compared to t0. The mean time of strength exhaustion increased from 31.7 s (sec) at t0 to 47.5 s at t1 (p < 0.05). Participants performed a higher number of repetitions (28.3 vs. 22.0; p < 0.05) during the one-minute chair stand test at

Published
2022

22. Spatio-temporal cluster analysis of recent Italian landslides.

Author

Tonini, M., Pecoraro, G., Romailler, K., and Calvello, M.

Subjects
LANDSLIDES, CLUSTER analysis (Statistics), ATTRIBUTION of news
Abstract

The present study addresses the pattern distribution of recent landslides in Italy. The main objective is the detection and mapping of spatio-temporal clusters of landslides that occurred in the period 2010–2017 in the country. To this aim, a subdivision of the national area into 158 warning zones, as identified by the 21 civil protection regional centres to deal with weather-induced hydro-geological hazards, is adopted. Information on landslides comes from FraneItalia, a geo-referenced catalogue developed consulting online news sources. Analyses are performed both at national scale and at a regional scale, focusing on the Campania region. The space–time permutation scan statistics model is applied to detect statistically significant clustering, accounting for the geographical spatial dimension and for the temporal dimension. Two types of analyses are performed: annual, considering each single year; and multi-annual, encompassing the entire 8-year study period. In both cases, spatio-temporal cluster analyses are able to detect areas and frame-periods characterised by relevant and recurrent landslide activity. Finally, the obtained results are compared with a standard landslide density map, highlighting the complementarity of the two approaches. [ABSTRACT FROM AUTHOR]

Published
2022
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24. A Meta-Analysis of Obesity and Risk of Colorectal Cancer in Patients with Lynch Syndrome: The Impact of Sex and Genetics

Author

Lazzeroni, M, Bellerba, F, Calvello, M, Macrae, F, Win, AK, Jenkins, M, Serrano, D, Marabelli, M, Cagnacci, S, Tolva, G, Macis, D, Raimondi, S, Mazzarella, L, Chiocca, S, Caini, S, Bertario, L, Bonanni, B, Gandini, S, Lazzeroni, M, Bellerba, F, Calvello, M, Macrae, F, Win, AK, Jenkins, M, Serrano, D, Marabelli, M, Cagnacci, S, Tolva, G, Macis, D, Raimondi, S, Mazzarella, L, Chiocca, S, Caini, S, Bertario, L, Bonanni, B, and Gandini, S

Abstract

There appears to be a sex-specific association between obesity and colorectal neoplasia in patients with Lynch Syndrome (LS). We meta-analyzed studies reporting on obesity and colorectal cancer (CRC) risk in LS patients to test whether obese subjects were at increased risk of cancer compared to those of normal weight. We explored also a possible sex-specific relationship between adiposity and CRC risk among patients with LS. The summary relative risk (SRR) and 95% confidence intervals (CI) were calculated through random effect models. We investigated the causes of between-study heterogeneity and assessed the presence of publication bias. We were able to retrieve suitable data from four independent studies. We found a twofold risk of CRC in obese men compared to nonobese men (SRR = 2.09; 95%CI: 1.23-3.55, I2 = 33%), and no indication of publication bias (p = 0.13). No significantly increased risk due to obesity was found for women. A 49% increased CRC risk for obesity was found for subjects with an MLH1 mutation (SRR = 1.49; 95%CI: 1.11-1.99, I2 = 0%). These results confirm the different effects of sex on obesity and CRC risk and also support the public measures to reduce overweight in people with LS, particularly for men.

Published
2021

25. Patient-reported outcomes and patient-reported outcome measures in interstitial lung disease: where to go from here?

Author

Kalluri, M, Luppi, F, Vancheri, A, Vancheri, C, Balestro, E, Varone, F, Mogulkoc, N, Cacopardo, G, Bargagli, E, Renzoni, E, Torrisi, S, Calvello, M, Libra, A, Pavone, M, Bonella, F, Cottin, V, Valenzuela, C, Wijsenbeek, M, Bendstrup, E, Kalluri, Meena, Luppi, Fabrizio, Vancheri, Ada, Vancheri, Carlo, Balestro, Elisabetta, Varone, Francesco, Mogulkoc, Nesrin, Cacopardo, Giulia, Bargagli, Elena, Renzoni, Elizabeth, Torrisi, Sebastiano, Calvello, Mariarosaria, Libra, Alessandro, Pavone, Mauro, Bonella, Francesco, Cottin, Vincent, Valenzuela, Claudia, Wijsenbeek, Marlies, Bendstrup, Elisabeth, Kalluri, M, Luppi, F, Vancheri, A, Vancheri, C, Balestro, E, Varone, F, Mogulkoc, N, Cacopardo, G, Bargagli, E, Renzoni, E, Torrisi, S, Calvello, M, Libra, A, Pavone, M, Bonella, F, Cottin, V, Valenzuela, C, Wijsenbeek, M, Bendstrup, E, Kalluri, Meena, Luppi, Fabrizio, Vancheri, Ada, Vancheri, Carlo, Balestro, Elisabetta, Varone, Francesco, Mogulkoc, Nesrin, Cacopardo, Giulia, Bargagli, Elena, Renzoni, Elizabeth, Torrisi, Sebastiano, Calvello, Mariarosaria, Libra, Alessandro, Pavone, Mauro, Bonella, Francesco, Cottin, Vincent, Valenzuela, Claudia, Wijsenbeek, Marlies, and Bendstrup, Elisabeth

Abstract

Patient-reported outcome measures (PROMs), tools to assess patient self-report of health status, are now increasingly used in research, care and policymaking. While there are two well-developed disease-specific PROMs for interstitial lung diseases (ILD) and idiopathic pulmonary fibrosis (IPF), many unmet and urgent needs remain. In December 2019, 64 international ILD experts convened in Erice, Italy to deliberate on many topics, including PROMs in ILD. This review summarises the history of PROMs in ILD, shortcomings of the existing tools, challenges of development, validation and implementation of their use in clinical trials, and the discussion held during the meeting. Development of disease-specific PROMs for ILD including IPF with robust methodology and validation in concordance with guidance from regulatory authorities have increased user confidence in PROMs. Minimal clinically important difference for bidirectional changes may need to be developed. Cross-cultural validation and linguistic adaptations are necessary in addition to robust psychometric properties for effective PROM use in multinational clinical trials. PROM burden of use should be reduced through appropriate use of digital technologies and computerised adaptive testing. Active patient engagement in all stages from development, testing, choosing and implementation of PROMs can help improve probability of success and further growth.

Published
2021

26. Genome-wide association study identifies 32 novel breast cancer susceptibility loci from overall and subtype-specific analyses

Author

Zhang, H, Ahearn, TU, Lecarpentier, J, Barnes, D, Beesley, J, Qi, G, Jiang, X, O’Mara, TA, Zhao, N, Bolla, MK, Dunning, AM, Dennis, J, Wang, Q, Ful, ZA, Aittomäki, K, Andrulis, IL, Anton-Culver, H, Arndt, V, Aronson, KJ, Arun, BK, Auer, PL, Azzollini, J, Barrowdale, D, Becher, H, Beckmann, MW, Behrens, S, Benitez, J, Bermisheva, M, Bialkowska, K, Blanco, A, Blomqvist, C, Bogdanova, NV, Bojesen, SE, Bonanni, B, Bondavalli, D, Borg, A, Brauch, H, Brenner, H, Briceno, I, Broeks, A, Brucker, SY, Brüning, T, Burwinkel, B, Buys, SS, Byers, H, Caldés, T, Caligo, MA, Calvello, M, Campa, D, Castelao, JE, Chang-Claude, J, Chanock, SJ, Christiaens, M, Christiansen, H, Chung, WK, Claes, KBM, Clarke, CL, Cornelissen, S, Couch, FJ, Cox, A, Cross, SS, Czene, K, Daly, MB, Devilee, P, Diez, O, Domchek, SM, Dörk, T, Dwek, M, Eccles, DM, Ekici, AB, Evans, DG, Fasching, PA, Figueroa, J, Foretova, L, Fostira, F, Friedman, E, Frost, D, Gago-Dominguez, M, Gapstur, SM, Garber, J, García-Sáenz, JA, Gaudet, MM, Gayther, SA, Giles, GG, Godwin, AK, Goldberg, MS, Goldgar, DE, González-Neira, A, Greene, MH, Gronwald, J, Guénel, P, Häberle, L, Hahnen, E, Haiman, CA, Hake, CR, Hall, P, Hamann, U, Harkness, EF, Heemskerk-Gerritsen, BAM, Hillemanns, P, Hogervorst, FBL, Holleczek, B, Hollestelle, A, Hooning, MJ, Hoover, RN, Hopper, JL, Howell, A, Huebner, H, Hulick, PJ, Imyanitov, EN, Isaacs, C, Izatt, L, Jager, A, Jakimovska, M, Jakubowska, A, James, P, Janavicius, R, Janni, W, John, EM, Jones, ME, Jung, A, Kaaks, R, Kapoor, PM, Karlan, BY, Keeman, R, Khan, S, Khusnutdinova, E, Kitahara, CM, Ko, Y-D, Konstantopoulou, I, Koppert, LB, Koutros, S, Kristensen, VN, Laenkholm, A-V, Lambrechts, D, Larsson, SC, Laurent-Puig, P, Lazaro, C, Lazarova, E, Lejbkowicz, F, Leslie, G, Lesueur, F, Lindblom, A, Lissowska, J, Lo, W-Y, Loud, JT, Lubinski, J, Lukomska, A, MacInnis, RJ, Mannermaa, A, Manoochehri, M, Manoukian, S, Margolin, S, Martinez, ME, Matricardi, L, McGuffog, L, McLean, C, Mebirouk, N, Meindl, A, Menon, U, Miller, A, Mingazheva, E, Montagna, M, Mulligan, AM, Mulot, C, Muranen, TA, Nathanson, KL, Neuhausen, SL, Nevanlinna, H, Neven, P, Newman, WG, Nielsen, FC, Nikitina-Zake, L, Nodora, J, Offit, K, Olah, E, Olopade, OI, Olsson, H, Orr, N, Papi, L, Papp, J, Park-Simon, T-W, Parsons, MT, Peissel, B, Peixoto, A, Peshkin, B, Peterlongo, P, Peto, J, Phillips, K-A, Piedmonte, M, Plaseska-Karanfilska, D, Prajzendanc, K, Prentice, R, Prokofyeva, D, Rack, B, Radice, P, Ramus, SJ, Rantala, J, Rashid, MU, Rennert, G, Rennert, HS, Risch, HA, Romero, A, Rookus, MA, Rübner, M, Rüdiger, T, Saloustros, E, Sampson, S, Sandler, DP, Sawyer, EJ, Scheuner, MT, Schmutzler, RK, Schneeweiss, A, Schoemaker, MJ, Schöttker, B, Schürmann, P, Senter, L, Sharma, P, Sherman, ME, Shu, X-O, Singer, CF, Smichkoska, S, Soucy, P, Southey, MC, Spinelli, JJ, Stone, J, Stoppa-Lyonnet, D, Swerdlow, AJ, Szabo, CI, Tamimi, RM, Tapper, WJ, Taylor, JA, Teixeira, MR, Terry, M, Thomassen, M, Thull, DL, Tischkowitz, M, Toland, AE, Tollenaar, RAEM, Tomlinson, I, Torres, D, Troester, MA, Truong, T, Tung, N, Untch, M, Vachon, CM, van den Ouweland, AMW, van der Kolk, LE, van Veen, EM, vanRensburg, EJ, Vega, A, Wappenschmidt, B, Weinberg, CR, Weitzel, JN, Wildiers, H, Winqvist, R, Wolk, A, Yang, XR, Yannoukakos, D, Zheng, W, Zorn, KK, Milne, RL, Kraft, P, Simard, J, Pharoah, PDP, Michailidou, K, Antoniou, AC, Schmidt, MK, Chenevix-Trench, G, Easton, DF, Chatterjee, N, and García-Closas, M

Abstract

Breast cancer susceptibility variants frequently show heterogeneity in associations by tumor subtype1,2,3. To identify novel loci, we performed a genome-wide association study including 133,384 breast cancer cases and 113,789 controls, plus 18,908 BRCA1 mutation carriers (9,414 with breast cancer) of European ancestry, using both standard and novel methodologies that account for underlying tumor heterogeneity by estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 status and tumor grade. We identified 32 novel susceptibility loci (P

Published
2020

27. Baricitinib as rescue therapy in a patient with COVID-19 with no complete response to sarilumab

Author

Cingolani, A., Tummolo, A. M., Montemurro, G., Gremese, E., Larosa, L., Cipriani, M. C., Pasciuto, G., Liperoti, R., Murri, R., Pirronti, T., Cauda, R., Fantoni, M., Bellieni, A., Brandi, V., Calabrese, A., Calvello, M. R., Ciccullo, A., Corbo, G., Falsiroli, C., Intini, E., Landi, G., Leone, P. M., Macagno, F., Martis, I., Pais, C., Potenza, A., Salini, S., Simonetti, J., Taddei, E., Tosato, M., Varone, F., Ventura, G., and Siciliano, M.

Subjects
0301 basic medicine, Male, Baricitinib, medicine.medical_treatment, Azithromycin, Lopinavir, 0302 clinical medicine, Respiratory function, 030212 general & internal medicine, Sulfonamides, Brief Report, General Medicine, Drug Combinations, Infectious Diseases, Treatment Outcome, Radiological weapon, Anesthesia, Acute Disease, Immunotherapy, Coronavirus Infections, Respiratory Insufficiency, medicine.drug, Hydroxychloroquine, Microbiology (medical), Coronavirus disease 2019 (COVID-19), 030106 microbiology, Pneumonia, Viral, Antibodies, Monoclonal, Humanized, Antiviral Agents, 03 medical and health sciences, Betacoronavirus, medicine, Humans, Pandemics, Aged, Ritonavir, business.industry, SARS-CoV-2, Sarilumab, Drug Repositioning, COVID-19, Respiratory failure, Purines, Azetidines, Pyrazoles, business
Abstract

A patient with COVID-19-related severe respiratory failure, with insufficient response to an antiretroviral therapy, hydroxychloroquine and Interleukin-6 (IL-6) antagonist therapy, presented a prompt resolution of the respiratory function and improvement in the radiological picture after baricitinib at an oral dose of 4 mg per day for 2 weeks.

