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1. Molecular characterization of fast-growing melanomas

Author: Anderson Loundou, Gabriela Gremel, Richard Marais, Martin G. Cook, Caroline Gaudy-Marqueste, Eduardo Nagore, Nicolas Macagno, Piyushkumar A. Mundra, Timothy Budden, Victoria Akhras, L'Houcine Ouafik, Lijing Lin, J.J. Grob, Eric Pellegrino, Rajesh Kumar, Amaya Viros, Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Assistance Publique - Hôpitaux de Marseille (APHM), Centre d'études et de recherche sur les services de santé et la qualité de vie (CEReSS), Aix Marseille Université (AMU), Laboratoire de Transfert d'Oncologie Biologique [Hôpital Nord - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital Nord [CHU - APHM], Institut de neurophysiopathologie (INP), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Cancer Research UK Manchester Institute, University of Manchester [Manchester], St George’s University Hospitals, Faculty of Biology, Medicine and Health [Manchester, UK], German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), and Instituto Valenciano de Oncologia
Subjects: Oncology, medicine.medical_specialty, Skin Neoplasms, medicine.medical_treatment, [SDV.CAN]Life Sciences [q-bio]/Cancer, Dermatology, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Humans, Prospective Studies, Prospective cohort study, Melanoma, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, 0303 health sciences, business.industry, Tumor biology, Fibroblast growth factor receptor 2, Prognosis, medicine.disease, Methods observational, 3. Good health, 030220 oncology & carcinogenesis, Mutation, business, Adjuvant, Memory bias, Rate of growth
Abstract: Background The rate of growth of primary melanoma is a robust predictor of aggressiveness, but the mutational profile of fast-growing melanomas (FGMM) and the potential to stratify patients at high risk of death has not been comprehensively studied. Objective To investigate the epidemiologic, clinical, and mutational profile of primary cutaneous melanomas with a thickness ≥ 1 mm, stratified by rate of growth. Methods Observational prospective study. Deep-targeted sequencing of 40 melanoma driver genes on formalin fixed, paraffin-embedded primary melanoma samples. Comparison of FGMM (rate of growth > 0.5 mm/month) and nonFGMM (rate of growth ≤ 0.5 mm/month). Results Two hundred patients were enrolled, among wom 70 had FGMM. The relapse-free survival was lower in the FGMM group (P = .014). FGMM had a higher number of predicted deleterious mutations within the 40 genes than nonFGMM (P = .033). Ulceration (P = .032), thickness (P = .006), lower sun exposure (P = .049), and fibroblast growth factor receptor 2 (FGFR2) mutations (P = .037) were significantly associated with fast growth. Limitations Single-center study, cohort size, potential memory bias, number of investigated genes. Conclusion Fast growth is linked to specific tumor biology and environmental factors. Ulceration, thickness, and FGFR2 mutations are associated with fast growth. Screening for FGFR2 mutations might provide an additional tool to better identify FGMM, which are probably good candidates for adjuvant therapies.
Published: 2022
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2. Association between age at disease onset of anti-neutrophil cytoplasmic antibody-associated vasculitis and clinical presentation and short-term outcomes

Author: Monti, S., Craven, A., Klersy, C., Montecucco, C., Caporali, R., Watts, R., Merkel, P. A., Luqmani, R., Achilleos, K., Adler, M., Alba, M. A., Albert, D. A., Alibaz-Oner, F., Allcoat, P., Amano, K., Amarasuriya, M., Amudala, N. A., Andrews, J., Archer, A. M., Arimura, Y., Atukorala, I., Azevedo, E., Bajad, S., Baldwin, C., Barra, L. J., Baslund, B., Basu, N., Baykal, M., Berger, C., Berglin, E., Besada, E., Bhardwaj, M., Bischof, A., Blockmans, D., Blood, J., Draibe, J. B., Brand, S., Brandao, M., Bruce, I. N., Butler, A., Calabrese, L. H., Ferrer, D. C., Carette, S., Carmona, D., Ceunen, H., Chakravarty, K., Chapman, P. T., Chocova, Z., Chung, S. A., Ci, W., Cid, M. C., Clark, T. M., Clarkson, M. R., De Jesus Contreras-Rodriguez, F., Conway, R., Cooke, K., Viros, X. C., Cordeiro, A., Costa, A., Culfear, K., Daikeler, T., Danda, D., Das, S. K., Dasgupta, B., De Castro, A. M., Dehghan, N., Devassy, R., Dhindsa, N., Diamantopoulos, A. P., Direskeneli, H., Dobashi, H., Juan, D., Durrani, M., Edelsten, C., Eifert, J., Elhayek, S., Elsideeg, S., Endo, T., Erden, A., Erer, B., Eriksson, P., Erturk, Z., Espigol-Frigole, G., Felicetti, M., Ferraro, A., Ferro, J. M., Fifi-Mah, A., Flores-Suarez, L. F., Flossmann, O., Flynn, D., Fonseca, J. E., Foot, J., Foote, M., Forbess, L., Fujimoto, S., Fukuoka, K., Furtado, C., Furuta, S., Gaffo, A. L., Gallagher, P., Gao, N., Gatenby, P., Gendi, N., Geraldes, R., Gerits, A., Gioffredi, A., Gomples, L., Goncalves, M. J., Gondo, P., Graham, A., Grainger, R., Gray, D. T., Grayson, P. C., Griffiths, L., Guo, Y., Gupta, R., Gylling, M., Hajj-Ali, R. A., Hammam, N., Harigai, M., Hartley, L., Haslett, J., Hassan, A., Hatemi, G., Hellmich, B., Henckaerts, L., Henes, J. C., Hepburn, J., Herd, V., Hess, C., Hill, C., Hinojosa-Azaola, A., Hirahashi, J., Hirano, F., Hocevar, A., Holle, J., Hollinger, N., Homma, S., Howard, T., Hoyles, R. K., Hruskova, Z., Hutcheon, G., Ignacak, M., Igney-Oertel, A., Ikeda, K., Ikegaya, N., Jagadeesh, S., Jaquith, J., Jayne, D. R. W., Jewell, T., Jones, C., Joshi, A., Kalyoncu, U., Kamall, S., Kamath, S., Lai, K. S., Kaname, S., Kanchinadham, S., Karadag, O., Karube, M., Kaszuba, M., Kaur, R., Kawakami, T., Kawashima, S., Khalidi, N., Khan, A., Kikuchi, M., Kilic, L., Kimura, M., King, M. J., Klapa, S., Klocke, R., Kobayashi, T., Kobayashi, S., Komagata, Y., Kronbichler, A., Kuczia, P., Kumar, M. S., Kurosawa, M., Lamprecht, P., Langford, C. A., Lanyon, P., Laversuch, C., Lee, S. J., Leoni, S., Li, J., Liang, K., Liang, P., Liao, H., Lee, L. A., Luqmani, R. A., Lyle, A., Macdonald, M., Mackie, S. L., Madden, L., Magliano, M., Makino, H., Makol, A., Malaiya, R., Malaviya, A., Manthri, R., Maritati, F., Da Silva, A. M., Mason, J. C., Matara, C., Matsui, K., Matteson, E. L., Mcbride, D., Mccullough, K., Mcgeoch, L., Mclaren, J., Mcmillian, C., Mendiratta, N., Menon, A., Merinopoulos, D., Merkel, P., Messier, S., Micheletti, R. G., Mills, K., Milman, N., Minoda, M., Minz, R. W., Mock, C., Mohammad, A. J., Moiseev, S., Moitinho, M., Molloy, E., Monach, P. A., Montgomery, M., Moosig, F., Moradizadeh, M., Morgan, M., Morgan, A. W., Morgan, A. -M., Muir, A., Mukhtyar, C., Muller, A., Muratore, F., Muso, E., Nada, R., Nakajima, H., Nakajima, T., Nakano, H., Nandagudi, A., Neumann, T., Y. F., Ng, K. H., Ng, Nogueira, E. L., Nolkha, N., Nordstrom, D., Novikov, P., Nugaliyadde, A., O'Donnell, J. L., O'Donoghue, J., O'Neill, L., O'Riordan, E., Oatley, M., Okubo, K., Oliva, E., Oshikawa, H., Ota, Y., Padoan, R., Pagnoux, C., Pan, L., Panaritis, K., Park, J. K., Patel, S., Patil, P., Pazzola, G., Peall, A., Pearce, F., Pehlevan, S., Pereira, L., Pettersson, T., Pineau, C. A., Pirila, L., Poglodek, B., Ponte, C., Prieto-Gonzalez, S., Priya, S. R., Purewal, B., Purschke, S., Putaala, J., Quickert, S., Quincey, V., Raghuvanshi, S., Rajasekhar, L., Ranganathan, D., Rathi, M., Rees, D., Rees, F., Renken, U., Restuccia, G., Rhee, R. L., Rice, B., Robins, D., Robson, J., Rodrigues, M., Romao, V. C., Rotar, C., Ruediger, C., Rutgers, A., A. C., Sa, Saavedra, M. J., Sada, K. -E., Sahbudin, I., Salvarani, C., Sandhu, N., Santos, E., Sato, Y., Schafer, V. S., Schiavon, F., Schmidt, W. A., Segelmark, M., Shahin, A., Sharma, A., Shotton, J., Silva, C., Singer, O. G., Sivasuthan, G., Smolen, S., Solanich-Moreno, X., Boixader, L. S., Song, Y. W., Springer, J., Sreih, A. G., Srivastava, R., Stamp, L. K., Stevens, R., Strbian, D., Sugino, K., Sunderkotter, C., Suppiah, R., Suzuki, K., Szekanecz, Z., Sznajd, J., Taimen, K., Tak, P. P., Takeuchi, T., Takizawa, N., Tames, L., Tan, B. E., Tanaka, M., Tang, M. W., Tatlisumak, T., Tesar, V., Thomas, A., Tian, X., Tokunaga, K., Tombetti, E., Tomsic, M., Toz, B., Tsukamoto, T., Uchida, S., Unal, A. U., Urban, M. L., Usui, J., Vaglio, A., Venkatachalam, S., Vermaak, E., Viswanath, V., Wada, T., Wagh, S., Wallace, D. J., Walters, G., Walz, B., Wan, J., Wang, T., Wang, G., Warrington, K. J., Watts, R. A., Wawrzycka-Adamczyk, K., Weeratunga, P., Weisman, M. H., Wickramasinghe, S., Williams, M., Wojcik, K., Woodruff, L., Xenitidis, T., Yamada, H., Yamagata, K., Yee, C. -S., Yoon, M., Yoshida, K., Yoshifuji, H., Ytterberg, S. R., Yumura, W., Zayed, H., Zeng, X., Zhao, M. -H., Zugaj, A., Zuk, J., İç Hastalıkları, Clinical Haematology, and Translational Immunology Groningen (TRIGR)
Subjects: Male, Outcome, Antineutrophil Cytoplasmic, 030232 urology & nephrology, 0302 clinical medicine, Risk Factors, 80 and over, Pharmacology (medical), Age of Onset, Young adult, Aged, 80 and over, education.field_of_study, age, anti-neutrophil cytoplasmic antibody-associated vasculitis, outcome, Adolescent, Adult, Aged, Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis, Antibodies, Antineutrophil Cytoplasmic, Female, Humans, Middle Aged, Morbidity, Prognosis, Retrospective Studies, Risk Assessment, Survival Rate, United Kingdom, Young Adult, Vasculitis, Systemic vasculitis, medicine.medical_specialty, Population, anti-neutrophil cytoplasmic antibody–associated vasculitis, Antibodies, 03 medical and health sciences, Rheumatology, Internal medicine, medicine, education, Anti-neutrophil cytoplasmic antibody–associated vasculitis, Survival rate, Anti-neutrophil cytoplasmic antibody, 030203 arthritis & rheumatology, business.industry, Retrospective cohort study, medicine.disease, Age of onset, business
Abstract: Objectives ANCA-associated vasculitis (AAV) can affect all age groups. We aimed to show that differences in disease presentation and 6 month outcome between younger- and older-onset patients are still incompletely understood. Methods We included patients enrolled in the Diagnostic and Classification Criteria for Primary Systemic Vasculitis (DCVAS) study between October 2010 and January 2017 with a diagnosis of AAV. We divided the population according to age at diagnosis: Results A total of 1338 patients with AAV were included: 66% had disease onset at Conclusion Within 6 months of diagnosis of AAV, patients >65 years of age display a different pattern of organ involvement and an increased risk of significant damage and mortality compared with younger patients.
Published: 2021
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3. The paradox-breaking panRAF plus SRC family kinase inhibitor, CCT3833, is effective in mutant KRAS-driven cancers

Author: Richard Marais, Grazia Saturno, Robert McLeary, Cyril Fisher, Udai Banerji, Alfonso Zambon, Lawrence Davies, Rebecca Lee, J.M.G. Larkin, Natasha Preece, Emma Dean, Paul Lorigan, Dan Niculescu-Duvaz, Matthew G Krebs, Amaya Viros, Nathalie Dhomen, Malin Pedersen, L. Johnson, Filipa Lopes, Caroline J. Springer, D. Holovanchuk, M. E. Gore, and Ion Niculescu-Duvaz
Subjects: 0301 basic medicine, Drug, Lung Neoplasms, media_common.quotation_subject, Phases of clinical research, medicine.disease_cause, NSCLC, CRC, KRAS, panRAF/SRC inhibitor, PDAC, Proto-Oncogene Proteins p21(ras), 03 medical and health sciences, Mice, 0302 clinical medicine, Pancreatic tumor, Carcinoma, Non-Small-Cell Lung, Cell Line, Tumor, Medicine, Animals, Humans, Src family kinase, Protein Kinase Inhibitors, media_common, Cell Proliferation, business.industry, Kinase, Hematology, medicine.disease, digestive system diseases, 030104 developmental biology, src-Family Kinases, Oncology, 030220 oncology & carcinogenesis, Mutation, Cancer research, Original Article, Spindle cell sarcoma, business, Proto-oncogene tyrosine-protein kinase Src
Abstract: Background KRAS is mutated in ∼90% of pancreatic ductal adenocarcinomas, ∼35% of colorectal cancers and ∼20% of non-small-cell lung cancers. There has been recent progress in targeting G12CKRAS specifically, but therapeutic options for other mutant forms of KRAS are limited, largely because the complexity of downstream signaling and feedback mechanisms mean that targeting individual pathway components is ineffective. Design The protein kinases RAF and SRC are validated therapeutic targets in KRAS-mutant pancreatic ductal adenocarcinomas, colorectal cancers and non-small-cell lung cancers and we show that both must be inhibited to block growth of these cancers. We describe CCT3833, a new drug that inhibits both RAF and SRC, which may be effective in KRAS-mutant cancers. Results We show that CCT3833 inhibits RAF and SRC in KRAS-mutant tumors in vitro and in vivo, and that it inhibits tumor growth at well-tolerated doses in mice. CCT3833 has been evaluated in a phase I clinical trial (NCT02437227) and we report here that it significantly prolongs progression-free survival of a patient with a G12VKRAS spindle cell sarcoma who did not respond to a multikinase inhibitor and therefore had limited treatment options. Conclusions New drug CCT3833 elicits significant preclinical therapeutic efficacy in KRAS-mutant colorectal, lung and pancreatic tumor xenografts, demonstrating a treatment option for several areas of unmet clinical need. Based on these preclinical data and the phase I clinical unconfirmed response in a patient with KRAS-mutant spindle cell sarcoma, CCT3833 requires further evaluation in patients with other KRAS-mutant cancers., Highlights • We synthesized new drug, CCT3833, that inhibits both RAF and SRC, and so may be effective in KRAS-mutant cancers. • CCT3833 inhibits both signaling pathways in vitro and in vivo, inhibits tumor growth and leads to regressions in mice. • CCT3833 significantly prolonged progression-free survival of a patient with a G12VKRAS spindle cell sarcoma. • CCT3833 is a potential treatment option for several areas of unmet clinical need.
Published: 2021
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4. Effectiveness of telemedicine in patients with heart failure according to frailty phenotypes: insights from the iCOR randomised controlled trial

Author: C. Enjuanes Grau, N Jose Bazan, A Garay Melero, S Yun Viladomat, E Calero Molina, Santiago Jiménez-Marrero, E Hidalgo Quiros, P Moliner Borja, Josep Comin-Colet, X Corbella Viros, and L Alcoberro Torres
Subjects: medicine.medical_specialty, Telemedicine, Randomized controlled trial, business.industry, law, Heart failure, medicine, In patient, Cardiology and Cardiovascular Medicine, medicine.disease, Intensive care medicine, business, law.invention
Abstract: Background/Introduction The potential impact of telemedicine (TM) in the monitoring of heart failure (HF) patients is still uncertain, largely due to the heterogeneity of the studies published to date. A subgroup of patients in which its key role is particularly uncertain is that of the frailest patients mainly due to TM-based strategies have been often discouraged on the basis of a foreseeable limited benefit in them. Purpose The aim of this study was to define the efficacy of a TM-based managed care solution across different HF patient frailty phenotypes in a cohort of HF patients recruited in a randomized clinical trial (The Insuficiència Cardíaca Optimitzaciό Remota [iCOR] study) evaluating the efficacy of a TM-based management compared to usual care (UC) in the early post-discharge period. Methods Five previously described frailty clusters were analysed. Cox proportional-hazards regression models were used to evaluate the effect of each cluster and group of treatment (and its interaction) on a series of endpoints (the incidence of non-fatal HF events as primary endpoint and all-cause hospitalization, all-cause death and the composite endpoint combining of all-cause death or non-fatal HF events as secondary endpoints). The incidence proportion of the first occurrence of each of the study endpoints was calculated for each study arm and for cluster, and these compared using χ2 tests. Additionally, a survival analysis was conducted using Cox regression to describe the event-free survival experience of the combination of the clusters with each of the 2 treatment groups for the study endpoints evaluated, and p-value was used to compare the different curves. Results The positive effect of TM compared to UC strategy was consistent across all frailty phenotypes (p-value for interaction 0.711). The risk of experiencing a primary event was significantly lower in patients that underwent allocation to the TM arm compared to UC (p-value=0.016). As shown for the primary endpoint, the positive effect of TM compared to UC strategy was consistent across all frailty phenotypes also for the secondary endpoints (all p-value for interaction >0.05). Likewise, the risk of all-cause hospitalization or the composite end-point of all-cause death or non-fatal HF event was significantly lower in patients that underwent allocation to the TM arm compared to UC (p-value=0.030 and 0.016 respectively). However, the risk of all-cause death did not differ across subgroup strata (p-value>0.05). Conclusion(s) This study showed that non-invasive TM-based follow-up tools are effective compared to UC in preventing fatal and non-fatal adverse events in the early post-discharge period, regardless of the 5 different frailty phenotypes. Importantly, when comparing TM-based follow-up with UC management in patients belonging to equal frailty cluster, those who were followed-up by eHealth had a considerably lower risk of non-fatal HF events, hospitalization or death. Funding Acknowledgement Type of funding sources: None. Cox regression non-fatal HF eventsCox regression all-cause hospitalization
Published: 2021
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5. Frailty phenotypes in patients with heart failure in the early post-discharge period: insights from the iCOR randomised controlled trial and a machine learning-based clustering analysis

Author: Santiago Jiménez-Marrero, S Yun Viladomat, A Garay Melero, X Corbella Viros, N Jose Bazan, P Moliner Borja, Josep Comin-Colet, E Calero Molina, E Hidalgo Quiros, L Aloberro Torres, and C. Enjuanes Grau
Subjects: medicine.medical_specialty, Post discharge, business.industry, Period (gene), medicine.disease, law.invention, Randomized controlled trial, law, Heart failure, Emergency medicine, medicine, In patient, Cardiology and Cardiovascular Medicine, Cluster analysis, business
Abstract: Background/Introduction Several variables such as clinical, socioeconomic, functional or cognitive, among others can have an impact on the prognosis of heart failure (HF) patients despite the optimisation of follow-up strategies (e.g. telemedicine [TM] solutions). The clustering of HF patients may to identify different patient frailty phenotypes. Purpose The aim of this study was to perform a machine learning-based clustering analysis to identify different patient frailty phenotypes in a cohort of HF patients recruited in a randomized clinical trial (The Insuficiència Cardíaca Optimitzaciό Remota [iCOR] study). Methods We performed the clustering analysis on the basis of 8 frailty-related dimensions. To define the number of clusters, dissimilarity matrix was calculated with Gower's distance. Then, hierarchical divisive clustering was performed. Using then Elbow and Silhouette to analyse how the within sum of squares changes for the different number of clusters, the final number of clusters were chosen. The incidence proportion of the each of the study endpoints (non-fatal HF events as primary endpoint and all-cause hospitalization, all-cause death and the composite endpoint combining of all-cause death or non-fatal HF events as secondary endpoints) was calculated for cluster. Results 5 different frailty phenotypes were identified. Cluster 1 (29 patients, 16%) comprised patients with the best reported self-perceived health status (QoL), fair emotional-affective status, but low levels of self-care. Cluster 2 (41 patients, 23%) included the youngest patients with the highest level of education and a better level of cognition. Cluster 3 (68, 38%) encompassed the patients who had the best level of self-care behaviour (18.9±9.8), greater physical and instrumental functioning for activities of daily living (ADL) and a lower rate of comorbidities. Patients in the Cluster 4 (30 patients, 17%) tended to be elderly females with poor health-related QoL, and a higher level of functional dependence. Finally, Cluster 5 was the smallest group (10 patients, 6%), encompassing the oldest patients with low level of education, a worse affective-emotional state, a significant cognitive decline and a higher proportion of comorbidities compared to the other clusters. Cluster 4 had the highest incidence rate of the primary endpoint (57 per 100 patient-years at risk, 95% CI [37.4–74–5]) and a higher incidence of all-cause hospitalization and of the combined variable of all-cause of death or non-fatal HF events. Conclusion(s) Using the cluster analysis, we were able to stratify HF patients according to the stage of their impairment and vulnerability in each of the different frailty domains. This will allow clinicians to incorporate holistic multi-domain assessments in HF programmes to identify patients' needs and provide each patient with personalised and structured follow-up programme according to patient's needs (personalised and precision medicine). Funding Acknowledgement Type of funding sources: None. Radar chart to compare frailty clustersClinical endpoints according clusters
Published: 2021
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6. Daphne: A Virtual Assistant for Designing Earth Observation Distributed Spacecraft Missions

Author: Daniel Selva and Antoni Viros Martin
Subjects: Atmospheric Science, Earth observation, Computer science, Design space exploration, Geophysics. Cosmic physics, 0211 other engineering and technologies, 02 engineering and technology, earth observation, USable, Task (project management), User experience design, Human–computer interaction, 0202 electrical engineering, electronic engineering, information engineering, Question answering, mixed initiative, Computers in Earth Sciences, TC1501-1800, 021106 design practice & management, Spacecraft, business.industry, QC801-809, Distributed spacecraft missions, Ocean engineering, machine learning, Systems design, virtual assistant, 020201 artificial intelligence & image processing, business
Abstract: This article describes Daphne, a virtual assistant for designing Earth observation distributed spacecraft missions. It is, to the best of our knowledge, the first virtual assistant for such application. The article provides a thorough description of Daphne, including its question answering system and the main features we have implemented to help system engineers design distributed spacecraft missions. In addition, the article describes a study performed at NASA's Jet Propulsion Laboratory (JPL) to assess the usefulness of Daphne in this use case. The study was conducted with N = 9 subjects from JPL, who were asked to work on a mission design task with two versions of Daphne, one that was fully featured implementing the cognitive assistance functions, and one that only had the features one would find in a traditional design space exploration tool. After the task, they filled out a standard user experience survey, completed a test to assess how much they learned about the task, and were asked a number of questions in a semi-structured exit interview. Results of the study suggest that Daphne can help improve performance during system design tasks compared to traditional tools, while keeping the system usable. However, the study also raises some concerns with respect to a potential reduction in human learning due to the use of the cognitive assistant. The article ends with a list of suggestions for future development of virtual assistants for space mission design.
Published: 2020

7. Positive Attributes of Anti-TERT CD4 T-Helper Type 1 Immune Responses in Melanoma

Author: Rajesh Kumar, Amaya Viros, and Eduardo Nagore
Subjects: Telomerase, business.industry, Melanoma, Immune checkpoint inhibitors, Immunity, Improved survival, Cell Biology, Dermatology, Th1 Cells, medicine.disease, Biochemistry, Immune system, Cancer research, Medicine, Humans, Immunotherapy, Th1 response, business, Molecular Biology
Abstract: Nardin et al's (2021) study on melanoma reports anti-TERT CD4 T helper type (Th) 1 responses in more than half of patients. Besides indicating a trend for improved survival, increased anti-TERT CD4 Th1 responses predicted better outcomes for patients treated with immune checkpoint inhibitors. Thus, harnessing systemic anti-TERT CD4 Th1 responses together with tumor-specific elevation of telomerase can potentially open new avenues for biomarkers and treatment in melanoma.
Published: 2021

8. Experimental Design & Pilot Testing for ECLSS Anomaly Resolution using Daphne-AT Virtual Assistant

Author: Raymond K. W. Wong, Daniel Selva, Oscar Balcells-Quintana, Renee Woodruff, Antoni Viros, Prachi Dutta, Logan Kluis, Ana Diaz-Artiles, Bonnie J. Dunbar, Poonampreet Kaur Josan, Kyle York, Nikita Beebe, and Ada-Rhodes Short
Subjects: Mission control center, Spacecraft, Situation awareness, business.industry, Computer science, Human spaceflight, Crew, Context (language use), 02 engineering and technology, NASA Deep Space Network, 01 natural sciences, Aeronautics, 0103 physical sciences, 0202 electrical engineering, electronic engineering, information engineering, 020201 artificial intelligence & image processing, business, 010303 astronomy & astrophysics, Life support system
Abstract: The Global Exploration Roadmap provides a pathway for humans to leave lower Earth orbit and develop a sustained presence in cislunar space as well as the lunar surface before embarking on a long journey to Mars. During these crewed Long Duration Exploration Missions (LDEM), communication delays will limit mission control availability to support the crew during critical in-flight anomalies. In order to address this challenge, future human spaceflight operations will benefit from intelligent Virtual Assistants (VAs) capable of assisting the crew in detecting, diagnosing, and resolving emergency anomalies. This intelligent technology could increase the probability of mission success and crew safety in emergency scenarios and could improve overall crew performance while operating in the hostile environment of deep space. Daphne-AT is a VA to support crewed LDEM in the context of diagnosing and resolving in-flight anomalies related to the Environmental Control and Life Support System (ECLSS) of a spacecraft. The overall research objective is to investigate the effect of Daphne-AT on human performance, cognitive workload, situational awareness, and trust in autonomous systems. Daphne-AT will be validated using controlled laboratory experiments, and further evaluation will occur during the Human Exploration Research Analog (HERA) C6 research campaign, consisting of four 45-day missions in 2020–21. In this paper, we provide an overview of our first version of Daphne-AT (i.e., baseline version), and discuss the design of anomaly scenarios using NASA's ECLSS simulator and the experimental set up for laboratory experiments. A preliminary within-subjects (i.e., with and without Daphne-AT) experiment was conducted with five human subjects, and preliminary results indicate that the use of Daphne-AT increases performance and decreases cognitive workload in the context of ECLSS anomaly scenarios. The data also show that subjects exhibited trust in using Daphne-AT, while it improved certain aspects of their situational awareness. Our work is part of the Human Capabilities Assessments for Autonomous Missions (HCAAM) Virtual NASA Science Center of Research (VNSCOR) within the NASA Human Research Program, and the ultimate goal is to generate standards and guidelines about how to design such VAs for future LDEMs.
Published: 2021
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9. Distribution and clinical role of KIT gene mutations in melanoma according to subtype: a study of 492 Spanish patients

Author: Esperanza Manrique-Silva, José Antonio López-Guerrero, David Millán-Esteban, Rajiv Kumar, Eduardo Nagore, Simon J Furney, Zaida García-Casado, Celia Requena, Amaya Viros, Victor Traves, and José Bañuls
Subjects: Oncology, medicine.medical_specialty, Skin Neoplasms, Databases, Factual, Kit gene, Dermatology, medicine.disease_cause, World health, Breslow Thickness, Internal medicine, medicine, Distribution (pharmacology), Humans, Neoplasm Invasiveness, Family history, skin and connective tissue diseases, neoplasms, Melanoma, Retrospective Studies, Mutation, integumentary system, business.industry, Mucosal melanoma, medicine.disease, Proto-Oncogene Proteins c-kit, Spain, business
Abstract: Background KIT mutations are primarily associated with acral and mucosal melanoma, and have been reported to show higher prevalence in chronic sun-damaged (CSD) than non-CSD melanomas. Objectives To investigate the prevalence of KIT mutations in melanoma according to subtype, and determine the clinical role of such mutations. Material & methods We present results from a study of a Spanish population of 492 melanomas, classified according to the latest World Health Organization (WHO) guidelines. We analysed the mutational status of KIT and correlated with different clinical variables related to sun exposure and family history. Results KIT mutations were significantly more frequent in acral (3/36; 8.3%) and mucosal (4/8; 50%) melanomas than non-acral cutaneous melanomas. No significant difference was observed in KIT mutational status between CSD and non-CSD melanomas. Conclusion Our results suggest that KIT mutations in melanoma tumours are unrelated to the development of nevi or chronic sun damage, but their presence is associated with aggressive melanomas which show ulceration, vascular invasiveness, and increased Breslow thickness. These findings are consistent with those reported by The Cancer Genome Atlas network.
Published: 2021