Published
2020

28. Genome-wide association study identifies 32 novel breast cancer susceptibility loci from overall and subtype-specific analyses

Author

Zhan, H.Y., Ahearn, T.U., Lecarpentier, J., Barnes, D., Beesley, J., Qi, G.H., Jiang, X., O'Mara, T.A., Zhao, N., Bolla, M.K., Dunning, A.M., Dennis, J., Wang, Q., Abu Ful, Z., Aittomaki, K., Andrulis, I.L., Anton-Culver, H., Arndt, V., Aronson, K.J., Arun, B.K., Auer, P.L., Azzollini, J., Barrowdale, D., Becher, H., Beckmann, M.W., Behrens, S., Benitez, J., Bermisheva, M., Bialkowska, K., Blanco, A., Blomqvist, C., Bogdanova, N.V., Bojesen, S.E., Bonanni, B., Bondavalli, D., Borg, A., Brauch, H., Brenner, H., Briceno, I., Broeks, A., Brucker, S.Y., Bruning, T., Burwinkel, B., Buys, S.S., Byers, H., Caldes, T., Caligo, M.A., Calvello, M., Campa, D., Castelao, J.E., Chang-Claude, J., Chanock, S.J., Christiaens, M., Christiansen, H., Chung, W.K., Claes, K.B.M., Clarke, C.L., Cornelissen, S., Couch, F.J., Cox, A., Cross, S.S., Czene, K., Daly, M.B., Devilee, P., Diez, O., Domchek, S.M., Dork, T., Dwek, M., Eccles, D.M., Ekici, A.B., Evans, D.G., Fasching, P.A., Figueroa, J., Foretova, L., Fostira, F., Friedman, E., Frost, D., Gago-Dominguez, M., Gapstur, S.M., Garber, J., Garcia-Saenz, J.A., Gaudet, M.M., Gayther, S.A., Giles, G.G., Godwin, A.K., Goldberg, M.S., Goldgar, D.E., Gonzalez-Neira, A., Greene, M.H., Gronwald, J., Guenel, P., Haberle, L., Hahnen, E., Haiman, C.A., Hake, C.R., Hall, P., Hamann, U., Harkness, E.F., Heemskerk-Gerritsen, B.A.M., Hillemanns, P., Hogervorst, F.B.L., Holleczek, B., Hollestelle, A., Hooning, M.J., Hoover, R.N., Hopper, J.L., Howell, A., Huebner, H., Hulick, P.J., Imyanitov, E.N., Isaacs, C., Izatt, L., Jager, A., Jakimovska, M., Jakubowska, A., James, P., Janavicius, R., Janni, W., John, E.M., Jones, M.E., Jung, A., Kaaks, R., Kapoor, P.M., Karlan, B.Y., Keeman, R., Khan, S., Khusnutdinova, E., Kitahara, C.M., Ko, Y.D., Konstantopoulou, I., Koppert, L.B., Koutros, S., Kristensen, V.N., Laenkholm, A.V., Lambrechts, D., Larsson, S.C., Laurent-Puig, P., Lazaro, C., Lazarova, E., Lejbkowicz, F., Leslie, G., Lesueur, F., Lindblom, A., Lissowska, J., W.Y. lo, Loud, J.T., Lubinski, J., Lukomska, A., MacInnis, R.J., Mannermaa, A., Manoochehri, M., Manoukian, S., Margolin, S., Martinez, M.E., Matricardi, L., McGuffog, L., McLean, C., Mebirouk, N., Meindl, A., Menon, U., Miller, A., Mingazheva, E., Montagna, M., Mulligan, A.M., Mulot, C., Muranen, T.A., Nathanson, K.L., Neuhausen, S.L., Nevanlinna, H., Neven, P., Newman, W.G., Nielsens, F.C., Nikitina-Zake, L., Nodora, J., Offit, K., Olah, E., Olopade, O.I., Olsson, H., Orr, N., Papi, L., Papp, J., Park-Simon, T.W., Parsons, M.T., Peissel, B., Peixoto, A., Peshkin, B., Peterlongo, P., Peto, J., Phillips, K.A., Piedmonte, M., Plaseska-Karanfilska, D., Prajzendanc, K., Prentice, R., Prokofyeva, D., Rack, B., Radice, P., Ramus, S.J., Rantala, J., Rashid, M.U., Rennert, G., Rennert, H.S., Risch, H.A., Romero, A., Rookus, M.A., Rubner, M., Rudiger, T., Saloustros, E., Sampson, S., Sandler, D.P., Sawyer, E.J., Scheuner, M.T., Schmutzler, R.K., Schneeweiss, A., Schoemaker, M.J., Schottker, B., Schurmann, P., Senter, L., Sharma, P., Sherman, M.E., Shu, X.O., Singer, C.F., Smichkoska, S., Soucy, P., Southey, M.C., Spinelli, J.J., Stone, J., Stoppa-Lyonnet, D., Swerdlow, A.J., Szabo, C.I., Tamimi, R.M., Tapper, W.J., Taylor, J.A., Teixeira, M.R., Terry, M., Thomassen, M., Thull, D.L., Tischkowitz, M., Toland, A.E., Tollenaar, R.A.E.M., Tomlinson, I., Torres, D., Troester, M.A., Truong, T., Tung, N., Untch, M., Vachon, C.M., Ouweland, A.M.W. van den, Kolk, L.E. van der, Veen, E.M. van, vanRensburg, E.J., Vega, A., Wappenschmidt, B., Weinberg, C.R., Weitzel, J.N., Wildiers, H., Winqvist, R., Wolk, A., Yang, X.H.R., Yannoukakos, D., Zheng, W., Zorn, K.K., Milne, R.L., Kraft, P., Simard, J., Pharoah, P.D.P., Michailidou, K., Antoniou, A.C., Schmidt, M.K., Chenevix-Trench, G., Easton, D.F., Chatterjee, N., Garcia-Closas, M., kConFab Investigators, ABCTB Investigators, EMBRACE Study, and GEMO Study Collaborators

Abstract

Genome-wide analysis identifies 32 loci associated with breast cancer susceptibility, accounting for estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 status and tumor grade.Breast cancer susceptibility variants frequently show heterogeneity in associations by tumor subtype(1-3). To identify novel loci, we performed a genome-wide association study including 133,384 breast cancer cases and 113,789 controls, plus 18,908 BRCA1 mutation carriers (9,414 with breast cancer) of European ancestry, using both standard and novel methodologies that account for underlying tumor heterogeneity by estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 status and tumor grade. We identified 32 novel susceptibility loci (P < 5.0 x 10(-8)), 15 of which showed evidence for associations with at least one tumor feature (false discovery rate < 0.05). Five loci showed associations (P < 0.05) in opposite directions between luminal and non-luminal subtypes. In silico analyses showed that these five loci contained cell-specific enhancers that differed between normal luminal and basal mammary cells. The genetic correlations between five intrinsic-like subtypes ranged from 0.35 to 0.80. The proportion of genome-wide chip heritability explained by all known susceptibility loci was 54.2% for luminal A-like disease and 37.6% for triple-negative disease. The odds ratios of polygenic risk scores, which included 330 variants, for the highest 1% of quantiles compared with middle quantiles were 5.63 and 3.02 for luminal A-like and triple-negative disease, respectively. These findings provide an improved understanding of genetic predisposition to breast cancer subtypes and will inform the development of subtype-specific polygenic risk scores.

Published
2020

29. Genome-wide association study identifies 32 novel breast cancer susceptibility loci from overall and subtype-specific analyses

Author

Zhang, H. (Haoyu), Ahearn, T. U. (Thomas U.), Lecarpentier, J. (Julie), Barnes, D. (Daniel), Beesley, J. (Jonathan), Qi, G. (Guanghao), Hang, X. (Xia), O'Mara, T. A. (Tracy A.), Zhao, N. (Ni), Bolla, M. K. (Manjeet K.), Dunning, A. M. (Alison M.), Dennis, J. (Joe), Wang, Q. (Qin), Abu Ful, Z. (Zumuruda), Aittomaki, K. (Kristiina), Andrulis, I. L. (Irene L.), Anton-Culver, H. (Hoda), Arndt, V. (Volker), Aronson, K. J. (Kristan J.), Arun, B. K. (Banu K.), Auer, P. L. (Paul L.), Azzollini, J. (Jacopo), Barrowdale, D. (Daniel), Becher, H. (Heiko), Beckmann, M. W. (Matthias W.), Behrens, S. (Sabine), Benitez, J. (Javier), Bermisheva, M. (Marina), Bialkowska, K. (Katarzyna), Blanco, A. (Ana), Blomqvist, C. (Carl), Bogdanova, N. V. (Natalia, V), Bojesen, S. E. (Stig E.), Bonanni, B. (Bernardo), Bondavalli, D. (Davide), Borg, A. (Ake), Brauch, H. (Hiltrud), Brenner, H. (Hermann), Briceno, I. (Ignacio), Broeks, A. (Annegien), Brucker, S. Y. (Sara Y.), Bruening, T. (Thomas), Burwinkel, B. (Barbara), Buys, S. S. (Saundra S.), Byers, H. (Helen), Caldes, T. (Trinidad), Caligo, M. A. (Maria A.), Calvello, M. (Mariarosaria), Campa, D. (Daniele), Castelao, J. E. (Jose E.), Chang-Claude, J. (Jenny), Chanock, S. J. (Stephen J.), Christiaens, M. (Melissa), Christiansen, H. (Hans), Chung, W. K. (Wendy K.), Claes, K. B. (Kathleen B. M.), Clarke, C. L. (Christine L.), Cornelissen, S. (Sten), Couch, F. J. (Fergus J.), Cox, A. (Angela), Cross, S. S. (Simon S.), Czene, K. (Kamila), Daly, M. B. (Mary B.), Devilee, P. (Peter), Diez, O. (Orland), Domchek, S. M. (Susan M.), Doerk, T. (Thilo), Dwek, M. (Miriam), Eccles, D. M. (Diana M.), Ekici, A. B. (Arif B.), Evans, D. G. (D. Gareth), Fasching, P. A. (Peter A.), Figueroa, J. (Jonine), Foretova, L. (Lenka), Fostira, F. (Florentia), Friedman, E. (Eitan), Frost, D. (Debra), Gago-Dominguez, M. (Manuela), Gapstur, S. M. (Susan M.), Garber, J. (Judy), Garcia-Saenz, J. A. (Jose A.), Gaudet, M. M. (Mia M.), Gayther, S. A. (Simon A.), Giles, G. G. (Graham G.), Godwin, A. K. (Andrew K.), Goldberg, M. S. (Mark S.), Goldgar, D. E. (David E.), Gonzalez-Neira, A. (Anna), Greene, M. H. (Mark H.), Gronwald, J. (Jacek), Guenel, P. (Pascal), Haeberle, L. (Lothar), Hahnen, E. (Eric), Haiman, C. A. (Christopher A.), Hake, C. R. (Christopher R.), Hall, P. (Per), Hamann, U. (Ute), Harkness, E. F. (Elaine F.), Heemskerk-Gerritsen, B. A. (Bernadette A. M.), Hillemanns, P. (Peter), Hogervorst, F. B. (Frans B. L.), Holleczek, B. (Bernd), Hollestelle, A. (Antoinette), Hooning, M. J. (Maartje J.), Hoover, R. N. (Robert N.), Hopper, J. L. (John L.), Howell, A. (Anthony), Huebner, H. (Hanna), Hulick, P. J. (Peter J.), Imyanitov, E. N. (Evgeny N.), Isaacs, C. (Claudine), Izatt, L. (Louise), Jager, A. (Agnes), Jakimovska, M. (Milena), Jakubowska, A. (Anna), James, P. (Paul), Janavicius, R. (Ramunas), Janni, W. (Wolfgang), John, E. M. (Esther M.), Jones, M. E. (Michael E.), Jung, A. (Audrey), Kaaks, R. (Rudolf), Kapoor, P. M. (Pooja Middha), Karlan, B. Y. (Beth Y.), Keeman, R. (Renske), Khan, S. (Sofia), Khusnutdinova, E. (Elza), Kitahara, C. M. (Cari M.), Ko, Y.-D. (Yon-Dschun), Konstantopoulou, I. (Irene), Koppert, L. B. (Linetta B.), Koutros, S. (Stella), Kristensen, V. N. (Vessela N.), Laenkholm, A.-V. (Anne-Vibeke), Lambrechts, D. (Diether), Larsson, S. C. (Susanna C.), Laurent-Puig, P. (Pierre), Lazaro, C. (Conxi), Lazarova, E. (Emilija), Lejbkowicz, F. (Flavio), Leslie, G. (Goska), Lesueur, F. (Fabienne), Lindblom, A. (Annika), Lissowska, J. (Jolanta), Lo, W.-Y. (Wing-Yee), Loud, J. T. (Jennifer T.), Lubinski, J. (Jan), Lukomska, A. (Alicja), Maclnnis, R. J. (Robert J.), Mannermaa, A. (Arto), Manoochehri, M. (Mehdi), Manoukian, S. (Siranoush), Margolin, S. (Sara), Martinez, M. E. (Maria Elena), Matricardi, L. (Laura), McGuffog, L. (Lesley), McLean, C. (Catriona), Mebirouk, N. (Noura), Meindl, A. (Alfons), Menon, U. (Usha), Miller, A. (Austin), Mingazheva, E. (Elvira), Montagna, M. (Marco), Mulligan, A. M. (Anna Marie), Mulot, C. (Claire), Muranen, T. A. (Taru A.), Nathanson, K. L. (Katherine L.), Neuhausen, S. L. (Susan L.), Nevanlinna, H. (Heli), Neven, P. (Patrick), Newman, W. G. (William G.), Nielsens, F. C. (Finn C.), Nikitina-Zake, L. (Liene), Nodora, J. (Jesse), Offit, K. (Kenneth), Olah, E. (Edith), Olopade, O. I. (Olufunmilayo, I), Olsson, H. (Hakan), Orr, N. (Nick), Papi, L. (Laura), Papp, J. (Janos), Park-Simon, T.-W. (Tjoung-Won), Parsons, M. T. (Michael T.), Peissel, B. (Bernard), Peixoto, A. (Ana), Peshkin, B. (Beth), Peterlongo, P. (Paolo), Peto, J. (Julian), Phillips, K.-A. (Kelly-Anne), Piedmonte, M. (Marion), Plaseska-Karanfilska, D. (Dijana), Prajzendanc, K. (Karolina), Prentice, R. (Ross), Prokofyeva, D. (Darya), Rack, B. (Brigitte), Radice, P. (Paolo), Ramus, S. J. (Susan J.), Rantala, J. (Johanna), Rashid, M. U. (Muhammad U.), Rennert, G. (Gad), Rennert, H. S. (Hedy S.), Risch, H. A. (Harvey A.), Romero, A. (Atocha), Rookus, M. A. (Matti A.), Ruebner, M. (Matthias), Ruediger, T. (Thomas), Saloustros, E. (Emmanouil), Sampson, S. (Sarah), Sandler, D. P. (Dale P.), Sawyer, E. J. (Elinor J.), Scheuner, M. T. (Maren T.), Schmutzler, R. K. (Rita K.), Schneeweiss, A. (Andreas), Schoemaker, M. J. (Minouk J.), Schoettker, B. (Ben), Schuermann, P. (Peter), Senter, L. (Leigha), Sharma, P. (Priyanka), Sherman, M. E. (Mark E.), Shu, X.-O. (Xiao-Ou), Singer, C. F. (Christian F.), Smichkoska, S. (Snezhana), Soucy, P. (Penny), Southey, M. C. (Melissa C.), Spinelli, J. J. (John J.), Stone, J. (Jennifer), Stoppa-Lyonnet, D. (Dominique), Swerdlow, A. J. (Anthony J.), Szabo, C. I. (Csilla, I), Tamimi, R. M. (Rulla M.), Tapper, W. J. (William J.), Taylor, J. A. (Jack A.), Teixeira, M. R. (Manuel R.), Terry, M. (MaryBeth), Thomassen, M. (Mads), Thull, D. L. (Darcy L.), Tischkowitz, M. (Marc), Toland, A. E. (Amanda E.), Tollenaar, R. A. (Rob A. E. M.), Tomlinson, I. (Ian), Torres, D. (Diana), Troester, M. A. (Melissa A.), Truong, T. (Therese), Tung, N. (Nadine), Untch, M. (Michael), Vachon, C. M. (Celine M.), van den Ouweland, A. M. (Ans M. W.), van der Kolk, L. E. (Lizet E.), van Veen, E. M. (Elke M.), vanRensburg, E. J. (Elizabeth J.), Vega, A. (Ana), Wappenschmidt, B. (Barbara), Weinberg, C. R. (Clarice R.), Weitzel, J. N. (Jeffrey N.), Wildiers, H. (Hans), Winqvist, R. (Robert), Wolk, A. (Alicja), Yang, X. R. (Xiaohong R.), Yannoukakos, D. (Drakoulis), Zheng, W. (Wei), Zorn, K. K. (Kristin K.), Milne, R. L. (Roger L.), Kraft, P. (Peter), Simard, J. (Jacques), Pharoah, P. D. (Paul D. P.), Michailidou, K. (Kyriaki), Antoniou, A. C. (Antonis C.), Schmidt, M. K. (Marjanka K.), Chenevix-Trench, G. (Georgia), Easton, D. F. (Douglas F.), Chatterjee, N. (Nilanjan), and Garcia-Closas, M. (Montserrat)

Abstract

Breast cancer susceptibility variants frequently show heterogeneity in associations by tumor subtype. To identify novel loci, we performed a genome-wide association study including 133,384 breast cancer cases and 113,789 controls, plus 18,908 BRCA1 mutation carriers (9,414 with breast cancer) of European ancestry, using both standard and novel methodologies that account for underlying tumor heterogeneity by estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 status and tumor grade. We identified 32 novel susceptibility loci (P

Published
2020

31. Association of Genomic Domains in BRCA1 and BRCA2 with Prostate Cancer Risk and Aggressiveness

Author

Patel, V.L., Busch, E.L., Friebel, T.M., Cronin, A., Leslie, G., McGuffog, L., Adlard, J., Agata, S., Agnarsson, B.A., Ahmed, M., Aittomaki, K., Alducci, E., Andrulis, I.L., Arason, A., Arnold, N., Artioli, G., Arver, B., Auber, B., Azzollini, J., Balmana, J., Barkardottir, R.B., Barnes, D.R., Barroso, A., Barrowdale, D., Belotti, M., Benitez, J., Bertelsen, B., Blok, M.J., Bodrogi, I., Bonadona, V., Bonanni, B., Bondavalli, D., Boonen, S.E., Borde, J., Borg, A., Bradbury, A.R., Brady, A., Brewer, C., Brunet, J., Buecher, B., Buys, S.S., Cabezas-Camarero, S., Caldes, T., Caliebe, A., Caligo, M.A., Calvello, M., Campbell, I.G., Carnevali, I., Carrasco, E., Chan, T.L., Chu, A.T.W., Chung, W.K., Claes, K.B.M., Cook, J., Cortesi, L., Couch, F.J., Daly, M.B., Damante, G., Darder, E., Davidson, R., Hoya, M. de la, Puppa, L.D., Dennis, J., Diez, O., Ding, Y.C., Ditsch, N., Domchek, S.M., Donaldson, A., Dworniczak, B., Easton, D.F., Eccles, D.M., Eeles, R.A., Ehrencrona, H., Ejlertsen, B., Engel, C., Evans, D.G., Faivre, L., Faust, U., Feliubadalo, L., Foretova, L., Fostira, F., Fountzilas, G., Frost, D., Garcia-Barberan, V., Garre, P., Gauthier-Villars, M., Geczi, L., Gehrig, A., Gerdes, A.M., Gesta, P., Giannini, G., Glendon, G., Godwin, A.K., Goldgar, D.E., Greene, M.H., Gutierrez-Barrera, A.M., Hahnen, E., Hamann, U., Mensenkamp, A.R., Nielsen, H., Rebbeck, T.R., Patel, V.L., Busch, E.L., Friebel, T.M., Cronin, A., Leslie, G., McGuffog, L., Adlard, J., Agata, S., Agnarsson, B.A., Ahmed, M., Aittomaki, K., Alducci, E., Andrulis, I.L., Arason, A., Arnold, N., Artioli, G., Arver, B., Auber, B., Azzollini, J., Balmana, J., Barkardottir, R.B., Barnes, D.R., Barroso, A., Barrowdale, D., Belotti, M., Benitez, J., Bertelsen, B., Blok, M.J., Bodrogi, I., Bonadona, V., Bonanni, B., Bondavalli, D., Boonen, S.E., Borde, J., Borg, A., Bradbury, A.R., Brady, A., Brewer, C., Brunet, J., Buecher, B., Buys, S.S., Cabezas-Camarero, S., Caldes, T., Caliebe, A., Caligo, M.A., Calvello, M., Campbell, I.G., Carnevali, I., Carrasco, E., Chan, T.L., Chu, A.T.W., Chung, W.K., Claes, K.B.M., Cook, J., Cortesi, L., Couch, F.J., Daly, M.B., Damante, G., Darder, E., Davidson, R., Hoya, M. de la, Puppa, L.D., Dennis, J., Diez, O., Ding, Y.C., Ditsch, N., Domchek, S.M., Donaldson, A., Dworniczak, B., Easton, D.F., Eccles, D.M., Eeles, R.A., Ehrencrona, H., Ejlertsen, B., Engel, C., Evans, D.G., Faivre, L., Faust, U., Feliubadalo, L., Foretova, L., Fostira, F., Fountzilas, G., Frost, D., Garcia-Barberan, V., Garre, P., Gauthier-Villars, M., Geczi, L., Gehrig, A., Gerdes, A.M., Gesta, P., Giannini, G., Glendon, G., Godwin, A.K., Goldgar, D.E., Greene, M.H., Gutierrez-Barrera, A.M., Hahnen, E., Hamann, U., Mensenkamp, A.R., Nielsen, H., and Rebbeck, T.R.

Abstract

Contains fulltext : 218251.pdf (Publisher’s version ) (Closed access), Pathogenic sequence variants (PSV) in BRCA1 or BRCA2 (BRCA1/2) are associated with increased risk and severity of prostate cancer. We evaluated whether PSVs in BRCA1/2 were associated with risk of overall prostate cancer or high grade (Gleason 8+) prostate cancer using an international sample of 65 BRCA1 and 171 BRCA2 male PSV carriers with prostate cancer, and 3,388 BRCA1 and 2,880 BRCA2 male PSV carriers without prostate cancer. PSVs in the 3' region of BRCA2 (c.7914+) were significantly associated with elevated risk of prostate cancer compared with reference bin c.1001-c.7913 [HR = 1.78; 95% confidence interval (CI), 1.25-2.52; P = 0.001], as well as elevated risk of Gleason 8+ prostate cancer (HR = 3.11; 95% CI, 1.63-5.95; P = 0.001). c.756-c.1000 was also associated with elevated prostate cancer risk (HR = 2.83; 95% CI, 1.71-4.68; P = 0.00004) and elevated risk of Gleason 8+ prostate cancer (HR = 4.95; 95% CI, 2.12-11.54; P = 0.0002). No genotype-phenotype associations were detected for PSVs in BRCA1. These results demonstrate that specific BRCA2 PSVs may be associated with elevated risk of developing aggressive prostate cancer. SIGNIFICANCE: Aggressive prostate cancer risk in BRCA2 mutation carriers may vary according to the specific BRCA2 mutation inherited by the at-risk individual.

Published
2020

32. The spectrum of fancm protein truncating variants in European breast cancer cases.

Author

Torngren T., Teixeira M., Toss A., Urioste M., Vega A., Vlckova Z., Yannoukakos D., Zampiga V., Kleibl Z., Radice P., Nevanlinna H., Ehrencrona H., Janavicius R., Peterlongo P., Figlioli G., Kvist A., Tham E., Soukupova J., Kleiblova P., Muranen T.A., Andrieu N., Azzollini J., Balmana J., Barroso A., Benitez J., Bertelsen B., Blanco A., Bonanni B., Borg A., Brunet J., Calistri D., Calvello M., Chvojka S., Cortesi L., Darder E., Del Valle J., Diez O., Eon-Marchais S., Fostira F., Gensini F., Houdayer C., Janatova M., Kiiski J.I., Konstantopoulou I., Kubelka-Sabit K., Lazaro C., Lesueur F., Manoukian S., Marcinkute R., Mickys U., Moncoutier V., Myszka A., Nguyen-Dumont T., Nielsen F.C., Norvilas R., Olah E., Osorio A., Papi L., Peissel B., Peixoto A., Plaseska-Karanfilska D., Pocza T., Rossing M., Rudaitis V., Santamarina M., Santos C., Smichkoska S., Southey M.C., Stoppa-Lyonnet D., Torngren T., Teixeira M., Toss A., Urioste M., Vega A., Vlckova Z., Yannoukakos D., Zampiga V., Kleibl Z., Radice P., Nevanlinna H., Ehrencrona H., Janavicius R., Peterlongo P., Figlioli G., Kvist A., Tham E., Soukupova J., Kleiblova P., Muranen T.A., Andrieu N., Azzollini J., Balmana J., Barroso A., Benitez J., Bertelsen B., Blanco A., Bonanni B., Borg A., Brunet J., Calistri D., Calvello M., Chvojka S., Cortesi L., Darder E., Del Valle J., Diez O., Eon-Marchais S., Fostira F., Gensini F., Houdayer C., Janatova M., Kiiski J.I., Konstantopoulou I., Kubelka-Sabit K., Lazaro C., Lesueur F., Manoukian S., Marcinkute R., Mickys U., Moncoutier V., Myszka A., Nguyen-Dumont T., Nielsen F.C., Norvilas R., Olah E., Osorio A., Papi L., Peissel B., Peixoto A., Plaseska-Karanfilska D., Pocza T., Rossing M., Rudaitis V., Santamarina M., Santos C., Smichkoska S., Southey M.C., and Stoppa-Lyonnet D.

Abstract

Germline protein truncating variants (PTVs) in the FANCM gene have been associated with a 2-4-fold increased breast cancer risk in case-control studies conducted in different European populations. However, the distribution and the frequency of FANCM PTVs in Europe have never been investigated. In the present study, we collected the data of 114 European female breast cancer cases with FANCM PTVs ascertained in 20 centers from 13 European countries. We identified 27 different FANCM PTVs. The p.Gln1701* PTV is the most common PTV in Northern Europe with a maximum frequency in Finland and a lower relative frequency in Southern Europe. On the contrary, p.Arg1931* seems to be the most common PTV in Southern Europe. We also showed that p.Arg658*, the third most common PTV, is more frequent in Central Europe, and p.Gln498Thrfs*7 is probably a founder variant from Lithuania. Of the 23 rare or unique FANCM PTVs, 15 have not been previously reported. We provide here the initial spectrum of FANCM PTVs in European breast cancer cases.Copyright © 2020 by the authors. Licensee MDPI, Basel, Switzerland.