10. Female immunity protects from cutaneous squamous cell carcinoma

Author: Victoria Akhras, Shilpa Gurung, Caroline Gaudy-Marqueste, Luisa Motta, Timothy Budden, Deemesh Oudit, Lynne Jamieson, Charles H. Earnshaw, Patrick Shenjere, Carlos Caulin, Amelle Ra, Amaya Viros, Simon J Furney, John T. Lear, Sarah Craig, Yuan Hu, and Ruth Green
Subjects: business.industry, medicine.medical_treatment, Cancer, Immunotherapy, medicine.disease, Transcriptome, Immune system, Immunity, Immunology, Adjuvant therapy, Carcinoma, medicine, business, Carcinogen
Abstract: Purpose Cancer susceptibility and mortality are higher in males, and the mutational and transcriptomic landscape of cancer differs by sex. The current assumption is that men are at higher risk of epithelial cancers as they expose more to carcinogens and accumulate more damage than women. We present data showing women are more protected from aggressive cutaneous squamous cell carcinoma (cSCC) due to strong immune activation. Methods We explored clinical and molecular sexual disparity in immunocompetent and immunosuppressed patients (N= 738, N=160) with carcinoma cSCC, in FVB/N mice exposed to equal doses of DMBA, and in human keratinocytes by whole exome sequencing, bulk and single cell RNA sequencing. Results We show cSCC is more aggressive in men, and immunocompetent women develop mild cSCC, later in life. To test if sex drives disparity, we exposed male and female mice to equal doses of carcinogen, and found males present more aggressive, metastatic cSCC than females. Critically, females activate cancer immune-related expression pathways and CD4 and CD8 T cell infiltration independently of mutations. In contrast, males increase the rate of mitoses and proliferation in response to carcinogen. Human female skin and keratinocytes also activate immune-cancer fighting pathways and immune cells at ultraviolet radiation-damaged sites. Critically, a compromised immune system leads to high-risk, aggressive cSCC specifically in women. Conclusions This work shows the immune response is sex biased in cSCC, and highlights female immunity offers greater protection than male immunity. Translational relevance Sex bias affects cancer incidence, mortality and therapy response; and the molecular landscape of cancer differs by sex. However, it is not known if the sex discrepancy is due to a difference in behaviour and exposure to carcinogens, or due to sex-linked susceptibility. This work reveals men are inherently more susceptible to cutaneous aggressive squamous cell carcinoma, in contrast to women who activate stronger immune responses when challenged with the same carcinogens. The loss of immunity particularly affects women. Personalised medicine approaches stratify cancer patients by genotype; however, to date, the potential for cancer stratification, prevention strategies and therapy by sex and immune competency has not been explored. These data indicate men require targeted prevention programs and increased monitoring. Furthermore, we provide a rationale to prioritise men and immunosuppressed women for adjuvant therapy and immunotherapy.
Published: 2021
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11. MOLECULAR LANDSCAPE OF OLD AGE MELANOMA BY SURVIVAL AND IMMUNOTHERAPY RESPONSE

Author: Richard Marais, Caroline Gaudy-Marqueste, Timothy Budden, Rajesh Kumar, Amaya Viros, Eduardo Nagore, and Stephen Smith
Subjects: Neuroblastoma RAS viral oncogene homolog, Oncology, medicine.medical_specialty, Mutation, IDH1, business.industry, Melanoma, medicine.medical_treatment, Immunotherapy, medicine.disease, medicine.disease_cause, Transcriptome, CDKN2A, Internal medicine, medicine, Age stratification, business
Abstract: Melanoma mortality particularly affects older patients, and age is a powerful independent predictor of death. The pathogenic mutations and transcriptomic changes associated with poor survival in aged patients are not known.We analyzed 5 cohorts of metastatic (N=324, N=18, N=66) and primary melanomas (N=103, N=30) to establish the effect of age on prognosis, identify age-specific driver genes and transcriptomic changes linked to survival and immunotherapy response.We identify the pathogenic mutations and transcriptomic changes associated with poor survival by age, and show mutations in BRAF, NRAS, CDKN2A or IDH1 identify metastatic and primary melanoma aged patients with worse outcome. In contrast, activation of immune-regulatory pathways is a hallmark of long-term survival. We tested if mutations in genes linked to poor outcome are associated to immunotherapy responders, exploring combinations of agespecific mutations in metastatic immune checkpoint inhibitor aged responders. Strikingly, aged patients with BRAF, NRAS, CDKN2A or IDH1 mutations and high tumor mutation burden treated with immunotherapy have an improved median survival of 12 months. These data highlight the molecular landscape of melanoma varies by age, and age stratification can refine prognosis and therapy rationales. A set of mutations identifies patients at highest risk of death who are likely immunotherapy responders.
Published: 2021
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12. Brain microenvironment-driven resistance to immune and targeted therapies in acral melanoma

Author: Elena Galvani, Garima Khandelwal, Paul Lorigan, Richard Marais, Franziska Baenke, Rebecca Lee, Kenneth G. MacLeod, Amaya Viros, Piyushkumar A. Mundra, Alessio Cannistraci, Matthew Smith, Crispin J. Miller, Neil O. Carragher, Nathalie Dhomen, Gabriela Gremel, Garry Ashton, and A. Mandal
Subjects: Cancer Research, Skin Neoplasms, medicine.medical_treatment, Cell, Targeted therapy, 03 medical and health sciences, 0302 clinical medicine, Immune system, Downregulation and upregulation, immune therapy, medicine, Tumor Microenvironment, Humans, brain metastasis, Molecular Targeted Therapy, Melanoma, 030304 developmental biology, Original Research, 0303 health sciences, Manchester Cancer Research Centre, business.industry, ResearchInstitutes_Networks_Beacons/mcrc, Brain, Dabrafenib, medicine.disease, targeted therapy, 3. Good health, acral melanoma, medicine.anatomical_structure, Oncology, 030220 oncology & carcinogenesis, Cancer research, Immunotherapy, Nivolumab, business, Brain metastasis, medicine.drug
Abstract: BackgroundCombination treatments targeting the MEK-ERK pathway and checkpoint inhibitors have improved overall survival in melanoma. Resistance to treatment especially in the brain remains challenging, and rare disease subtypes such as acral melanoma are not typically included in trials. Here we present analyses from longitudinal sampling of a patient with metastatic acral melanoma that became resistant to successive immune and targeted therapy.MethodsWe performed whole-exome and RNA-sequencing on an acral melanoma that progressed on successive immune (nivolumab) and targeted (dabrafenib) therapy in the brain to identify resistance mechanisms. In addition, we performed growth inhibition assays, reverse phase protein arrays and immunoblotting on patient-derived cell lines using dabrafenib in the presence or absence of cerebrospinal fluid (CSF) in vitro. Patient derived xenografts were also developed to analyse response to dabrafenib.ResultsImmune escape following checkpoint blockade was not due to loss of tumour cell recognition by the immune system or low neoantigen burden, but was associated with distinct changes in the microenvironment. Similarly, resistance to targeted therapy was not associated with acquired mutations but up-regulation of the AKT/PI3kinase pathway in the presence of cerebrospinal fluid. ConclusionHeterogeneous tumour interactions within the brain microenvironment enables progression on immune and targeted therapy and should be targeted in salvage treatments. SIGNIFICANCE • What is already known about this subject?Cutaneous melanoma brain metastases have been shown to respond to both immune and targeted therapies, however response and resistance in acral melanoma remains poorly characterised.The PI3K pathway has been shown to be important in the brain, however its influence on response to treatment has not previously been tested using patient-derived models of melanoma and specifically acral melanoma brain metastases.• What does this study add?Despite low neoantigen burden, patients with acral melanoma can derive benefit from immune therapy. Immune therapy escape in the brain was not associated with mutational changes, however there was decreased infiltration of effector T cells, an increase in alternatively activated macrophages and distinct changes in gene expression, suggesting the brain microenvironment enabled immune escape. In addition, testing of patient derived xenografts and cell lines showed that resistance to targeted therapy in the brain was mediated by extrinsic factors resulting in activation of the PI3K/AKT pathway.• How might this impact on clinical practice?The PI3K/AKT pathway is an important target for melanoma brain metastases. Precision medicine must address the interactions of the tumour with the brain microenvironment and tailor therapies according to the site of progression in addition to its genomic features.
Published: 2020
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13. Polypharmacy in older people: lessons from 10 years of experience with the REPOSI register

Author: Mannucci, Pier Mannuccio, Nobili, Alessandro, Pasina, Luca, Tettamanti, Mauro, Franchi, Carlotta, Corrao, Salvatore, Marengoni, Alessandra, Salerno, Francesco, Cesari, Matteo, Perticone, Francesco, Licata, Giuseppe, Violi, Francesco, Corazza, Gino Roberto, Cortesi, Laura, Ardoino, Ilaria, Prisco, Domenico, Silvestri, Elena, Cenci, Caterina, Emmi, Giacomo, Biolo, Gianni, Zanetti, Michela, Guadagni, Martina, Zaccari, Michele, Vanoli, Massimo, Grignani, Giulia, Pulixi, Edoardo Alessandro, Bernardi, Mauro, Bassi, Silvia Li, Santi, Luca, Zaccherini, Giacomo, Mannarino, Elmo, Lupattelli, Graziana, Bianconi, Vanessa, Paciullo, Francesco, Nuti, Ranuccio, Valenti, Roberto, Ruvio, Martina, Cappelli, Silvia, Palazzuoli, Alberto, Olivieri, Oliviero, Girelli, Domenico, Matteazzi, Thomas, Barbagallo, Mario, Dominguez, Ligia, Cocita, Floriana, Beneduce, Vincenza, Plances, Lidia, Zoli, Marco, Lazzari, Ilaria, Brunori, Mattia, Pasini, Franco Laghi, Capecchi, Pier Leopoldo, Palasciano, Giuseppe, Modeo, Maria Ester, Di Gennaro, Carla, Cappellini, Maria Domenica, Maira, Diletta, Di Stefano, Valeria, Fabio, Giovanna, Seghezzi, Sonia, Mancarella, Marta, Rossi, Paolo Dionigi, Damanti, Sarah, Clerici, Marta, Conti, Federica, Miceli, Emanuela, Lenti, Marco Vincenzo, Pisati, Martina, Dominioni, Costanza Caccia, Murialdo, Giovanni, Marra, Alessio, Cattaneo, Federico, Secchi, Maria Beatrice, Ghelfi, Davide, Anastasio, Luigi, Sofia, Lucia, Carbone, Maria, Cipollone, Francesco, Guagnano, Maria Teresa, Angelucci, Ermanno, Valeriani, Emanuele, Mancuso, Gerardo, Calipari, Daniela, Bartone, Mosè, Delitala, Giuseppe, Berria, Maria, Muscaritoli, Maurizio, Molfino, Alessio, Petrillo, Enrico, Zuccalà, Giuseppe, D’Aurizio, Gabriella, Romanelli, Giuseppe, Zucchelli, Alberto, Picardi, Antonio, Gentilucci, Umberto Vespasiani, Gallo, Paolo, Dell’Unto, Chiara, Annoni, Giorgio, Corsi, Maurizio, Bellelli, Giuseppe, Zazzetta, Sara, Mazzola, Paolo, Szabo, Hajnalka, Bonfanti, Alessandra, Arturi, Franco, Succurro, Elena, Rubino, Mariangela, Serra, Maria Grazia, Bleve, Maria Antonietta, Gasbarrone, Laura, Sajeva, Maria Rosaria, Brucato, Antonio, Ghidoni, Silvia, Fabris, Fabrizio, Bertozzi, Irene, Bogoni, Giulia, Rabuini, Maria Victoria, Cosi, Elisabetta, Manfredini, Roberto, Fabbian, Fabio, Boari, Benedetta, De Giorgi, Alfredo, Tiseo, Ruana, Paolisso, Giuseppe, Rizzo, Maria Rosaria, Borghi, Claudio, Strocchi, Enrico, De Sando, Valeria, Pareo, Ilenia, Sabbà, Carlo, Vella, Francesco Saverio, Suppressa, Patrizia, Agosti, Pasquale, Schilardi, Andrea, Loparco, Francesca, Fenoglio, Luigi, Bracco, Christian, Giraudo, Alessia Valentina, Fargion, Silvia, Periti, Giulia, Porzio, Marianna, Tiraboschi, Slivia, Peyvandi, Flora, Rossio, Raffaella, Ferrari, Barbara, Colombo, Giulia, Monzani, Valter, Savojardo, Valeria, Folli, Christian, Ceriani, Giuliana, Pallini, Giada, Dallegri, Franco, Ottonello, Luciano, Liberale, Luca, Caserza, Lara, Salam, Kassem, Liberato, Nicola Lucio, Tognin, Tiziana, Bianchi, Giovanni Battista, Giaquinto, Sabrina, Purrello, Francesco, Di Pino, Antonino, Piro, Salvatore, Rozzini, Renzo, Falanga, Lina, Spazzini, Elena, Ferrandina, Camillo, Montrucchio, Giuseppe, Petitti, Paolo, Salmi, Raffaella, Gaudenzi, Piergiorgio, Perri, Ludovica, Landolfi, Raffaele, Montalto, Massimo, Mirijello, Antonio, Guasti, Luigina, Castiglioni, Luana, Maresca, Andrea, Squizzato, Alessandro, Molaro, Marta, Grossi, Alessandra, Bertolotti, Marco, Mussi, Chiara, Libbra, Maria Vittoria, Dondi, Giulia, Pellegrini, Elisa, Carulli, Lucia, COLANGELO, LIDIA, Falbo, Tania, Stanghellini, Vincenzo, De Giorgio, Roberto, Ruggeri, Eugenio, del Vecchio, Sara, Salvi, Andrea, LEONARDI, ROBERTO, Damiani, Giampaolo, Gabrielli, Armando, Capeci, William, Mattioli, Massimo, Martino, Giuseppe Pio, Biondi, Lorenzo, Pettinari, Pietro, Ghio, Riccardo, Col, Anna Dal, Minisola, Salvatore, Colangelo, Luciano, Afeltra, Antonella, Marigliano, Benedetta, Pipita, Maria Elena, Castellino, Pietro, Blanco, Julien, Zanoli, Luca, Pignataro, Samuele, Saracco, Valter, Fogliati, Marisa, Bussolino, Carlo, Mete, Francesca, Gino, Miriam, Cittadini, Antonio, Vigorito, Carlo, Arcopinto, Michele, Salzano, Andrea, Bobbio, Emanuele, Marra, Alberto Maria, Sirico, Domenico, Moreo, Guido, Gasparini, Francesca, Prolo, Silvia, Pina, Gloria, Ballestrero, Alberto, Ferrando, Fabio, Berra, Sergio, Dassi, Simonetta, Nava, Maria Cristina, Graziella, Bruno, Baldassarre, Stefano, Fragapani, Salvatore, Gruden, Gabriella, Galanti, Giorgio, Mascherini, Gabriele, Petri, Cristian, Stefani, Laura, Girino, Margherita, Piccinelli, Valeria, Nasso, Francesco, Gioffrè, Vincenza, DI PASQUALE, MARIA GRAZIA, Scattolin, Giuseppe, Martinelli, Sergio, Turrin, Mauro, Sechi, Leonardo, Catena, Cristina, Colussi, Gianluca, Passariello, Nicola, Rinaldi, Luca, Berti, Franco, Famularo, Giuseppe, Patrizia, Tarsitani, Castello, Roberto, Pasino, Michela, Ceda, Gian Paolo, Maggio, Marcello Giuseppe, Morganti, Simonetta, Artoni, Andrea, Del Giacco, Stefano, Firinu, Davide, Losa, Francesca, Paoletti, Giovanni, Montalto, Giuseppe, Licata, Anna, Malerba, Valentina, Antonino, Lasco, Basile, Giorgio, Antonino, Catalano, Malatino, Lorenzo, Stancanelli, Benedetta, Terranova, Valentina, Di Marca, Salvatore, Mecocci, Patrizia, Ruggiero, Carmelinda, Boccardi, Virginia, Meschi, Tiziana, Lauretani, Fulvio, Ticinesi, Andrea, Minuz, Pietro, Fondrieschi, Luigi, Pirisi, Mario, Fra, Gian Paolo, Sola, Daniele, Porta, Massimo, Riva, Piero, Quadri, Roberto, Scanzi, Giorgio, Mengoli, Caterina, Provini, Stella, Ricevuti, Laura, Simeone, Emilio, Scurti, Rosa, Tolloso, Fabio, Tarquini, Roberto, Valoriani, Alice, Dolenti, Silvia, Vannini, Giulia, Tedeschi, Alberto, Trotta, Lucia, Volpi, Riccardo, Bocchi, Pietro, Vignali, Alessandro, Harari, Sergio, Lonati, Chiara, Cattaneo, Mara, Nieves, Ramirez Duque, Alberto, Muela Molinero, Pedro, Abad Requejo, Vanessa, Lopez Pelaez, Lara, Tamargo, Xavier, Corbella Viros, Francesc, Formiga, Jesus, Diez Manglano, Esperanza, Bejarano Tello, Esther, Del Corral Behamonte, Maria, Sevil Puras, Romero, Manuel, Blanca, Pinilla Llorente, Cristina, Lopez Gonzalez-Cobos, Victoria, Villalba Garcia M., Saez, Lopez, Bosco, Juan, Susana, Sanz Baena, Marta, Arroyo Gallego, Concepcion, Gonzalez Becerra, Antonio, Fernandez Moyano, Hernandez, Mercedes Gomez, Borrego, Manuel Poyato, Raquel, Pacheco Cuadros, Florencia, Perez Rojas, Beatriz, Garcia Olid, Sara, Carrascosa Garcia, Alfonso, Gonzalez-Cruz Cervellera, Marta, Peinado Martinez, Garcia, Sara Carrascosa, Alberto, Ruiz Cantero, Antonio, Albarracín Arraigosa, Montserrat, Godoy Guerrero, Ángel, Barón Ramos Miguel, Manuel, Machin Jose, Ignacio, Novo Veleiro, Lucía, Alvela Suarez, Alfonso, Lopez, David, Rubal Bran, Iria, Iñiguez Vazquez, Monica, Rios Prego, Mannucci, Pier Mannuccio, Nobili, Alessandro, Pasina, Luca, Tettamanti, Mauro, Franchi, Carlotta, Corrao, Salvatore, Marengoni, Alessandra, Salerno, Francesco, Cesari, Matteo, Perticone, Francesco, Licata, Giuseppe, Violi, Francesco, Corazza, Gino Roberto, Cortesi, Laura, Ardoino, Ilaria, Prisco, Domenico, Silvestri, Elena, Cenci, Caterina, Emmi, Giacomo, Biolo, Gianni, Zanetti, Michela, Guadagni, Martina, Zaccari, Michele, Vanoli, Massimo, Grignani, Giulia, Pulixi, Edoardo Alessandro, Bernardi, Mauro, Bassi, Silvia Li, Santi, Luca, Zaccherini, Giacomo, Mannarino, Elmo, Lupattelli, Graziana, Bianconi, Vanessa, Paciullo, Francesco, Nuti, Ranuccio, Valenti, Roberto, Ruvio, Martina, Cappelli, Silvia, Palazzuoli, Alberto, Olivieri, Oliviero, Girelli, Domenico, Matteazzi, Thoma, Barbagallo, Mario, Dominguez, Ligia, Cocita, Floriana, Beneduce, Vincenza, Plances, Lidia, Zoli, Marco, Lazzari, Ilaria, Brunori, Mattia, Pasini, Franco Laghi, Capecchi, Pier Leopoldo, Palasciano, Giuseppe, Modeo, Maria Ester, Di Gennaro, Carla, Cappellini, Maria Domenica, Maira, Diletta, Di Stefano, Valeria, Fabio, Giovanna, Seghezzi, Sonia, Mancarella, Marta, Rossi, Paolo Dionigi, Damanti, Sarah, Clerici, Marta, Conti, Federica, Miceli, Emanuela, Lenti, Marco Vincenzo, Pisati, Martina, Dominioni, Costanza Caccia, Murialdo, Giovanni, Marra, Alessio, Cattaneo, Federico, Secchi, Maria Beatrice, Ghelfi, Davide, Anastasio, Luigi, Sofia, Lucia, Carbone, Maria, Cipollone, Francesco, Guagnano, Maria Teresa, Angelucci, Ermanno, Valeriani, Emanuele, Mancuso, Gerardo, Calipari, Daniela, Bartone, Mosè, Delitala, Giuseppe, Berria, Maria, Muscaritoli, Maurizio, Molfino, Alessio, Petrillo, Enrico, Zuccalà, Giuseppe, D’Aurizio, Gabriella, Romanelli, Giuseppe, Zucchelli, Alberto, Picardi, Antonio, Gentilucci, Umberto Vespasiani, Gallo, Paolo, Dell’Unto, Chiara, Annoni, Giorgio, Corsi, Maurizio, Bellelli, Giuseppe, Zazzetta, Sara, Mazzola, Paolo, Szabo, Hajnalka, Bonfanti, Alessandra, Arturi, Franco, Succurro, Elena, Rubino, Mariangela, Serra, Maria Grazia, Bleve, Maria Antonietta, Gasbarrone, Laura, Sajeva, Maria Rosaria, Brucato, Antonio, Ghidoni, Silvia, Fabris, Fabrizio, Bertozzi, Irene, Bogoni, Giulia, Rabuini, Maria Victoria, Cosi, Elisabetta, Manfredini, Roberto, Fabbian, Fabio, Boari, Benedetta, De Giorgi, Alfredo, Tiseo, Ruana, Paolisso, Giuseppe, Rizzo, Maria Rosaria, Borghi, Claudio, Strocchi, Enrico, De Sando, Valeria, Pareo, Ilenia, Sabbà, Carlo, Vella, Francesco Saverio, Suppressa, Patrizia, Agosti, Pasquale, Schilardi, Andrea, Loparco, Francesca, Fenoglio, Luigi, Bracco, Christian, Giraudo, Alessia Valentina, Fargion, Silvia, Periti, Giulia, Porzio, Marianna, Tiraboschi, Slivia, Peyvandi, Flora, Rossio, Raffaella, Ferrari, Barbara, Colombo, Giulia, Monzani, Valter, Savojardo, Valeria, Folli, Christian, Ceriani, Giuliana, Pallini, Giada, Dallegri, Franco, Ottonello, Luciano, Liberale, Luca, Caserza, Lara, Salam, Kassem, Liberato, Nicola Lucio, Tognin, Tiziana, Bianchi, Giovanni Battista, Giaquinto, Sabrina, Purrello, Francesco, Di Pino, Antonino, Piro, Salvatore, Rozzini, Renzo, Falanga, Lina, Spazzini, Elena, Ferrandina, Camillo, Montrucchio, Giuseppe, Petitti, Paolo, Salmi, Raffaella, Gaudenzi, Piergiorgio, Perri, Ludovica, Landolfi, Raffaele, Montalto, Massimo, Mirijello, Antonio, Guasti, Luigina, Castiglioni, Luana, Maresca, Andrea, Squizzato, Alessandro, Molaro, Marta, Grossi, Alessandra, Bertolotti, Marco, Mussi, Chiara, Libbra, Maria Vittoria, Dondi, Giulia, Pellegrini, Elisa, Carulli, Lucia, Colangelo, Lidia, Falbo, Tania, Stanghellini, Vincenzo, De Giorgio, Roberto, Ruggeri, Eugenio, del Vecchio, Sara, Salvi, Andrea, Leonardi, Roberto, Damiani, Giampaolo, Gabrielli, Armando, Capeci, William, Mattioli, Massimo, Martino, Giuseppe Pio, Biondi, Lorenzo, Pettinari, Pietro, Ghio, Riccardo, Col, Anna Dal, Minisola, Salvatore, Colangelo, Luciano, Afeltra, Antonella, Marigliano, Benedetta, Pipita, Maria Elena, Castellino, Pietro, Blanco, Julien, Zanoli, Luca, Pignataro, Samuele, Saracco, Valter, Fogliati, Marisa, Bussolino, Carlo, Mete, Francesca, Gino, Miriam, Cittadini, Antonio, Vigorito, Carlo, Arcopinto, Michele, Salzano, Andrea, Bobbio, Emanuele, Marra, Alberto Maria, Sirico, Domenico, Moreo, Guido, Gasparini, Francesca, Prolo, Silvia, Pina, Gloria, Ballestrero, Alberto, Ferrando, Fabio, Berra, Sergio, Dassi, Simonetta, Nava, Maria Cristina, Graziella, Bruno, Baldassarre, Stefano, Fragapani, Salvatore, Gruden, Gabriella, Galanti, Giorgio, Mascherini, Gabriele, Petri, Cristian, Stefani, Laura, Girino, Margherita, Piccinelli, Valeria, Nasso, Francesco, Gioffrè, Vincenza, Pasquale, Maria, Scattolin, Giuseppe, Martinelli, Sergio, Turrin, Mauro, Sechi, Leonardo, Catena, Cristina, Colussi, Gianluca, Passariello, Nicola, Rinaldi, Luca, Berti, Franco, Famularo, Giuseppe, Patrizia, Tarsitani, Castello, Roberto, Pasino, Michela, Ceda, Gian Paolo, Maggio, Marcello Giuseppe, Morganti, Simonetta, Artoni, Andrea, Del Giacco, Stefano, Firinu, Davide, Losa, Francesca, Paoletti, Giovanni, Montalto, Giuseppe, Licata, Anna, Malerba, Valentina, Antonino, Lasco, Basile, Giorgio, Antonino, Catalano, Malatino, Lorenzo, Stancanelli, Benedetta, Terranova, Valentina, Di Marca, Salvatore, Mecocci, Patrizia, Ruggiero, Carmelinda, Boccardi, Virginia, Meschi, Tiziana, Lauretani, Fulvio, Ticinesi, Andrea, Minuz, Pietro, Fondrieschi, Luigi, Pirisi, Mario, Fra, Gian Paolo, Sola, Daniele, Porta, Massimo, Riva, Piero, Quadri, Roberto, Scanzi, Giorgio, Mengoli, Caterina, Provini, Stella, Ricevuti, Laura, Simeone, Emilio, Scurti, Rosa, Tolloso, Fabio, Tarquini, Roberto, Valoriani, Alice, Dolenti, Silvia, Vannini, Giulia, Tedeschi, Alberto, Trotta, Lucia, Volpi, Riccardo, Bocchi, Pietro, Vignali, Alessandro, Harari, Sergio, Lonati, Chiara, Cattaneo, Mara, Nieves, Ramirez Duque, Alberto, Muela Molinero, Pedro, Abad Requejo, Vanessa, Lopez Pelaez, Lara, Tamargo, Xavier, Corbella Viro, Francesc, Formiga, Jesus, Diez Manglano, Esperanza, Bejarano Tello, Esther, Del Corral Behamonte, Maria, Sevil Pura, Romero, Manuel, Blanca, Pinilla Llorente, Cristina, Lopez Gonzalez-Cobo, Victoria, Villalba Garcia M., Saez, Lopez, Bosco, Juan, Susana, Sanz Baena, Marta, Arroyo Gallego, Concepcion, Gonzalez Becerra, Antonio, Fernandez Moyano, Hernandez, Mercedes Gomez, Borrego, Manuel Poyato, Raquel, Pacheco Cuadro, Florencia, Perez Roja, Beatriz, Garcia Olid, Sara, Carrascosa Garcia, Alfonso, Gonzalez-Cruz Cervellera, Marta, Peinado Martinez, Garcia, Sara Carrascosa, Alberto, Ruiz Cantero, Antonio, Albarracín Arraigosa, Montserrat, Godoy Guerrero, Ángel, Barón Ramos Miguel, Manuel, Machin Jose, Ignacio, Novo Veleiro, Lucía, Alvela Suarez, Alfonso, Lopez, David, Rubal Bran, Iria, Iñiguez Vazquez, Monica, Rios Prego, Pier Mannuccio Mannucci, Alessandro Nobili, Luca Pasina, REPOSI Collaborators [.., Gino Roberto Corazza, Elena Silvestri, Mauro Bernardi, Silvia Li Bassi, Luca Santi, Giacomo Zaccherini, Marco Zoli, Ilaria Lazzari, Mattia Brunori, Claudio Borghi, Enrico Strocchi, Valeria De Sando, Ilenia Pareo, Vincenzo Stanghellini, Roberto De Giorgio, Eugenio Ruggeri, Sara del Vecchio, ], Mannucci, P, Nobili, A, Pasina, L, Dominguez Rodriguez, L, Barbagallo, M, Licata, A, Tettamanti, M, Franchi, C, Corrao, S, Marengoni, A, Salerno, F, Cesari, M, Perticone, F, Licata, G, Violi, F, Corazza, G, Cortesi, L, Ardoino, I, Prisco, D, Silvestri, E, Cenci, C, Emmi, G, Biolo, G, Zanetti, M, Guadagni, M, Zaccari, M, Vanoli, M, Grignani, G, Pulixi, E, Bernardi, M, Bassi, S, Santi, L, Zaccherini, G, Mannarino, E, Lupattelli, G, Bianconi, V, Paciullo, F, Nuti, R, Valenti, R, Ruvio, M, Cappelli, S, Palazzuoli, A, Olivieri, O, Girelli, D, Matteazzi, T, Dominguez, L, Cocita, F, Beneduce, V, Plances, L, Zoli, M, Lazzari, I, Brunori, M, Pasini, F, Capecchi, P, Palasciano, G, Modeo, M, di Gennaro, C, Cappellini, M, Maira, D, di Stefano, V, Fabio, G, Seghezzi, S, Mancarella, M, Rossi, P, Damanti, S, Clerici, M, Conti, F, Miceli, E, Lenti, M, Pisati, M, Dominioni, C, Murialdo, G, Marra, A, Cattaneo, F, Secchi, M, Ghelfi, D, Anastasio, L, Sofia, L, Carbone, M, Cipollone, F, Guagnano, M, Angelucci, E, Valeriani, E, Mancuso, G, Calipari, D, Bartone, M, Delitala, G, Berria, M, Muscaritoli, M, Molfino, A, Petrillo, E, Zuccala, G, D'Aurizio, G, Romanelli, G, Zucchelli, A, Picardi, A, Gentilucci, U, Gallo, P, Dell'Unto, C, Annoni, G, Corsi, M, Bellelli, G, Zazzetta, S, Mazzola, P, Szabo, H, Bonfanti, A, Arturi, F, Succurro, E, Rubino, M, Serra, M, Bleve, M, Gasbarrone, L, Sajeva, M, Brucato, A, Ghidoni, S, Fabris, F, Bertozzi, I, Bogoni, G, Rabuini, M, Cosi, E, Manfredini, R, Fabbian, F, Boari, B, de Giorgi, A, Tiseo, R, Paolisso, G, Rizzo, M, Borghi, C, Strocchi, E, de Sando, V, Pareo, I, Sabba, C, Vella, F, Suppressa, P, Agosti, P, Schilardi, A, Loparco, F, Fenoglio, L, Bracco, C, Giraudo, A, Fargion, S, Periti, G, Porzio, M, Tiraboschi, S, Peyvandi, F, Rossio, R, Ferrari, B, Colombo, G, Monzani, V, Savojardo, V, Folli, C, Ceriani, G, Pallini, G, Dallegri, F, Ottonello, L, Liberale, L, Caserza, L, Salam, K, Liberato, N, Tognin, T, Bianchi, G, Giaquinto, S, Purrello, F, di Pino, A, Piro, S, Rozzini, R, Falanga, L, Spazzini, E, Ferrandina, C, Montrucchio, G, Petitti, P, Salmi, R, Gaudenzi, P, Perri, L, Landolfi, R, Montalto, M, Mirijello, A, Guasti, L, Castiglioni, L, Maresca, A, Squizzato, A, Molaro, M, Grossi, A, Bertolotti, M, Mussi, C, Libbra, M, Dondi, G, Pellegrini, E, Carulli, L, Colangelo, L, Falbo, T, Stanghellini, V, De Giorgio, R, Ruggeri, E, del Vecchio, S, Salvi, A, Leonardi, R, Damiani, G, Gabrielli, A, Capeci, W, Mattioli, M, Martino, G, Biondi, L, Pettinari, P, Ghio, R, Col, A, Minisola, S, Afeltra, A, Marigliano, B, Pipita, M, Castellino, P, Blanco, J, Zanoli, L, Pignataro, S, Saracco, V, Fogliati, M, Bussolino, C, Mete, F, Gino, M, Cittadini, A, Vigorito, C, Arcopinto, M, Salzano, A, Bobbio, E, Sirico, D, Moreo, G, Gasparini, F, Prolo, S, Pina, G, Ballestrero, A, Ferrando, F, Berra, S, Dassi, S, Nava, M, Graziella, B, Baldassarre, S, Fragapani, S, Gruden, G, Galanti, G, Mascherini, G, Petri, C, Stefani, L, Girino, M, Piccinelli, V, Nasso, F, Gioffre, V, Pasquale, M, Scattolin, G, Martinelli, S, Turrin, M, Sechi, L, Catena, C, Colussi, G, Passariello, N, Rinaldi, L, Berti, F, Famularo, G, Patrizia, T, Castello, R, Pasino, M, Ceda, G, Maggio, M, Morganti, S, Artoni, A, Giacco, S, Firinu, D, Losa, F, Paoletti, G, Montalto, G, Malerba, V, Antonino, L, Basile, G, Antonino, C, Malatino, L, Stancanelli, B, Terranova, V, di Marca, S, Mecocci, P, Ruggiero, C, Boccardi, V, Meschi, T, Lauretani, F, Ticinesi, A, Minuz, P, Fondrieschi, L, Pirisi, M, Fra, G, Sola, D, Porta, M, Riva, P, Quadri, R, Scanzi, G, Mengoli, C, Provini, S, Ricevuti, L, Simeone, E, Scurti, R, Tolloso, F, Tarquini, R, Valoriani, A, Dolenti, S, Vannini, G, Tedeschi, A, Trotta, L, Volpi, R, Bocchi, P, Vignali, A, Harari, S, Lonati, C, Cattaneo, M, Nieves, R, Alberto, M, Pedro, A, Vanessa, L, Lara, T, Xavier, C, Francesc, F, Jesus, D, Esperanza, B, Esther, D, Maria, S, Romero, M, Blanca, P, Cristina, L, Victoria, V, Saez, L, Bosco, J, Susana, S, Marta, A, Concepcion, G, Antonio, F, Hernandez, M, Borrego, M, Raquel, P, Florencia, P, Beatriz, G, Sara, C, Alfonso, G, Marta, P, Garcia, S, Alberto, R, Antonio, A, Montserrat, G, Angel, B, Manuel, M, Ignacio, N, Lucia, A, Alfonso, L, David, R, Iria, I, Monica, R, DI PASQUALE, MARIA GRAZIA, di Gennaro, Carla, di Stefano, Valeria, de Giorgi, Alfredo, de Sando, Valeria, di Pino, Antonino, Giacco, Stefano Del, and di Marca, Salvatore
Subjects: Male, medicine.medical_specialty, Population ageing, Deprescribing, Inappropriate prescription, Medication reconciliation, Multimorbidity, Polypharmacy, Population, Socio-culturale, 030204 cardiovascular system & hematology, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, 80 and over, Internal Medicine, Emergency Medicine, medicine, Deprescribing, Inappropriate prescription, Medication reconciliation, Multimorbidity, Polypharmacy, Humans, Registries, 030212 general & internal medicine, Medical prescription, Adverse effect, education, Aged, Aged, 80 and over, Geriatrics, education.field_of_study, business.industry, Patient Discharge, Hospitalization, Female, Italy, Family medicine, business
Abstract: As a consequence of population aging, we have witnessed in internal medicine hospital wards a progressive shift from a population of in-patients relatively young and mainly affected by a single ailment to one of ever older and more and more complex patients with multiple chronic diseases, followed as out-patients by many different specialists with poor integration andinevitably treated with multiple medications. Polypharmacy (defined as the chronic intake of five or more drugs) is associated with increased risks of drug-drug interactions and related adverse effects, prescription and intake errors, poor compliance, re-hospitalization and mortality. With this background, the Italian Society of Internal Medicine chose to start in 2008 a prospective register called REPOSI (REgistro POliterapie SIMI, Società Italiana di Medicina Interna) in internal medicine and geriatric hospital wards. The country wide register is an ongoing observatory on multimorbidity and polypharmacy in the oldest old, with the goal to improve prescription appropriateness and, thus to avoid potentially inappropriate medications. The main findings of the register, that has accrued so far, 7005 older patients throughout a 10year period, are summarized herewith, with special emphasis on the main patterns of poor prescription appropriateness and related risks of adverse events.
Published: 2018
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14. Prognostic relevance of glomerular filtration rate estimation obtained through different equations in hospitalized elderly patients