Published
2020

33. Association of genomic domains in BRCA1 and BRCA2 with prostate cancer risk and aggressiveness.

Author

Engel C., Schmutzler R.K., Schuster H., Senter L., Seynaeve C.M., Shah P.D., Sharma P., Shin V.Y., Silvestri V., Simard J., Singer C.F., Skytte A.-B., Snape K., Solano A.R., Soucy P., Southey M.C., Spurdle A.B., Steele L., Steinemann D., Stoppa-Lyonnet D., Stradella A., Sunde L., Sutter C., Tan Y.Y., Teixeira M.R., Teo S.H., Thomassen M., Tibiletti M.G., Tischkowitz M., Tognazzo S., Toland A.E., Tommasi S., Torres D., Toss A., Trainer A.H., Tung N., Van Asperen C.J., Van Der Baan F.H., Van Der Kolk L.E., Van Der Luijt R.B., Van Hest L.P., Varesco L., Varon-Mateeva R., Viel A., Vierstrate J., Villa R., Von Wachenfeldt A., Wagner P., Wang-Gohrke S., Wappenschmidt B., Weitzel J.N., Wieme G., Yadav S., Yannoukakos D., Yoon S.-Y., Zanzottera C., Zorn K.K., D'Amico A.V., Freedman M.L., Pomerantz M.M., Chenevix-Trench G., Antoniou A.C., Neuhausen S.L., Ottini L., Nielsen H.R., Rebbeck T.R., Patel V.L., Busch E.L., Friebel T.M., Cronin A., Leslie G., McGuffog L., Adlard J., Agata S., Agnarsson B.A., Ahmed M., Aittom K., Alducci E., Andrulis I.L., Arason A., Arnold N., Artioli G., Arver B., Auber B., Azzollini J., Balmana J., Barkardottir R.B., Barnes D.R., Barroso A., Barrowdale D., Belotti M., Benitez J., Bertelsen B., Blok M.J., Bodrogi I., Bonadona V., Bonanni B., Bondavalli D., Boonen S.E., Borde J., Borg A., Bradbury A.R., Brady A., Brewer C., Brunet J., Buecher B., Buys S.S., Cabezas-Camarero S., Caldes T., Caliebe A., Caligo M.A., Calvello M., Campbell I.G., Carnevali I., Carrasco E., Chan T.L., Chu A.T.W., Chung W.K., Claes K.B.M., Cook J., Cortesi L., Couch F.J., Daly M.B., Damante G., Darder E., Davidson R., De La Hoya M., Della Puppa L., Dennis J., Diez O., Ding Y.C., Ditsch N., Domchek S.M., Donaldson A., Dworniczak B., Easton D.F., Eccles D.M., Eeles R.A., Ehrencrona H., Ejlertsen B., Evans D.G., Faivre L., Faust U., Feliubadalo L., Foretova L., Fostira F., Fountzilas G., Frost D., Garcia-Barberan V., Garre P., Gauthier-Villars M., Geczi L., Gehrig A., Gerdes A.-M., Gesta P., Giannini G., Glendon G., Godwin A.K., Goldgar D.E., Greene M.H., Gutierrez-Barrera A.M., Hahnen E., Hamann U., Hauke J., Herold N., Hogervorst F.B.L., Honisch E., Hopper J.L., Hulick P.J., Izatt L., Jager A., James P., Janavicius R., Jensen U.B., Jensen T.D., Johannsson O.Th., John E.M., Joseph V., Kang E., Kast K., Kiiski J.I., Kim S.-W., Kim Z., Ko K.-P., Konstantopoulou I., Kramer G., Krogh L., Kruse T.A., Kwong A., Larsen M., Lasset C., Lautrup C., Lazaro C., Lee J., Lee J.W., Lee M.H., Lemke J., Lesueur F., Liljegren A., Lindblom A., Llovet P., Lopez-Fernandez A., Lopez-Perolio I., Lorca V., Loud J.T., Ma E.S.K., Mai P.L., Manoukian S., Mari V., Martin L., Matricardi L., Mebirouk N., Medici V., Meijers-Heijboer H.E.J., Meindl A., Mensenkamp A.R., Miller C., Gomes D.M., Montagna M., Mooij T.M., Moserle L., Mouret-Fourme E., Mulligan A.M., Nathanson K.L., Navratilova M., Nevanlinna H., Niederacher D., Cilius Nielsen F.C., Nikitina-Zake L., Offit K., Olah E., Olopade O.I., Ong K.-R., Osorio A., Ott C.-E., Palli D., Park S.K., Parsons M.T., Pedersen I.S., Peissel B., Peixoto A., Perez-Segura P., Peterlongo P., Petersen A.H., Porteous M.E., Pujana M.A., Radice P., Ramser J., Rantala J., Rashid M.U., Rhiem K., Rizzolo P., Robson M.E., Rookus M.A., Rossing C.M., Ruddy K.J., Santos C., Saule C., Scarpitta R., Engel C., Schmutzler R.K., Schuster H., Senter L., Seynaeve C.M., Shah P.D., Sharma P., Shin V.Y., Silvestri V., Simard J., Singer C.F., Skytte A.-B., Snape K., Solano A.R., Soucy P., Southey M.C., Spurdle A.B., Steele L., Steinemann D., Stoppa-Lyonnet D., Stradella A., Sunde L., Sutter C., Tan Y.Y., Teixeira M.R., Teo S.H., Thomassen M., Tibiletti M.G., Tischkowitz M., Tognazzo S., Toland A.E., Tommasi S., Torres D., Toss A., Trainer A.H., Tung N., Van Asperen C.J., Van Der Baan F.H., Van Der Kolk L.E., Van Der Luijt R.B., Van Hest L.P., Varesco L., Varon-Mateeva R., Viel A., Vierstrate J., Villa R., Von Wachenfeldt A., Wagner P., Wang-Gohrke S., Wappenschmidt B., Weitzel J.N., Wieme G., Yadav S., Yannoukakos D., Yoon S.-Y., Zanzottera C., Zorn K.K., D'Amico A.V., Freedman M.L., Pomerantz M.M., Chenevix-Trench G., Antoniou A.C., Neuhausen S.L., Ottini L., Nielsen H.R., Rebbeck T.R., Patel V.L., Busch E.L., Friebel T.M., Cronin A., Leslie G., McGuffog L., Adlard J., Agata S., Agnarsson B.A., Ahmed M., Aittom K., Alducci E., Andrulis I.L., Arason A., Arnold N., Artioli G., Arver B., Auber B., Azzollini J., Balmana J., Barkardottir R.B., Barnes D.R., Barroso A., Barrowdale D., Belotti M., Benitez J., Bertelsen B., Blok M.J., Bodrogi I., Bonadona V., Bonanni B., Bondavalli D., Boonen S.E., Borde J., Borg A., Bradbury A.R., Brady A., Brewer C., Brunet J., Buecher B., Buys S.S., Cabezas-Camarero S., Caldes T., Caliebe A., Caligo M.A., Calvello M., Campbell I.G., Carnevali I., Carrasco E., Chan T.L., Chu A.T.W., Chung W.K., Claes K.B.M., Cook J., Cortesi L., Couch F.J., Daly M.B., Damante G., Darder E., Davidson R., De La Hoya M., Della Puppa L., Dennis J., Diez O., Ding Y.C., Ditsch N., Domchek S.M., Donaldson A., Dworniczak B., Easton D.F., Eccles D.M., Eeles R.A., Ehrencrona H., Ejlertsen B., Evans D.G., Faivre L., Faust U., Feliubadalo L., Foretova L., Fostira F., Fountzilas G., Frost D., Garcia-Barberan V., Garre P., Gauthier-Villars M., Geczi L., Gehrig A., Gerdes A.-M., Gesta P., Giannini G., Glendon G., Godwin A.K., Goldgar D.E., Greene M.H., Gutierrez-Barrera A.M., Hahnen E., Hamann U., Hauke J., Herold N., Hogervorst F.B.L., Honisch E., Hopper J.L., Hulick P.J., Izatt L., Jager A., James P., Janavicius R., Jensen U.B., Jensen T.D., Johannsson O.Th., John E.M., Joseph V., Kang E., Kast K., Kiiski J.I., Kim S.-W., Kim Z., Ko K.-P., Konstantopoulou I., Kramer G., Krogh L., Kruse T.A., Kwong A., Larsen M., Lasset C., Lautrup C., Lazaro C., Lee J., Lee J.W., Lee M.H., Lemke J., Lesueur F., Liljegren A., Lindblom A., Llovet P., Lopez-Fernandez A., Lopez-Perolio I., Lorca V., Loud J.T., Ma E.S.K., Mai P.L., Manoukian S., Mari V., Martin L., Matricardi L., Mebirouk N., Medici V., Meijers-Heijboer H.E.J., Meindl A., Mensenkamp A.R., Miller C., Gomes D.M., Montagna M., Mooij T.M., Moserle L., Mouret-Fourme E., Mulligan A.M., Nathanson K.L., Navratilova M., Nevanlinna H., Niederacher D., Cilius Nielsen F.C., Nikitina-Zake L., Offit K., Olah E., Olopade O.I., Ong K.-R., Osorio A., Ott C.-E., Palli D., Park S.K., Parsons M.T., Pedersen I.S., Peissel B., Peixoto A., Perez-Segura P., Peterlongo P., Petersen A.H., Porteous M.E., Pujana M.A., Radice P., Ramser J., Rantala J., Rashid M.U., Rhiem K., Rizzolo P., Robson M.E., Rookus M.A., Rossing C.M., Ruddy K.J., Santos C., Saule C., and Scarpitta R.

Abstract

Pathogenic sequence variants (PSV) in BRCA1 or BRCA2 (BRCA1/2) are associated with increased risk and severity of prostate cancer. We evaluated whether PSVs in BRCA1/2 were associated with risk of overall prostate cancer or high grade (Gleason 8) prostate cancer using an international sample of 65 BRCA1 and 171 BRCA2 male PSV carriers with prostate cancer, and 3,388 BRCA1 and 2,880 BRCA2 male PSV carriers without prostate cancer. PSVs in the 30 region of BRCA2 (c.7914) were significantly associated with elevated risk of prostate cancer compared with reference bin c.1001c.7913 [HR 1/4 1.78; 95% confidence interval (CI), 1.25-2.52; P 1/4 0.001], as well as elevated risk of Gleason 8 prostate cancer (HR 1/4 3.11; 95% CI, 1.63-5.95; P 1/4 0.001). c.756-c.1000 was also associated with elevated prostate cancer risk (HR 1/4 2.83; 95% CI, 1.71-4.68; P 1/4 0.00004) and elevated risk of Gleason 8 prostate cancer (HR 1/4 4.95; 95% CI, 2.12-11.54; P 1/4 0.0002). No genotype-phenotype associations were detected for PSVs in BRCA1. These results demonstrate that specific BRCA2 PSVs may be associated with elevated risk of developing aggressive prostate cancer.Copyright © 2020 American Association for Cancer Research.

Published
2020

34. Genome-wide association study identifies 32 novel breast cancer susceptibility loci from overall and subtype-specific analyses.

Author

Goldgar D.E., Newman W.G., Nielsen F.C., Nikitina-Zake L., Nodora J., Offit K., Olah E., Olopade O.I., Olsson H., Orr N., Papi L., Papp J., Park-Simon T.-W., Parsons M.T., Peissel B., Peixoto A., Peshkin B., Peterlongo P., Peto J., Phillips K.-A., Piedmonte M., Plaseska-Karanfilska D., Prajzendanc K., Prentice R., Prokofyeva D., Rack B., Radice P., Ramus S.J., Rantala J., Rashid M.U., Rennert G., Rennert H.S., Risch H.A., Romero A., Rookus M.A., Rubner M., Rudiger T., Saloustros E., Sampson S., Sandler D.P., Sawyer E.J., Scheuner M.T., Schmutzler R.K., Schneeweiss A., Schoemaker M.J., Schottker B., Schurmann P., Senter L., Sharma P., Sherman M.E., Shu X.-O., Singer C.F., Smichkoska S., Soucy P., Southey M.C., Spinelli J.J., Stone J., Stoppa-Lyonnet D., Swerdlow A.J., Szabo C.I., Tamimi R.M., Tapper W.J., Taylor J.A., Teixeira M.R., Terry M.B., Thomassen M., Thull D.L., Tischkowitz M., Toland A.E., Tollenaar R.A.E.M., Tomlinson I., Torres D., Troester M.A., Truong T., Tung N., Untch M., Vachon C.M., van den Ouweland A.M.W., van der Kolk L.E., van Veen E.M., vanRensburg E.J., Vega A., Wappenschmidt B., Weinberg C.R., Weitzel J.N., Wildiers H., Winqvist R., Wolk A., Yang X.R., Yannoukakos D., Zheng W., Zorn K.K., Milne R.L., Kraft P., Simard J., Pharoah P.D.P., Michailidou K., Antoniou A.C., Schmidt M.K., Chenevix-Trench G., Easton D.F., Chatterjee N., Garcia-Closas M., Zhang H., Ahearn T.U., Lecarpentier J., Barnes D., Beesley J., Qi G., Jiang X., O'Mara T.A., Zhao N., Bolla M.K., Dunning A.M., Dennis J., Wang Q., Ful Z.A., Aittomaki K., Andrulis I.L., Anton-Culver H., Arndt V., Aronson K.J., Arun B.K., Auer P.L., Azzollini J., Barrowdale D., Becher H., Beckmann M.W., Behrens S., Benitez J., Bermisheva M., Bialkowska K., Blanco A., Blomqvist C., Bogdanova N.V., Bojesen S.E., Bonanni B., Bondavalli D., Borg A., Brauch H., Brenner H., Briceno I., Broeks A., Brucker S.Y., Bruning T., Burwinkel B., Buys S.S., Byers H., Caldes T., Caligo M.A., Calvello M., Campa D., Castelao J.E., Chang-Claude J., Chanock S.J., Christiaens M., Christiansen H., Chung W.K., Claes K.B.M., Clarke C.L., Cornelissen S., Couch F.J., Cox A., Cross S.S., Czene K., Daly M.B., Devilee P., Diez O., Domchek S.M., Dork T., Dwek M., Eccles D.M., Ekici A.B., Evans D.G., Fasching P.A., Figueroa J., Foretova L., Fostira F., Friedman E., Frost D., Gago-Dominguez M., Gapstur S.M., Garber J., Garcia-Saenz J.A., Gaudet M.M., Gayther S.A., Giles G.G., Godwin A.K., Goldberg M.S., Gonzalez-Neira A., Greene M.H., Gronwald J., Guenel P., Haberle L., Hahnen E., Haiman C.A., Hake C.R., Hall P., Hamann U., Harkness E.F., Heemskerk-Gerritsen B.A.M., Hillemanns P., Hogervorst F.B.L., Holleczek B., Hollestelle A., Hooning M.J., Hoover R.N., Hopper J.L., Howell A., Huebner H., Hulick P.J., Imyanitov E.N., Isaacs C., Izatt L., Jager A., Jakimovska M., Jakubowska A., James P., Janavicius R., Janni W., John E.M., Jones M.E., Jung A., Kaaks R., Kapoor P.M., Karlan B.Y., Keeman R., Khan S., Khusnutdinova E., Kitahara C.M., Ko Y.-D., Konstantopoulou I., Koppert L.B., Koutros S., Kristensen V.N., Laenkholm A.-V., Lambrechts D., Larsson S.C., Laurent-Puig P., Lazaro C., Lazarova E., Lejbkowicz F., Leslie G., Lesueur F., Lindblom A., Lissowska J., Lo W.-Y., Loud J.T., Lubinski J., Lukomska A., MacInnis R.J., Mannermaa A., Manoochehri M., Manoukian S., Margolin S., Martinez M.E., Matricardi L., McGuffog L., McLean C., Mebirouk N., Meindl A., Menon U., Miller A., Mingazheva E., Montagna M., Mulligan A.M., Mulot C., Muranen T.A., Nathanson K.L., Neuhausen S.L., Nevanlinna H., Neven P., Goldgar D.E., Newman W.G., Nielsen F.C., Nikitina-Zake L., Nodora J., Offit K., Olah E., Olopade O.I., Olsson H., Orr N., Papi L., Papp J., Park-Simon T.-W., Parsons M.T., Peissel B., Peixoto A., Peshkin B., Peterlongo P., Peto J., Phillips K.-A., Piedmonte M., Plaseska-Karanfilska D., Prajzendanc K., Prentice R., Prokofyeva D., Rack B., Radice P., Ramus S.J., Rantala J., Rashid M.U., Rennert G., Rennert H.S., Risch H.A., Romero A., Rookus M.A., Rubner M., Rudiger T., Saloustros E., Sampson S., Sandler D.P., Sawyer E.J., Scheuner M.T., Schmutzler R.K., Schneeweiss A., Schoemaker M.J., Schottker B., Schurmann P., Senter L., Sharma P., Sherman M.E., Shu X.-O., Singer C.F., Smichkoska S., Soucy P., Southey M.C., Spinelli J.J., Stone J., Stoppa-Lyonnet D., Swerdlow A.J., Szabo C.I., Tamimi R.M., Tapper W.J., Taylor J.A., Teixeira M.R., Terry M.B., Thomassen M., Thull D.L., Tischkowitz M., Toland A.E., Tollenaar R.A.E.M., Tomlinson I., Torres D., Troester M.A., Truong T., Tung N., Untch M., Vachon C.M., van den Ouweland A.M.W., van der Kolk L.E., van Veen E.M., vanRensburg E.J., Vega A., Wappenschmidt B., Weinberg C.R., Weitzel J.N., Wildiers H., Winqvist R., Wolk A., Yang X.R., Yannoukakos D., Zheng W., Zorn K.K., Milne R.L., Kraft P., Simard J., Pharoah P.D.P., Michailidou K., Antoniou A.C., Schmidt M.K., Chenevix-Trench G., Easton D.F., Chatterjee N., Garcia-Closas M., Zhang H., Ahearn T.U., Lecarpentier J., Barnes D., Beesley J., Qi G., Jiang X., O'Mara T.A., Zhao N., Bolla M.K., Dunning A.M., Dennis J., Wang Q., Ful Z.A., Aittomaki K., Andrulis I.L., Anton-Culver H., Arndt V., Aronson K.J., Arun B.K., Auer P.L., Azzollini J., Barrowdale D., Becher H., Beckmann M.W., Behrens S., Benitez J., Bermisheva M., Bialkowska K., Blanco A., Blomqvist C., Bogdanova N.V., Bojesen S.E., Bonanni B., Bondavalli D., Borg A., Brauch H., Brenner H., Briceno I., Broeks A., Brucker S.Y., Bruning T., Burwinkel B., Buys S.S., Byers H., Caldes T., Caligo M.A., Calvello M., Campa D., Castelao J.E., Chang-Claude J., Chanock S.J., Christiaens M., Christiansen H., Chung W.K., Claes K.B.M., Clarke C.L., Cornelissen S., Couch F.J., Cox A., Cross S.S., Czene K., Daly M.B., Devilee P., Diez O., Domchek S.M., Dork T., Dwek M., Eccles D.M., Ekici A.B., Evans D.G., Fasching P.A., Figueroa J., Foretova L., Fostira F., Friedman E., Frost D., Gago-Dominguez M., Gapstur S.M., Garber J., Garcia-Saenz J.A., Gaudet M.M., Gayther S.A., Giles G.G., Godwin A.K., Goldberg M.S., Gonzalez-Neira A., Greene M.H., Gronwald J., Guenel P., Haberle L., Hahnen E., Haiman C.A., Hake C.R., Hall P., Hamann U., Harkness E.F., Heemskerk-Gerritsen B.A.M., Hillemanns P., Hogervorst F.B.L., Holleczek B., Hollestelle A., Hooning M.J., Hoover R.N., Hopper J.L., Howell A., Huebner H., Hulick P.J., Imyanitov E.N., Isaacs C., Izatt L., Jager A., Jakimovska M., Jakubowska A., James P., Janavicius R., Janni W., John E.M., Jones M.E., Jung A., Kaaks R., Kapoor P.M., Karlan B.Y., Keeman R., Khan S., Khusnutdinova E., Kitahara C.M., Ko Y.-D., Konstantopoulou I., Koppert L.B., Koutros S., Kristensen V.N., Laenkholm A.-V., Lambrechts D., Larsson S.C., Laurent-Puig P., Lazaro C., Lazarova E., Lejbkowicz F., Leslie G., Lesueur F., Lindblom A., Lissowska J., Lo W.-Y., Loud J.T., Lubinski J., Lukomska A., MacInnis R.J., Mannermaa A., Manoochehri M., Manoukian S., Margolin S., Martinez M.E., Matricardi L., McGuffog L., McLean C., Mebirouk N., Meindl A., Menon U., Miller A., Mingazheva E., Montagna M., Mulligan A.M., Mulot C., Muranen T.A., Nathanson K.L., Neuhausen S.L., Nevanlinna H., and Neven P.