Author: Gallo, Paolo, De Vincentis, Antonio, Pedone, Claudio, Nobili, Alessandro, Tettamanti, Mauro, Gentilucci, Umberto Vespasiani, Picardi, Antonio, Mannucci, Pier Mannuccio, Incalzi, Raffaele Antonelli, Prisco, Domenico, Silvestri, Elena, Emmi, Giacomo, Bettiol, Alessandra, Caterina, Cenci, Biolo, Gianni, Zanetti, Michela, Guadagni, Martina, Zaccari, Michele, Chiuch, Massimiliano, Vanoli, Massimo, Grignani, Giulia, Pulixi, Edoardo Alessandro, Bernardi, Mauro, Bassi, Silvia Li, Santi, Luca, Zaccherini, Giacomo, Lupattelli, Graziana, Mannarino, Elmo, Bianconi, Vanessa, Paciullo, Francesco, Alcidi, Riccardo, Nuti, Ranuccio, Valenti, Roberto, Ruvio, Martina, Cappelli, Silvia, Palazzuoli, Alberto, Girelli, Domenico, Busti, Fabiana, Marchi, Giacomo, Barbagallo, Mario, Dominguez, Ligia, Cocita, Floriana, Beneduce, Vincenza, Plances, Lidia, Corrao, Salvatore, Natoli, Giuseppe, Mularo, Salvatore, Raspanti, Massimo, Cavallaro, Federica, Zoli, Marco, Lazzari, Ilaria, Brunori, Mattia, Fabbri, Elisa, Magalotti, Donatella, Arno, Raffaella, Pasini, Franco Laghi, Capecchi, Pier Leopoldo, Palasciano, Giuseppe, Modeo, Maria Ester, Di Gennaro, Carla, Cappellini, Maria Domenica, Maira, Diletta, Di Stefano, Valeria, Fabio, Giovanna, Seghezzi, Sonia, Mancarella, Marta, De Amicis, Margherita Migone, De Luca, Giacomo, Scaramellini, Natalia, Cesari, Matteo, Rossi, Paolo Dionigi, Damanti, Sarah, Clerici, Marta, Conti, Federica, Bonini, Giulia, Ottolini, Barbara Brignolo, Di Sabatino, Antonio, Miceli, Emanuela, Lenti, Marco Vincenzo, Pisati, Martina, Dominioni, Costanza Caccia, Murialdo, Giovanni, Marra, Alessio, Cattaneo, Federico, Pontremoli, Roberto, Beccati, Valentina, Nobili, Giulia, Secchi, Maria Beatrice, Ghelfi, Davide, Anastasio, Luigi, Sofia, Lucia, Carbone, Maria, Cipollone, Francesco, Guagnano, Maria Teresa, Valeriani, Emanuele, Rossi, Ilaria, Mancuso, Gerardo, Calipari, Daniela, Bartone, Mose, Delitala, Giuseppe, Berria, Maria, Pes, Chiara, Delitala, Alessandro, Muscaritoli, Maurizio, Molfino, Alessio, Petrillo, Enrico, Zuccala, Giuseppe, D'Aurizio, Gabriella, Romanelli, Giuseppe, Marengoni, Alessandra, Zucchelli, Alberto, Manzoni, Francesca, Volpini, Andrea, Dell'Unto, Chiara, Annoni, Giorgio, Corsi, Maurizio, Bellelli, Giuseppe, Zazzetta, Sara, Mazzola, Paolo, Szabo, Hajnalka, Bonfanti, Alessandra, Arturi, Franco, Succurro, Elena, Rubino, Mariangela, Tassone, Bruno, Sesti, Giorgio, Serra, Maria Grazia, Bleve, Maria Antonietta, Gasbarrone, Laura, Sajeva, Maria Rosaria, Brucato, Antonio, Ghidoni, Silvia, Fabris, Fabrizio, Bertozzi, Irene, Bogoni, Giulia, Rabuini, Maria Victoria, Cosi, Elisabetta, Scarinzi, Paolo, Amabile, Annalisa, Omenetto, Elisabetta, Prandini, Tancredi, Manfredini, Roberto, Fabbian, Fabio, Boari, Benedetta, De Giorgi, Alfredo, Tiseo, Ruana, De Giorgio, Roberto, Paolisso, Giuseppe, Rizzo, Maria Rosaria, Borghi, Claudio, Strocchi, Enrico, Ianniello, Eugenia, Soldati, Mario, Sabba, Carlo, Vella, Francesco Saverio, Suppressa, Patrizia, Agosti, Pasquale, Schilardi, Andrea, Loparco, Francesca, De Vincenzo, Giovanni Michele, Comitangelo, Alessio, Amoruso, Emanuele, Fenoglio, Luigi, Falcetta, Andrea, Bracco, Christian, Fracanzani, Anna L., Fargion, Silvia, Tiraboschi, Silvia, Cespiati, Annalisa, Oberti, Giovanna, Sigon, Giordano, Peyvandi, Flora, Rossio, Raffaella, Ferrari, Barbara, Colombo, Giulia, Monzani, Valter, Savojardo, Valeria, Folli, Christian, Ceriani, Giuliana, Salerno, Francesco, Pallini, Giada, Dallegri, Franco, Ottonello, Luciano, Liberale, Luca, Caserza, Lara, Salam, Kassem, Liberato, Nicola Lucio, Tognin, Tiziana, Bianchi, Giovanni Battista, Giaquinto, Sabrina, Purrello, Francesco, Di Pino, Antonino, Piro, Salvatore, Rozzini, Renzo, Falanga, Lina, Spazzini, Elena, Ferrandina, Camillo, Montrucchio, Giuseppe, Petitti, Paolo, Peasso, Paolo, Favale, Edoardo, Poletto, Cesare, Salmi, Raffaella, Gaudenzi, Piergiorgio, Violi, Francesco, Perri, Ludovica, Landolfi, Raffaele, Montalto, Massimo, Mirijello, Antonio, Guasti, Luigina, Castiglioni, Luana, Maresca, Andrea, Squizzato, Alessandro, Campiotti, Leonardo, Grossi, Alessandra, Bertolotti, Marco, Mussi, Chiara, Lancellotti, Giulia, Libbra, Maria Vittoria, Dondi, Giulia, Pellegrini, Elisa, Carulli, Lucia, Galassi, Matteo, Grassi, Yasmine, Perticone, Francesco, Perticone, Maria, Battaglia, Rosa, Filice, Marco, Maio, Raffaele, Stanghellini, Vincenzo, Ruggeri, Eugenio, del Vecchio, Sara, Salvi, Andrea, Leonardi, Roberto, Damiani, Giampaolo, Capeci, William, Gabrielli, Armando, Mattioli, Massimo, Martino, Giuseppe Pio, Biondi, Lorenzo, Pettinari, Pietro, Ghio, Riccardo, Dal Col, Anna, Minisola, Salvatore, Colangelo, Luciano, Cilli, Mirella, Labbadia, Giancarlo, Afeltra, Antonella, Marigliano, Benedetta, Pipita, Maria Elena, Castellino, Pietro, Zanoli, Luca, Pignataro, Samuele, Gennaro, Alfio, Blanco, Julien, Saracco, Valter, Fogliati, Marisa, Bussolino, Carlo, Mete, Francesca, Gino, Miriam, Cittadini, Antonio, Vigorito, Carlo, Arcopinto, Michele, Salzano, Andrea, Bobbio, Emanuele, Marra, Alberto Maria, Sirico, Domenico, Moreo, Guido, Gasparini, Francesca, Prolo, Silvia, Pina, Gloria, Ballestrero, Alberto, Ferrando, Fabio, Berra, Sergio, Dassi, Simonetta, Nava, Maria Cristina, Graziella, Bruno, Baldassarre, Stefano, Fragapani, Salvatore, Gruden, Gabriella, Galanti, Giorgio, Mascherini, Gabriele, Petri, Cristian, Stefani, Laura, Girino, Margherita, Piccinelli, Valeria, Nasso, Francesco, Gioffre, Vincenza, Pasquale, Maria, Scattolin, Giuseppe, Martinelli, Sergio, Turrin, Mauro, Sechi, Leonardo, Catena, Cristina, Colussi, Gianluca, Passariello, Nicola, Rinaldi, Luca, Berti, Franco, Famularo, Giuseppe, Tarsitani, Patrizia, Castello, Roberto, Pasino, Michela, Ceda, Gian Paolo, Maggio, Marcello Giuseppe, Morganti, Simonetta, Artoni, Andrea, Del Giacco, Stefano, Firinu, Davide, Losa, Francesca, Paoletti, Giovanni, Costanzo, Giulia, Montalto, Giuseppe, Licata, Anna, Malerba, Valentina, Montalto, Filippo Alessandro, Lasco, Antonino, Basile, Giorgio, Catalano, Antonino, Malatino, Lorenzo, Stancanelli, Benedetta, Terranova, Valentina, Di Marca, Salvatore, Di Quattro, Rosario, La Malfa, Lara, Caruso, Rossella, Mecocci, Patrizia, Ruggiero, Carmelinda, Boccardi, Virginia, Meschi, Tiziana, Lauretani, Fulvio, Ticinesi, Andrea, Nouvenne, Antonio, Minuz, Pietro, Fondrieschi, Luigi, Pirisi, Mario, Fra, Gian Paolo, Sola, Daniele, Porta, Massimo, Riva, Piero, Quadri, Roberto, Larovere, Erica, Novelli, Marco, Scanzi, Giorgio, Mengoli, Caterina, Provini, Stella, Ricevuti, Laura, Simeone, Emilio, Scurti, Rosa, Tolloso, Fabio, Tarquini, Roberto, Valoriani, Alice, Dolenti, Silvia, Vannini, Giulia, Tedeschi, Alberto, Trotta, Lucia, Volpi, Riccardo, Bocchi, Pietro, Vignali, Alessandro, Harari, Sergio, Lonati, Chiara, Cattaneo, Mara, Duque Nieves, Ramirez, Molinero Alberto, Muela, Requejo Pedro, Abad, Pelaez Vanessa, Lopez, Lara, Tamargo, Viros Xavier, Corbella, Francesc, Formiga, Manglano Jesus, Diez, Tello Esperanza, Bejarano, Behamonte Esther, Del Corral, Puras Maria, Sevil, Romero, Manuel, Llorente Blanca, Pinilla, Gonzalez-Cobos Cristina, Lopez, Victoria, Villalba Garcia M., Saez, Lopez, Bosco, Juan, Baena Susana, Sanz, Gallego Marta, Arroyo, Becerra Concepcion, Gonzalez, Moyano Antonio, Fernandez, Gomez Hernandez, Mercedes, Poyato Borrego, Manuel, Cuadros Raquel, Pacheco, Rojas Florencia, Perez, Olid Beatriz, Garcia, Garcia Sara, Carrascosa, Cervellera Alfonso, Gonzalez-Cruz, Martinez Marta, Peinado, Cantero Alberto, Ruiz, Arraigosa Antonio, Albarracin, Guerrero Montserrat, Godoy, Miguel Angel, Baron Ramos, Jose Manuel, Machin, Veleiro Ignacio, Novo, Suarez Lucia, Alvela, Alfonso, Lopez, Bran David, Rubal, Vazquez Iria, Iniguez, and Prego Monica, Rios
Subjects: Male, medicine.medical_specialty, Population, Socio-culturale, Renal function, Disease, 030204 cardiovascular system & hematology, Elderly in-patients, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Internal medicine, Acute care, Epidemiology, eGFR, 80 and over, Internal Medicine, medicine, Humans, Renal Insufficiency, Hospital Mortality, 030212 general & internal medicine, Renal Insufficiency, Chronic, Chronic, education, Glomerular filtration rate estimation, Aged, Aged, 80 and over, Estimation, Creatinine, education.field_of_study, business.industry, Prognosis, Female, Italy, Glomerular Filtration Rate, Hospitalization, medicine.disease, Elderly in-patients, Glomerular filtration rate estimation, Prognosis, eGFR, chemistry, business, Kidney disease
Abstract: The estimated glomerular filtration rate (eGFR) is a predictor of important outcomes and its reduction has been associated with the risk of all-cause mortality in both general population and elderly patients. However while reduced renal function is common in older people, the best method for estimating GFR remains unclear, especially in an acute care setting. Most studies analyzing the accuracy of eGFR in the elderly were carried out in different heterogeneous settings. In this study, we compare the prognostic value of different formulas estimating GFR in predicting the risk of in-hospital morbidity and mortality within 3 months from discharge in elderly hospitalized patients. Data were extracted from “Registro Politerapia Societa Italiana di Medicina Interna (REPOSI)”. Patients with available creatinine values at hospital admission were selected and eGFR was calculated according to the different formulas: Cockcroft-Gault, Modification of Diet in Renal Disease equation, Chronic Kidney Disease Epidemiology Collaboration, Berlin Initiative Study and Full Age Spectrum. 4621 patients were included in the analysis. Among these, 4.2% and 14.2% died during hospitalization and within 3 months from discharge, respectively. eGFR > 60 ml/min/1.73 m2 at admission was associated with a very low risk of mortality during the hospital stay and within 90 days from discharge, while an eGFR
Published: 2018
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15. Ultraviolet light and melanoma

Author: Amaya Viros, Charles H. Earnshaw, and Sarah Craig
Subjects: 0301 basic medicine, business.industry, Somatic cell, Melanoma, Disease, medicine.disease, Phenotype, Pathology and Forensic Medicine, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, 030220 oncology & carcinogenesis, Ultraviolet light, Cancer research, Medicine, business, Pathological, Ultraviolet radiation, Advanced melanoma
Abstract: Melanoma is a clinically heterogeneous disease, and current strategies for treatment of the primary tumour are based on pathological criteria alone. In the recent past, several DNA-sequencing and RNA-sequencing studies of primary and advanced melanoma samples have identified unique relationships between somatic mutations, genomic aberrations, and the genetic fingerprint of ultraviolet radiation (UVR). The recurrent patterns of genomic alterations reveal different disease pathways, drug targets and mechanisms limiting drug response. Here, we examine the known associations between the molecular categories of melanoma and the multidimensional UVR damage. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Published: 2018
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16. New biomarkers improve stratification of patients with melanoma

Author: Amaya Viros and Sarah Craig
Subjects: Oncology, medicine.medical_specialty, Skin Neoplasms, business.industry, Melanoma, Stratification (water), Dermatology, Original Articles, medicine.disease, Internal medicine, Translational Research, medicine, Humans, Female, business, Biomarkers
Abstract: Summary Background The updated American Joint Committee on Cancer (AJCC) staging criteria for melanoma remain unable to identify high‐risk stage I tumour subsets. Objectives To determine the utility of epidermal autophagy and beclin 1 regulator 1 (AMBRA1)/loricrin (AMLo) expression as a prognostic biomarker for AJCC stage I cutaneous melanoma. Methods Peritumoral AMBRA1 expression was evaluated in a retrospective discovery cohort of 76 AJCC stage I melanomas. AMLo expression was correlated with clinical outcomes up to 12 years in two independent powered, retrospective validation and qualification cohorts comprising 379 AJCC stage I melanomas. Results Decreased AMBRA1 expression in the epidermis overlying primary melanomas in a discovery cohort of 76 AJCC stage I tumours was associated with a 7‐year disease‐free survival (DFS) rate of 81·5% vs. 100% survival with maintained AMBRA1 (P < 0·081). Following an immunohistochemistry protocol for semi‐quantitative analysis of AMLo, analysis was undertaken in validation (n = 218) and qualification cohorts (n = 161) of AJCC stage I melanomas. Combined cohort analysis revealed a DFS rate of 98·3% in the AMLo low‐risk group (n = 239) vs. 85·4% in the AMLo high‐risk cohort (n = 140; P < 0·001). Subcohort multivariate analysis revealed that an AMLo hazard ratio (HR) of 4·04 [95% confidence interval (CI) 1·69–9·66; P = 0·002] is a stronger predictor of DFS than Breslow depth (HR 2·97, 95% CI 0·93–9·56; P = 0·068) in stage IB patients. Conclusions Loss of AMLo expression in the epidermis overlying primary AJCC stage I melanomas identifies high‐risk tumour subsets independently of Breslow depth. What's already known about this topic? There is an unmet clinical need for biomarkers of early‐stage melanoma.Autophagy and beclin 1 regulator 1 (AMBRA1) is a proautophagy regulatory protein with known roles in cell proliferation and differentiation, and is a known tumour suppressor.Loricrin is a marker of epidermal terminal differentiation. What does this study add? AMBRA1 has a functional role in keratinocyte/epidermal proliferation and differentiation.The combined decrease/loss of peritumoral AMBRA1 and loricrin is associated with a significantly increased risk of metastatic spread in American Joint Committee on Cancer (AJCC) stage I tumours vs. melanomas, in which peritumoral AMBRA1 and loricrin are maintained, independently of Breslow depth. What is the translational message? The integration of peritumoral epidermal AMBRA1/loricrin biomarker expression into melanoma care guidelines will facilitate more accurate, personalized risk stratification for patients with AJCC stage I melanomas, thereby facilitating stratification for appropriate follow‐up and informing postdiagnostic investigations, including sentinel lymph node biopsy, ultimately resulting in improved disease outcomes and rationalization of healthcare costs., https://doi.org/10.1111/bjd.18658 available online Linked Editorial: https://doi.org/10.1111/bjd.18555
Published: 2020

17. Transoral robotic surgery for squamous cell carcinoma of the oropharynx in a primarily human papillomavirus-negative patient population

Author: C. Pollan Guisasola, B. Cirauqui Cirauqui, L Pardo Muñoz, C. Viña Soria, D. Viros Porcuna, F Collurá, and R. Mesia Nin
Subjects: 0301 basic medicine, Adult, Male, Cancer Research, medicine.medical_specialty, Reconstructive surgery, Population, Alphapapillomavirus, Head and neck cancer, Oropharyngeal cancer, Reconstructive surgery, Salvage surgery, Squamous cell carcinoma, TORS, 03 medical and health sciences, 0302 clinical medicine, Robotic Surgical Procedures, Transoral robotic surgery, medicine, Humans, Stage (cooking), education, Aged, Retrospective Studies, Aged, 80 and over, Salvage Therapy, education.field_of_study, Mouth, business.industry, Squamous Cell Carcinoma of Head and Neck, Incidence (epidemiology), Head and neck cancer, Cancer, Human Papillomavirus Negative, General Medicine, Middle Aged, medicine.disease, Surgery, Deglutition, Oropharyngeal Neoplasms, 030104 developmental biology, Oncology, 030220 oncology & carcinogenesis, Female, business, Negative Results
Abstract: Transoral robotic surgery (TORS) is one of the main treatment options for non-locally advanced primary oropharyngeal cancer in the United States. However, its use is more limited in countries with a low incidence of human papillomavirus (HPV), such as Spain, in patients with advanced disease, and as salvage surgery. To shed light on the use and potential benefit of TORS in Spanish patients, we analyzed the functional and oncologic outcomes of TORS as both primary and salvage surgery in a primarily HPV-negative population which is representative of oropharyngeal squamous cell carcinoma (OPSCC) patients in Spain. This is a retrospective analysis of prospectively collected data on OPSCC patients treated with TORS at our center between February 2017 and February 2019. Fifty-four OPSCC patients were included; 79.6% were males and 80.5% were HPV negative. Median age was 62 years. Primary surgery was performed on 73.7% (48.1% stage I–II; 51.9% stage III–IV) and salvage surgery on 25.9% of patients. Positive margin rates were 4.3% for T1–2 and 25.8% for T3–4. None of the stage I–II patients and 27.7% of stage III–IV patients required adjuvant treatment. Reconstructive surgery was performed in 19.2% of all patients. Normal swallowing was achieved in 92.7% of patients at 6 months after surgery. 1- and 2-year survival rates for all patients were 94.5% and 89%, respectively. The overall complication rate was 16.1%. Bleeding occurred in 11.5% of patients. Longer hospitalization time was associated with surgical complications (P = 0.03) and reconstructive surgery (P = 0.03) but not with salvage surgery. TORS is a safe and effective treatment for HPV-negative T1–2 OPSCC patients. The positive margin rate was worse in T3–4 patients, indicating the need for careful patient selection in this subgroup.
Published: 2020

18. Histologic Features Associated With an Invasive Component in Lentigo Maligna Lesions

Author: Eduardo Nagore, Celia Requena, Onofre Sanmartín, Ángela Moreno, Amaya Viros, Esperanza Manrique-Silva, and Victor Traves
Subjects: Male, medicine.medical_specialty, Skin Neoplasms, Biopsy, Dermatology, Lentigo maligna, Logistic regression, Hutchinson's Melanotic Freckle, 030207 dermatology & venereal diseases, 03 medical and health sciences, symbols.namesake, 0302 clinical medicine, medicine, Humans, In patient, Neoplasm Invasiveness, Lentigo maligna melanoma, Melanoma, Fisher's exact test, Aged, Retrospective Studies, Aged, 80 and over, medicine.diagnostic_test, business.industry, Odds ratio, Middle Aged, medicine.disease, Cross-Sectional Studies, Spain, 030220 oncology & carcinogenesis, Cutaneous melanoma, symbols, Disease Progression, Melanocytes, Female, Radiology, business
Abstract: Importance Lentigo maligna (LM) presents an invasive component in up to 20% of biopsied cases, but to date the histologic features useful in detecting this invasive component have not been described. Some histologic characteristics are hypothesized to contribute to the progression of LM invasion. Objective To identify the histologic characteristics associated with lentigo maligna melanoma (LMM) in patients with LM diagnosed by a partial diagnostic biopsy. Design, Setting, and Participants A retrospective cross-sectional study of patients treated between January 1, 2000, and December 31, 2017, was conducted in a referral oncology center in Valencia, Spain. Data and specimens of patients (n = 96) with a diagnosis of primary cutaneous melanoma in the form of either LM or LMM who had undergone surgical treatment, a complete histologic examination of the whole tumor, and an initial diagnostic partial biopsy of LM were included in the study. Histologic assessment was blinded to the presence of an invasive component. Interventions All biopsy specimens were evaluated for the presence of certain histologic characteristics. Main Outcomes and Measures Comparisons between invasive samples and samples without an invasive component were performed. The differences in the distribution of variables between the groups were assessed using the χ2and Fisher exact tests, and the degree of association of the relevant variables was quantified by logistic regression models. A classification and regression tree analysis was performed to rank the variables by importance. Results In total, 96 patients had sufficient histologic material that could be evaluated. The patients were predominantly male (56 [58.3%]) and had a mean (SD) age at diagnosis of 72 (12) years. Of these patients, 63 (65.6%) had an LM diagnosis and 33 (34.4%) had an LMM diagnosis (an invasive component). The histologic variables associated with the presence of an invasive component were melanocytes forming rows (odds ratio [OR], 11.5; 95% CI, 1.4-94.1;P = .02), subepidermal clefts (OR, 2.8; 95% CI, 1.0-7.9;P = .049), nests (OR, 3.0; 95% CI, 1.1-8.6;P = .04), and a lesser degree of solar elastosis (OR, 0.4; 95% CI, 0.1-1.1;P = .07). A classification and regression tree analysis of the relevant histologic features was able to accurately identify lentigo maligna with an invasive component (LMM) in more than 60% of patients. Conclusions and Relevance These findings may be useful in classifying early LM specimens at higher risk of invasion, which may eventually be relevant in identifying the most appropriate management for LM.
Published: 2019