Abstract

Breast cancer susceptibility variants frequently show heterogeneity in associations by tumor subtype1-3. To identify novel loci, we performed a genome-wide association study including 133,384 breast cancer cases and 113,789 controls, plus 18,908 BRCA1 mutation carriers (9,414 with breast cancer) of European ancestry, using both standard and novel methodologies that account for underlying tumor heterogeneity by estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 status and tumor grade. We identified 32 novel susceptibility loci (P < 5.0 x 10-8), 15 of which showed evidence for associations with at least one tumor feature (false discovery rate < 0.05). Five loci showed associations (P < 0.05) in opposite directions between luminal and non-luminal subtypes. In silico analyses showed that these five loci contained cell-specific enhancers that differed between normal luminal and basal mammary cells. The genetic correlations between five intrinsic-like subtypes ranged from 0.35 to 0.80. The proportion of genome-wide chip heritability explained by all known susceptibility loci was 54.2% for luminal A-like disease and 37.6% for triple-negative disease. The odds ratios of polygenic risk scores, which included 330 variants, for the highest 1% of quantiles compared with middle quantiles were 5.63 and 3.02 for luminal A-like and triple-negative disease, respectively. These findings provide an improved understanding of genetic predisposition to breast cancer subtypes and will inform the development of subtype-specific polygenic risk scores.Copyright © 2020, The Author(s), under exclusive licence to Springer Nature America, Inc.

Published
2020

35. Genome-wide association study identifies 32 novel breast cancer susceptibility loci from overall and subtype-specific analyses

Author

Zhan, H, Ahearn, TU, Lecarpentier, J, Barnes, D, Beesley, J, Qi, G, Jiang, X, O'Mara, TA, Zhao, N, Bolla, MK, Dunning, AM, Dennis, J, Wang, Q, Abu Ful, Z, Aittomaki, K, Andrulis, IL, Anton-Culver, H, Arndt, V, Aronson, KJ, Arun, BK, Auer, PL, Azzollini, J, Barrowdale, D, Becher, H, Beckmann, MW, Behrens, S, Benitez, J, Bermisheva, M, Bialkowska, K, Blanco, A, Blomqvist, C, Bogdanova, N, Bojesen, SE, Bonanni, B, Bondavalli, D, Borg, A, Brauch, H, Brenner, H, Briceno, I, Broeks, A, Brucker, SY, Bruening, T, Burwinkel, B, Buys, SS, Byers, H, Caldes, T, Caligo, MA, Calvello, M, Campa, D, Castelao, JE, Chang-Claude, J, Chanock, SJ, Christiaens, M, Christiansen, H, Chung, WK, Claes, KBM, Clarke, CL, Cornelissen, S, Couch, FJ, Cox, A, Cross, SS, Czene, K, Daly, MB, Devilee, P, Diez, O, Domchek, SM, Doerk, T, Dwek, M, Eccles, DM, Ekici, AB, Evans, DG, Fasching, PA, Figueroa, J, Foretova, L, Fostira, F, Friedman, E, Frost, D, Gago-Dominguez, M, Gapstur, SM, Garber, J, Garcia-Saenz, JA, Gaudet, MM, Gayther, SA, Giles, GG, Godwin, AK, Goldberg, MS, Goldgar, DE, Gonzalez-Neira, A, Greene, MH, Gronwald, J, Guenel, P, Haeberle, L, Hahnen, E, Haiman, CA, Hake, CR, Hall, P, Hamann, U, Harkness, EF, Heemskerk-Gerritsen, BAM, Hillemanns, P, Hogervorst, FBL, Holleczek, B, Hollestelle, A, Hooning, MJ, Hoover, RN, Hopper, JL, Howell, A, Huebner, H, Hulick, PJ, Imyanitov, EN, Isaacs, C, Izatt, L, Jager, A, Jakimovska, M, Jakubowska, A, James, P, Janavicius, R, Janni, W, John, EM, Jones, ME, Jung, A, Kaaks, R, Kapoor, PM, Karlan, BY, Keeman, R, Khan, S, Khusnutdinova, E, Kitahara, CM, Ko, Y-D, Konstantopoulou, I, Koppert, LB, Koutros, S, Kristensen, VN, Laenkholm, A-V, Lambrechts, D, Larsson, SC, Laurent-Puig, P, Lazaro, C, Lazarova, E, Lejbkowicz, F, Leslie, G, Lesueur, F, Lindblom, A, Lissowska, J, Lo, W-Y, Loud, JT, Lubinski, J, Lukomska, A, MacInnis, RJ, Mannermaa, A, Manoochehri, M, Manoukian, S, Margolin, S, Martinez, ME, Matricardi, L, McGuffog, L, McLean, C, Mebirouk, N, Meindl, A, Menon, U, Miller, A, Mingazheva, E, Montagna, M, Mulligan, AM, Mulot, C, Muranen, TA, Nathanson, KL, Neuhausen, SL, Nevanlinna, H, Neven, P, Newman, WG, Nielsens, FC, Nikitina-Zake, L, Nodora, J, Offit, K, Olah, E, Olopade, O, Olsson, H, Orr, N, Papi, L, Papp, J, Park-Simon, T-W, Parsons, MT, Peissel, B, Peixoto, A, Peshkin, B, Peterlongo, P, Peto, J, Phillips, K-A, Piedmonte, M, Plaseska-Karanfilska, D, Prajzendanc, K, Prentice, R, Prokofyeva, D, Rack, B, Radice, P, Ramus, SJ, Rantala, J, Rashid, MU, Rennert, G, Rennert, HS, Risch, HA, Romero, A, Rookus, MA, Ruebner, M, Ruediger, T, Saloustros, E, Sampson, S, Sandler, DP, Sawyer, EJ, Scheuner, MT, Schmutzler, RK, Schneeweiss, A, Schoemaker, MJ, Schoettker, B, Schuermann, P, Senter, L, Sharma, P, Sherman, ME, Shu, X-O, Singer, CF, Smichkoska, S, Soucy, P, Southey, MC, Spinelli, JJ, Stone, J, Stoppa-Lyonnet, D, Swerdlow, AJ, Szabo, C, Tamimi, RM, Tapper, WJ, Taylor, JA, Teixeira, MR, Terry, M, Thomassen, M, Thull, DL, Tischkowitz, M, Toland, AE, Tollenaar, RAEM, Tomlinson, I, Torres, D, Troester, MA, Truong, T, Tung, N, Untch, M, Vachon, CM, van den Ouweland, AMW, van der Kolk, LE, van Veen, EM, vanRensburg, EJ, Vega, A, Wappenschmidt, B, Weinberg, CR, Weitzel, JN, Wildiers, H, Winqvist, R, Wolk, A, Yang, XR, Yannoukakos, D, Zheng, W, Zorn, KK, Milne, RL, Kraft, P, Simard, J, Pharoah, PDP, Michailidou, K, Antoniou, AC, Schmidt, MK, Chenevix-Trench, G, Easton, DF, Chatterjee, N, Garcia-Closas, M, Zhan, H, Ahearn, TU, Lecarpentier, J, Barnes, D, Beesley, J, Qi, G, Jiang, X, O'Mara, TA, Zhao, N, Bolla, MK, Dunning, AM, Dennis, J, Wang, Q, Abu Ful, Z, Aittomaki, K, Andrulis, IL, Anton-Culver, H, Arndt, V, Aronson, KJ, Arun, BK, Auer, PL, Azzollini, J, Barrowdale, D, Becher, H, Beckmann, MW, Behrens, S, Benitez, J, Bermisheva, M, Bialkowska, K, Blanco, A, Blomqvist, C, Bogdanova, N, Bojesen, SE, Bonanni, B, Bondavalli, D, Borg, A, Brauch, H, Brenner, H, Briceno, I, Broeks, A, Brucker, SY, Bruening, T, Burwinkel, B, Buys, SS, Byers, H, Caldes, T, Caligo, MA, Calvello, M, Campa, D, Castelao, JE, Chang-Claude, J, Chanock, SJ, Christiaens, M, Christiansen, H, Chung, WK, Claes, KBM, Clarke, CL, Cornelissen, S, Couch, FJ, Cox, A, Cross, SS, Czene, K, Daly, MB, Devilee, P, Diez, O, Domchek, SM, Doerk, T, Dwek, M, Eccles, DM, Ekici, AB, Evans, DG, Fasching, PA, Figueroa, J, Foretova, L, Fostira, F, Friedman, E, Frost, D, Gago-Dominguez, M, Gapstur, SM, Garber, J, Garcia-Saenz, JA, Gaudet, MM, Gayther, SA, Giles, GG, Godwin, AK, Goldberg, MS, Goldgar, DE, Gonzalez-Neira, A, Greene, MH, Gronwald, J, Guenel, P, Haeberle, L, Hahnen, E, Haiman, CA, Hake, CR, Hall, P, Hamann, U, Harkness, EF, Heemskerk-Gerritsen, BAM, Hillemanns, P, Hogervorst, FBL, Holleczek, B, Hollestelle, A, Hooning, MJ, Hoover, RN, Hopper, JL, Howell, A, Huebner, H, Hulick, PJ, Imyanitov, EN, Isaacs, C, Izatt, L, Jager, A, Jakimovska, M, Jakubowska, A, James, P, Janavicius, R, Janni, W, John, EM, Jones, ME, Jung, A, Kaaks, R, Kapoor, PM, Karlan, BY, Keeman, R, Khan, S, Khusnutdinova, E, Kitahara, CM, Ko, Y-D, Konstantopoulou, I, Koppert, LB, Koutros, S, Kristensen, VN, Laenkholm, A-V, Lambrechts, D, Larsson, SC, Laurent-Puig, P, Lazaro, C, Lazarova, E, Lejbkowicz, F, Leslie, G, Lesueur, F, Lindblom, A, Lissowska, J, Lo, W-Y, Loud, JT, Lubinski, J, Lukomska, A, MacInnis, RJ, Mannermaa, A, Manoochehri, M, Manoukian, S, Margolin, S, Martinez, ME, Matricardi, L, McGuffog, L, McLean, C, Mebirouk, N, Meindl, A, Menon, U, Miller, A, Mingazheva, E, Montagna, M, Mulligan, AM, Mulot, C, Muranen, TA, Nathanson, KL, Neuhausen, SL, Nevanlinna, H, Neven, P, Newman, WG, Nielsens, FC, Nikitina-Zake, L, Nodora, J, Offit, K, Olah, E, Olopade, O, Olsson, H, Orr, N, Papi, L, Papp, J, Park-Simon, T-W, Parsons, MT, Peissel, B, Peixoto, A, Peshkin, B, Peterlongo, P, Peto, J, Phillips, K-A, Piedmonte, M, Plaseska-Karanfilska, D, Prajzendanc, K, Prentice, R, Prokofyeva, D, Rack, B, Radice, P, Ramus, SJ, Rantala, J, Rashid, MU, Rennert, G, Rennert, HS, Risch, HA, Romero, A, Rookus, MA, Ruebner, M, Ruediger, T, Saloustros, E, Sampson, S, Sandler, DP, Sawyer, EJ, Scheuner, MT, Schmutzler, RK, Schneeweiss, A, Schoemaker, MJ, Schoettker, B, Schuermann, P, Senter, L, Sharma, P, Sherman, ME, Shu, X-O, Singer, CF, Smichkoska, S, Soucy, P, Southey, MC, Spinelli, JJ, Stone, J, Stoppa-Lyonnet, D, Swerdlow, AJ, Szabo, C, Tamimi, RM, Tapper, WJ, Taylor, JA, Teixeira, MR, Terry, M, Thomassen, M, Thull, DL, Tischkowitz, M, Toland, AE, Tollenaar, RAEM, Tomlinson, I, Torres, D, Troester, MA, Truong, T, Tung, N, Untch, M, Vachon, CM, van den Ouweland, AMW, van der Kolk, LE, van Veen, EM, vanRensburg, EJ, Vega, A, Wappenschmidt, B, Weinberg, CR, Weitzel, JN, Wildiers, H, Winqvist, R, Wolk, A, Yang, XR, Yannoukakos, D, Zheng, W, Zorn, KK, Milne, RL, Kraft, P, Simard, J, Pharoah, PDP, Michailidou, K, Antoniou, AC, Schmidt, MK, Chenevix-Trench, G, Easton, DF, Chatterjee, N, and Garcia-Closas, M

Abstract

Breast cancer susceptibility variants frequently show heterogeneity in associations by tumor subtype1-3. To identify novel loci, we performed a genome-wide association study including 133,384 breast cancer cases and 113,789 controls, plus 18,908 BRCA1 mutation carriers (9,414 with breast cancer) of European ancestry, using both standard and novel methodologies that account for underlying tumor heterogeneity by estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 status and tumor grade. We identified 32 novel susceptibility loci (P < 5.0 × 10-8), 15 of which showed evidence for associations with at least one tumor feature (false discovery rate < 0.05). Five loci showed associations (P < 0.05) in opposite directions between luminal and non-luminal subtypes. In silico analyses showed that these five loci contained cell-specific enhancers that differed between normal luminal and basal mammary cells. The genetic correlations between five intrinsic-like subtypes ranged from 0.35 to 0.80. The proportion of genome-wide chip heritability explained by all known susceptibility loci was 54.2% for luminal A-like disease and 37.6% for triple-negative disease. The odds ratios of polygenic risk scores, which included 330 variants, for the highest 1% of quantiles compared with middle quantiles were 5.63 and 3.02 for luminal A-like and triple-negative disease, respectively. These findings provide an improved understanding of genetic predisposition to breast cancer subtypes and will inform the development of subtype-specific polygenic risk scores.

Published
2020

36. Association of Genomic Domains in BRCA1 and BRCA2 with Prostate Cancer Risk and Aggressiveness

Author

Patel, VL, Busch, EL, Friebel, TM, Cronin, A, Leslie, G, McGuffog, L, Adlard, J, Agata, S, Agnarsson, BA, Ahmed, M, Aittomaki, K, Alducci, E, Andrulis, IL, Arason, A, Arnold, N, Artioli, G, Arver, B, Auber, B, Azzollini, J, Balmana, J, Barkardottir, RB, Barnes, DR, Barroso, A, Barrowdale, D, Belotti, M, Benitez, J, Bertelsen, B, Blok, MJ, Bodrogi, I, Bonadona, V, Bonanni, B, Bondavalli, D, Boonen, SE, Borde, J, Borg, A, Bradbury, AR, Brady, A, Brewer, C, Brunet, J, Buecher, B, Buys, SS, Cabezas-Camarero, S, Caldes, T, Caliebe, A, Caligo, MA, Calvello, M, Campbell, IG, Carnevali, I, Carrasco, E, Chan, TL, Chu, ATW, Chung, WK, Claes, KBM, Cook, J, Cortesi, L, Couch, FJ, Daly, MB, Damante, G, Darder, E, Davidson, R, de la Hoya, M, Della Puppa, L, Dennis, J, Diez, O, Ding, YC, Ditsch, N, Domchek, SM, Donaldson, A, Dworniczak, B, Easton, DF, Eccles, DM, Eeles, RA, Ehrencrona, H, Ejlertsen, B, Engel, C, Evans, DG, Faivre, L, Faust, U, Feliubadalo, L, Foretova, L, Fostira, F, Fountzilas, G, Frost, D, Garcia-Barberan, V, Garre, P, Gauthier-Villars, M, Geczi, L, Gehrig, A, Gerdes, A-M, Gesta, P, Giannini, G, Glendon, G, Godwin, AK, Goldgar, DE, Greene, MH, Gutierrez-Barrera, AM, Hahnen, E, Hamann, U, Hauke, J, Herold, N, Hogervorst, FBL, Honisch, E, Hopper, JL, Hulick, PJ, Izatt, L, Jager, A, James, P, Janavicius, R, Jensen, UB, Jensen, TD, Johannsson, OT, John, EM, Joseph, V, Kang, E, Kast, K, Kiiski, J, Kim, S-W, Kim, Z, Ko, K-P, Konstantopoulou, I, Kramer, G, Krogh, L, Kruse, TA, Kwong, A, Larsen, M, Lasset, C, Lautrup, C, Lazaro, C, Lee, J, Lee, JW, Lee, MH, Lemke, J, Lesueur, F, Liljegren, A, Lindblom, A, Llovet, P, Lopez-Fernandez, A, Lopez-Perolio, I, Lorca, V, Loud, JT, Ma, ESK, Mai, PL, Manoukian, S, Mari, V, Martin, L, Matricardi, L, Mebirouk, N, Medici, V, Meijers-Heijboer, HEJ, Meindl, A, Mensenkamp, AR, Miller, C, Gomes, DM, Montagna, M, Mooij, TM, Moserle, L, Mouret-Fourme, E, Mulligan, AM, Nathanson, KL, Navratilova, M, Nevanlinna, H, Niederacher, D, Nielsen, FCC, Nikitina-Zake, L, Offit, K, Olah, E, Olopade, O, Ong, K-R, Osorio, A, Ott, C-E, Palli, D, Park, SK, Parsons, MT, Pedersen, IS, Peissel, B, Peixoto, A, Perez-Segura, P, Peterlongo, P, Petersen, AH, Porteous, ME, Angel Pujana, M, Radice, P, Ramser, J, Rantala, J, Rashid, MU, Rhiem, K, Rizzolo, P, Robson, ME, Rookus, MA, Rossing, CM, Ruddy, KJ, Santos, C, Saule, C, Scarpitta, R, Schmutzler, RK, Schuster, H, Senter, L, Seynaeve, CM, Shah, PD, Sharma, P, Shin, VY, Silvestri, V, Simard, J, Singer, CF, Skytte, A-B, Snape, K, Solano, AR, Soucy, P, Southey, MC, Spurdle, AB, Steele, L, Steinemann, D, Stoppa-Lyonnet, D, Stradella, A, Sunde, L, Sutter, C, Tan, YY, Teixeira, MR, Teo, SH, Thomassen, M, Tibiletti, MG, Tischkowitz, M, Tognazzo, S, Toland, AE, Tommasi, S, Torres, D, Toss, A, Trainer, AH, Tung, N, van Asperen, CJ, van der Baan, FH, van der Kolk, LE, van der Luijt, RB, van Hest, LP, Varesco, L, Varon-Mateeva, R, Viel, A, Vierstraete, J, Villa, R, von Wachenfeldt, A, Wagner, P, Wang-Gohrke, S, Wappenschmidt, B, Weitzel, JN, Wieme, G, Yadav, S, Yannoukakos, D, Yoon, S-Y, Zanzottera, C, Zorn, KK, D'Amico, A, Freedman, ML, Pomerantz, MM, Chenevix-Trench, G, Antoniou, AC, Neuhausen, SL, Ottini, L, Nielsen, HR, Rebbeck, TR, Patel, VL, Busch, EL, Friebel, TM, Cronin, A, Leslie, G, McGuffog, L, Adlard, J, Agata, S, Agnarsson, BA, Ahmed, M, Aittomaki, K, Alducci, E, Andrulis, IL, Arason, A, Arnold, N, Artioli, G, Arver, B, Auber, B, Azzollini, J, Balmana, J, Barkardottir, RB, Barnes, DR, Barroso, A, Barrowdale, D, Belotti, M, Benitez, J, Bertelsen, B, Blok, MJ, Bodrogi, I, Bonadona, V, Bonanni, B, Bondavalli, D, Boonen, SE, Borde, J, Borg, A, Bradbury, AR, Brady, A, Brewer, C, Brunet, J, Buecher, B, Buys, SS, Cabezas-Camarero, S, Caldes, T, Caliebe, A, Caligo, MA, Calvello, M, Campbell, IG, Carnevali, I, Carrasco, E, Chan, TL, Chu, ATW, Chung, WK, Claes, KBM, Cook, J, Cortesi, L, Couch, FJ, Daly, MB, Damante, G, Darder, E, Davidson, R, de la Hoya, M, Della Puppa, L, Dennis, J, Diez, O, Ding, YC, Ditsch, N, Domchek, SM, Donaldson, A, Dworniczak, B, Easton, DF, Eccles, DM, Eeles, RA, Ehrencrona, H, Ejlertsen, B, Engel, C, Evans, DG, Faivre, L, Faust, U, Feliubadalo, L, Foretova, L, Fostira, F, Fountzilas, G, Frost, D, Garcia-Barberan, V, Garre, P, Gauthier-Villars, M, Geczi, L, Gehrig, A, Gerdes, A-M, Gesta, P, Giannini, G, Glendon, G, Godwin, AK, Goldgar, DE, Greene, MH, Gutierrez-Barrera, AM, Hahnen, E, Hamann, U, Hauke, J, Herold, N, Hogervorst, FBL, Honisch, E, Hopper, JL, Hulick, PJ, Izatt, L, Jager, A, James, P, Janavicius, R, Jensen, UB, Jensen, TD, Johannsson, OT, John, EM, Joseph, V, Kang, E, Kast, K, Kiiski, J, Kim, S-W, Kim, Z, Ko, K-P, Konstantopoulou, I, Kramer, G, Krogh, L, Kruse, TA, Kwong, A, Larsen, M, Lasset, C, Lautrup, C, Lazaro, C, Lee, J, Lee, JW, Lee, MH, Lemke, J, Lesueur, F, Liljegren, A, Lindblom, A, Llovet, P, Lopez-Fernandez, A, Lopez-Perolio, I, Lorca, V, Loud, JT, Ma, ESK, Mai, PL, Manoukian, S, Mari, V, Martin, L, Matricardi, L, Mebirouk, N, Medici, V, Meijers-Heijboer, HEJ, Meindl, A, Mensenkamp, AR, Miller, C, Gomes, DM, Montagna, M, Mooij, TM, Moserle, L, Mouret-Fourme, E, Mulligan, AM, Nathanson, KL, Navratilova, M, Nevanlinna, H, Niederacher, D, Nielsen, FCC, Nikitina-Zake, L, Offit, K, Olah, E, Olopade, O, Ong, K-R, Osorio, A, Ott, C-E, Palli, D, Park, SK, Parsons, MT, Pedersen, IS, Peissel, B, Peixoto, A, Perez-Segura, P, Peterlongo, P, Petersen, AH, Porteous, ME, Angel Pujana, M, Radice, P, Ramser, J, Rantala, J, Rashid, MU, Rhiem, K, Rizzolo, P, Robson, ME, Rookus, MA, Rossing, CM, Ruddy, KJ, Santos, C, Saule, C, Scarpitta, R, Schmutzler, RK, Schuster, H, Senter, L, Seynaeve, CM, Shah, PD, Sharma, P, Shin, VY, Silvestri, V, Simard, J, Singer, CF, Skytte, A-B, Snape, K, Solano, AR, Soucy, P, Southey, MC, Spurdle, AB, Steele, L, Steinemann, D, Stoppa-Lyonnet, D, Stradella, A, Sunde, L, Sutter, C, Tan, YY, Teixeira, MR, Teo, SH, Thomassen, M, Tibiletti, MG, Tischkowitz, M, Tognazzo, S, Toland, AE, Tommasi, S, Torres, D, Toss, A, Trainer, AH, Tung, N, van Asperen, CJ, van der Baan, FH, van der Kolk, LE, van der Luijt, RB, van Hest, LP, Varesco, L, Varon-Mateeva, R, Viel, A, Vierstraete, J, Villa, R, von Wachenfeldt, A, Wagner, P, Wang-Gohrke, S, Wappenschmidt, B, Weitzel, JN, Wieme, G, Yadav, S, Yannoukakos, D, Yoon, S-Y, Zanzottera, C, Zorn, KK, D'Amico, A, Freedman, ML, Pomerantz, MM, Chenevix-Trench, G, Antoniou, AC, Neuhausen, SL, Ottini, L, Nielsen, HR, and Rebbeck, TR

Abstract

Pathogenic sequence variants (PSV) in BRCA1 or BRCA2 (BRCA1/2) are associated with increased risk and severity of prostate cancer. We evaluated whether PSVs in BRCA1/2 were associated with risk of overall prostate cancer or high grade (Gleason 8+) prostate cancer using an international sample of 65 BRCA1 and 171 BRCA2 male PSV carriers with prostate cancer, and 3,388 BRCA1 and 2,880 BRCA2 male PSV carriers without prostate cancer. PSVs in the 3' region of BRCA2 (c.7914+) were significantly associated with elevated risk of prostate cancer compared with reference bin c.1001-c.7913 [HR = 1.78; 95% confidence interval (CI), 1.25-2.52; P = 0.001], as well as elevated risk of Gleason 8+ prostate cancer (HR = 3.11; 95% CI, 1.63-5.95; P = 0.001). c.756-c.1000 was also associated with elevated prostate cancer risk (HR = 2.83; 95% CI, 1.71-4.68; P = 0.00004) and elevated risk of Gleason 8+ prostate cancer (HR = 4.95; 95% CI, 2.12-11.54; P = 0.0002). No genotype-phenotype associations were detected for PSVs in BRCA1. These results demonstrate that specific BRCA2 PSVs may be associated with elevated risk of developing aggressive prostate cancer. SIGNIFICANCE: Aggressive prostate cancer risk in BRCA2 mutation carriers may vary according to the specific BRCA2 mutation inherited by the at-risk individual.