19. Nodular Melanoma: A Histopathologic Entity?

Author: Maria Celia B. Hughes, Richard Marais, Victoria Akhras, Caroline Gaudy-Marqueste, Adèle C. Green, Amaya Viros, and Martin G. Cook
Subjects: Adult, Male, Pathology, medicine.medical_specialty, Skin Neoplasms, Time Factors, Adolescent, Dermatology, Nodular melanoma, Disease-Free Survival, Young Adult, 030207 dermatology & venereal diseases, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Terminology as Topic, Mitotic Index, medicine, Humans, Melanoma, Aged, Neoplasm Staging, business.industry, Australia, General Medicine, Middle Aged, medicine.disease, Treatment Outcome, England, 030220 oncology & carcinogenesis, RL1-803, Female, business
Published: 2018
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20. 940P Analysis of a cohort of elderly patients (p) with head and neck cancer (HNC) managed within a multidisciplinary head and neck cancer unit (HNCU)

Author: M.D.M. Palau Viarnes, C. Pollan Guisasola, J. Garcia Linares, B. Cirauqui Cirauqui, A. Massuet Vilamajo, P. Puyalto de Pablo, A. Quer Pi-Sunyer, I. Teruel García, J.A. Perez Gomez, C. Viña Soria, A. Ferrando Diez, D. Viros Porcuna, I. Planas Toledano, M.J. Sendros Madroño, S. Bordonaba Leiva, P. Hernandez Vergara, T. Traboulsi Garet, C. Carrasco Lopez, J. Vila Poyatos, and P. Cuadras Collsamata
Subjects: medicine.medical_specialty, Oncology, business.industry, Multidisciplinary approach, General surgery, Head and neck cancer, Cohort, Medicine, Hematology, business, medicine.disease, Unit (housing)
Published: 2020
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21. Correction: Cutaneous melanoma primary site is linked to nevus density

Author: Marta Llinares, Eduardo Nagore, Rajesh Kumar, Zaida García-Casado, Victor Traves, Alejandro Martin-Gorgojo, Celia Requena, and Amaya Viros
Subjects: medicine.medical_specialty, Primary (chemistry), integumentary system, business.industry, Correction, medicine.disease, Dermatology, sunburn, Oncology, Cutaneous melanoma, medicine, melanoma, solar elastosis, Nevus, business, skin and connective tissue diseases, neoplasms, Research Paper, nevus, risk
Abstract: There are at least two pathways driving cutaneous melanoma; one is linked to an inherent melanoma susceptibility to nevi development and the second to environmental cumulative ultraviolet light exposure. In this study, we examined the relation between nevus density, accrued sun damage and the site of primary melanoma excision. In a series of 888 consecutive cutaneous melanoma patients, melanomas appearing in skin areas with a high relative nevus density were most prominent in men, with an elevated nevus count, at sites without solar elastosis, but with an epidemiological history of previous sunburn. The present study associates melanoma development to sites with high nevus density. Our study supports more careful surveillance of body areas with increased nevus density in patients with high total body number of nevi, especially when they report a history of sunburns at these sites.
Published: 2019

22. Application of Sequencing, Liquid Biopsies, and Patient-Derived Xenografts for Personalized Medicine in Melanoma

Author: Franziska Baenke, Ged Brady, Jacqueline Swan, Dominic G. Rothwell, Deemesh Oudit, Grazia Saturno, Simon J. Furney, Matthew R. Smith, Paul Lorigan, Jane Rogan, Richard Marais, Elena Galvani, Rebecca Lee, Caroline Dive, Alberto Fusi, Amaya Viros, A. Mandal, Maria Romina Girotti, Nathalie Dhomen, Malin Pedersen, Kok Haw Jonathan Lim, and Gabriela Gremel
Subjects: 0301 basic medicine, Oncology, medicine.medical_specialty, Biopsy, medicine.medical_treatment, Antineoplastic Agents, Disease, Bioinformatics, Targeted therapy, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Biomarkers, Tumor, medicine, Cluster Analysis, Humans, Molecular Targeted Therapy, Precision Medicine, Melanoma, Exome sequencing, Neoplasm Staging, medicine.diagnostic_test, business.industry, Gene Expression Profiling, Disease Management, High-Throughput Nucleotide Sequencing, Reproducibility of Results, Cancer, medicine.disease, Precision medicine, Xenograft Model Antitumor Assays, 3. Good health, Treatment Outcome, 030104 developmental biology, Drug Resistance, Neoplasm, 030220 oncology & carcinogenesis, Mutation, Disease Progression, Personalized medicine, business
Abstract: Targeted therapies and immunotherapies have transformed melanoma care, extending median survival from ∼9 to over 25 months, but nevertheless most patients still die of their disease. The aim of precision medicine is to tailor care for individual patients and improve outcomes. To this end, we developed protocols to facilitate individualized treatment decisions for patients with advanced melanoma, analyzing 364 samples from 214 patients. Whole exome sequencing (WES) and targeted sequencing of circulating tumor DNA (ctDNA) allowed us to monitor responses to therapy and to identify and then follow mechanisms of resistance. WES of tumors revealed potential hypothesis-driven therapeutic strategies for BRAF wild-type and inhibitor-resistant BRAF-mutant tumors, which were then validated in patient-derived xenografts (PDX). We also developed circulating tumor cell–derived xenografts (CDX) as an alternative to PDXs when tumors were inaccessible or difficult to biopsy. Thus, we describe a powerful technology platform for precision medicine in patients with melanoma. Significance: Although recent developments have revolutionized melanoma care, most patients still die of their disease. To improve melanoma outcomes further, we developed a powerful precision medicine platform to monitor patient responses and to identify and validate hypothesis-driven therapies for patients who do not respond, or who develop resistance to current treatments. Cancer Discov; 6(3); 286–99. ©2015 AACR. This article is highlighted in the In This Issue feature, p. 217
Published: 2016
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23. Prevalence, characteristics and treatment of chronic pain in elderly patients hospitalized in internal medicine wards

Author: Corsi, Nicole, Roberto, Anna, Cortesi, Laura, Nobili, Alessandro, Mannucci, Pier Mannuccio, Corli, Oscar, Prisco, Domenico, Silvestri, Elena, Emmi, Giacomo, Bettiol, Alessandra, Caterina, Cenci, Biolo, Gianni, Zanetti, Michela, Guadagni, Martina, Zaccari, Michele, Chiuch, Massimiliano, Vanoli, Massimo, Grignani, Giulia, Pulixi, Edoardo Alessandro, Bernardi, Mauro, Bassi, Silvia Li, Santi, Luca, Zaccherini, Giacomo, Lupattelli, Graziana, Mannarino, Elmo, Bianconi, Vanessa, Paciullo, Francesco, Alcidi, Riccardo, Nuti, Ranuccio, Valenti, Roberto, Ruvio, Martina, Cappelli, Silvia, Palazzuoli, Alberto, Girelli, Domenico, Busti, Fabiana, Marchi, Giacomo, Barbagallo, Mario, Dominguez, Ligia, Cocita, Floriana, Beneduce, Vincenza, Plances, Lidia, Corrao, Salvatore, Natoli, Giuseppe, Mularo, Salvatore, Raspanti, Massimo, Cavallaro, Federica, Zoli, Marco, Lazzari, Ilaria, Brunori, Mattia, Fabbri, Elisa, Magalotti, Donatella, Arno, Raffaella, Pasini, Franco Laghi, Capecchi, Pier Leopoldo, Palasciano, Giuseppe, Modeo, Maria Ester, Di Gennaro, Carla, Cappellini, Maria Domenica, Maira, Diletta, Di Stefano, Valeria, Fabio, Giovanna, Seghezzi, Sonia, Mancarella, Marta, De Amicis, Margherita Migone, De Luca, Giacomo, Scaramellini, Natalia, Cesari, Matteo, Rossi, Paolo Dionigi, Damanti, Sarah, Clerici, Marta, Conti, Federica, Bonini, Giulia, Ottolini, Barbara Brignolo, Di Sabatino, Antonio, Miceli, Emanuela, Lenti, Marco Vincenzo, Pisati, Martina, Dominioni, Costanza Caccia, Murialdo, Giovanni, Marra, Alessio, Cattaneo, Federico, Pontremoli, Roberto, Beccati, Valentina, Nobili, Giulia, Secchi, Maria Beatrice, Ghelfi, Davide, Anastasio, Luigi, Sofia, Lucia, Carbone, Maria, Cipollone, Francesco, Guagnano, Maria Teresa, Valeriani, Emanuele, Rossi, Ilaria, Mancuso, Gerardo, Calipari, Daniela, Bartone, Mose, Delitala, Giuseppe, Berria, Maria, Pes, Chiara, Delitala, Alessandro, Muscaritoli, Maurizio, Molfino, Alessio, Petrillo, Enrico, Zuccala, Giuseppe, D'Aurizio, Gabriella, Romanelli, Giuseppe, Marengoni, Alessandra, Zucchelli, Alberto, Manzoni, Francesca, Volpini, Andrea, Picardi, Antonio, Gentilucci, Umberto Vespasiani, Gallo, Paolo, Dell'Unto, Chiara, Annoni, Giorgio, Corsi, Maurizio, Bellelli, Giuseppe, Zazzetta, Sara, Mazzola, Paolo, Szabo, Hajnalka, Bonfanti, Alessandra, Arturi, Franco, Succurro, Elena, Rubino, Mariangela, Tassone, Bruno, Sesti, Giorgio, Serra, Maria Grazia, Bleve, Maria Antonietta, Gasbarrone, Laura, Sajeva, Maria Rosaria, Brucato, Antonio, Ghidoni, Silvia, Fabris, Fabrizio, Bertozzi, Irene, Bogoni, Giulia, Rabuini, Maria Victoria, Cosi, Elisabetta, Scarinzi, Paolo, Amabile, Annalisa, Omenetto, Elisabetta, Prandini, Tancredi, Manfredini, Roberto, Fabbian, Fabio, Boari, Benedetta, De Giorgi, Alfredo, Tiseo, Ruana, De Giorgio, Roberto, Paolisso, Giuseppe, Rizzo, Maria Rosaria, Borghi, Claudio, Strocchi, Enrico, Ianniello, Eugenia, Soldati, Mario, Sabba, Carlo, Vella, Francesco Saverio, Suppressa, Patrizia, Agosti, Pasquale, Schilardi, Andrea, Loparco, Francesca, De Vincenzo, Giovanni Michele, Comitangelo, Alessio, Amoruso, Emanuele, Fenoglio, Luigi, Falcetta, Andrea, Bracco, Christian, Fracanzani, Anna L., Fargion, Silvia, Tiraboschi, Silvia, Cespiati, Annalisa, Oberti, Giovanna, Sigon, Giordano, Peyvandi, Flora, Rossio, Raffaella, Ferrari, Barbara, Colombo, Giulia, Monzani, Valter, Savojardo, Valeria, Folli, Christian, Ceriani, Giuliana, Salerno, Francesco, Pallini, Giada, Dallegri, Franco, Ottonello, Luciano, Liberale, Luca, Caserza, Lara, Salam, Kassem, Liberato, Nicola Lucio, Tognin, Tiziana, Bianchi, Giovanni Battista, Giaquinto, Sabrina, Purrello, Francesco, Di Pino, Antonino, Piro, Salvatore, Rozzini, Renzo, Falanga, Lina, Spazzini, Elena, Ferrandina, Camillo, Montrucchio, Giuseppe, Petitti, Paolo, Peasso, Paolo, Favale, Edoardo, Poletto, Cesare, Salmi, Raffaella, Gaudenzi, Piergiorgio, Violi, Francesco, Perri, Ludovica, Landolfi, Raffaele, Montalto, Massimo, Mirijello, Antonio, Guasti, Luigina, Castiglioni, Luana, Maresca, Andrea, Squizzato, Alessandro, Campiotti, Leonardo, Grossi, Alessandra, Bertolotti, Marco, Mussi, Chiara, Lancellotti, Giulia, Libbra, Maria Vittoria, Dondi, Giulia, Pellegrini, Elisa, Carulli, Lucia, Galassi, Matteo, Grassi, Yasmine, Perticone, Francesco, Perticone, Maria, Battaglia, Rosa, Filice, Marco, Maio, Raffaele, Stanghellini, Vincenzo, Ruggeri, Eugenio, del Vecchio, Sara, Salvi, Andrea, Leonardi, Roberto, Damiani, Giampaolo, Capeci, William, Gabrielli, Armando, Mattioli, Massimo, Martino, Giuseppe Pio, Biondi, Lorenzo, Pettinari, Pietro, Ghio, Riccardo, Dal Col, Anna, Minisola, Salvatore, Colangelo, Luciano, Cilli, Mirella, Labbadia, Giancarlo, Afeltra, Antonella, Marigliano, Benedetta, Pipita, Maria Elena, Castellino, Pietro, Zanoli, Luca, Pignataro, Samuele, Gennaro, Alfio, Blanco, Julien, Saracco, Valter, Fogliati, Marisa, Bussolino, Carlo, Mete, Francesca, Gino, Miriam, Cittadini, Antonio, Vigorito, Carlo, Arcopinto, Michele, Salzano, Andrea, Bobbio, Emanuele, Marra, Alberto Maria, Sirico, Domenico, Moreo, Guido, Gasparini, Francesca, Prolo, Silvia, Pina, Gloria, Ballestrero, Alberto, Ferrando, Fabio, Berra, Sergio, Dassi, Simonetta, Nava, Maria Cristina, Graziella, Bruno, Baldassarre, Stefano, Fragapani, Salvatore, Gruden, Gabriella, Galanti, Giorgio, Mascherini, Gabriele, Petri, Cristian, Stefani, Laura, Girino, Margherita, Piccinelli, Valeria, Nasso, Francesco, Gioffre, Vincenza, Pasquale, Maria, Scattolin, Giuseppe, Martinelli, Sergio, Turrin, Mauro, Sechi, Leonardo, Catena, Cristina, Colussi, Gianluca, Passariello, Nicola, Rinaldi, Luca, Berti, Franco, Famularo, Giuseppe, Tarsitani, Patrizia, Castello, Roberto, Pasino, Michela, Ceda, Gian Paolo, Maggio, Marcello Giuseppe, Morganti, Simonetta, Artoni, Andrea, Del Giacco, Stefano, Firinu, Davide, Losa, Francesca, Paoletti, Giovanni, Costanzo, Giulia, Montalto, Giuseppe, Licata, Anna, Malerba, Valentina, Montalto, Filippo Alessandro, Lasco, Antonino, Basile, Giorgio, Catalano, Antonino, Malatino, Lorenzo, Stancanelli, Benedetta, Terranova, Valentina, Di Marca, Salvatore, Di Quattro, Rosario, La Malfa, Lara, Caruso, Rossella, Mecocci, Patrizia, Ruggiero, Carmelinda, Boccardi, Virginia, Meschi, Tiziana, Lauretani, Fulvio, Ticinesi, Andrea, Nouvenne, Antonio, Minuz, Pietro, Fondrieschi, Luigi, Pirisi, Mario, Fra, Gian Paolo, Sola, Daniele, Porta, Massimo, Riva, Piero, Quadri, Roberto, Larovere, Erica, Novelli, Marco, Scanzi, Giorgio, Mengoli, Caterina, Provini, Stella, Ricevuti, Laura, Simeone, Emilio, Scurti, Rosa, Tolloso, Fabio, Tarquini, Roberto, Valoriani, Alice, Dolenti, Silvia, Vannini, Giulia, Tedeschi, Alberto, Trotta, Lucia, Volpi, Riccardo, Bocchi, Pietro, Vignali, Alessandro, Harari, Sergio, Lonati, Chiara, Cattaneo, Mara, Duque Nieves, Ramirez, Molinero Alberto, Muela, Requejo Pedro, Abad, Pelaez Vanessa, Lopez, Lara, Tamargo, Viros Xavier, Corbella, Francesc, Formiga, Manglano Jesus, Diez, Tello Esperanza, Bejarano, Behamonte Esther, Del Corral, Puras Maria, Sevil, Romero, Manuel, Llorente Blanca, Pinilla, Gonzalez-Cobos Cristina, Lopez, Victoria, Villalba Garcia M., Saez, Lopez, Bosco, Juan, Baena Susana, Sanz, Gallego Marta, Arroyo, Becerra Concepcion, Gonzalez, Moyano Antonio, Fernandez, Gomez Hernandez, Mercedes, Poyato Borrego, Manuel, Cuadros Raquel, Pacheco, Rojas Florencia, Perez, Olid Beatriz, Garcia, Garcia Sara, Carrascosa, Cervellera Alfonso, Gonzalez-Cruz, Martinez Marta, Peinado, Cantero Alberto, Ruiz, Arraigosa Antonio, Albarracin, Guerrero Montserrat, Godoy, Miguel Angel, Baron Ramos, Jose Manuel, Machin, Veleiro Ignacio, Novo, Suarez Lucia, Alvela, Alfonso, Lopez, Bran David, Rubal, Vazquez Iria, Iniguez, and Prego Monica, Rios
Subjects: Male, medicine.medical_specialty, Aging, Pharmacological therapy, Undertreatment, Socio-culturale, Chronic pain, Comorbidity, Pharmacological treatment, 03 medical and health sciences, 0302 clinical medicine, Cognition, Aging, Analgesic treatment, Chronic pain, Pain management, Undertreatment, Internal medicine, medicine, Hospital discharge, 80 and over, Internal Medicine, Elderly people, Cognitive status, Humans, 030212 general & internal medicine, Registries, Depression (differential diagnoses), Aged, Aged, 80 and over, Analgesics, business.industry, Depression, Settore MED/09 - MEDICINA INTERNA, medicine.disease, Pain management, Logistic Models, Italy, Analgesic treatment, Spain, Chronic Pain, Female, Hospital Units, Multivariate Analysis, Pain Management, business, Hospital stay, 030217 neurology & neurosurgery
Abstract: Chronic pain is a frequent characteristic of elderly people and represents an actual and still poorly debated topic.We investigated pain prevalence and intensity, and its pharmacological therapy in elderly patients hospitalized in 101 internal medicine wards.Taking advantage of the "REgistro POliterapie Società Italiana Medicina Interna" (REPOSI), we collected 2535 patients of whom almost a quarter was older than 85 years old. Among them, 582 patients were affected by pain (either chronic or acute) and 296 were diagnosed with chronic pain.Patients with pain showed worse cognitive status, higher depression and comorbidities, and a longer duration of hospital stay compared to those without pain (all p .0366). Patients with chronic pain revealed lower level of independency in their daily life, worse cognitive status and higher level of depression compared to acute pain patients (all p .0156). Moreover, most of them were not treated for pain at admission (73.4%) and half of them was not treated with any analgesic drug at discharge (50.5%). This difference affected also the reported levels of pain intensity. Patients who received analgesics at both admission and discharge remained stable (p = .172). Conversely, those not treated at admission who received an analgesic treatment during the hospital stay decreased their perceived pain (p .0001).Our results show the need to focus more attention on the pharmacological treatment of chronic pain, especially in hospitalized elderly patients, in order to support them and facilitate their daily life after hospital discharge.
Published: 2018

24. Implementation of the Frailty Index in hospitalized older patients: Results from the REPOSI register

Author: Matteo, Cesari, Carlotta, Franchi, Laura, Cortesi, Alessandro, Nobili, Ilaria, Ardoino, Pier Mannuccio Mannucci, Mauro, Tettamanti, Luca, Pasina, Francesco, Perticone, Francesco, Salerno, Salvatore, Corrao, Alessandra, Marengoni, Giuseppe, Licata, Francesco, Violi, Gino Roberto Corazza, Tarek Kamal Eldin, Maria Pia Donatella Di Blanca, Giovanna, Lanzo, Sarah, Astuto, Prisco, Domenico, Elena, Silvestri, Caterina, Cenci, Giacomo, Emmi, Gianni, Biolo, Gianfranco, Guarnieri, Michela, Zanetti, Giovanni, Fernandes, Massimiliano, Chiuch, Massimo, Vanoli, Giulia, Grignani, Gianluca, Casella, Edoardo Alessandro Pulixi, Mauro, Bernardi, Silvia Li Bassi, Luca, Santi, Giacomo, Zaccherini, Mannarino, Elmo, Lupattelli, Graziana, Bianconi, Vanessa, Paciullo, Francesco, Ranuccio, Nuti, Roberto, Valenti, Martina, Ruvio, Silvia, Cappelli, Alberto, Palazzuoli, Teresa, Salvatore, Ferdinando Carlo Sasso, Domenico, Girelli, Olivieri, Oliviero, Thomas, Matteazzi, Mario, Barbagallo, Lidia, Plances, Roberta, Alcamo, Luigi, Calvo, Maria, Valenti, Marco, Zoli, Raffaella, Arnò, Franco Laghi Pasini, Pier Leopoldo Capecchi, Maurizio, Bicchi, Giuseppe, Palasciano, Maria Ester Modeo, Maria, Peragine, Fabrizio, Pappagallo, Stefania, Pugliese, Carla Di Gennaro, Alfredo, Postiglione, Maria Rosaria Barbella, Francesco De Stefano, Cappellini, MARIA DOMENICA, Giovanna, Fabio, Sonia, Seghezzi, Margherita Migone De Amicis, Marta, Mancarella, Daniela, Mari, Paolo Dionigi Rossi, Sarah, Damanti, Barbara Brignolo Ottolini, Giulia, Bonini, Emanuela, Miceli, Marco Vincenzo Lenti, Donatella, Padula, Giovanni, Murialdo, Alessio, Marra, Federico, Cattaneo, Maria Beatrice Secchi, Davide, Ghelfi, Luigi, Anastasio, Lucia, Sofia, Carbone, LUIGI MARIA, Giovanni, Davì, Maria Teresa Guagnano, Simona, Sestili, Gerardo, Mancuso, Daniela, Calipari, Mosè, Bartone, Maria Rachele Meroni, Paolo Cavallo Perin, Bartolomeo, Lorenzati, Gabriella, Gruden, Graziella, Bruno, Cristina, Amione, Paolo, Fornengo, Rodolfo, Tassara, Deborah, Melis, Lara, Rebella, Giuseppe, Delitala, Vincenzo, Pretti, Maristella Salvatora Masala, Chiara, Pes, Luigi, Bolondi, Leonardo, Rasciti, Ilaria, Serio, Filippo Rossi Fanelli, Antonio, Amoroso, Alessio, Molfino, Enrico, Petrillo, Giuseppe, Zuccalà, Francesco, Franceschi, Guido De Marco, Cordischi, Chiara, Sabbatini, Marta, Gabriella, D'Aurizio, Giuseppe, Romanelli, Claudia, Amolini, Deborah, Chiesa, Antonio, Picardi, Umberto Vespasiani Gentilucci, Paolo, Gallo, Giorgio, Annoni, Maurizio, Corsi, Sara, Zazzetta, Giuseppe, Bellelli, Hajnalka, Szabo, Franco, Arturi, Elena, Succurro, Mariangela, Rubino, Giorgio, Sesti, Paola, Loria, Maria Angela Becchi, Gianfranco, Martucci, Alessandra, Fantuzzi, Mauro, Maurantonio, Maria Grazia Serra, Maria Antonietta Bleve, Laura, Gasbarrone, Maria Rosaria Sajeva, Antonio, Brucato, Silvia, Ghidoni, Paola Di Corato, Agnelli, Giancarlo, Marchesini, Emanuela, Fabrizio, Fabris, Michela, Carlon, Francesca, Turatto, Aldo, Baritusso, Annalisa, Amabile, Elisabetta, Omenetto, Paolo, Scarinzi, Roberto, Manfredini, Christian, Molino, Marco, Pala, Fabio, Fabbian, Benedetta, Boari, Alfredo De Giorgi, Giuseppe, Paolisso, Maria Rosaria Rizzo, Maria Teresa Laieta, Giovanbattista, Rini, Pasquale, Mansueto, Ilenia, Pepe, Claudio, Borghi, Enrico, Strocchi, Valeria De Sando, Ilaria, Pareo, Carlo, Sabbà, Francesco Saverio Vella, Patrizia, Suppressa, Raffaella, Valerio, Pasquale, Agosti, Flavia, Fontana, Francesca, Loparco, Caterina, Capobianco, Luigi, Fenoglio, Christian, Bracco, Alessia Valentina Giraudo, Elisa, Testa, Cristina, Serraino, Silvia, Fargion, Paola, Bonara, Giulia, Periti, Marianna, Porzio, Slivia, Tiraboschi, Flora, Peyvandi, Alberto, Tedeschi, Raffaella, Rossio, Valter, Monzani, Valeria, Savojardo, Christian, Folli, Maria, Magnini, Alessio, Conca, Giulia, Gobbo, Giada, Pallini, Miriam, Valenti, Balduini, Carlo L., Giampiera, Bertolino, Stella, Provini, Federica, Quaglia, Franco, Dallegri, Luciano, Ottonello, Luca, Liberale, Wu Sheng Chin, Laura, Carassale, Silvia, Caporotundo, Giancarlo, Traisci, Lucrezia De Feudis, Silvia Di Carlo, Nicola Lucio Liberato, Alberto, Buratti, Tiziana, Tognin, Giovanni Battista Bianchi, Sabrina, Giaquinto, Francesco, Purrello, Antonino Di Pino, Salvatore, Piro, Renzo, Rozzini, Lina, Falanga, Elena, Spazzini, Giuseppe, Montrucchio, Elisabetta, Greco, Pietro, Tizzani, Paolo, Petitti, Antonio, Perciccante, Alessia, Coralli, Raffaella, Salmi, Piergiorgio, Gaudenzi, Susanna, Gamberini, Andrea, Semplicini, Lucia, Gottardo, Gianluigi, Vendemiale, Gaetano, Serviddio, Roberta, Forlano, Cesare, Masala, Antonio, Mammarella, Valeria, Raparelli, Stefania, Basili, Ludovica, Perri, Raffaele, Landolfi, Massimo, Montalto, Antonio, Mirijello, Carla, Vallone, Martino, Bellusci, Donatella, Setti, Filippo, Pedrazzoli, Luigina, Guasti, Luana, Castiglioni, Andrea, Maresca, Alessandro, Squizzato, Marta, Molaro, Bertolotti, Marco, Chiara, Mussi, Maria Vittoria Libbra, DI MICELI, Andrea, Pellegrini, Elisa, Lucia, Carulli, Francesca, Veltri, Angela, Sciacqua, Michele, Quero, Chiara, Bagnato, Lidia, Colangelo, Tania, Falbo, Roberto De Giorgio, DALLA SERRA, Mauro, Valentina, Grasso, Eugenio, Ruggeri, Benzoni, Ilaria, Andrea, Salvi, Leonardi, Roberto, Chiara, Grassini, Ilenia, Mascherona, Minelli, Giorgio, Francesca, Maltese, Giampaolo, Damiani, William, Capeci, Mattioli, Massimo, Giuseppe Pio Martino, Biondi, Lorenzo, Monica, Ormas, Pietro, Pettinari, Roberto, Romiti, Silvia, Messina, Federica, Cavallaro, Riccardi, Ghio, Serena, Favorini, Anna Dal Col, Salvatore, Minisola, Luciano, Colangelo, Antonella, Afeltra, Pamela, Alemanno, Benedetta, Marigliano, Maria Elena Pipita, Pietro, Castellino, Julien, Blanco, Luca, Zanoli, Cattaneo, Marco Natale, Paola, Fracasso, Amoruso, MARIA VALENTINA, Valter, Saracco, Marisa, Fogliati, Carlo, Bussolino, Vittorio, Durante, Giovanna, Eusebi, Daniela, Tirotta, Francesca, Mete, Miriam, Gino, Antonio, Cittadini, Carlo, Vigorito, Michele, Arcopinto, Andrea, Salzano, Emanuele, Bobbio, Alberto Maria Marra, Domenico, Sirico, Guido, Moreo, Francesco, Scopelliti, Francesca, Gasparini, Melissa, Cocca, Alberto, Ballestrero, Fabio, Ferrando, Sergio, Berra, Simonetta, Dassi, Maria Cristina Nava, Bruno, Graziella, Stefano, Baldassarre, Salvatore, Fragapani, Giorgio, Galanti, Gabriele, Mascherini, Cristian, Petri, Laura, Stefani, Margherita, Girino, Valeria, Piccinelli, Francesco, Nasso, Vincenza, Gioffrè, Maria, Pasquale, Giuseppe, Scattolin, Sergio, Martinelli, Mauro, Turrin, Leonardo, Sechi, Cristina, Catena, Gianluca, Colussi, Ramirez Duque Nieves, Muela Molinero Alberto, Abad Requejo Pedro, Lopez Pelaez Vanessa, Tamargo, Lara, Corbella Viros Xavier, Formiga, Francesc, Diez Manglano Jesus, Bejarano Tello Esperanza, Del Corral Behamonte Esther, Sevil Puras Maria, Manuel, Romero, Pinilla Llorente Blanca, Lopez Gonzalez-Cobos Cristina, Victoria, Villalba Garcia M., Lopez, Saez, Juan, Bosco, Sanz Baena Susana, Arroyo Gallego Marta, Gonzalez Becerra Concepcion, Fernandez Moyano Antonio, Mercedes Gomez Hernandez, Manuel Poyato Borrego, Pacheco Cuadros Raquel, Perez Rojas Florencia, Garcia Olid Beatriz, Carrascosa Garcia Sara, Gonzalez-Cruz Cervellera Alfonso, Peinado Martinez Marta, Sara Carrascosa Garcia, Ruiz Cantero Alberto, Albarracín Arraigosa Antonio, Godoy Guerrero Montserrat, Barón Ramos Miguel Ángel, Machin Jose Manuel, Novo Veleiro Ignacio, Alvela Suarez Lucía, Lopez, Alfonso, Rubal Bran David, Iñiguez Vazquez Iria, Rios Prego Monica, Cesari M., Franchi C., Cortesi L., Nobili A., Ardoino I., Mannucci P.M., Tettamanti M., Pasina L., Perticone F., Salerno F., Corrao S., Marengoni A., Licata G., Violi F., Corazza G.R., Eldin T.K., Di Blanca M.P.D., Lanzo G., Astuto S., Prisco D., Silvestri E., Cenci C., Emmi G., Biolo G., Guarnieri G., Zanetti M., Fernandes G., Chiuch M., Vanoli M., Grignani G., Casella G., Pulixi E.A., Bernardi M., Bassi S.L., Santi L., Zaccherini G., Mannarino E., Lupattelli G., Bianconi V., Paciullo F., Nuti R., Valenti R., Ruvio M., Cappelli S., Palazzuoli A., Salvatore T., Sasso F.C., Girelli D., Olivieri O., Matteazzi T., Barbagallo M., Plances L., Alcamo R., Calvo L., Valenti M., Zoli M., Arno R., Pasini F.L., Capecchi P.L., Bicchi M., Palasciano G., Modeo M.E., Peragine M., Pappagallo F., Pugliese S., Gennaro C.D., Postiglione A., Barbella M.R., De Stefano F., Cappellini M.D., Fabio G., Seghezzi S., De Amicis M.M., Mancarella M., Mari D., Rossi P.D., Damanti S., Ottolini B.B., Bonini G., Miceli E., Lenti M.V., Padula D., Murialdo G., Marra A., Cattaneo F., Secchi M.B., Ghelfi D., Anastasio L., Sofia L., Carbone M., Davi G., Guagnano M.T., Sestili S., Mancuso G., Calipari D., Bartone M., Meroni M.R., Perin P.C., Lorenzati B., Gruden G., Bruno G., Amione C., Fornengo P., Tassara R., Melis D., Rebella L., Delitala G., Pretti V., Masala M.S., Pes C., Bolondi L., Rasciti L., Serio I., Fanelli F.R., Amoroso A., Molfino A., Petrillo E., Zuccala G., Franceschi F., De Marco G., Chiara C., Marta S., D'aurizio G., Romanelli G., Amolini C., Chiesa D., Picardi A., Gentilucci U.V., Gallo P., Annoni G., Corsi M., Zazzetta S., Bellelli G., Szabo H., Arturi F., Succurro E., Rubino M., Sesti G., Loria P., Becchi M.A., Martucci G., Fantuzzi A., Maurantonio M., Serra M.G., Bleve M.A., Gasbarrone L., Sajeva M.R., Brucato A., Ghidoni S., Di Corato P., Agnelli G., Marchesini E., Fabris F., Carlon M., Turatto F., Baritusso A., Amabile A., Omenetto E., Scarinzi P., Manfredini R., Molino C., Pala M., Fabbian F., Boari B., De Giorgi A., Paolisso G., Rizzo M.R., Laieta M.T., Rini G., Mansueto P., Pepe I., Borghi C., Strocchi E., De Sando V., Pareo I., Sabba C., Vella F.S., Suppressa P., Valerio R., Agosti P., Fontana F., Loparco F., Capobianco C., Fenoglio L., Bracco C., Giraudo A.V., Testa E., Serraino C., Fargion S., Bonara P., Periti G., Porzio M., Tiraboschi S., Peyvandi F., Tedeschi A., Rossio R., Monzani V., Savojardo V., Folli C., Magnini M., Conca A., Gobbo G., Pallini G., Balduini C.L., Bertolino G., Provini S., Quaglia F., Dallegri F., Ottonello L., Liberale L., Chin W.S., Carassale L., Caporotundo S., Traisci G., De Feudis L., Di Carlo S., Liberato N.L., Buratti A., Tognin T., Bianchi G.B., Giaquinto S., Purrello F., Di Pino A., Piro S., Rozzini R., Falanga L., Spazzini E., Montrucchio G., Greco E., Tizzani P., Petitti P., Perciccante A., Coralli A., Salmi R., Gaudenzi P., Gamberini S., Semplicini A., Gottardo L., Vendemiale G., Serviddio G., Forlano R., Masala C., Mammarella A., Raparelli V., Basili S., Perri L., Landolfi R., Montalto M., Mirijello A., Vallone C., Bellusci M., Setti D., Pedrazzoli F., Guasti L., Castiglioni L., Maresca A., Squizzato A., Molaro M., Bertolotti M., Mussi C., Libbra M.V., Miceli A., Pellegrini E., Carulli L., Veltri F., Sciacqua A., Quero M., Bagnato C., Colangelo L., Falbo T., De Giorgio R., Serra M., Grasso V., Ruggeri E., Ilaria B., Salvi A., Leonardi R., Grassini C., Mascherona I., Minelli G., Maltese F., Damiani G., Capeci W., Mattioli M., Martino G.P., Biondi L., Ormas M., Pettinari P., Romiti R., Messina S., Cavallaro F., Ghio R., Favorini S., Col A.D., Minisola S., Afeltra A., Alemanno P., Marigliano B., Pipita M.E., Castellino P., Blanco J., Zanoli L., Cattaneo M., Fracasso P., Amoruso M.V., Saracco V., Fogliati M., Bussolino C., Durante V., Eusebi G., Tirotta D., Mete F., Gino M., Cittadini A., Vigorito C., Arcopinto M., Salzano A., Bobbio E., Marra A.M., Sirico D., Moreo G., Scopelliti F., Gasparini F., Cocca M., Ballestrero A., Ferrando F., Berra S., Dassi S., Nava M.C., Graziella B., Baldassarre S., Fragapani S., Galanti G., Mascherini G., Petri C., Stefani L., Girino M., Piccinelli V., Nasso F., Gioffre V., Pasquale M., Scattolin G., Martinelli S., Turrin M., Sechi L., Catena C., Colussi G., Nieves R.D., Alberto M.M., Pedro A.R., Vanessa L.P., Lara T., Xavier C.V., Francesc F., Jesus D.M., Esperanza B.T., Esther D.C.B., Maria S.P., Romero M., Blanca P.L., Cristina L.G.-C., Victoria V.G.M., Saez L., Bosco J., Susana S.B., Marta A.G., Concepcion G.B., Antonio F.M., Hernandez M.G., Borrego M.P., Raquel P.C., Florencia P.R., Beatriz G.O., Sara C.G., Alfonso G.-C.C., Marta P.M., Garcia S.C., Alberto R.C., Antonio A.A., Montserrat G.G., Angel B.R.M., Manuel M.J., Ignacio N.V., Lucia A.S., Alfonso L., David R.B., Iria I.V., Monica R.P., Cesari, M., Franchi, C., Cortesi, L., Nobili, A., Ardoino, I., Mannucci, P. M., Tettamanti, M., Pasina, L., Perticone, F., Salerno, F., Corrao, S., Marengoni, A., Licata, G., Violi, F., Corazza, G. R., Eldin, T. K., Di Blanca, M. P. D., Lanzo, G., Astuto, S., Prisco, D., Silvestri, E., Cenci, C., Emmi, G., Biolo, G., Guarnieri, G., Zanetti, M., Fernandes, G., Chiuch, M., Vanoli, M., Grignani, G., Casella, G., Pulixi, E. A., Bernardi, M., Bassi, S. L., Santi, L., Zaccherini, G., Mannarino, E., Lupattelli, G., Bianconi, V., Paciullo, F., Nuti, R., Valenti, R., Ruvio, M., Cappelli, S., Palazzuoli, A., Salvatore, T., Sasso, F. C., Girelli, D., Olivieri, O., Matteazzi, T., Barbagallo, M., Plances, L., Alcamo, R., Calvo, L., Valenti, M., Zoli, M., Arno, R., Pasini, F. L., Capecchi, P. L., Bicchi, M., Palasciano, G., Modeo, M. E., Peragine, M., Pappagallo, F., Pugliese, S., Gennaro, C. D., Postiglione, A., Barbella, M. R., De Stefano, F., Cappellini, M. D., Fabio, G., Seghezzi, S., De Amicis, M. M., Mancarella, M., Mari, D., Rossi, P. D., Damanti, S., Ottolini, B. B., Bonini, G., Miceli, E., Lenti, M. V., Padula, D., Murialdo, G., Marra, A., Cattaneo, F., Secchi, M. B., Ghelfi, D., Anastasio, L., Sofia, L., Carbone, M., Davi, G., Guagnano, M. T., Sestili, S., Mancuso, G., Calipari, D., Bartone, M., Meroni, M. R., Perin, P. C., Lorenzati, B., Gruden, G., Bruno, G., Amione, C., Fornengo, P., Tassara, R., Melis, D., Rebella, L., Delitala, G., Pretti, V., Masala, M. S., Pes, C., Bolondi, L., Rasciti, L., Serio, I., Fanelli, F. R., Amoroso, A., Molfino, A., Petrillo, E., Zuccala, G., Franceschi, F., De Marco, G., Chiara, C., Marta, S., D'Aurizio, G., Romanelli, G., Amolini, C., Chiesa, D., Picardi, A., Gentilucci, U. V., Gallo, P., Annoni, G., Corsi, M., Zazzetta, S., Bellelli, G., Szabo, H., Arturi, F., Succurro, E., Rubino, M., Sesti, G., Loria, P., Becchi, M. A., Martucci, G., Fantuzzi, A., Maurantonio, M., Serra, M. G., Bleve, M. A., Gasbarrone, L., Sajeva, M. R., Brucato, A., Ghidoni, S., Di Corato, P., Agnelli, G., Marchesini, E., Fabris, F., Carlon, M., Turatto, F., Baritusso, A., Amabile, A., Omenetto, E., Scarinzi, P., Manfredini, R., Molino, C., Pala, M., Fabbian, F., Boari, B., De Giorgi, A., Paolisso, G., Rizzo, M. R., Laieta, M. T., Rini, G., Mansueto, P., Pepe, I., Borghi, C., Strocchi, E., De Sando, V., Pareo, I., Sabba, C., Vella, F. S., Suppressa, P., Valerio, R., Agosti, P., Fontana, F., Loparco, F., Capobianco, C., Fenoglio, L., Bracco, C., Giraudo, A. V., Testa, E., Serraino, C., Fargion, S., Bonara, P., Periti, G., Porzio, M., Tiraboschi, S., Peyvandi, F., Tedeschi, A., Rossio, R., Monzani, V., Savojardo, V., Folli, C., Magnini, M., Conca, A., Gobbo, G., Pallini, G., Balduini, C. L., Bertolino, G., Provini, S., Quaglia, F., Dallegri, F., Ottonello, L., Liberale, L., Chin, W. S., Carassale, L., Caporotundo, S., Traisci, G., De Feudis, L., Di Carlo, S., Liberato, N. L., Buratti, A., Tognin, T., Bianchi, G. B., Giaquinto, S., Purrello, F., Di Pino, A., Piro, S., Rozzini, R., Falanga, L., Spazzini, E., Montrucchio, G., Greco, E., Tizzani, P., Petitti, P., Perciccante, A., Coralli, A., Salmi, R., Gaudenzi, P., Gamberini, S., Semplicini, A., Gottardo, L., Vendemiale, G., Serviddio, G., Forlano, R., Masala, C., Mammarella, A., Raparelli, V., Basili, S., Perri, L., Landolfi, R., Montalto, M., Mirijello, A., Vallone, C., Bellusci, M., Setti, D., Pedrazzoli, F., Guasti, L., Castiglioni, L., Maresca, A., Squizzato, A., Molaro, M., Bertolotti, M., Mussi, C., Libbra, M. V., Miceli, A., Pellegrini, E., Carulli, L., Veltri, F., Sciacqua, A., Quero, M., Bagnato, C., Colangelo, L., Falbo, T., De Giorgio, R., Serra, M., Grasso, V., Ruggeri, E., Ilaria, B., Salvi, A., Leonardi, R., Grassini, C., Mascherona, I., Minelli, G., Maltese, F., Damiani, G., Capeci, W., Mattioli, M., Martino, G. P., Biondi, L., Ormas, M., Pettinari, P., Romiti, R., Messina, S., Cavallaro, F., Ghio, R., Favorini, S., Col, A. D., Minisola, S., Afeltra, A., Alemanno, P., Marigliano, B., Pipita, M. E., Castellino, P., Blanco, J., Zanoli, L., Cattaneo, M., Fracasso, P., Amoruso, M. V., Saracco, V., Fogliati, M., Bussolino, C., Durante, V., Eusebi, G., Tirotta, D., Mete, F., Gino, M., Cittadini, A., Vigorito, C., Arcopinto, M., Salzano, A., Bobbio, E., Marra, A. M., Sirico, D., Moreo, G., Scopelliti, F., Gasparini, F., Cocca, M., Ballestrero, A., Ferrando, F., Berra, S., Dassi, S., Nava, M. C., Graziella, B., Baldassarre, S., Fragapani, S., Galanti, G., Mascherini, G., Petri, C., Stefani, L., Girino, M., Piccinelli, V., Nasso, F., Gioffre, V., Pasquale, M., Scattolin, G., Martinelli, S., Turrin, M., Sechi, L., Catena, C., Colussi, G., Nieves, R. D., Pedro, A. R., Vanessa, L. P., Lara, T., Xavier, C. V., Francesc, F., Jesus, D. M., Esperanza, B. T., Esther, D. C. B., Maria, S. P., Romero, M., Blanca, P. L., Cristina, L. G. -C., Victoria, V. G. M., Saez, L., Bosco, J., Susana, S. B., Marta, A. G., Concepcion, G. B., Antonio, F. M., Hernandez, M. G., Borrego, M. P., Raquel, P. C., Florencia, P. R., Beatriz, G. O., Sara, C. G., Alfonso, G. -C. C., Marta, P. M., Garcia, S. C., Alberto, R. C., Antonio, A. A., Montserrat, G. G., Angel, B. R. M., Manuel, M. J., Ignacio, N. V., Lucia, A. S., Alfonso, L., David, R. B., Iria, I. V., Monica, R. P., Cesari, M, Franchi, C, Cortesi, L, Nobili, A, Ardoino, I, Mannucci, P, Tettamanti, M, Pasina, L, Perticone, F, Salerno, F, Corrao, S, Marengoni, A, Licata, G, Violi, F, Corazza, G, Eldin, T, Di Blanca, M, Lanzo, G, Astuto, S, Prisco, D, Silvestri, E, Cenci, C, Emmi, G, Biolo, G, Guarnieri, G, Zanetti, M, Fernandes, G, Chiuch, M, Vanoli, M, Grignani, G, Casella, G, Pulixi, E, Bernardi, M, Bassi, S, Santi, L, Zaccherini, G, Mannarino, E, Lupattelli, G, Bianconi, V, Paciullo, F, Nuti, R, Valenti, R, Ruvio, M, Cappelli, S, Palazzuoli, A, Salvatore, T, Sasso, F, Girelli, D, Olivieri, O, Matteazzi, T, Barbagallo, M, Plances, L, Alcamo, R, Calvo, L, Valenti, M, Zoli, M, Arno, R, Pasini, F, Capecchi, P, Bicchi, M, Palasciano, G, Modeo, M, Peragine, M, Pappagallo, F, Pugliese, S, Gennaro, C, Postiglione, A, Barbella, M, De Stefano, F, Cappellini, M, Fabio, G, Seghezzi, S, De Amicis, M, Mancarella, M, Mari, D, Rossi, P, Damanti, S, Ottolini, B, Bonini, G, Miceli, E, Lenti, M, Padula, D, Murialdo, G, Marra, A, Cattaneo, F, Secchi, M, Ghelfi, D, Anastasio, L, Sofia, L, Carbone, M, Davi, G, Guagnano, M, Sestili, S, Mancuso, G, Calipari, D, Bartone, M, Meroni, M, Perin, P, Lorenzati, B, Gruden, G, Bruno, G, Amione, C, Fornengo, P, Tassara, R, Melis, D, Rebella, L, Delitala, G, Pretti, V, Masala, M, Pes, C, Bolondi, L, Rasciti, L, Serio, I, Fanelli, F, Amoroso, A, Molfino, A, Petrillo, E, Zuccala, G, Franceschi, F, De Marco, G, Chiara, C, Marta, S, D'Aurizio, G, Romanelli, G, Amolini, C, Chiesa, D, Picardi, A, Gentilucci, U, Gallo, P, Annoni, G, Corsi, M, Zazzetta, S, Bellelli, G, Szabo, H, Arturi, F, Succurro, E, Rubino, M, Sesti, G, Loria, P, Becchi, M, Martucci, G, Fantuzzi, A, Maurantonio, M, Serra, M, Bleve, M, Gasbarrone, L, Sajeva, M, Brucato, A, Ghidoni, S, Di Corato, P, Agnelli, G, Marchesini, E, Fabris, F, Carlon, M, Turatto, F, Baritusso, A, Amabile, A, Omenetto, E, Scarinzi, P, Manfredini, R, Molino, C, Pala, M, Fabbian, F, Boari, B, De Giorgi, A, Paolisso, G, Rizzo, M, Laieta, M, Rini, G, Mansueto, P, Pepe, I, Borghi, C, Strocchi, E, De Sando, V, Pareo, I, Sabba, C, Vella, F, Suppressa, P, Valerio, R, Agosti, P, Fontana, F, Loparco, F, Capobianco, C, Fenoglio, L, Bracco, C, Giraudo, A, Testa, E, Serraino, C, Fargion, S, Bonara, P, Periti, G, Porzio, M, Tiraboschi, S, Peyvandi, F, Tedeschi, A, Rossio, R, Monzani, V, Savojardo, V, Folli, C, Magnini, M, Conca, A, Gobbo, G, Pallini, G, Balduini, C, Bertolino, G, Provini, S, Quaglia, F, Dallegri, F, Ottonello, L, Liberale, L, Chin, W, Carassale, L, Caporotundo, S, Traisci, G, De Feudis, L, Di Carlo, S, Liberato, N, Buratti, A, Tognin, T, Bianchi, G, Giaquinto, S, Purrello, F, Di Pino, A, Piro, S, Rozzini, R, Falanga, L, Spazzini, E, Montrucchio, G, Greco, E, Tizzani, P, Petitti, P, Perciccante, A, Coralli, A, Salmi, R, Gaudenzi, P, Gamberini, S, Semplicini, A, Gottardo, L, Vendemiale, G, Serviddio, G, Forlano, R, Masala, C, Mammarella, A, Raparelli, V, Basili, S, Perri, L, Landolfi, R, Montalto, M, Mirijello, A, Vallone, C, Bellusci, M, Setti, D, Pedrazzoli, F, Guasti, L, Castiglioni, L, Maresca, A, Squizzato, A, Molaro, M, Bertolotti, M, Mussi, C, Libbra, M, Miceli, A, Pellegrini, E, Carulli, L, Veltri, F, Sciacqua, A, Quero, M, Bagnato, C, Colangelo, L, Falbo, T, De Giorgio, R, Grasso, V, Ruggeri, E, Ilaria, B, Salvi, A, Leonardi, R, Grassini, C, Mascherona, I, Minelli, G, Maltese, F, Damiani, G, Capeci, W, Mattioli, M, Martino, G, Biondi, L, Ormas, M, Pettinari, P, Romiti, R, Messina, S, Cavallaro, F, Ghio, R, Favorini, S, Col, A, Minisola, S, Afeltra, A, Alemanno, P, Marigliano, B, Pipita, M, Castellino, P, Blanco, J, Zanoli, L, Cattaneo, M, Fracasso, P, Amoruso, M, Saracco, V, Fogliati, M, Bussolino, C, Durante, V, Eusebi, G, Tirotta, D, Mete, F, Gino, M, Cittadini, A, Vigorito, C, Arcopinto, M, Salzano, A, Bobbio, E, Sirico, D, Moreo, G, Scopelliti, F, Gasparini, F, Cocca, M, Ballestrero, A, Ferrando, F, Berra, S, Dassi, S, Nava, M, Graziella, B, Baldassarre, S, Fragapani, S, Galanti, G, Mascherini, G, Petri, C, Stefani, L, Girino, M, Piccinelli, V, Nasso, F, Gioffre, V, Pasquale, M, Scattolin, G, Martinelli, S, Turrin, M, Sechi, L, Catena, C, Colussi, G, Nieves, R, Alberto, M, Pedro, A, Vanessa, L, Lara, T, Xavier, C, Francesc, F, Jesus, D, Esperanza, B, Esther, D, Maria, S, Romero, M, Blanca, P, Cristina, L, Victoria, V, Saez, L, Bosco, J, Susana, S, Marta, A, Concepcion, G, Antonio, F, Hernandez, M, Borrego, M, Raquel, P, Florencia, P, Beatriz, G, Sara, C, Alfonso, G, Marta, P, Garcia, S, Alberto, R, Antonio, A, Montserrat, G, Angel, B, Manuel, M, Ignacio, N, Lucia, A, Alfonso, L, David, R, Iria, I, Monica, R, Franchi, Carlotta, Cortesi, Laura, Nobili, Alessandro, Ardoino, Ilaria, Mannucci, Pier Mannuccio, Tettamanti, Mauro, Pasina, Luca, Perticone, Francesco, Salerno, Francesco, Corrao, Salvatore, Marengoni, Alessandra, Licata, Giuseppe, Violi, Francesco, Corazza, Gino Roberto, Eldin, Tarek Kamal, Di Blanca, Maria Pia Donatella, Lanzo, Giovanna, Astuto, Sarah, Prisco, Domenico, Silvestri, Elena, Cenci, Caterina, Emmi, Giacomo, Biolo, Gianni, Guarnieri, Gianfranco, Zanetti, Michela, Fernandes, Giovanni, Chiuch, Massimiliano, Vanoli, Massimo, Grignani, Giulia, Casella, Gianluca, Pulixi, Edoardo Alessandro, Bernardi, Mauro, Bassi, Silvia Li, Santi, Luca, Zaccherini, Giacomo, Mannarino, Elmo, Lupattelli, Graziana, Bianconi, Vanessa, Paciullo, Francesco, Nuti, Ranuccio, Valenti, Roberto, Ruvio, Martina, Cappelli, Silvia, Palazzuoli, Alberto, Salvatore, Teresa, Sasso, Ferdinando Carlo, Girelli, Domenico, Olivieri, Oliviero, Matteazzi, Thoma, Barbagallo, Mario, Plances, Lidia, Alcamo, Roberta, Calvo, Luigi, Valenti, Maria, Zoli, Marco, Arnò, Raffaella, Pasini, Franco Laghi, Capecchi, Pier Leopoldo, Bicchi, Maurizio, Palasciano, Giuseppe, Modeo, Maria Ester, Peragine, Maria, Pappagallo, Fabrizio, Pugliese, Stefania, Gennaro, Carla Di, Postiglione, Alfredo, Barbella, Maria Rosaria, De Stefano, Francesco, Cappellini, Maria Domenica, Fabio, Giovanna, Seghezzi, Sonia, De Amicis, Margherita Migone, Mancarella, Marta, Mari, Daniela, Rossi, Paolo Dionigi, Damanti, Sarah, Ottolini, Barbara Brignolo, Bonini, Giulia, Miceli, Emanuela, Lenti, Marco Vincenzo, Padula, Donatella, Murialdo, Giovanni, Marra, Alessio, Cattaneo, Federico, Secchi, Maria Beatrice, Ghelfi, Davide, Anastasio, Luigi, Sofia, Lucia, Carbone, Maria, Davì, Giovanni, Guagnano, Maria Teresa, Sestili, Simona, Mancuso, Gerardo, Calipari, Daniela, Bartone, Mosè, Meroni, Maria Rachele, Perin, Paolo Cavallo, Lorenzati, Bartolomeo, Gruden, Gabriella, Bruno, Graziella, Amione, Cristina, Fornengo, Paolo, Tassara, Rodolfo, Melis, Deborah, Rebella, Lara, Delitala, Giuseppe, Pretti, Vincenzo, Masala, Maristella Salvatora, Pes, Chiara, Bolondi, Luigi, Rasciti, Leonardo, Serio, Ilaria, Fanelli, Filippo Rossi, Amoroso, Antonio, Molfino, Alessio, Petrillo, Enrico, Zuccalà, Giuseppe, Franceschi, Francesco, De Marco, Guido, Chiara, Cordischi, Marta, Sabbatini, D'Aurizio, Gabriella, Romanelli, Giuseppe, Amolini, Claudia, Chiesa, Deborah, Picardi, Antonio, Gentilucci, Umberto Vespasiani, Gallo, Paolo, Annoni, Giorgio, Corsi, Maurizio, Zazzetta, Sara, Bellelli, Giuseppe, Szabo, Hajnalka, Arturi, Franco, Succurro, Elena, Rubino, Mariangela, Sesti, Giorgio, Loria, Paola, Becchi, Maria Angela, Martucci, Gianfranco, Fantuzzi, Alessandra, Maurantonio, Mauro, Serra, Maria Grazia, Bleve, Maria Antonietta, Gasbarrone, Laura, Sajeva, Maria Rosaria, Brucato, Antonio, Ghidoni, Silvia, Di Corato, Paola, Agnelli, Giancarlo, Marchesini, Emanuela, Fabris, Fabrizio, Carlon, Michela, Turatto, Francesca, Baritusso, Aldo, Amabile, Annalisa, Omenetto, Elisabetta, Scarinzi, Paolo, Manfredini, Roberto, Molino, Christian, Pala, Marco, Fabbian, Fabio, Boari, Benedetta, De Giorgi, Alfredo, Paolisso, Giuseppe, Rizzo, Maria Rosaria, Laieta, Maria Teresa, Rini, Giovanbattista, Mansueto, Pasquale, Pepe, Ilenia, Borghi, Claudio, Strocchi, Enrico, De Sando, Valeria, Pareo, Ilaria, Sabbà, Carlo, Vella, Francesco Saverio, Suppressa, Patrizia, Valerio, Raffaella, Agosti, Pasquale, Fontana, Flavia, Loparco, Francesca, Capobianco, Caterina, Fenoglio, Luigi, Bracco, Christian, Giraudo, Alessia Valentina, Testa, Elisa, Serraino, Cristina, Fargion, Silvia, Bonara, Paola, Periti, Giulia, Porzio, Marianna, Tiraboschi, Slivia, Peyvandi, Flora, Tedeschi, Alberto, Rossio, Raffaella, Monzani, Valter, Savojardo, Valeria, Folli, Christian, Magnini, Maria, Conca, Alessio, Gobbo, Giulia, Pallini, Giada, Valenti, Miriam, Balduini, Carlo L., Bertolino, Giampiera, Provini, Stella, Quaglia, Federica, Dallegri, Franco, Ottonello, Luciano, Liberale, Luca, Chin, Wu Sheng, Carassale, Laura, Caporotundo, Silvia, Traisci, Giancarlo, De Feudis, Lucrezia, Di Carlo, Silvia, Liberato, Nicola Lucio, Buratti, Alberto, Tognin, Tiziana, Bianchi, Giovanni Battista, Giaquinto, Sabrina, Purrello, Francesco, Di Pino, Antonino, Piro, Salvatore, Rozzini, Renzo, Falanga, Lina, Spazzini, Elena, Montrucchio, Giuseppe, Greco, Elisabetta, Tizzani, Pietro, Petitti, Paolo, Perciccante, Antonio, Coralli, Alessia, Salmi, Raffaella, Gaudenzi, Piergiorgio, Gamberini, Susanna, Semplicini, Andrea, Gottardo, Lucia, Vendemiale, Gianluigi, Serviddio, Gaetano, Forlano, Roberta, Masala, Cesare, Mammarella, Antonio, Raparelli, Valeria, Basili, Stefania, Perri, Ludovica, Landolfi, Raffaele, Montalto, Massimo, Mirijello, Antonio, Vallone, Carla, Bellusci, Martino, Setti, Donatella, Pedrazzoli, Filippo, Guasti, Luigina, Castiglioni, Luana, Maresca, Andrea, Squizzato, Alessandro, Molaro, Marta, Bertolotti, Marco, Mussi, Chiara, Libbra, Maria Vittoria, Miceli, Andrea, Pellegrini, Elisa, Carulli, Lucia, Veltri, Francesca, Sciacqua, Angela, Quero, Michele, Bagnato, Chiara, Colangelo, Lidia, Falbo, Tania, De Giorgio, Roberto, Serra, Mauro, Grasso, Valentina, Ruggeri, Eugenio, Ilaria, Benzoni, Salvi, Andrea, Leonardi, Roberto, Grassini, Chiara, Mascherona, Ilenia, Minelli, Giorgio, Maltese, Francesca, Damiani, Giampaolo, Capeci, William, Mattioli, Massimo, Martino, Giuseppe Pio, Biondi, Lorenzo, Ormas, Monica, Pettinari, Pietro, Romiti, Roberto, Messina, Silvia, Cavallaro, Federica, Ghio, Riccardi, Favorini, Serena, Col, Anna Dal, Minisola, Salvatore, Colangelo, Luciano, Afeltra, Antonella, Alemanno, Pamela, Marigliano, Benedetta, Pipita, Maria Elena, Castellino, Pietro, Blanco, Julien, Zanoli, Luca, Cattaneo, Marco, Fracasso, Paola, Amoruso, Maria Valentina, Saracco, Valter, Fogliati, Marisa, Bussolino, Carlo, Durante, Vittorio, Eusebi, Giovanna, Tirotta, Daniela, Mete, Francesca, Gino, Miriam, Cittadini, Antonio, Vigorito, Carlo, Arcopinto, Michele, Salzano, Andrea, Bobbio, Emanuele, Marra, Alberto Maria, Sirico, Domenico, Moreo, Guido, Scopelliti, Francesco, Gasparini, Francesca, Cocca, Melissa, Ballestrero, Alberto, Ferrando, Fabio, Berra, Sergio, Dassi, Simonetta, Nava, Maria Cristina, Graziella, Bruno, Baldassarre, Stefano, Fragapani, Salvatore, Galanti, Giorgio, Mascherini, Gabriele, Petri, Cristian, Stefani, Laura, Girino, Margherita, Piccinelli, Valeria, Nasso, Francesco, Gioffrè, Vincenza, Pasquale, Maria, Scattolin, Giuseppe, Martinelli, Sergio, Turrin, Mauro, Sechi, Leonardo, Catena, Cristina, Colussi, Gianluca, Nieves, Ramirez Duque, Alberto, Muela Molinero, Pedro, Abad Requejo, Vanessa, Lopez Pelaez, Lara, Tamargo, Xavier, Corbella Viro, Francesc, Formiga, Jesus, Diez Manglano, Esperanza, Bejarano Tello, Esther, Del Corral Behamonte, Maria, Sevil Pura, Romero, Manuel, Blanca, Pinilla Llorente, Cristina, Lopez Gonzalez-Cobo, Victoria, Villalba Garcia M., Saez, Lopez, Bosco, Juan, Susana, Sanz Baena, Marta, Arroyo Gallego, Concepcion, Gonzalez Becerra, Antonio, Fernandez Moyano, Hernandez, Mercedes Gomez, Borrego, Manuel Poyato, Raquel, Pacheco Cuadro, Florencia, Perez Roja, Beatriz, Garcia Olid, Sara, Carrascosa Garcia, Alfonso, Gonzalez-Cruz Cervellera, Marta, Peinado Martinez, Garcia, Sara Carrascosa, Alberto, Ruiz Cantero, Antonio, Albarracín Arraigosa, Montserrat, Godoy Guerrero, Ángel, Barón Ramos Miguel, Manuel, Machin Jose, Ignacio, Novo Veleiro, Lucía, Alvela Suarez, Alfonso, Lopez, David, Rubal Bran, Iria, Iñiguez Vazquez, Monica, Rios Prego, and Alberto, M. M.
Subjects: Gerontology, Male, Multivariate analysis, Frailty, Internal medicine and geriatric wards, Multimorbidity, Physical and cognitive impairment, Internal Medicine, Psychological intervention, Predictive Value of Test, Severity of Illness Index, 0302 clinical medicine, Interquartile range, Frailty, Internal medicine and geriatric wards, Multimorbidity, Physical and cognitive impairment, 80 and over, Medicine, 030212 general & internal medicine, Prospective Studies, Hospital Mortality, Prospective cohort study, Multivariate Analysi, Aged, 80 and over, Prognosis, Aged, Female, Geriatric Assessment, Hospitalization, Humans, Italy, Multivariate Analysis, Predictive Value of Tests, Regression Analysis, Survival Analysis, Frail Elderly, Predictive value of tests, Survival Analysi, Cohort study, Human, Prognosi, Socio-culturale, Regression Analysi, 03 medical and health sciences, Severity of illness, Survival analysis, business.industry, Internal medicine and geriatric ward, Prospective Studie, business, 030217 neurology & neurosurgery
Abstract: Background Frailty is a state of increased vulnerability to stressors, associated to poor health outcomes. The aim of this study was to design and introduce a Frailty Index (FI; according to the age-related accumulation of deficit model) in a large cohort of hospitalized older persons, in order to benefit from its capacity to comprehensively weight the risk profile of the individual. Methods Patients aged 65 and older enrolled in the REPOSI register from 2010 to 2016 were considered in the present analyses. Variables recorded at the hospital admission (including socio-demographic, physical, cognitive, functional and clinical factors) were used to compute the FI. The prognostic impact of the FI on in-hospital and 12-month mortality was assessed. Results Among the 4488 patients of the REPOSI register, 3847 were considered eligible for a 34-item FI computation. The median FI in the sample was 0.27 (interquartile range 0.21–0.37). The FI was significantly predictive of both in-hospital (OR 1.61, 95%CI 1.38–1.87) and overall (HR 1.46, 95%CI 1.32–1.62) mortality, also after adjustment for age and sex. Conclusions The FI confirms its strong predictive value for negative outcomes. Its implementation in cohort studies (including those conducted in the hospital setting) may provide useful information for better weighting the complexity of the older person and accordingly design personalized interventions.
Published: 2018