Published
2020

37. The Spectrum of FANCM Protein Truncating Variants in European Breast Cancer Cases

Author

Figlioli, G, Kvist, A, Tham, E, Soukupova, J, Kleiblova, P, Muranen, TA, Andrieu, N, Azzollini, J, Balmana, J, Barroso, A, Benitez, J, Bertelsen, B, Blanco, A, Bonanni, B, Borg, A, Brunet, J, Calistri, D, Calvello, M, Chvojka, S, Cortesi, L, Darder, E, Del Valle, J, Diez, O, Eon-Marchais, S, Fostira, F, Gensini, F, Houdayer, C, Janatova, M, Kiiski, J, Konstantopoulou, I, Kubelka-Sabit, K, Lazaro, C, Lesueur, F, Manoukian, S, Marcinkute, R, Mickys, U, Moncoutier, V, Myszka, A, Tu, N-D, Nielsen, FC, Norvilas, R, Olah, E, Osorio, A, Papi, L, Peissel, B, Peixoto, A, Plaseska-Karanfilska, D, Pocza, T, Rossing, M, Rudaitis, V, Santamarina, M, Santos, C, Smichkoska, S, Southey, MC, Stoppa-Lyonnet, D, Teixeira, M, Torngren, T, Toss, A, Urioste, M, Vega, A, Vlckova, Z, Yannoukakos, D, Zampiga, V, Kleibl, Z, Radice, P, Nevanlinna, H, Ehrencrona, H, Janavicius, R, Peterlongo, P, Figlioli, G, Kvist, A, Tham, E, Soukupova, J, Kleiblova, P, Muranen, TA, Andrieu, N, Azzollini, J, Balmana, J, Barroso, A, Benitez, J, Bertelsen, B, Blanco, A, Bonanni, B, Borg, A, Brunet, J, Calistri, D, Calvello, M, Chvojka, S, Cortesi, L, Darder, E, Del Valle, J, Diez, O, Eon-Marchais, S, Fostira, F, Gensini, F, Houdayer, C, Janatova, M, Kiiski, J, Konstantopoulou, I, Kubelka-Sabit, K, Lazaro, C, Lesueur, F, Manoukian, S, Marcinkute, R, Mickys, U, Moncoutier, V, Myszka, A, Tu, N-D, Nielsen, FC, Norvilas, R, Olah, E, Osorio, A, Papi, L, Peissel, B, Peixoto, A, Plaseska-Karanfilska, D, Pocza, T, Rossing, M, Rudaitis, V, Santamarina, M, Santos, C, Smichkoska, S, Southey, MC, Stoppa-Lyonnet, D, Teixeira, M, Torngren, T, Toss, A, Urioste, M, Vega, A, Vlckova, Z, Yannoukakos, D, Zampiga, V, Kleibl, Z, Radice, P, Nevanlinna, H, Ehrencrona, H, Janavicius, R, and Peterlongo, P

Abstract

Germline protein truncating variants (PTVs) in the FANCM gene have been associated with a 2-4-fold increased breast cancer risk in case-control studies conducted in different European populations. However, the distribution and the frequency of FANCM PTVs in Europe have never been investigated. In the present study, we collected the data of 114 European female breast cancer cases with FANCM PTVs ascertained in 20 centers from 13 European countries. We identified 27 different FANCM PTVs. The p.Gln1701* PTV is the most common PTV in Northern Europe with a maximum frequency in Finland and a lower relative frequency in Southern Europe. On the contrary, p.Arg1931* seems to be the most common PTV in Southern Europe. We also showed that p.Arg658*, the third most common PTV, is more frequent in Central Europe, and p.Gln498Thrfs*7 is probably a founder variant from Lithuania. Of the 23 rare or unique FANCM PTVs, 15 have not been previously reported. We provide here the initial spectrum of FANCM PTVs in European breast cancer cases.

Published
2020

38. Mediastinal lymph node enlargement in idiopathic pulmonary fibrosis: Relationships with disease progression and pulmonary function trends

Author

Sgalla, Giacomo, Larici, Anna Rita, Golfi, N., Calvello, M., Farchione, Alessandra, Del Ciello, Annemilia, Varone, Francesco, Iovene, Bruno, Manfredi, Riccardo, Richeldi, Luca, Sgalla G. (ORCID:0000-0003-3130-9388), Larici A. R. (ORCID:0000-0002-1882-6244), Farchione A., Del Ciello A., Varone F., Iovene B., Manfredi R. (ORCID:0000-0002-4972-9500), Richeldi L. (ORCID:0000-0001-8594-1448), Sgalla, Giacomo, Larici, Anna Rita, Golfi, N., Calvello, M., Farchione, Alessandra, Del Ciello, Annemilia, Varone, Francesco, Iovene, Bruno, Manfredi, Riccardo, Richeldi, Luca, Sgalla G. (ORCID:0000-0003-3130-9388), Larici A. R. (ORCID:0000-0002-1882-6244), Farchione A., Del Ciello A., Varone F., Iovene B., Manfredi R. (ORCID:0000-0002-4972-9500), and Richeldi L. (ORCID:0000-0001-8594-1448)

Abstract

Background and objectives: Evidence of mediastinal Lymph Node Enlargement (LNE) on CT scan is a common finding in idiopathic pulmonary fibrosis (IPF). We sought to investigate whether the involvement of mediastinal lymph nodes is associated with accelerated disease progression, and explored the changes occurring in mediastinal lymph nodes during the radiological follow up of these patients. Methods: This retrospective study included IPF patients referred to a single ILD centre in Italy. A consensus-based assessment of mediastinal LNE on chest CT scan was performed by two thoracic radiologists. Kaplan-Meier curves and multivariate Cox proportional hazards regression were used to assess hazard ratios for mortality and disease progression (defined as categorical FVC decline ≥10%). The annualized rates of change in functional parameters for each patient were calculated using mixed linear models. Results: The study population consisted of 152 IPF patients, of whom 135 (89%) received antifibrotic treatment for IPF during the study follow up. Patients having evidence of 3 or more enlarged mediastinal lymph nodes on baseline CT scan showed increased rates of mortality (HR 5.03, 95% CI 1.86-13.62, p ≤ 0.001) and significant disease progression (HR 2.99, 95% CI 1.22-7.33, p = 0.17) as compared to patients without LNE, after adjusting for GAP stage. Among 62 patients with LNE who underwent a follow up CT scan of the chest and received antifibrotic treatment, 57 (92%) maintained evidence mediastinal LNE over time. Conclusions: Diffuse mediastinal lymph node involvement predicts clinically meaningful functional deterioration in patients with IPF.

Published
2020

39. Fibrotic Hypersensitivity Pneumonitis: Diagnosis and Management

Author

Varone, Francesco, Iovene, Bruno, Sgalla, Giacomo, Calvello, M., Calabrese, Anna Chiara, Larici, Anna Rita, Richeldi, Luca, Varone F., Iovene B., Sgalla G. (ORCID:0000-0003-3130-9388), Calabrese A., Larici A. R. (ORCID:0000-0002-1882-6244), Richeldi L. (ORCID:0000-0001-8594-1448), Varone, Francesco, Iovene, Bruno, Sgalla, Giacomo, Calvello, M., Calabrese, Anna Chiara, Larici, Anna Rita, Richeldi, Luca, Varone F., Iovene B., Sgalla G. (ORCID:0000-0003-3130-9388), Calabrese A., Larici A. R. (ORCID:0000-0002-1882-6244), and Richeldi L. (ORCID:0000-0001-8594-1448)

Abstract

Fibrotic hypersensitivity pneumonitis is a complex interstitial lung disease that is not entirely understood. In its chronic and fibrotic form, hypersensitivity pneumonitis is one of the main mimickers of idiopathic pulmonary fibrosis (IPF). Distinguishing between these two conditions is challenging but is of particular clinical relevance. Two approved therapies are available for IPF, and a considerable number of clinical trials are now exploring newer pharmacological options. This impressive research effort is a consequence of new pathogenetic understanding, updated diagnostic criteria and a long history of pharmacological trials. Conversely, current knowledge gaps on pathogenesis of chronic hypersensitivity pneumonitis, coupled with lack of validated diagnostic criteria, make the management of this disease an unsolved clinical challenge. This also reflects the paucity of therapeutic clinical trials in this field. In this review, we describe the current evidence and the possible future options to approach this complex disease.