25. Choice and Outcomes of Rate Control versus Rhythm Control in Elderly Patients with Atrial Fibrillation: A Report from the REPOSI Study

Author: Paciullo, Francesco, Proietti, Marco, Bianconi, Vanessa, Nobili, Alessandro, Pirro, Matteo, Mannucci, Pier Mannuccio, Lip, Gregory Y. H., Lupattelli, Graziana, Tettamanti, Mauro, Pasina, Luca, Franchi, Carlotta, Perticone, Francesco, Salerno, Francesco, Corrao, Salvatore, Marengoni, Alessandra, Licata, Giuseppe, Violi, Francesco, Corazza, Gino Roberto, Marcucci, Maura, Eldin, Tarek Kamal, Di Blanca, Maria Pia Donatella, Lanzo, Giovanna, Astuto, Sarah, Ardoino, Ilaria, Cortesi, Laura, Prisco, Domenico, Silvestri, Elena, Cenci, Caterina, Emmi, Giacomo, Biolo, Gianni, Guarnieri, Gianfranco, Zanetti, Michela, Fernandes, Giovanni, Chiuch, Massimiliano, Vanoli, Massimo, Grignani, Giulia, Casella, Gianluca, Pulixi, Edoardo Alessandro, Bernardi, Mauro, Bassi, Silvia Li, Santi, Luca, Zaccherini, Giacomo, Mannarino, Elmo, Nuti, Ranuccio, Valenti, Roberto, Ruvio, Martina, Cappelli, Silvia, Palazzuoli, Alberto, Salvatore, Teresa, Sasso, Ferdinando Carlo, Girelli, Domenico, Olivieri, Oliviero, Matteazzi, Thomas, Barbagallo, Mario, Plances, Lidia, Alcamo, Roberta, Calvo, Luigi, Valenti, Maria, Zoli, Marco, Arnò, Raffaella, Pasini, Franco Laghi, Capecchi, Pier Leopoldo, Bicchi, Maurizio, Palasciano, Giuseppe, Modeo, Maria Ester, Peragine, Maria, Pappagallo, Fabrizio, Pugliese, Stefania, Di Gennaro, Carla, Postiglione, Alfredo, Barbella, Maria Rosaria, de Stefano, Francesco, Cappellini, Maria Domenica, Fabio, Giovanna, Seghezzi, Sonia, de Amicis, Margherita Migone, Mancarella, Marta, Mari, Daniela, Rossi, Paolo Dionigi, Damanti, Sarah, Ottolini, Barbara Brignolo, Bonini, Giulia, Miceli, Emanuela, Lenti, Marco Vincenzo, Padula, Donatella, Murialdo, Giovanni, Marra, Alessio, Cattaneo, Federico, Secchi, Maria Beatrice, Ghelfi, Davide, Anastasio, Luigi, Sofia, Lucia, Carbone, Maria, Davì, Giovanni, Guagnano, Maria Teresa, Sestili, Simona, Mancuso, Gerardo, Calipari, Daniela, Bartone, Mosè, Meroni, Maria Rachele, Perin, Paolo Cavallo, Lorenzati, Bartolomeo, Gruden, Gabriella, Bruno, Graziella, Amione, Cristina, Fornengo, Paolo, Tassara, Rodolfo, Melis, Deborah, Rebella, Lara, Delitala, Giuseppe, Pretti, Vincenzo, Masala, Maristella Salvatora, Pes, Chiara, Bolondi, Luigi, Rasciti, Leonardo, Serio, Ilaria, Fanelli, Filippo Rossi, Amoroso, Antonio, Molfino, Alessio, Petrillo, Enrico, Zuccalà, Giuseppe, Franceschi, Francesco, de Marco, Guido, Chiara, Cordischi, Marta, Sabbatini, D’Aurizio, Gabriella, Romanelli, Giuseppe, Amolini, Claudia, Chiesa, Deborah, Picardi, Antonio, Gentilucci, Umberto Vespasiani, Gallo, Paolo, Annoni, Giorgio, Corsi, Maurizio, Zazzetta, Sara, Bellelli, Giuseppe, Szabo, Hajnalka, Arturi, Franco, Succurro, Elena, Rubino, Mariangela, Sesti, Giorgio, Loria, Paola, Becchi, Maria Angela, Martucci, Gianfranco, Fantuzzi, Alessandra, Maurantonio, Mauro, Serra, Maria Grazia, Bleve, Maria Antonietta, Gasbarrone, Laura, Sajeva, Maria Rosaria, Brucato, Antonio, Ghidoni, Silvia, Di Corato, Paola, Agnelli, Giancarlo, Marchesini, Emanuela, Fabris, Fabrizio, Carlon, Michela, Turatto, Francesca, Baritusso, Aldo, Amabile, Annalisa, Omenetto, Elisabetta, Scarinzi, Paolo, Manfredini, Roberto, Molino, Christian, Pala, Marco, Fabbian, Fabio, Boari, Benedetta, de Giorgi, Alfredo, Paolisso, Giuseppe, Rizzo, Maria Rosaria, Laieta, Maria Teresa, Rini, Giovanbattista, Mansueto, Pasquale, Pepe, Ilenia, Borghi, Claudio, Strocchi, Enrico, de Sando, Valeria, Pareo, Ilaria, Sabbà, Carlo, Vella, Francesco Saverio, Suppressa, Patrizia, Valerio, Raffaella, Agosti, Pasquale, Fontana, Flavia, Loparco, Francesca, Capobianco, Caterina, Fenoglio, Luigi, Bracco, Christian, Giraudo, Alessia Valentina, Testa, Elisa, Serraino, Cristina, Fargion, Silvia, Bonara, Paola, Periti, Giulia, Porzio, Marianna, Tiraboschi, Slivia, Peyvandi, Flora, Tedeschi, Alberto, Rossio, Raffaella, Ferrari, Barbara, Monzani, Valter, Savojardo, Valeria, Folli, Christian, Magnini, Maria, Conca, Alessio, Gobbo, Giulia, Pallini, Giada, Valenti, Miriam, Balduini, Carlo L., Bertolino, Giampiera, Provini, Stella, Quaglia, Federica, Dallegri, Franco, Ottonello, Luciano, Liberale, Luca, Chin, Wu Sheng, Carassale, Laura, Caporotundo, Silvia, Traisci, Giancarlo, de Feudis, Lucrezia, Di Carlo, Silvia, Liberato, Nicola Lucio, Buratti, Alberto, Tognin, Tiziana, Bianchi, Giovanni Battista, Giaquinto, Sabrina, Purrello, Francesco, Di Pino, Antonino, Piro, Salvatore, Rozzini, Renzo, Falanga, Lina, Spazzini, Elena, Montrucchio, Giuseppe, Greco, Elisabetta, Tizzani, Pietro, Petitti, Paolo, Perciccante, Antonio, Coralli, Alessia, Salmi, Raffaella, Gaudenzi, Piergiorgio, Gamberini, Susanna, Semplicini, Andrea, Gottardo, Lucia, Vendemiale, Gianluigi, Serviddio, Gaetano, Forlano, Roberta, Masala, Cesare, Mammarella, Antonio, Raparelli, Valeria, Basili, Stefania, Perri, Ludovica, Landolfi, Raffaele, Montalto, Massimo, Mirijello, Antonio, Vallone, Carla, Bellusci, Martino, Setti, Donatella, Pedrazzoli, Filippo, Guasti, Luigina, Castiglioni, Luana, Maresca, Andrea, Squizzato, Alessandro, Molaro, Marta, Bertolotti, Marco, Mussi, Chiara, Libbra, Maria Vittoria, Miceli, Andrea, Pellegrini, Elisa, Carulli, Lucia, Veltri, Francesca, Sciacqua, Angela, Quero, Michele, Bagnato, Chiara, Colangelo, Lidia, Falbo, Tania, de Giorgio, Roberto, Serra, Mauro, Grasso, Valentina, Ruggeri, Eugenio, Ilaria, Benzoni, Salvi, Andrea, Leonardi, Roberto, Grassini, Chiara, Mascherona, Ilenia, Minelli, Giorgio, Maltese, Francesca, Damiani, Giampaolo, Capeci, William, Mattioli, Massimo, Martino, Giuseppe Pio, Biondi, Lorenzo, Ormas, Monica, Pettinari, Pietro, Romiti, Roberto, Messina, Silvia, Cavallaro, Federica, Ghio, Riccardi, Favorini, Serena, Col, Anna Dal, Minisola, Salvatore, Colangelo, Luciano, Afeltra, Antonella, Alemanno, Pamela, Marigliano, Benedetta, Pipita, Maria Elena, Castellino, Pietro, Blanco, Julien, Zanoli, Luca, Cattaneo, Marco, Fracasso, Paola, Amoruso, Maria Valentina, Saracco, Valter, Fogliati, Marisa, Bussolino, Carlo, Durante, Vittorio, Eusebi, Giovanna, Tirotta, Daniela, Mete, Francesca, Gino, Miriam, Cittadini, Antonio, Vigorito, Carlo, Arcopinto, Michele, Salzano, Andrea, Bobbio, Emanuele, Marra, Alberto Maria, Sirico, Domenico, Moreo, Guido, Scopelliti, Francesco, Gasparini, Francesca, Cocca, Melissa, Ballestrero, Alberto, Ferrando, Fabio, Berra, Sergio, Dassi, Simonetta, Nava, Maria Cristina, Graziella, Bruno, Baldassarre, Stefano, Fragapani, Salvatore, Galanti, Giorgio, Mascherini, Gabriele, Petri, Cristian, Stefani, Laura, Girino, Margherita, Piccinelli, Valeria, Nasso, Francesco, Gioffrè, Vincenza, Pasquale, Maria, Scattolin, Giuseppe, Martinelli, Sergio, Turrin, Mauro, Sechi, Leonardo, Catena, Cristina, Colussi, Gianluca, Nieves, Ramirez Duque, Alberto, Muela Molinero, Pedro, Abad Requejo, Vanessa, Lopez Pelaez, Lara, Tamargo, Xavier, Corbella Viros, Francesc, Formiga, Jesus, Diez Manglano, Esperanza, Bejarano Tello, Esther, Del Corral Behamonte, Maria, Sevil Puras, Romero, Manuel, Blanca, Pinilla Llorente, Cristina, Lopez Gonzalez-Cobos, Victoria, Villalba Garcia M., Saez, Lopez, Bosco, Juan, Susana, Sanz Baena, Marta, Arroyo Gallego, Concepcion, Gonzalez Becerra, Antonio, Fernandez Moyano, Hernandez, Mercedes Gomez, Borrego, Manuel Poyato, Raquel, Pacheco Cuadros, Florencia, Perez Rojas, Beatriz, Garcia Olid, Sara, Carrascosa Garcia, Alfonso, Gonzalez-Cruz Cervellera, Marta, Peinado Martinez, Garcia, Sara Carrascosa, Alberto, Ruiz Cantero, Antonio, Albarracín Arraigosa, Montserrat, Godoy Guerrero, Ángel, Barón Ramos Miguel, Manuel, Machin Jose, Ignacio, Novo Veleiro, Lucía, Alvela Suarez, Alfonso, Lopez, David, Rubal Bran, Iria, Iñiguez Vazquez, Monica, Rios Prego, Paciullo F., Proietti M., Bianconi V., Nobili A., Pirro M., Mannucci P.M., Lip G.Y.H., Lupattelli G., Tettamanti M., Pasina L., Franchi C., Perticone F., Salerno F., Corrao S., Marengoni A., Licata G., Violi F., Corazza G.R., Marcucci M., Eldin T.K., Di Blanca M.P.D., Lanzo G., Astuto S., Ardoino I., Cortesi L., Prisco D., Silvestri E., Cenci C., Emmi G., Biolo G., Guarnieri G., Zanetti M., Fernandes G., Chiuch M., Vanoli M., Grignani G., Casella G., Pulixi E.A., Bernardi M., Bassi S.L., Santi L., Zaccherini G., Mannarino E., Nuti R., Valenti R., Ruvio M., Cappelli S., Palazzuoli A., Salvatore T., Sasso F.C., Girelli D., Olivieri O., Matteazzi T., Barbagallo M., Plances L., Alcamo R., Calvo L., Valenti M., Zoli M., Arno R., Pasini F.L., Capecchi P.L., Bicchi M., Palasciano G., Modeo M.E., Peragine M., Pappagallo F., Pugliese S., Di Gennaro C., Postiglione A., Barbella M.R., De Stefano F., Cappellini M.D., Fabio G., Seghezzi S., De Amicis M.M., Mancarella M., Mari D., Rossi P.D., Damanti S., Ottolini B.B., Bonini G., Miceli E., Lenti M.V., Padula D., Murialdo G., Marra A., Cattaneo F., Secchi M.B., Ghelfi D., Anastasio L., Sofia L., Carbone M., Davi G., Guagnano M.T., Sestili S., Mancuso G., Calipari D., Bartone M., Meroni M.R., Perin P.C., Lorenzati B., Gruden G., Bruno G., Amione C., Fornengo P., Tassara R., Melis D., Rebella L., Delitala G., Pretti V., Masala M.S., Pes C., Bolondi L., Rasciti L., Serio I., Fanelli F.R., Amoroso A., Molfino A., Petrillo E., Zuccala G., Franceschi F., De Marco G., Chiara C., Marta S., D'Aurizio G., Romanelli G., Amolini C., Chiesa D., Picardi A., Gentilucci U.V., Gallo P., Annoni G., Corsi M., Zazzetta S., Bellelli G., Szabo H., Arturi F., Succurro E., Rubino M., Sesti G., Loria P., Becchi M.A., Martucci G., Fantuzzi A., Maurantonio M., Serra M.G., Bleve M.A., Gasbarrone L., Sajeva M.R., Brucato A., Ghidoni S., Di Corato P., Agnelli G., Marchesini E., Fabris F., Carlon M., Turatto F., Baritusso A., Amabile A., Omenetto E., Scarinzi P., Manfredini R., Molino C., Pala M., Fabbian F., Boari B., De Giorgi A., Paolisso G., Rizzo M.R., Laieta M.T., Rini G., Mansueto P., Pepe I., Borghi C., Strocchi E., De Sando V., Pareo I., Sabba C., Vella F.S., Suppressa P., Valerio R., Agosti P., Fontana F., Loparco F., Capobianco C., Fenoglio L., Bracco C., Giraudo A.V., Testa E., Serraino C., Fargion S., Bonara P., Periti G., Porzio M., Tiraboschi S., Peyvandi F., Tedeschi A., Rossio R., Ferrari B., Monzani V., Savojardo V., Folli C., Magnini M., Conca A., Gobbo G., Pallini G., Balduini C.L., Bertolino G., Provini S., Quaglia F., Dallegri F., Ottonello L., Liberale L., Chin W.S., Carassale L., Caporotundo S., Traisci G., De Feudis L., Di Carlo S., Liberato N.L., Buratti A., Tognin T., Bianchi G.B., Giaquinto S., Purrello F., Di Pino A., Piro S., Rozzini R., Falanga L., Spazzini E., Montrucchio G., Greco E., Tizzani P., Petitti P., Perciccante A., Coralli A., Salmi R., Gaudenzi P., Gamberini S., Semplicini A., Gottardo L., Vendemiale G., Serviddio G., Forlano R., Masala C., Mammarella A., Raparelli V., Basili S., Perri L., Landolfi R., Montalto M., Mirijello A., Vallone C., Bellusci M., Setti D., Pedrazzoli F., Guasti L., Castiglioni L., Maresca A., Squizzato A., Molaro M., Bertolotti M., Mussi C., Libbra M.V., Miceli A., Pellegrini E., Carulli L., Veltri F., Sciacqua A., Quero M., Bagnato C., Colangelo L., Falbo T., De Giorgio R., Serra M., Grasso V., Ruggeri E., Ilaria B., Salvi A., Leonardi R., Grassini C., Mascherona I., Minelli G., Maltese F., Damiani G., Capeci W., Mattioli M., Martino G.P., Biondi L., Ormas M., Pettinari P., Romiti R., Messina S., Cavallaro F., Ghio R., Favorini S., Col A.D., Minisola S., Afeltra A., Alemanno P., Marigliano B., Pipita M.E., Castellino P., Blanco J., Zanoli L., Cattaneo M., Fracasso P., Amoruso M.V., Saracco V., Fogliati M., Bussolino C., Durante V., Eusebi G., Tirotta D., Mete F., Gino M., Cittadini A., Vigorito C., Arcopinto M., Salzano A., Bobbio E., Marra A.M., Sirico D., Moreo G., Scopelliti F., Gasparini F., Cocca M., Ballestrero A., Ferrando F., Berra S., Dassi S., Nava M.C., Graziella B., Baldassarre S., Fragapani S., Galanti G., Mascherini G., Petri C., Stefani L., Girino M., Piccinelli V., Nasso F., Gioffre V., Pasquale M., Scattolin G., Martinelli S., Turrin M., Sechi L., Catena C., Colussi G., Nieves R.D., Alberto M.M., Pedro A.R., Vanessa L.P., Lara T., Xavier C.V., Francesc F., Jesus D.M., Esperanza B.T., Esther D.C.B., Maria S.P., Romero M., Blanca P.L., Cristina L.G.-C., Victoria V.G.M., Saez L., Bosco J., Susana S.B., Marta A.G., Concepcion G.B., Antonio F.M., Hernandez M.G., Borrego M.P., Raquel P.C., Florencia P.R., Beatriz G.O., Sara C.G., Alfonso G.-C.C., Marta P.M., Garcia S.C., Alberto R.C., Antonio A.A., Montserrat G.G., Angel B.R.M., Manuel M.J., Ignacio N.V., Lucia A.S., Alfonso L., David R.B., Iria I.V., Monica R.P., Paciullo, Francesco, Proietti, Marco, Bianconi, Vanessa, Nobili, Alessandro, Pirro, Matteo, Mannucci, Pier Mannuccio, Lip, Gregory Y. H., Lupattelli, Graziana, Tettamanti, Mauro, Pasina, Luca, Franchi, Carlotta, Perticone, Francesco, Salerno, Francesco, Corrao, Salvatore, Marengoni, Alessandra, Licata, Giuseppe, Violi, Francesco, Corazza, Gino Roberto, Marcucci, Maura, Eldin, Tarek Kamal, Di Blanca, Maria Pia Donatella, Lanzo, Giovanna, Astuto, Sarah, Ardoino, Ilaria, Cortesi, Laura, Prisco, Domenico, Silvestri, Elena, Cenci, Caterina, Emmi, Giacomo, Biolo, Gianni, Guarnieri, Gianfranco, Zanetti, Michela, Fernandes, Giovanni, Chiuch, Massimiliano, Vanoli, Massimo, Grignani, Giulia, Casella, Gianluca, Pulixi, Edoardo Alessandro, Bernardi, Mauro, Bassi, Silvia Li, Santi, Luca, Zaccherini, Giacomo, Mannarino, Elmo, Nuti, Ranuccio, Valenti, Roberto, Ruvio, Martina, Cappelli, Silvia, Palazzuoli, Alberto, Salvatore, Teresa, Sasso, Ferdinando Carlo, Girelli, Domenico, Olivieri, Oliviero, Matteazzi, Thoma, Barbagallo, Mario, Plances, Lidia, Alcamo, Roberta, Calvo, Luigi, Valenti, Maria, Zoli, Marco, Arnò, Raffaella, Pasini, Franco Laghi, Capecchi, Pier Leopoldo, Bicchi, Maurizio, Palasciano, Giuseppe, Modeo, Maria Ester, Peragine, Maria, Pappagallo, Fabrizio, Pugliese, Stefania, Di Gennaro, Carla, Postiglione, Alfredo, Barbella, Maria Rosaria, de Stefano, Francesco, Cappellini, Maria Domenica, Fabio, Giovanna, Seghezzi, Sonia, de Amicis, Margherita Migone, Mancarella, Marta, Mari, Daniela, Rossi, Paolo Dionigi, Damanti, Sarah, Ottolini, Barbara Brignolo, Bonini, Giulia, Miceli, Emanuela, Lenti, Marco Vincenzo, Padula, Donatella, Murialdo, Giovanni, Marra, Alessio, Cattaneo, Federico, Secchi, Maria Beatrice, Ghelfi, Davide, Anastasio, Luigi, Sofia, Lucia, Carbone, Maria, Davì, Giovanni, Guagnano, Maria Teresa, Sestili, Simona, Mancuso, Gerardo, Calipari, Daniela, Bartone, Mosè, Meroni, Maria Rachele, Perin, Paolo Cavallo, Lorenzati, Bartolomeo, Gruden, Gabriella, Bruno, Graziella, Amione, Cristina, Fornengo, Paolo, Tassara, Rodolfo, Melis, Deborah, Rebella, Lara, Delitala, Giuseppe, Pretti, Vincenzo, Masala, Maristella Salvatora, Pes, Chiara, Bolondi, Luigi, Rasciti, Leonardo, Serio, Ilaria, Fanelli, Filippo Rossi, Amoroso, Antonio, Molfino, Alessio, Petrillo, Enrico, Zuccalà, Giuseppe, Franceschi, Francesco, de Marco, Guido, Chiara, Cordischi, Marta, Sabbatini, D’Aurizio, Gabriella, Romanelli, Giuseppe, Amolini, Claudia, Chiesa, Deborah, Picardi, Antonio, Gentilucci, Umberto Vespasiani, Gallo, Paolo, Annoni, Giorgio, Corsi, Maurizio, Zazzetta, Sara, Bellelli, Giuseppe, Szabo, Hajnalka, Arturi, Franco, Succurro, Elena, Rubino, Mariangela, Sesti, Giorgio, Loria, Paola, Becchi, Maria Angela, Martucci, Gianfranco, Fantuzzi, Alessandra, Maurantonio, Mauro, Serra, Maria Grazia, Bleve, Maria Antonietta, Gasbarrone, Laura, Sajeva, Maria Rosaria, Brucato, Antonio, Ghidoni, Silvia, Di Corato, Paola, Agnelli, Giancarlo, Marchesini, Emanuela, Fabris, Fabrizio, Carlon, Michela, Turatto, Francesca, Baritusso, Aldo, Amabile, Annalisa, Omenetto, Elisabetta, Scarinzi, Paolo, Manfredini, Roberto, Molino, Christian, Pala, Marco, Fabbian, Fabio, Boari, Benedetta, de Giorgi, Alfredo, Paolisso, Giuseppe, Rizzo, Maria Rosaria, Laieta, Maria Teresa, Rini, Giovanbattista, Mansueto, Pasquale, Pepe, Ilenia, Borghi, Claudio, Strocchi, Enrico, de Sando, Valeria, Pareo, Ilaria, Sabbà, Carlo, Vella, Francesco Saverio, Suppressa, Patrizia, Valerio, Raffaella, Agosti, Pasquale, Fontana, Flavia, Loparco, Francesca, Capobianco, Caterina, Fenoglio, Luigi, Bracco, Christian, Giraudo, Alessia Valentina, Testa, Elisa, Serraino, Cristina, Fargion, Silvia, Bonara, Paola, Periti, Giulia, Porzio, Marianna, Tiraboschi, Slivia, Peyvandi, Flora, Tedeschi, Alberto, Rossio, Raffaella, Ferrari, Barbara, Monzani, Valter, Savojardo, Valeria, Folli, Christian, Magnini, Maria, Conca, Alessio, Gobbo, Giulia, Pallini, Giada, Valenti, Miriam, Balduini, Carlo L., Bertolino, Giampiera, Provini, Stella, Quaglia, Federica, Dallegri, Franco, Ottonello, Luciano, Liberale, Luca, Chin, Wu Sheng, Carassale, Laura, Caporotundo, Silvia, Traisci, Giancarlo, de Feudis, Lucrezia, Di Carlo, Silvia, Liberato, Nicola Lucio, Buratti, Alberto, Tognin, Tiziana, Bianchi, Giovanni Battista, Giaquinto, Sabrina, Purrello, Francesco, Di Pino, Antonino, Piro, Salvatore, Rozzini, Renzo, Falanga, Lina, Spazzini, Elena, Montrucchio, Giuseppe, Greco, Elisabetta, Tizzani, Pietro, Petitti, Paolo, Perciccante, Antonio, Coralli, Alessia, Salmi, Raffaella, Gaudenzi, Piergiorgio, Gamberini, Susanna, Semplicini, Andrea, Gottardo, Lucia, Vendemiale, Gianluigi, Serviddio, Gaetano, Forlano, Roberta, Masala, Cesare, Mammarella, Antonio, Raparelli, Valeria, Basili, Stefania, Perri, Ludovica, Landolfi, Raffaele, Montalto, Massimo, Mirijello, Antonio, Vallone, Carla, Bellusci, Martino, Setti, Donatella, Pedrazzoli, Filippo, Guasti, Luigina, Castiglioni, Luana, Maresca, Andrea, Squizzato, Alessandro, Molaro, Marta, Bertolotti, Marco, Mussi, Chiara, Libbra, Maria Vittoria, Miceli, Andrea, Pellegrini, Elisa, Carulli, Lucia, Veltri, Francesca, Sciacqua, Angela, Quero, Michele, Bagnato, Chiara, Colangelo, Lidia, Falbo, Tania, de Giorgio, Roberto, Serra, Mauro, Grasso, Valentina, Ruggeri, Eugenio, Ilaria, Benzoni, Salvi, Andrea, Leonardi, Roberto, Grassini, Chiara, Mascherona, Ilenia, Minelli, Giorgio, Maltese, Francesca, Damiani, Giampaolo, Capeci, William, Mattioli, Massimo, Martino, Giuseppe Pio, Biondi, Lorenzo, Ormas, Monica, Pettinari, Pietro, Romiti, Roberto, Messina, Silvia, Cavallaro, Federica, Ghio, Riccardi, Favorini, Serena, Col, Anna Dal, Minisola, Salvatore, Colangelo, Luciano, Afeltra, Antonella, Alemanno, Pamela, Marigliano, Benedetta, Pipita, Maria Elena, Castellino, Pietro, Blanco, Julien, Zanoli, Luca, Cattaneo, Marco, Fracasso, Paola, Amoruso, Maria Valentina, Saracco, Valter, Fogliati, Marisa, Bussolino, Carlo, Durante, Vittorio, Eusebi, Giovanna, Tirotta, Daniela, Mete, Francesca, Gino, Miriam, Cittadini, Antonio, Vigorito, Carlo, Arcopinto, Michele, Salzano, Andrea, Bobbio, Emanuele, Marra, Alberto Maria, Sirico, Domenico, Moreo, Guido, Scopelliti, Francesco, Gasparini, Francesca, Cocca, Melissa, Ballestrero, Alberto, Ferrando, Fabio, Berra, Sergio, Dassi, Simonetta, Nava, Maria Cristina, Graziella, Bruno, Baldassarre, Stefano, Fragapani, Salvatore, Galanti, Giorgio, Mascherini, Gabriele, Petri, Cristian, Stefani, Laura, Girino, Margherita, Piccinelli, Valeria, Nasso, Francesco, Gioffrè, Vincenza, Pasquale, Maria, Scattolin, Giuseppe, Martinelli, Sergio, Turrin, Mauro, Sechi, Leonardo, Catena, Cristina, Colussi, Gianluca, Nieves, Ramirez Duque, Alberto, Muela Molinero, Pedro, Abad Requejo, Vanessa, Lopez Pelaez, Lara, Tamargo, Xavier, Corbella Viro, Francesc, Formiga, Jesus, Diez Manglano, Esperanza, Bejarano Tello, Esther, Del Corral Behamonte, Maria, Sevil Pura, Romero, Manuel, Blanca, Pinilla Llorente, Cristina, Lopez Gonzalez-Cobo, Victoria, Villalba Garcia M., Saez, Lopez, Bosco, Juan, Susana, Sanz Baena, Marta, Arroyo Gallego, Concepcion, Gonzalez Becerra, Antonio, Fernandez Moyano, Hernandez, Mercedes Gomez, Borrego, Manuel Poyato, Raquel, Pacheco Cuadro, Florencia, Perez Roja, Beatriz, Garcia Olid, Sara, Carrascosa Garcia, Alfonso, Gonzalez-Cruz Cervellera, Marta, Peinado Martinez, Garcia, Sara Carrascosa, Alberto, Ruiz Cantero, Antonio, Albarracín Arraigosa, Montserrat, Godoy Guerrero, Ángel, Barón Ramos Miguel, Manuel, Machin Jose, Ignacio, Novo Veleiro, Lucía, Alvela Suarez, Alfonso, Lopez, David, Rubal Bran, Iria, Iñiguez Vazquez, Monica, Rios Prego, De Stefano, Francesco, De Amicis, Margherita Migone, De Marco, Guido, De Giorgi, Alfredo, De Sando, Valeria, De Feudis, Lucrezia, De Giorgio, Roberto, Mannucci, Pm, Nobili, A, Tettamanti, M, Pasina, L, Franchi, C, Perticone, F, Salerno, F, Corrao, S, Marengoni, A, Licata, G, Violi, F, Corazza, Gr, Marcucci, M, Eldin, Tk, Di Blanca, Mpd, Lanzo, G, Astuto, S, Ardoino, I, Cortesi, L, Prisco, D, Silvestri, E, Cenci, C, Emmi, G, Biolo, G, Guarnieri, G, Zanetti, M, Fernandes, G, Chiuch, M, Vanoli, M, Grignani, G, Casella, G, Pulixi, Ea, Bernardi, M, Bassi, Sl, Santi, L, Zaccherini, G, Mannarino, E, Lupattelli, G, Bianconi, V, Paciullo, F, Nuti, R, Valenti, R, Ruvio, M, Cappelli, S, Palazzuoli, A, Salvatore, T, Sasso, Fc, Girelli, D, Olivieri, O, Matteazzi, T, Barbagallo, M, Plances, L, Alcamo, R, Calvo, L, Valenti, M, Zoli, M, Arnò, R, Pasini, Fl, Capecchi, Pl, Bicchi, M, Palasciano, G, Modeo, Me, Peragine, M, Pappagallo, F, Pugliese, S, Di Gennaro, C, Postiglione, A, Barbella, Mr, De Stefano, F, Cappellini, Md, Fabio, G, Seghezzi, S, De Amicis, Mm, Mancarella, M, Mari, D, Rossi, Pd, Damanti, S, Ottolini, Bb, Bonini, G, Miceli, E, Lenti, Mv, Padula, D, Murialdo, G, Marra, A, Cattaneo, F, Secchi, Mb, Ghelfi, D, Anastasio, L, Sofia, L, Carbone, M, Davì, G, Guagnano, Mt, Sestili, S, Mancuso, G, Calipari, D, Bartone, M, Meroni, Mr, Perin, Pc, Lorenzati, B, Gruden, G, Bruno, G, Amione, C, Fornengo, P, Tassara, R, Melis, D, Rebella, L, Delitala, G, Pretti, V, Masala, M, Pes, C, Bolondi, L, Rasciti, L, Serio, I, Fanelli, Fr, Amoroso, A, Molfino, A, Petrillo, E, Zuccalà, G, Franceschi, F, De Marco, G, Chiara, C, Marta, S, D'Aurizio, G, Romanelli, G, Amolini, C, Chiesa, D, Picardi, A, Gentilucci, Uv, Gallo, P, Annoni, G, Corsi, M, Zazzetta, S, Bellelli, G, Szabo, H, Arturi, F, Succurro, E, Rubino, M, Sesti, G, Loria, P, Becchi, Ma, Martucci, G, Fantuzzi, A, Maurantonio, M, Serra, Mg, Bleve, Ma, Gasbarrone, L, Sajeva, Mr, Brucato, A, Ghidoni, S, Di Corato, P, Agnelli, G, Marchesini, E, Fabris, F, Carlon, M, Turatto, F, Baritusso, A, Amabile, A, Omenetto, E, Scarinzi, P, Manfredini, R, Molino, C, Pala, M, Fabbian, F, Boari, B, De Giorgi, A, Paolisso, G, Rizzo, Mr, Laieta, Mt, Rini, G, Mansueto, P, Pepe, I, Borghi, C, Strocchi, E, De Sando, V, Pareo, I, Sabbà, C, Vella, F, Suppressa, P, Valerio, R, Agosti, P, Fontana, F, Loparco, F, Capobianco, C, Fenoglio, L, Bracco, C, Giraudo, Av, Testa, E, Serraino, C, Fargion, S, Bonara, P, Periti, G, Porzio, M, Tiraboschi, S, Peyvandi, F, Tedeschi, A, Rossio, R, Ferrari, B, Monzani, V, Savojardo, V, Folli, C, Magnini, M, Conca, A, Gobbo, G, Pallini, G, Balduini, Cl, Bertolino, G, Provini, S, Quaglia, F, Dallegri, F, Ottonello, L, Liberale, L, Chin, W, Carassale, L, Caporotundo, S, Traisci, G, De Feudis, L, Di Carlo, S, Liberato, Nl, Buratti, A, Tognin, T, Bianchi, Gb, Giaquinto, S, Purrello, F, Di Pino, A, Piro, S, Rozzini, R, Falanga, L, Spazzini, E, Montrucchio, G, Greco, E, Tizzani, P, Petitti, P, Perciccante, A, Coralli, A, Salmi, R, Gaudenzi, P, Gamberini, S, Semplicini, A, Gottardo, L, Vendemiale, G, Serviddio, G, Forlano, R, Masala, C, Mammarella, A, Raparelli, V, Basili, S, Perri, L, Landolfi, R, Montalto, M, Mirijello, A, Vallone, C, Bellusci, M, Setti, D, Pedrazzoli, F, Guasti, L, Castiglioni, L, Maresca, A, Squizzato, A, Molaro, M, Bertolotti, M, Mussi, C, Libbra, Mv, Miceli, A, Pellegrini, E, Carulli, L, Veltri, F, Sciacqua, A, Quero, M, Bagnato, C, Colangelo, L, Falbo, T, De Giorgio, R, Serra, M, Grasso, V, Ruggeri, E, Ilaria, B, Salvi, A, Leonardi, R, Grassini, C, Mascherona, I, Minelli, G, Maltese, F, Damiani, G, Capeci, W, Mattioli, M, Martino, Gp, Biondi, L, Ormas, M, Pettinari, P, Romiti, R, Messina, S, Cavallaro, F, Ghio, R, Favorini, S, Col, Ad, Minisola, S, Afeltra, A, Alemanno, P, Marigliano, B, Pipita, Me, Castellino, P, Blanco, J, Zanoli, L, Cattaneo, M, Fracasso, P, Amoruso, Mv, Saracco, V, Fogliati, M, Bussolino, C, Durante, V, Eusebi, G, Tirotta, D, Mete, F, Gino, M, Cittadini, A, Vigorito, C, Arcopinto, M, Salzano, A, Bobbio, E, Marra, Am, Sirico, D, Moreo, G, Scopelliti, F, Gasparini, F, Cocca, M, Ballestrero, A, Ferrando, F, Berra, S, Dassi, S, Nava, Mc, Graziella, B, Baldassarre, S, Fragapani, S, Galanti, G, Mascherini, G, Petri, C, Stefani, L, Girino, M, Piccinelli, V, Nasso, F, Gioffrè, V, Pasquale, M, Scattolin, G, Martinelli, S, Turrin, M, Sechi, L, Catena, C, Colussi, G, Nieves, Rd, Alberto, Mm, Pedro, Ar, Vanessa, Lp, Lara, T, Xavier, Cv, Francesc, F, Jesus, Dm, Esperanza, Bt, Esther, Dcb, Maria, Sp, Romero, M, Blanca, Pl, Cristina, Lg, Victoria, Vgm, Saez, L, Bosco, J, Susana, Sb, Marta, Ag, Concepcion, Gb, Antonio, Fm, Hernandez, Mg, Borrego, Mp, Raquel, Pc, Florencia, Pr, Beatriz, Go, Sara, Cg, Alfonso, Gc, Marta, Pm, Garcia, Sc, Alberto, Rc, Antonio, Aa, Montserrat, Gg, Ángel, Brm, Manuel, Mj, Ignacio, Nv, Lucía, A, Alfonso, L, David, Rb, Iria, Iv, Monica, Rp., Paciullo, F., Proietti, M., Bianconi, V., Nobili, A., Pirro, M., Mannucci, P. M., Lip, G. Y. H., Lupattelli, G., Tettamanti, M., Pasina, L., Franchi, C., Perticone, F., Salerno, F., Corrao, S., Marengoni, A., Licata, G., Violi, F., Corazza, G. R., Marcucci, M., Eldin, T. K., Di Blanca, M. P. D., Lanzo, G., Astuto, S., Ardoino, I., Cortesi, L., Prisco, D., Silvestri, E., Cenci, C., Emmi, G., Biolo, G., Guarnieri, G., Zanetti, M., Fernandes, G., Chiuch, M., Vanoli, M., Grignani, G., Casella, G., Pulixi, E. A., Bernardi, M., Bassi, S. L., Santi, L., Zaccherini, G., Mannarino, E., Nuti, R., Valenti, R., Ruvio, M., Cappelli, S., Palazzuoli, A., Salvatore, T., Sasso, F. C., Girelli, D., Olivieri, O., Matteazzi, T., Barbagallo, M., Plances, L., Alcamo, R., Calvo, L., Valenti, M., Zoli, M., Arno, R., Pasini, F. L., Capecchi, P. L., Bicchi, M., Palasciano, G., Modeo, M. E., Peragine, M., Pappagallo, F., Pugliese, S., Di Gennaro, C., Postiglione, A., Barbella, M. R., De Stefano, F., Cappellini, M. D., Fabio, G., Seghezzi, S., De Amicis, M. M., Mancarella, M., Mari, D., Rossi, P. D., Damanti, S., Ottolini, B. B., Bonini, G., Miceli, E., Lenti, M. V., Padula, D., Murialdo, G., Marra, A., Cattaneo, F., Secchi, M. B., Ghelfi, D., Anastasio, L., Sofia, L., Carbone, M., Davi, G., Guagnano, M. T., Sestili, S., Mancuso, G., Calipari, D., Bartone, M., Meroni, M. R., Perin, P. C., Lorenzati, B., Gruden, G., Bruno, G., Amione, C., Fornengo, P., Tassara, R., Melis, D., Rebella, L., Delitala, G., Pretti, V., Masala, M. S., Pes, C., Bolondi, L., Rasciti, L., Serio, I., Fanelli, F. R., Amoroso, A., Molfino, A., Petrillo, E., Zuccala, G., Franceschi, F., De Marco, G., Chiara, C., Marta, S., D'Aurizio, G., Romanelli, G., Amolini, C., Chiesa, D., Picardi, A., Gentilucci, U. V., Gallo, P., Annoni, G., Corsi, M., Zazzetta, S., Bellelli, G., Szabo, H., Arturi, F., Succurro, E., Rubino, M., Sesti, G., Loria, P., Becchi, M. A., Martucci, G., Fantuzzi, A., Maurantonio, M., Serra, M. G., Bleve, M. A., Gasbarrone, L., Sajeva, M. R., Brucato, A., Ghidoni, S., Di Corato, P., Agnelli, G., Marchesini, E., Fabris, F., Carlon, M., Turatto, F., Baritusso, A., Amabile, A., Omenetto, E., Scarinzi, P., Manfredini, R., Molino, C., Pala, M., Fabbian, F., Boari, B., De Giorgi, A., Paolisso, G., Rizzo, M. R., Laieta, M. T., Rini, G., Mansueto, P., Pepe, I., Borghi, C., Strocchi, E., De Sando, V., Pareo, I., Sabba, C., Vella, F. S., Suppressa, P., Valerio, R., Agosti, P., Fontana, F., Loparco, F., Capobianco, C., Fenoglio, L., Bracco, C., Giraudo, A. V., Testa, E., Serraino, C., Fargion, S., Bonara, P., Periti, G., Porzio, M., Tiraboschi, S., Peyvandi, F., Tedeschi, A., Rossio, R., Ferrari, B., Monzani, V., Savojardo, V., Folli, C., Magnini, M., Conca, A., Gobbo, G., Pallini, G., Balduini, C. L., Bertolino, G., Provini, S., Quaglia, F., Dallegri, F., Ottonello, L., Liberale, L., Chin, W. S., Carassale, L., Caporotundo, S., Traisci, G., De Feudis, L., Di Carlo, S., Liberato, N. L., Buratti, A., Tognin, T., Bianchi, G. B., Giaquinto, S., Purrello, F., Di Pino, A., Piro, S., Rozzini, R., Falanga, L., Spazzini, E., Montrucchio, G., Greco, E., Tizzani, P., Petitti, P., Perciccante, A., Coralli, A., Salmi, R., Gaudenzi, P., Gamberini, S., Semplicini, A., Gottardo, L., Vendemiale, G., Serviddio, G., Forlano, R., Masala, C., Mammarella, A., Raparelli, V., Basili, S., Perri, L., Landolfi, R., Montalto, M., Mirijello, A., Vallone, C., Bellusci, M., Setti, D., Pedrazzoli, F., Guasti, L., Castiglioni, L., Maresca, A., Squizzato, A., Molaro, M., Bertolotti, M., Mussi, C., Libbra, M. V., Miceli, A., Pellegrini, E., Carulli, L., Veltri, F., Sciacqua, A., Quero, M., Bagnato, C., Colangelo, L., Falbo, T., De Giorgio, R., Serra, M., Grasso, V., Ruggeri, E., Ilaria, B., Salvi, A., Leonardi, R., Grassini, C., Mascherona, I., Minelli, G., Maltese, F., Damiani, G., Capeci, W., Mattioli, M., Martino, G. P., Biondi, L., Ormas, M., Pettinari, P., Romiti, R., Messina, S., Cavallaro, F., Ghio, R., Favorini, S., Col, A. D., Minisola, S., Afeltra, A., Alemanno, P., Marigliano, B., Pipita, M. E., Castellino, P., Blanco, J., Zanoli, L., Cattaneo, M., Fracasso, P., Amoruso, M. V., Saracco, V., Fogliati, M., Bussolino, C., Durante, V., Eusebi, G., Tirotta, D., Mete, F., Gino, M., Cittadini, A., Vigorito, C., Arcopinto, M., Salzano, A., Bobbio, E., Marra, A. M., Sirico, D., Moreo, G., Scopelliti, F., Gasparini, F., Cocca, M., Ballestrero, A., Ferrando, F., Berra, S., Dassi, S., Nava, M. C., Graziella, B., Baldassarre, S., Fragapani, S., Galanti, G., Mascherini, G., Petri, C., Stefani, L., Girino, M., Piccinelli, V., Nasso, F., Gioffre, V., Pasquale, M., Scattolin, G., Martinelli, S., Turrin, M., Sechi, L., Catena, C., Colussi, G., Nieves, R. D., Alberto, M. M., Pedro, A. R., Vanessa, L. P., Lara, T., Xavier, C. V., Francesc, F., Jesus, D. M., Esperanza, B. T., Esther, D. C. B., Maria, S. P., Romero, M., Blanca, P. L., Cristina, L. G. -C., Victoria, V. G. M., Saez, L., Bosco, J., Susana, S. B., Marta, A. G., Concepcion, G. B., Antonio, F. M., Hernandez, M. G., Borrego, M. P., Raquel, P. C., Florencia, P. R., Beatriz, G. O., Sara, C. G., Alfonso, G. -C. C., Marta, P. M., Garcia, S. C., Alberto, R. C., Antonio, A. A., Montserrat, G. G., Angel, B. R. M., Manuel, M. J., Ignacio, N. V., Lucia, A. S., Alfonso, L., David, R. B., Iria, I. V., Monica, R. P., Proietti, M, Pirro, M, Mannucci, P, Lip, G, Corazza, G, Eldin, T, Di Blanca, M, Pulixi, E, Bassi, S, Sasso, F, Pasini, F, Capecchi, P, Modeo, M, Barbella, M, de Stefano, F, Cappellini, M, de Amicis, M, Rossi, P, Ottolini, B, Lenti, M, Secchi, M, Guagnano, M, Meroni, M, Perin, P, Fanelli, F, de Marco, G, D’Aurizio, G, Gentilucci, U, Becchi, M, Bleve, M, Sajeva, M, de Giorgi, A, Rizzo, M, Laieta, M, de Sando, V, Giraudo, A, Balduini, C, de Feudis, L, Liberato, N, Bianchi, G, Libbra, M, de Giorgio, R, Martino, G, Col, A, Pipita, M, Amoruso, M, Nava, M, Nieves, R, Alberto, M, Pedro, A, Vanessa, L, Xavier, C, Jesus, D, Esperanza, B, Esther, D, Maria, S, Blanca, P, Cristina, L, Victoria, V, Susana, S, Marta, A, Concepcion, G, Antonio, F, Hernandez, M, Borrego, M, Raquel, P, Florencia, P, Beatriz, G, Sara, C, Alfonso, G, Marta, P, Garcia, S, Alberto, R, Antonio, A, Montserrat, G, Ángel, B, Manuel, M, Ignacio, N, David, R, Iria, I, and Monica, R
Subjects: Male, Anti-Arrhythmia Agents/therapeutic use, antiarrhythmic agent, Comorbidity, Aged, Aged, 80 and over, Anti-Arrhythmia Agents, Atrial Fibrillation, Diabetes Mellitus, Female, Heart Failure, Heart Rate, Hospitalization, Humans, Odds Ratio, Polypharmacy, Prevalence, Geriatrics and Gerontology, Pharmacology (medical), 030204 cardiovascular system & hematology, anticoagulant agent, Diabetes Mellitus/drug therapy, 0302 clinical medicine, 80 and over, 030212 general & internal medicine, LS4_4, antiarrhythmic agent, anticoagulant agent, antithrombocytic agent, calcium channel blocking agent, digoxin, Heart Rate/drug effects, Diabetes Mellitu, Atrial fibrillation, antithrombocytic agent, digoxin, Anti-Arrhythmia Agent, Human, medicine.medical_specialty, Socio-culturale, 03 medical and health sciences, Internal medicine, Diabetes mellitus, Heart rate, calcium channel blocking agent, medicine, business.industry, Atrial Fibrillation/drug therapy, Odds ratio, medicine.disease, Heart Failure/drug therapy, Confidence interval, Heart failure, business
Abstract: Background: Among rate-control or rhythm-control strategies, there is conflicting evidence as to which is the best management approach for non-valvular atrial fibrillation (AF) in elderly patients. Design: We performed an ancillary analysis from the ‘Registro Politerapie SIMI’ study, enrolling elderly inpatients from internal medicine and geriatric wards. Methods: We considered patients enrolled from 2008 to 2014 with an AF diagnosis at admission, treated with a rate-control-only or rhythm-control-only strategy. Results: Among 1114 patients, 241 (21.6%) were managed with observation only and 122 (11%) were managed with both the rate- and rhythm-control approaches. Of the remaining 751 patients, 626 (83.4%) were managed with a rate-control-only strategy and 125 (16.6%) were managed with a rhythm-control-only strategy. Rate-control-managed patients were older (p=0.002), had a higher Short Blessed Test (SBT; p=0.022) and a lower Barthel Index (p=0.047). Polypharmacy (p=0.001), heart failure (p=0.005) and diabetes (p=0.016) were more prevalent among these patients. Median CHA2DS2-VASc score was higher among rate-control-managed patients (p=0.001). SBT [odds ratio (OR) 0.97, 95% confidence interval (CI) 0.94–1.00, p=0.037], diabetes (OR 0.48, 95% CI 0.26–0.87, p=0.016) and polypharmacy (OR 0.58, 95% CI 0.34–0.99, p=0.045) were negatively associated with a rhythm-control strategy. At follow-up, no difference was found between rate- and rhythm-control strategies for cardiovascular (CV) and all-cause deaths (6.1 vs. 5.6%, p=0.89; and 15.9 vs. 14.1%, p=0.70, respectively). Conclusion: A rate-control strategy is the most widely used among elderly AF patients with multiple comorbidities and polypharmacy. No differences were evident in CV death and all-cause death at follow-up.
Published: 2018
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26. Risk factors for three-month mortality after discharge in a cohort of non-oncologic hospitalized elderly patients: Results from the REPOSI study