Published
2020

40. Assessment of neurological manifestations in hospitalized patients with COVID-19

Author

Luigetti, Marco, Iorio, Raffaele, Bentivoglio, Anna Rita, Tricoli, Luca, Riso, Vittorio, Marotta, Jessica, Piano, Carla, Primiano, Guido Alessandro, Zileri Del Verme, L., Lo Monaco, Maria Rita, Calabresi, Paolo, Abbate, V., Acampora, N., Addolorato, G., Agostini, F., Ainora, M. E., Akacha, K., Amato, E., Andreani, F., Andriollo, G., Annetta, Maria Giuseppina, Annicchiarico, B. E., Antonelli, Massimo, Antonucci, G., Anzellotti, G. M., Armuzzi, A., Baldi, F., Barattucci, I., Barillaro, C., Barone, F., Bellantone, R. D. A., Bellieni, A., Bello, G., Benicchi, A., Benvenuto, F., Berardini, L., Berloco, F., Bernabei, R., Bianchi, A., Biasucci, D. G., Biasucci, L. M., Bibbo, S., Bini, A., Bisanti, A., Biscetti, F., Bocci, M. G., Bonadia, N., Bongiovanni, F., Borghetti, A., Bosco, G., Bosello, Silvia Laura, Bove, V., Bramato, G., Brandi, V., Bruni, T., Bruno, C., Bruno, D., Bungaro, M. C., Buonomo, A., Burzo, L., Calabrese, A., Calvello, M. R., Cambieri, A., Cambise, C., Camma, G., Candelli, M., Canistro, G., Cantanale, A., Capalbo, G., Capaldi, L., Capone, E., Capristo, E., Carbone, L., Cardone, S., Carelli, S., Carfi, A., Carnicelli, A., Caruso, C., Casciaro, F. A., Catalano, L., Cauda, R., Cecchini, A. L., Cerrito, L., Cesarano, M., Chiarito, A., Cianci, Rossella, Cicchinelli, S., Ciccullo, A., Cicetti, M., Ciciarello, F., Cingolani, A., Cipriani, M. C., Consalvo, M. L., Coppola, G., Corbo, G. M., Corsello, A., Costante, F., Costanzi, M., Covino, M., Crupi, D., Cutuli, S. L., D'Addio, S., D'Alessandro, A., D'Alfonso, M. E., D'Angelo, E., D'Aversa, F., Damiano, F., De Berardinis, G. M., De Cunzo, T., De Gaetano, D. K., De Luca, G., De Matteis, G., De Pascale, G., De Santis, P., De Siena, M., De Vito, F., Del Gatto, V., Del Giacomo, P., Del Zompo, F., Dell'Anna, A. M., Della, P. D., Di Gialleonardo, L., Di Giambenedetto, S., Di Luca, R., Di Maurizio, L., Di Muro, M., Dusina, A., Eleuteri, D., Esperide, A., Fachechi, D., Faliero, D., Falsiroli, C., Fantoni, M., Fedele, A., Feliciani, D., Ferrante, C., Ferrone, G., Festa, R., Fiore, M. C., Flex, A., Forte, E., Franceschi, Francesco, Francesconi, A., Franza, L., Funaro, B., Fuorlo, M., Fusco, D., Gabrielli, M., Gaetani, E., Galletta, C., Gallo, A., Gambassi, G., Garcovich, M., Gasbarrini, A., Gasparrini, I., Gelli, S., Giampietro, A., Gigante, L., Giuliano, G., Giupponi, B., Gremese, E., Grieco, Domenico Luca, Guerrera, M., Guglielmi, V., Guidone, C., Gulli, A., Iaconelli, A., Iafrati, A., Ianiro, Gianluca, Iaquinta, A., Impagnatiello, M., Inchingolo, R., Intini, E., Iorio, R., Izzi, I. M., Jovanovic, T., Kadhim, C., La Macchia, R., La Milia, D. I., Landi, F., Landi, G., Landi, R., Landolfi, R., Leo, M., Leone, P. M., Levantesi, L., Liguori, A., Liperoti, R., Lizzio, M. M., Lo Monaco Maria, R., Locantore, P., Lombardi, F., Lombardi, G., Lopetuso, L., Loria, V., Losito, A. R., Lucia, M. B. P., Macagno, F., Macerola, N., Maggi, G., Maiuro, G., Mancarella, F., Mangiola, F., Manno, A., Marchesini, D., Maresca, G. M., Marrone, G., Martis, I., Martone, A. M., Marzetti, Emanuele, Mattana, C., Matteo, M. V., Maviglia, R., Mazzarella, A., Memoli, C., Miele, Luca, Migneco, A., Mignini, I., Milani, A., Milardi, D., Montalto, M., Montemurro, G., Monti, F., Montini, Luca, Morena, T. C., Morra, V., Morretta, C., Moschese, D., Murace, C. A., Murdolo, M., Murri, Rita, Napoli, M., Nardella, E., Natalello, G., Natalini, D., Navarra, S. M., Nesci, A., Nicoletti, A., Nicoletti, R., Nicoletti, T. F., Nicolo, R., Nicolotti, N., Nista, E. C., Nuzzo, E., Oggiano, M., Ojetti, V., Pagano, F. C., Paiano, G., Pais, C., Pallavicini, F., Palombo, A., Paolillo, F., Papa, Alfredo, Papanice, D., Papparella, L. G., Paratore, M., Parrinello, G., Pasciuto, G., Pasculli, P., Pecorini, G., Perniola, S., Pero, E., Petricca, L., Petrucci, M., Picarelli, C., Piccioni, A., Piccolo, A., Piervincenzi, E., Pignataro, G., Pignataro, R., Pintaudi, G., Pisapia, L., Pizzoferrato, M., Pizzolante, F., Pola, R., Policola, C., Pompili, M., Pontecorvi, F., Pontecorvi, V., Ponziani, F., Popolla, V., Porceddu, E., Porfidia, A., Porro, L. M., Potenza, A., Pozzana, F., Privitera, G., Pugliese, D., Pulcini, G., Racco, S., Raffaelli, F., Ramunno, V., Rapaccini, G. L., Richeldi, Luca, Rinninella, Emanuele, Rocchi, S., Romano, B., Romano, S., Rosa, F., Rossi, L., Rossi, R., Rossini, E., Rota, E., Rovedi, F., Rubino, C., Rumi, G., Russo, A., Sabia, L., Salerno, A., Salini, S., Salvatore, L., Samori, D., Sandroni, Claudio, Sanguinetti, M., Santarelli, L., Santini, P., Santolamazza, D., Santoliquido, A., Santopaolo, F., Santoro, M. C., Sardeo, F., Sarnari, C., Saviano, A., Saviano, L., Scaldaferri, Franco, Scarascia, R., Schepis, T., Schiavello, F., Scoppettuolo, G., Sedda, D., Sessa, F., Sestito, L., Settanni, C., Siciliano, M., Siciliano, V., Sicuranza, R., Simeoni, B., Simonetti, J., Smargiassi, A., Soave, P. M., Sonnino, C., Staiti, D., Stella, C., Stella, L., Stival, E., Taddei, E., Talerico, R., Tamburello, E., Tamburrini, E., Tanzarella, E. S., Tarascio, E., Tarli, C., Tersali, A., Tilli, P., Timpano, J., Torelli, E., Torrini, F., Tosato, M., Tosoni, A., Tricoli, L., Tritto, M., Tumbarello, M., Tummolo, A. M., Vallecoccia, M. S., Valletta, F., Varone, F., Vassalli, F., Ventura, G., Verardi, L., Vetrone, L., Vetrugno, G., Visconti, E., Visconti, F., Viviani, A., Zaccaria, R., Zaccone, C., Zelano, L., Zileri Dal Verme, L., Zuccala, G., Luigetti M. (ORCID:0000-0001-7539-505X), Iorio R. (ORCID:0000-0002-6270-0956), Bentivoglio A. R. (ORCID:0000-0002-9663-095X), Tricoli L., Riso V., Marotta J., Piano C., Primiano G., Lo Monaco M. R. (ORCID:0000-0002-1457-7981), Calabresi P. (ORCID:0000-0003-0326-5509), Annetta M. G. (ORCID:0000-0001-7574-1311), Antonelli M. (ORCID:0000-0003-3007-1670), Bosello S. (ORCID:0000-0002-4837-447X), Cianci R. (ORCID:0000-0001-5378-8442), Franceschi F. (ORCID:0000-0001-6266-445X), Grieco D. L. (ORCID:0000-0002-4557-6308), Ianiro G. (ORCID:0000-0002-8318-0515), Marzetti E. (ORCID:0000-0001-9567-6983), Miele L. (ORCID:0000-0003-3464-0068), Montini L. (ORCID:0000-0003-4602-5134), Murri R. (ORCID:0000-0003-4263-7854), Papa A. (ORCID:0000-0002-4186-7298), Richeldi L. (ORCID:0000-0001-8594-1448), Rinninella E. (ORCID:0000-0002-9165-2367), Sandroni C. (ORCID:0000-0002-8878-2611), Scaldaferri F. (ORCID:0000-0001-8334-7541), Luigetti, Marco, Iorio, Raffaele, Bentivoglio, Anna Rita, Tricoli, Luca, Riso, Vittorio, Marotta, Jessica, Piano, Carla, Primiano, Guido Alessandro, Zileri Del Verme, L., Lo Monaco, Maria Rita, Calabresi, Paolo, Abbate, V., Acampora, N., Addolorato, G., Agostini, F., Ainora, M. E., Akacha, K., Amato, E., Andreani, F., Andriollo, G., Annetta, Maria Giuseppina, Annicchiarico, B. E., Antonelli, Massimo, Antonucci, G., Anzellotti, G. M., Armuzzi, A., Baldi, F., Barattucci, I., Barillaro, C., Barone, F., Bellantone, R. D. A., Bellieni, A., Bello, G., Benicchi, A., Benvenuto, F., Berardini, L., Berloco, F., Bernabei, R., Bianchi, A., Biasucci, D. G., Biasucci, L. M., Bibbo, S., Bini, A., Bisanti, A., Biscetti, F., Bocci, M. G., Bonadia, N., Bongiovanni, F., Borghetti, A., Bosco, G., Bosello, Silvia Laura, Bove, V., Bramato, G., Brandi, V., Bruni, T., Bruno, C., Bruno, D., Bungaro, M. C., Buonomo, A., Burzo, L., Calabrese, A., Calvello, M. R., Cambieri, A., Cambise, C., Camma, G., Candelli, M., Canistro, G., Cantanale, A., Capalbo, G., Capaldi, L., Capone, E., Capristo, E., Carbone, L., Cardone, S., Carelli, S., Carfi, A., Carnicelli, A., Caruso, C., Casciaro, F. A., Catalano, L., Cauda, R., Cecchini, A. L., Cerrito, L., Cesarano, M., Chiarito, A., Cianci, Rossella, Cicchinelli, S., Ciccullo, A., Cicetti, M., Ciciarello, F., Cingolani, A., Cipriani, M. C., Consalvo, M. L., Coppola, G., Corbo, G. M., Corsello, A., Costante, F., Costanzi, M., Covino, M., Crupi, D., Cutuli, S. L., D'Addio, S., D'Alessandro, A., D'Alfonso, M. E., D'Angelo, E., D'Aversa, F., Damiano, F., De Berardinis, G. M., De Cunzo, T., De Gaetano, D. K., De Luca, G., De Matteis, G., De Pascale, G., De Santis, P., De Siena, M., De Vito, F., Del Gatto, V., Del Giacomo, P., Del Zompo, F., Dell'Anna, A. M., Della, P. D., Di Gialleonardo, L., Di Giambenedetto, S., Di Luca, R., Di Maurizio, L., Di Muro, M., Dusina, A., Eleuteri, D., Esperide, A., Fachechi, D., Faliero, D., Falsiroli, C., Fantoni, M., Fedele, A., Feliciani, D., Ferrante, C., Ferrone, G., Festa, R., Fiore, M. C., Flex, A., Forte, E., Franceschi, Francesco, Francesconi, A., Franza, L., Funaro, B., Fuorlo, M., Fusco, D., Gabrielli, M., Gaetani, E., Galletta, C., Gallo, A., Gambassi, G., Garcovich, M., Gasbarrini, A., Gasparrini, I., Gelli, S., Giampietro, A., Gigante, L., Giuliano, G., Giupponi, B., Gremese, E., Grieco, Domenico Luca, Guerrera, M., Guglielmi, V., Guidone, C., Gulli, A., Iaconelli, A., Iafrati, A., Ianiro, Gianluca, Iaquinta, A., Impagnatiello, M., Inchingolo, R., Intini, E., Iorio, R., Izzi, I. M., Jovanovic, T., Kadhim, C., La Macchia, R., La Milia, D. I., Landi, F., Landi, G., Landi, R., Landolfi, R., Leo, M., Leone, P. M., Levantesi, L., Liguori, A., Liperoti, R., Lizzio, M. M., Lo Monaco Maria, R., Locantore, P., Lombardi, F., Lombardi, G., Lopetuso, L., Loria, V., Losito, A. R., Lucia, M. B. P., Macagno, F., Macerola, N., Maggi, G., Maiuro, G., Mancarella, F., Mangiola, F., Manno, A., Marchesini, D., Maresca, G. M., Marrone, G., Martis, I., Martone, A. M., Marzetti, Emanuele, Mattana, C., Matteo, M. V., Maviglia, R., Mazzarella, A., Memoli, C., Miele, Luca, Migneco, A., Mignini, I., Milani, A., Milardi, D., Montalto, M., Montemurro, G., Monti, F., Montini, Luca, Morena, T. C., Morra, V., Morretta, C., Moschese, D., Murace, C. A., Murdolo, M., Murri, Rita, Napoli, M., Nardella, E., Natalello, G., Natalini, D., Navarra, S. M., Nesci, A., Nicoletti, A., Nicoletti, R., Nicoletti, T. F., Nicolo, R., Nicolotti, N., Nista, E. C., Nuzzo, E., Oggiano, M., Ojetti, V., Pagano, F. C., Paiano, G., Pais, C., Pallavicini, F., Palombo, A., Paolillo, F., Papa, Alfredo, Papanice, D., Papparella, L. G., Paratore, M., Parrinello, G., Pasciuto, G., Pasculli, P., Pecorini, G., Perniola, S., Pero, E., Petricca, L., Petrucci, M., Picarelli, C., Piccioni, A., Piccolo, A., Piervincenzi, E., Pignataro, G., Pignataro, R., Pintaudi, G., Pisapia, L., Pizzoferrato, M., Pizzolante, F., Pola, R., Policola, C., Pompili, M., Pontecorvi, F., Pontecorvi, V., Ponziani, F., Popolla, V., Porceddu, E., Porfidia, A., Porro, L. M., Potenza, A., Pozzana, F., Privitera, G., Pugliese, D., Pulcini, G., Racco, S., Raffaelli, F., Ramunno, V., Rapaccini, G. L., Richeldi, Luca, Rinninella, Emanuele, Rocchi, S., Romano, B., Romano, S., Rosa, F., Rossi, L., Rossi, R., Rossini, E., Rota, E., Rovedi, F., Rubino, C., Rumi, G., Russo, A., Sabia, L., Salerno, A., Salini, S., Salvatore, L., Samori, D., Sandroni, Claudio, Sanguinetti, M., Santarelli, L., Santini, P., Santolamazza, D., Santoliquido, A., Santopaolo, F., Santoro, M. C., Sardeo, F., Sarnari, C., Saviano, A., Saviano, L., Scaldaferri, Franco, Scarascia, R., Schepis, T., Schiavello, F., Scoppettuolo, G., Sedda, D., Sessa, F., Sestito, L., Settanni, C., Siciliano, M., Siciliano, V., Sicuranza, R., Simeoni, B., Simonetti, J., Smargiassi, A., Soave, P. M., Sonnino, C., Staiti, D., Stella, C., Stella, L., Stival, E., Taddei, E., Talerico, R., Tamburello, E., Tamburrini, E., Tanzarella, E. S., Tarascio, E., Tarli, C., Tersali, A., Tilli, P., Timpano, J., Torelli, E., Torrini, F., Tosato, M., Tosoni, A., Tricoli, L., Tritto, M., Tumbarello, M., Tummolo, A. M., Vallecoccia, M. S., Valletta, F., Varone, F., Vassalli, F., Ventura, G., Verardi, L., Vetrone, L., Vetrugno, G., Visconti, E., Visconti, F., Viviani, A., Zaccaria, R., Zaccone, C., Zelano, L., Zileri Dal Verme, L., Zuccala, G., Luigetti M. (ORCID:0000-0001-7539-505X), Iorio R. (ORCID:0000-0002-6270-0956), Bentivoglio A. R. (ORCID:0000-0002-9663-095X), Tricoli L., Riso V., Marotta J., Piano C., Primiano G., Lo Monaco M. R. (ORCID:0000-0002-1457-7981), Calabresi P. (ORCID:0000-0003-0326-5509), Annetta M. G. (ORCID:0000-0001-7574-1311), Antonelli M. (ORCID:0000-0003-3007-1670), Bosello S. (ORCID:0000-0002-4837-447X), Cianci R. (ORCID:0000-0001-5378-8442), Franceschi F. (ORCID:0000-0001-6266-445X), Grieco D. L. (ORCID:0000-0002-4557-6308), Ianiro G. (ORCID:0000-0002-8318-0515), Marzetti E. (ORCID:0000-0001-9567-6983), Miele L. (ORCID:0000-0003-3464-0068), Montini L. (ORCID:0000-0003-4602-5134), Murri R. (ORCID:0000-0003-4263-7854), Papa A. (ORCID:0000-0002-4186-7298), Richeldi L. (ORCID:0000-0001-8594-1448), Rinninella E. (ORCID:0000-0002-9165-2367), Sandroni C. (ORCID:0000-0002-8878-2611), and Scaldaferri F. (ORCID:0000-0001-8334-7541)

Abstract

Background and purpose: The objective of this study was to assess the neurological manifestations in a series of consecutive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-positive patients, comparing their frequency with a population hospitalized in the same period for flu/respiratory symptoms, finally not related to SARS-CoV-2. Methods: Patients with flu/respiratory symptoms admitted to Fondazione Policlinico Gemelli hospital from 14 March 2020 to 20 April 2020 were retrospectively enrolled. The frequency of neurological manifestations of patients with SARS-CoV-2 infection was compared with a control group. Results: In all, 213 patients were found to be positive for SARS-CoV-2, after reverse transcriptase polymerase chain reaction on nasal or throat swabs, whilst 218 patients were found to be negative and were used as a control group. Regarding central nervous system manifestations, in SARS-CoV-2-positive patients a higher frequency of headache, hyposmia and encephalopathy always related to systemic conditions (fever or hypoxia) was observed. Furthermore, muscular involvement was more frequent in SARS-CoV-2 infection. Conclusions: Patients with COVID-19 commonly have neurological manifestations but only hyposmia and muscle involvement seem more frequent compared with other flu diseases.

Published
2020

41. Disease progression across the spectrum of idiopathic pulmonary fibrosis: A multicentre study

Author

Sgalla, Giacomo, Lo Greco, E., Calvello, M., Varone, Francesco, Iovene, Bruno, Cerri, S., Donatelli, P., Vancheri, A., Pavone, Matteo, Luppi, F., Vancheri, C., Richeldi, Luca, Sgalla G. (ORCID:0000-0003-3130-9388), Varone F., Iovene B., Pavone M., Richeldi L. (ORCID:0000-0001-8594-1448), Sgalla, Giacomo, Lo Greco, E., Calvello, M., Varone, Francesco, Iovene, Bruno, Cerri, S., Donatelli, P., Vancheri, A., Pavone, Matteo, Luppi, F., Vancheri, C., Richeldi, Luca, Sgalla G. (ORCID:0000-0003-3130-9388), Varone F., Iovene B., Pavone M., and Richeldi L. (ORCID:0000-0001-8594-1448)

Abstract

Background and objective: In clinical practice, a working diagnosis of IPF may be performed to provide effective antifibrotic treatment to patients who cannot undergo SLB. In this study, we compared the disease course across IPF diagnostic categories in a real-life clinical setting to clarify the appropriateness of a working diagnosis of IPF and treatment initiation in these patients. Methods: Longitudinal data from IPF patients receiving antifibrotic treatment (pirfenidone or nintedanib) were retrospectively collected at three tertiary centres in Italy. Univariate and multivariate analyses were performed to compare time to death and to a composite endpoint of disease progression between two diagnostic subgroups, that is, patients with UIP on HRCT and/or SLB, and patients with possible UIP and no histological confirmation. Results: A total of 249 IPF patients were included in the analysis. Among patients with a possible UIP pattern on HRCT, 41 (55%) were prescribed antifibrotic treatment (either nintedanib or pirfenidone) despite absence of histological confirmation. This group demonstrated similar mortality and disease progression as compared to patients with a definite diagnosis of IPF as per diagnostic guidelines (log-rank test P = 0.771 and P = 0.139, respectively). Such findings were confirmed on multivariate analysis (HR: 1.19, 95% CI: 0.49–2.89, P = 0.7 for death; HR: 1.42, 95% CI: 0.83–2.44, P = 0.201 for disease progression). Conclusion: In patients receiving antifibrotics following a working diagnosis of IPF, disease progression rates were similar to patients with a confident diagnosis of IPF according to consensus guidelines, supporting the rationale for treatment initiation in these patients by expert multidisciplinary teams.

Published
2020

44. The LARAM School

Author

Cascini, L, primary, Sorbino, G, additional, Calvello, M, additional, and Cuomo, S, additional

Published
2012
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