Author: Luca, Pasina, Laura, Cortesi, Mara, Tiraboschi, Alessandro, Nobili, Giovanna, Lanzo, Mauro, Tettamanti, Carlotta, Franchi, Pier Mannuccio Mannucci, Silvia, Ghidoni, Andrea, Assolari, Antonio, Brucato, Domenico, Prisco, Elena, Silvestri, Caterina, Cenci, Giacomo, Emmi, Gianni, Biolo, Gianfranco, Guarnieri, Michela, Zanetti, Giovanni, Fernandes, Massimo, Vanoli, Giulia, Grignani, Gianluca, Casella, Mauro, Bernardi, Silvia Li Bassi, Luca, Santi, Giacomo, Zaccherini, Elmo, Mannarino, Graziana, Lupattelli, Vanessa, Bianconi, Francesco, Paciullo, Ranuccio, Nuti, Roberto, Valenti, Martina, Ruvio, Silvia, Cappelli, Alberto, Palazzuoli, Teresa, Salvatore, Ferdinando Carlo Sasso, Domenico, Girelli, Oliviero, Olivieri, Thomas, Matteazzi, Mario, Barbagallo, Lidia, Plances, Roberta, Alcamo, Giuseppe, Licata, Luigi, Calvo, Maria, Valenti, Marco, Zoli, Raffaella, Arnò, Franco Laghi Pasini, Pier Leopoldo Capecchi, Maurizio, Bicchi, Giuseppe, Palasciano, Maria Ester Modeo, Maria, Peragine, Fabrizio, Pappagallo, Stefania, Pugliese, Carla Di Gennaro, Alfredo, Postiglione, Maria Rosaria Barbella, Francesco De Stefano, Maria Domenica Cappellini, Giovanna, Fabio, Sonia, Seghezzi, Margherita Migone De Amicis, Daniela, Mari, Paolo Dionigi Rossi, Sarah, Damanti, Barbara Brignolo Ottolini, Gino Roberto Corazza, Emanuela, Miceli, Marco Vincenzo Lenti, Donatella, Padula, Giovanni, Murialdo, Alessio, Marra, Federico, Cattaneo, Maria Beatrice Secchi, Davide, Ghelfi, Luigi, Anastasio, Lucia, Sofia, Maria, Carbone, Giovanni, Davì, Maria Teresa Guagnano, Simona, Sestili, Gerardo, Mancuso, Daniela, Calipari, Mosè, Bartone, Maria Rachele Meroni, Paolo Cavallo Perin, Bartolomeo, Lorenzati, Gabriella, Gruden, Graziella, Bruno, Cristina, Amione, Paolo, Fornengo, Rodolfo, Tassara, Deborah, Melis, Lara, Rebella, Giuseppe, Delitala, Vincenzo, Pretti, Maristella Salvatora Masala, Luigi, Bolondi, Leonardo, Rasciti, Ilaria, Serio, Filippo Rossi Fanelli, Antonio, Amoroso, Alessio, Molfino, Enrico, Petrillo, Giuseppe, Zuccalà, Francesco, Franceschi, Guido De Marco, Cordischi, Chiara, Sabbatini, Marta, Giuseppe, Romanelli, Claudia, Amolini, Deborah, Chiesa, Alessandra, Marengoni, Antonio, Picardi, Umberto Vespasiani Gentilucci, Paolo, Gallo, Giorgio, Annoni, Maurizio, Corsi, Sara, Zazzetta, Giuseppe, Bellelli, Franco, Arturi, Elena, Succurro, Mariangela, Rubino, Giorgio, Sesti, Paola, Loria, Maria Angela Becchi, Gianfranco, Martucci, Alessandra, Fantuzzi, Mauro, Maurantonio, Stefano, Carta, Sebastiana, Atzori, Maria Grazia Serra, Maria Antonietta Bleve, Laura, Gasbarrone, Maria Rosaria Sajeva, Paola Di Corato, Giancarlo, Agnelli, Emanuela, Marchesini, Fabrizio, Fabris, Michela, Carlon, Francesca, Turatto, Aldo, Baritusso, Manfredini, Roberto, Christian, Molino, Marco, Pala, Fabbian, Fabio, Benedetta, Boari, Alfredo De Giorgi, Giuseppe, Paolisso, Maria Rosaria Rizzo, Maria Teresa Laieta, Giovanbattista, Rini, Pasquale, Mansueto, Ilenia, Pepe, Claudio, Borghi, Enrico, Strocchi, Valeria De Sando, Carlo, Sabbà, Francesco Saverio Vella, Patrizia, Suppressa, Raffaella, Valerio, Caterina, Capobianco, Luigi, Fenoglio, Christian, Bracco, Alessia Valentina Giraudo, Elisa, Testa, Cristina, Serraino, Silvia, Fargion, Paola, Bonara, Giulia, Periti, Marianna, Porzio, Flora, Peyvandi, Alberto, Tedeschi, Raffaella, Rossio, Valter, Monzani, Valeria, Savojardo, Christian, Folli, Maria, Magnini, Francesco, Salerno, Alessio, Conca, Giulia, Gobbo, Balduini, Carlo L., Giampiera, Bertolino, Stella, Provini, Federica, Quaglia, Franco, Dallegri, Luciano, Ottonello, Luca, Liberale, Wu Sheng Chin, Laura, Carassale, Silvia, Caporotundo, Giancarlo, Traisci, Lucrezia De Feudis, Silvia Di Carlo, Nicola Lucio Liberato, Alberto, Buratti, Tiziana, Tognin, Giovanni Battista Bianchi, Sabrina, Giaquinto, Francesco, Purrello, Antonino Di Pino, Salvatore, Piro, Renzo, Rozzini, Lina, Falanga, Giuseppe, Montrucchio, Elisabetta, Greco, Pietro, Tizzani, Paolo, Petitti, Antonio, Perciccante, Alessia, Coralli, Raffaella, Salmi, Piergiorgio, Gaudenzi, Susanna, Gamberini, Andrea, Semplicini, Lucia, Gottardo, Gianluigi, Vendemiale, Gaetano, Serviddio, Roberta, Forlano, Cesare, Masala, Antonio, Mammarella, Raparelli, Valeria, Francesco, Violi, Stefania, Basili, Ludovica, Perri, Raffaele, Landolfi, Massimo, Montalto, Antonio, Mirijello, Carla, Vallone, Martino, Bellusci, Donatella, Setti, Filippo, Pedrazzoli, Luigina, Guasti, Luana, Castiglioni, Andrea, Maresca, Alessandro, Squizzato, Marta, Molaro, Marco, Bertolotti, Chiara, Mussi, Maria Vittoria Libbra, Andrea, Miceli, Elisa, Pellegrini, Lucia, Carulli, Francesco, Perticone, Angela, Sciacqua, Michele, Quero, Chiara, Bagnato, Roberto, Corinaldesi, DE GIORGIO, Roberto, Mauro, Serra, Valentina, Grasso, Eugenio, Ruggeri, Andrea, Salvi, Roberto, Leonardi, Chiara, Grassini, Ilenia, Mascherona, Giorgio, Minelli, Francesca, Maltese, Armando, Gabrielli, Massimo, Mattioli, William, Capeci, Giuseppe Pio Martino, Salvatore, Corrao, Silvia, Messina, Riccardi, Ghio, Serena, Favorini, Anna Dal Col, Salvatore, Minisola, Luciano, Colangelo, Antonella, Afeltra, Pamela, Alemanno, Benedetta, Marigliano, Pietro, Castellino, Julien, Blanco, Luca, Zanoli, Marco, Cattaneo, Paola, Fracasso, Maria Valentina Amoruso, Valter, Saracco, Marisa, Fogliati, Carlo, Bussolino, Vittorio, Durante, Giovanna, Eusebi, Daniela, Tirotta, Francesca, Mete, Miriam, Gino, Antonio, Cittadini, Michele, Arcopinto, Andrea, Salzano, Emanuele, Bobbio, Alberto Maria Marra, Domenico, Sirico, Guido, Moreo, Francesco, Scopelliti, Francesca, Gasparini, Melissa, Cocca, Nieves Ramirez Duque, Alberto Muela Molinero, Pedro Abad Requejo, Vanessa Lopez Pelaez, Lara, Tamargo, Xavier Corbella Viros, Francesc, Formiga, Jesus Diez Manglano, Esperanza Bejarano Tello, Esther Del Corral Behamonte, Maria Sevil Puras, Manuel, Romero, Blanca Pinilla Llorente, Cristina Lopez Gonzalez-Cobos, Victoria Villalba Garcia, M., Juan Bosco Lopez Saez, Susana Sanz Baena, Marta Arroyo Gallego, Concepcion Gonzalez Becerra, Antonio Fernandez Moyano, Mercedes Gomez Hernandez, Manuel Poyato Borrego, Raquel Pacheco Cuadros, Florencia Perez Rojas, Beatriz Garcia Olid, Sara Carrascosa Garcia, Alfonso Gonzalez-Cruz Cervellera, Marta Peinado Martinez, Alberto Ruiz Cantero, Antonio Albarracín Arraigosa, Montserrat Godoy Guerrero, Miguel Angel Barón Ramos, Jose Manuel Machin, Ignacio Novo Veleiro, Lucia Alvela Suarez, Alfonso, Lopez, David Rubal Bran, Iria Iñiguez Vazquez, and Monica Rios, Prego.
Subjects: Male, Aging, Pediatrics, Health (social science), Bedridden, 030204 cardiovascular system & hematology, Logistic regression, DISEASE, PALLIATIVE CARE, Bedridden Persons, 0302 clinical medicine, Risk Factors, 80 and over, Medicine, 030212 general & internal medicine, Hypoalbuminemia, Prospective Studies, Prospective cohort study, PREDICTORS, Aged, 80 and over, Frailty, Mortality, Prognosis, Aged, Female, Follow-Up Studies, Frail Elderly, Hospital Units, Humans, Internal Medicine, Italy, Logistic Models, Patient Discharge, Absolute risk reduction, CANCER, Severe dementia, Cohort, medicine.medical_specialty, Renal function, Socio-culturale, ILLNESS, VALIDATION, 03 medical and health sciences, SCORE, OLDER PATIENTS, business.industry, Mortality, Bedridden, Prognosis, Frailty, PALLIATIVE CARE, 6-MONTH MORTALITY, OLDER PATIENTS, VALIDATION, DISEASE, SCORE, PREDICTORS, ILLNESS, CANCER, ADULTS, ADULTS, medicine.disease, 6-MONTH MORTALITY, Physical therapy, Geriatrics and Gerontology, business, Gerontology
Abstract: Background Short-term prognosis, e.g. mortality at three months, has many important implications in planning the overall management of patients, particularly non-oncologic patients in order to avoid futile practices. The aims of this study were: i) to investigate the risk of three-month mortality after discharge from internal medicine and geriatric wards of non-oncologic patients with at least one of the following conditions: permanent bedridden status during the hospital stay; severely reduced kidney function; hypoalbuminemia; hospital admissions in the previous six months; severe dementia; ii) to establish the absolute risk difference of three-month mortality of bedridden compared to non-bedridden patients. Methods This prospective cohort study was run in 102 Italian internal medicine and geriatric hospital wards. The sample included all patients with three-months follow-up data. Bedridden condition was defined as the inability to walk or stand upright during the whole hospital stay. The following parameters were also recorded: estimated GFR ≤ 29 mL/min/1.73 m2; severe dementia; albuminemia ≪2.5 g/dL; hospital admissions in the six months before the index admission. Results Of 3915 patients eligible for the analysis, three-month follow-up were available for 2058, who were included in the study. Bedridden patients were 112 and the absolute risk difference of mortality at three months was 0.13 (CI 95% 0.08–0.19, p ≪ 0.0001). Logistic regression analysis also adjusted for age, sex, number of drugs and comorbidity index found that bedridden condition (OR 2.10, CI 95% 1.12–3.94), severely reduced kidney function (OR 2.27, CI 95% 1.22–4.21), hospital admission in the previous six months (OR 1.96, CI 95% 1.22–3.14), severe dementia (with total or severe physical dependence) (OR 4.16, CI 95% 2.39–7.25) and hypoalbuminemia (OR 2.47, CI 95% 1.12–5.44) were significantly associated with higher risk of three-month mortality. Conclusions Bedridden status, severely reduced kidney function, recent hospital admissions, severe dementia and hypoalbuminemia were associated with higher risk of three-month mortality in non-oncologic patients after discharge from internal medicine and geriatric hospital wards.
Published: 2018

27. Cutaneous melanoma primary site is linked to nevus density

Author: Celia Requena, Amaya Viros, Alejandro Martin-Gorgojo, Victor Traves, Eduardo Nagore, Zaida García-Casado, Rajesh Kumar, and Marta Llinares
Subjects: 0301 basic medicine, medicine.medical_specialty, nevus density, 03 medical and health sciences, 0302 clinical medicine, medicine, melanoma, Nevus, In patient, Sunburn, skin and connective tissue diseases, neoplasms, Ultraviolet light exposure, integumentary system, Manchester Cancer Research Centre, business.industry, ResearchInstitutes_Networks_Beacons/mcrc, Sun damage, Total body, medicine.disease, Dermatology, anatomic site, 3. Good health, 030104 developmental biology, Oncology, 030220 oncology & carcinogenesis, Cutaneous melanoma, Skin cancer, business
Abstract: // Alejandro Martin-Gorgojo 1, * , Marta Llinares 2, * , Amaya Viros 3, 4, * , Celia Requena 2 , Zaida Garcia-Casado 5 , Victor Traves 6 , Rajiv Kumar 7 and Eduardo Nagore 2, 8 1 Escuela de Doctorado, Universidad Catolica de Valencia “San Vicente Martir”, Valencia, Spain 2 Department of Dermatology, Instituto Valenciano de Oncologia (IVO), Valencia, Spain 3 Skin Cancer and Ageing Laboratory, CRUK Manchester Institute, Manchester, UK 4 Salford Royal NHS Foundation Trust, Manchester, UK 5 Department of Molecular Biology, Instituto Valenciano de Oncologia (IVO), Valencia, Spain 6 Department of Pathology, Instituto Valenciano de Oncologia (IVO), Valencia, Spain 7 Division of Molecular Genetic Epidemiology, German Cancer Research Center, Heidelberg, Germany 8 Dermatology Department, School of Medicine, Universidad Catolica de Valencia “San Vicente Martir”, Valencia, Spain * These authors have contributed equally to this work Correspondence to: Eduardo Nagore, email: eduardo_nagore@ono.com Keywords: melanoma; nevus; risk; sunburn; solar elastosis Received: July 20, 2017 Accepted: September 23, 2017 Published: October 24, 2017 ABSTRACT There are at least two pathways driving cutaneous melanoma; one is linked to an inherent melanoma susceptibility to nevi development and the second to environmental cumulative ultraviolet light exposure. In this study, we examined the relation between nevus density, accrued sun damage and the site of primary melanoma excision. In a series of 888 consecutive cutaneous melanoma patients, melanomas appearing in skin areas with a high relative nevus density were most prominent in men, with an elevated nevus count, at sites without solar elastosis, but with an epidemiological history of previous sunburn. The present study associates melanoma development to sites with high nevus density. Our study supports more careful surveillance of body areas with increased nevus density in patients with high total body number of nevi, especially when they report a history of sunburns at these sites.
Published: 2017
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28. Abstract 3994: Genomic characterization of melanoma in the elderly reveals molecular drivers of progression and prognosis associated with immunotherapy response

Author: Caroline Gaudy-Marqueste, Stephen Smith, Richard Marais, Eduardo Nagore, Amaya Viros, and Rajive Kumar
Subjects: Oncology, Cancer Research, medicine.medical_specialty, education.field_of_study, business.industry, medicine.medical_treatment, Incidence (epidemiology), Melanoma, Population, Cancer, Immunotherapy, medicine.disease, Internal medicine, medicine, Genetic risk, Stage (cooking), business, education, Adjuvant
Abstract: Melanoma incidence and mortality particularly affects elderly patients. 85% of melanoma deaths occur in patients older than 60, and age is a powerful independent predictor of outcome. The genomic characteristics driving melanoma in the aged population have not been previously investigated. We have undertaken a comprehensive genomic analysis of age-specific molecular characteristics in metastatic cutaneous melanoma and discovered a core set of 4 driver genes that when mutated in older patients is a powerful predictor of poor outcome. We validate these findings in international independent primary melanoma replication cohorts. This signature stratifies patient prognosis more accurately than the current staging guidelines from early to late stages, making it relevant to immediate clinical practice. Checkpoint inhibitors are showing promising results in the adjuvant setting to treat early stage melanoma patients, and the cost burden to health care will limit access to these drugs. Importantly, elderly patients benefit from immune checkpoint inhibitor therapies, and there are currently no accepted predictors of response used to prioritize patients for these costly therapies in the adjuvant or advanced disease stages. Previous studies have shown a higher mutation burden and neo-antigen load are indicators of response. Critically, we show elderly melanoma patients are the population subset most likely to present with a higher mutation burden, and our signature strongly correlates with melanomas of higher mutation burden and neo-antigen load. We validate these findings across multiple primary and metastatic melanoma cohorts. Finally, stratifying old patients by our 4-gene outcome signature is also associated with immunotherapy response in the metastatic stage. Our study demonstrates that stratifying patients by age will allow improved discrimination of prognosis and association with response to treatment. Current selection of patients is based on AJCC stage alone, which means more patients have to be enrolled and more time is required to discriminate the effect of novel adjuvant immunotherapy strategies. Our work, validated across multiple cohorts, directly proposes enrolling patients with high genetic risk of poor outcome and improved rate of immunotherapy response using a simple 4-gene DNA signature that can be easily translated into clinical practice. Citation Format: Stephen P. Smith, Caroline Gaudy-Marqueste, Rajive Kumar, Richard Marais, Eduardo Nagore, Amaya Viros. Genomic characterization of melanoma in the elderly reveals molecular drivers of progression and prognosis associated with immunotherapy response [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3994.
Published: 2019
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29. Abstract 2022: Chronic UV damage of the stroma improves melanoma survival

Author: Simon J Furney, Timothy Budden, Amaya Viros, Eduardo Nagore, Stephen Smith, Martin Lotz, Katharina Roeck, Jean Krutmann, and Sarah Craig
Subjects: Cancer Research, Oncology, Stroma, business.industry, Melanoma, Cancer research, medicine, medicine.disease, business
Abstract: Introduction Skin that is exposed to chronic UV presents a distinct pattern of structural degradation compared to age-matched, sun-protected skin. The morphological change underpinning chronic UV cutaneous damage is collagen degradation of the dermis. Molecularly, UV-aged skin accumulates primarily UV-driven mutations, in contrast to UV-protected skin where mutations are rare. The enrichment of mutations in non-neoplastic, aged cells is a defining feature of skin ageing. Melanoma increases with age, and most patients who die are older than 55. Age is the most important independent marker of adverse outcome together with tumor thickness. Old patients commonly present melanoma over chronic UV-damaged skin with a high number of mutations, and some studies suggest these may be linked to better outcome. Here we explore the relationship between tumor mutation burden, stromal DNA damage and outcome of elderly primary melanoma patients. Results We examined the types of mutations contributing to the somatic mutation load in melanoma. We inferred the signature linked to accumulated UV DNA damage (signature 7 from COSMIC), as well as the intrinsic, proliferation and age-related signature (signature 1). Logistic regression models of signature 1 and 7 demonstrate both correlate with age, and elderly patients are at higher risk of death in this cohort. These data are in contrast to studies suggesting melanomas arising at sites of chronic sun exposure (CSE) have an improved survival, and studies showing higher mutation rates in melanoma are linked to better outcome. To test this, we generated isogenic melanoma cell lines with high versus low UV-mutation burden, and found CSE melanoma cells were more proliferative, invasive and migratory. We next investigated if a higher rate of UV damage to dermal fibroblasts affects outcome by generating isogenic CSE and noCSE dermal fibroblast lines and found melanoma cells exposed to noCSE fibroblasts were more invasive than melanoma cells exposed to CSE fibroblasts. We validated this in human dermal fibroblasts. Dermal fibroblasts from protected sites presented few mutations and promoted melanoma invasion, whereas fibroblasts from chronic UV skin had more mutations and did not drive melanoma invasion. Furthermore, CSE fibroblasts with many mutations present a distinct expression and metabolic profile linked to the sunburn response genes that blocks melanoma invasion. We validated our findings in 490 specimens of elderly primary cutaneous melanoma patients. Multivariate analysis shows the presence of degraded collagen, a surrogate marker of UV damage, is an independent marker of better outcome in the elderly population. Discussion Our study shows UV-driven damage in aged dermal fibroblasts protects from primary melanoma invasion and humans with extensive dermal UV damage present an improved outcome. Our finding that excessive UV can improve outcome of patients with melanoma is a paradigm shift. Citation Format: Eduardo Nagore, Katharina Roeck, Timothy Budden, Stephen P. Smith, Sarah Craig, Jean Krutmann, Martin Lotz, Simon Furney, Amaya Viros. Chronic UV damage of the stroma improves melanoma survival [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2022.
Published: 2019
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30. Defining aging phenotypes and related outcomes: Clues to recognize frailty in hospitalized older patients

Author: Marcucci, Maura, Carlotta, Franchi, Alessandro, Nobili, Pier Mannuccio Mannucci, Ilaria, Ardoino, Mauro, Tettamanti, Luca, Pasina, Francesco, Perticone, Francesco, Salerno, Salvatore, Corrao, Giuseppe, Licata, Francesco, Violi, Gino Roberto Corazza, Tarek Kamal Eldin, Maria Pia Donatella Di Blanca, Prisco, Domenico, Elena, Silvestri, Caterina, Cenci, Giacomo, Emmi, Gianni, Biolo, Gianfranco, Guarnieri, Michela, Zanetti, Giovanni, Fernandes, Massimo, Vanoli, Giulia, Grignani, Gianluca, Casella, Mauro, Bernardi, Silvia Li Bassi, Luca, Santi, Giacomo, Zaccherini, Mannarino, Elmo, Lupattelli, Graziana, Bianconi, Vanessa, Paciullo, Francesco, Ranuccio, Nuti, Roberto, Valenti, Martina, Ruvio, Silvia, Cappelli, Alberto, Palazzuoli, Teresa, Salvatore, Ferdinando Carlo Sasso, Domenico, Girelli, Olivieri, Oliviero, Thomas, Matteazzi, Mario, Barbagallo, Lidia, Plances, Roberta, Alcamo, Luigi, Calvo, Maria, Valenti, Marco, Zoli, Raffaella, Arnò, Franco Laghi Pasini, Pier Leopoldo Capecchi, Maurizio, Bicchi, Giuseppe, Palasciano, Maria Ester Modeo, Maria, Peragine, Fabrizio, Pappagallo, Stefania, Pugliese, Carla Di Gennaro, Alfredo, Postiglione, Maria Rosaria Barbella, Francesco De Stefano, Cappellini, MARIA DOMENICA, Giovanna, Fabio, Sonia, Seghezzi, Margherita Migone De Amicis, Daniela, Mari, Paolo Dionigi Rossi, Sarah, Damanti, Barbara Brignolo Ottolini, Emanuela, Miceli, Marco Vincenzo Lenti, Donatella, Padula, Giovanni, Murialdo, Alessio, Marra, Federico, Cattaneo, Maria Beatrice Secchi, Davide, Ghelfi, Luigi, Anastasio, Lucia, Sofia, Carbone, LUIGI MARIA, Giovanni, Davì, Maria Teresa Guagnano, Simona, Sestili, Gerardo, Mancuso, Daniela, Calipari, Mosè, Bartone, Maria Rachele Meroni, Paolo Cavallo Perin, Bartolomeo, Lorenzati, Gabriella, Gruden, Graziella, Bruno, Cristina, Amione, Paolo, Fornengo, Rodolfo, Tassara, Deborah, Melis, Lara, Rebella, Giuseppe, Delitala, Vincenzo, Pretti, Maristella Salvatora Masala, Luigi, Bolondi, Leonardo, Rasciti, Ilaria, Serio, Filippo Rossi Fanelli, Antonio, Amoroso, Alessio, Molfino, Enrico, Petrillo, Giuseppe, Zuccalà, Francesco, Franceschi, Guido De Marco, Cordischi, Chiara, Sabbatini, Marta, Giuseppe, Romanelli, Claudia, Amolini, Deborah, Chiesa, Alessandra, Marengoni, Antonio, Picardi, Umberto Vespasiani Gentilucci, Paolo, Gallo, Giorgio, Annoni, Maurizio, Corsi, Sara, Zazzetta, Giuseppe, Bellelli, Franco, Arturi, Elena, Succurro, Mariangela, Rubino, Giorgio, Sesti, Paola, Loria, Maria Angela Becchi, Gianfranco, Martucci, Alessandra, Fantuzzi, Mauro, Maurantonio, Stefano, Carta, Sebastiana, Atzori, Maria Grazia Serra, Maria Antonietta Bleve, Laura, Gasbarrone, Maria Rosaria Sajeva, Antonio, Brucato, Silvia, Ghidoni, Paola Di Corato, Agnelli, Giancarlo, Marchesini, Emanuela, Fabrizio, Fabris, Michela, Carlon, Francesca, Turatto, Aldo, Baritusso, Roberto, Manfredini, Christian, Molino, Marco, Pala, Fabio, Fabbian, Benedetta, Boari, Alfredo De Giorgi, Giuseppe, Paolisso, Maria Rosaria Rizzo, Maria Teresa Laieta, Giovanbattista, Rini, Pasquale, Mansueto, Ilenia, Pepe, Claudio, Borghi, Enrico, Strocchi, Valeria De Sando, Carlo, Sabbà, Francesco Saverio Vella, Patrizia, Suppressa, Raffaella, Valerio, Caterina, Capobianco, Luigi, Fenoglio, Christian, Bracco, Alessia Valentina Giraudo, Elisa, Testa, Cristina, Serraino, Silvia, Fargion, Paola, Bonara, Giulia, Periti, Marianna, Porzio, Flora, Peyvandi, Alberto, Tedeschi, Raffaella, Rossio, Valter, Monzani, Valeria, Savojardo, Christian, Folli, Maria, Magnini, Alessio, Conca, Giulia, Gobbo, Balduini, Carlo L., Giampiera, Bertolino, Stella, Provini, Federica, Quaglia, Franco, Dallegri, Luciano, Ottonello, Luca, Liberale, Wu Sheng Chin, Laura, Carassale, Silvia, Caporotundo, Giancarlo, Traisci, Lucrezia De Feudis, Silvia Di Carlo, Nicola Lucio Liberato, Alberto, Buratti, Tiziana, Tognin, Giovanni Battista Bianchi, Sabrina, Giaquinto, Francesco, Purrello, Antonino Di Pino, Salvatore, Piro, Renzo, Rozzini, Lina, Falanga, Giuseppe, Montrucchio, Elisabetta, Greco, Pietro, Tizzani, Paolo, Petitti, Antonio, Perciccante, Alessia, Coralli, Raffaella, Salmi, Piergiorgio, Gaudenzi, Susanna, Gamberini, Andrea, Semplicini, Lucia, Gottardo, Gianluigi, Vendemiale, Gaetano, Serviddio, Roberta, Forlano, Cesare, Masala, Antonio, Mammarella, Valeria, Raparelli, Stefania, Basili, Ludovica, Perri, Raffaele, Landolfi, Massimo, Montalto, Antonio, Mirijello, Carla, Vallone, Martino, Bellusci, Donatella, Setti, Filippo, Pedrazzoli, Luigina, Guasti, Luana, Castiglioni, Andrea, Maresca, Alessandro, Squizzato, Marta, Molaro, Bertolotti, Marco, Chiara, Mussi, Maria Vittoria Libbra, DI MICELI, Andrea, Pellegrini, Elisa, Lucia, Carulli, Angela, Sciacqua, Michele, Quero, Chiara, Bagnato, Roberto, Corinaldesi, Roberto De Giorgio, DALLA SERRA, Mauro, Valentina, Grasso, Eugenio, Ruggeri, Andrea, Salvi, Leonardi, Roberto, Chiara, Grassini, Ilenia, Mascherona, Minelli, Giorgio, Francesca, Maltese, Armando, Gabrielli, Mattioli, Massimo, William, Capeci, Giuseppe Pio Martino, Silvia, Messina, Riccardi, Ghio, Serena, Favorini, Anna Dal Col, Salvatore, Minisola, Luciano, Colangelo, Antonella, Afeltra, Pamela, Alemanno, Benedetta, Marigliano, Pietro, Castellino, Julien, Blanco, Luca, Zanoli, Cattaneo, Marco Natale, Paola, Fracasso, Amoruso, MARIA VALENTINA, Valter, Saracco, Marisa, Fogliati, Carlo, Bussolino, Vittorio, Durante, Giovanna, Eusebi, Daniela, Tirotta, Francesca, Mete, Miriam, Gino, Antonio, Cittadini, Michele, Arcopinto, Andrea, Salzano, Emanuele, Bobbio, Alberto Maria Marra, Domenico, Sirico, Guido, Moreo, Francesco, Scopelliti, Francesca, Gasparini, Melissa, Cocca, Ramirez Duque Nieves, Muela Molinero Alberto, Abad Requejo Pedro, Lopez Pelaez Vanessa, Tamargo, Lara, Corbella Viros Xavier, Formiga, Francesc, Diez Manglano Jesus, Bejarano Tello Esperanza, Del Corral Behamonte Esther, Sevil Puras Maria, Manuel, Romero, Pinilla Llorente Blanca, Lopez Gonzalez-Cobos Cristina, Victoria, Villalba Garcia M., Lopez, Saez, Juan, Bosco, Sanz Baena Susana, Arroyo Gallego Marta, Gonzalez Becerra Concepcion, Fernandez Moyano Antonio, Mercedes Gomez Hernandez, Manuel Poyato Borrego, Pacheco Cuadros Raquel, Perez Rojas Florencia, Garcia Olid Beatriz, Carrascosa Garcia Sara, Gonzalez-Cruz Cervellera Alfonso, Peinado Martinez Marta, Ruiz Cantero Alberto, Albarracín Arraigosa Antonio, Godoy Guerrero Montserrat, Barón Ramos Miguel Ángel, Machin Jose Manuel, Novo Veleiro Ignacio, Alvela Suarez Lucía, Lopez, Alfonso, Rubal Bran David, Iñiguez Vazquez Iria, Rios Prego Monica, Marcucci, M., Franchi, C., Nobili, A., Mannucci, P. M., Ardoino, I., Tettamanti, M., Pasina, L., Perticone, F., Salerno, F., Corrao, S., Marengoni, A., Licata, G., Violi, F., Corazza, G. R., Eldin, T. K., Di Blanca, M. P. D., Djade, C. D., Cortesi, L., Prisco, D., Silvestri, E., Cenci, C., Emmi, G., Biolo, G., Guarnieri, G., Zanetti, M., Fernandes, G., Vanoli, M., Grignani, G., Casella, G., Bernardi, M., Bassi, S. L., Santi, L., Zaccherini, G., Mannarino, E., Lupattelli, G., Bianconi, V., Paciullo, F., Nuti, R., Valenti, R., Ruvio, M., Cappelli, S., Palazzuoli, A., Salvatore, T., Sasso, F. C., Girelli, D., Olivieri, O., Matteazzi, T., Barbagallo, M., Plances, L., Alcamo, R., Calvo, L., Valenti, M., Zoli, M., Arno, R., Pasini, F. L., Capecchi, P. L., Bicchi, M., Palasciano, G., Modeo, M. E., Peragine, M., Pappagallo, F., Pugliese, S., Di Gennaro, C., Postiglione, A., Barbella, M. R., De Stefano, F., Cappellini, M. D., Fabio, G., Seghezzi, S., De Amicis, M. M., Mari, D., Rossi, P. D., Damanti, S., Ottolini, B. B., Miceli, E., Lenti, M. V., Padula, D., Murialdo, G., Marra, A., Cattaneo, F., Secchi, M. B., Ghelfi, D., Anastasio, L., Leiter, Sofia, Carbone, M., Davi, G., Guagnano, M. T., Sestili, S., Mancuso, G., Calipari, D., Bartone, M., Meroni, M. R., Perin, P. C., Lorenzati, B., Gruden, G., Bruno, G., Amione, C., Fornengo, P., Tassara, R., Melis, D., Rebella, L., Delitala, G., Pretti, V., Masala, M. S., Bolondi, L., Rasciti, L., Serio, I., Fanelli, F. R., Amoroso, A., Molfino, A., Petrillo, E., Zuccala, G., Franceschi, F., De Marco, G., Chiara, C., Marta, S., Romanelli, G., Amolini, C., Chiesa, D., Picardi, A., Gentilucci, U. V., Gallo, P., Annoni, G., Corsi, M., Zazzetta, S., Bellelli, G., Arturi, F., Succurro, E., Rubino, M., Sesti, G., Loria, P., Becchi, M. A., Martucci, G., Fantuzzi, A., Maurantonio, M., Carta, S., Atzori, S., Serra, M. G., Bleve, M. A., Gasbarrone, L., Sajeva, M. R., Brucato, A., Ghidoni, S., Di Corato, P., Agnelli, G., Marchesini, E., Fabris, F., Carlon, M., Turatto, F., Baritusso, A., Manfredini, R., Molino, C., Pala, M., Fabbian, F., Boari, B., De Giorgi, A., Paolisso, G., Rizzo, M. R., Laieta, M. T., Rini, G., Mansueto, P., Pepe, I., Borghi, C., Strocchi, E., De Sando, V., Sabba, C., Vella, F. S., Suppressa, P., Valerio, R., Capobianco, C., Fenoglio, L., Bracco, C., Giraudo, A. V., Testa, E., Serraino, C., Fargion, S., Bonara, P., Periti, G., Porzio, M., Peyvandi, F., Tedeschi, A., Rossio, R., Monzani, V., Savojardo, V., Folli, C., Magnini, M., Conca, A., Gobbo, G., Balduini, C. L., Bertolino, G., Provini, S., Quaglia, F., Dallegri, F., Ottonello, L., Liberale, L., Chin, W. S., Carassale, L., Caporotundo, S., Traisci, G., De Feudis, L., Di Carlo, S., Liberato, N. L., Buratti, A., Tognin, T., Bianchi, G. B., Giaquinto, S., Purrello, F., Di Pino, A., Piro, S., Rozzini, R., Falanga, L., Montrucchio, G., Greco, E., Tizzani, P., Petitti, P., Perciccante, A., Coralli, A., Salmi, R., Gaudenzi, P., Gamberini, S., Semplicini, A., Gottardo, L., Vendemiale, G., Serviddio, G., Forlano, R., Masala, C., Mammarella, A., Raparelli, V., Basili, S., Perri, L., Landolfi, R., Montalto, M., Mirijello, A., Vallone, C., Bellusci, M., Setti, D., Pedrazzoli, F., Guasti, L., Castiglioni, L., Maresca, A., Squizzato, A., Molaro, M., Bertolotti, M., Mussi, C., Libbra, M. V., Miceli, A., Pellegrini, E., Carulli, L., Sciacqua, A., Quero, M., Bagnato, C., Corinaldesi, R., De Giorgio, R., Serra, M., Grasso, V., Ruggeri, E., Salvi, A., Leonardi, R., Grassini, C., Mascherona, I., Minelli, G., Maltese, F., Gabrielli, A., Mattioli, M., Capeci, W., Martino, G. P., Messina, S., Ghio, R., Favorini, S., Dal Col, A., Minisola, S., Colangelo, L., Afeltra, A., Alemanno, P., Marigliano, B., Castellino, P., Blanco, J., Zanoli, L., Cattaneo, M., Fracasso, P., Amoruso, M. V., Saracco, V., Fogliati, M., Bussolino, C., Durante, V., Eusebi, G., Tirotta, D., Mete, F., Gino, M., Cittadini, A., Arcopinto, M., Salzano, A., Bobbio, E., Marra, A. M., Sirico, D., Moreo, G., Scopelliti, F., Gasparini, F., Cocca, M., Nieves, R. D., Alberto, M. M., Pedro, A. R., Vanessa, L. P., Lara, T., Xavier, C. V., Francesc, F., Jesus, D. M., Esperanza, B. T., Esther, D. C. B., Maria, S. P., Romero, M., Blanca, P. L., Cristina, L. G. -C., Victoria, V. G. M., Saez, L., Bosco, J., Susana, S. B., Marta, A. G., Concepcion, G. B., Antonio, F. M., Hernandez, M. G., Borrego, M. P., Raquel, P. C., Florencia, P. R., Beatriz, G. O., Sara, C. G., Alfonso, G. -C. C., Marta, P. M., Alberto, R. C., Antonio, A. A., Montserrat, G. G., Angel, B. R. M., Manuel, M. J., Ignacio, N. V., Lucia, A. S., Alfonso, L., David, R. B., Iria, I. V., Monica, R. P., Sofia, L., Marcucci, M, Franchi, C, Nobili, A, Mannucci, P, Ardoino, I, Tettamanti, M, Pasina, L, Perticone, F, Salerno, F, Corrao, S, Marengoni, A, Licata, G, Violi, F, Corazza, G, Eldin, T, Di Blanca, M, Djade, C, Cortesi, L, Prisco, D, Silvestri, E, Cenci, C, Emmi, G, Biolo, G, Guarnieri, G, Zanetti, M, Fernandes, G, Vanoli, M, Grignani, G, Casella, G, Bernardi, M, Bassi, S, Santi, L, Zaccherini, G, Mannarino, E, Lupattelli, G, Bianconi, V, Paciullo, F, Nuti, R, Valenti, R, Ruvio, M, Cappelli, S, Palazzuoli, A, Salvatore, T, Sasso, F, Girelli, D, Olivieri, O, Matteazzi, T, Barbagallo, M, Plances, L, Alcamo, R, Calvo, L, Valenti, M, Zoli, M, Arno, R, Pasini, F, Capecchi, P, Bicchi, M, Palasciano, G, Modeo, M, Peragine, M, Pappagallo, F, Pugliese, S, Di Gennaro, C, Postiglione, A, Barbella, M, De Stefano, F, Cappellini, M, Fabio, G, Seghezzi, S, De Amicis, M, Mari, D, Rossi, P, Damanti, S, Ottolini, B, Miceli, E, Lenti, M, Padula, D, Murialdo, G, Marra, A, Cattaneo, F, Secchi, M, Ghelfi, D, Anastasio, L, Sofia, L, Carbone, M, Davi, G, Guagnano, M, Sestili, S, Mancuso, G, Calipari, D, Bartone, M, Meroni, M, Perin, P, Lorenzati, B, Gruden, G, Bruno, G, Amione, C, Fornengo, P, Tassara, R, Melis, D, Rebella, L, Delitala, G, Pretti, V, Masala, M, Bolondi, L, Rasciti, L, Serio, I, Fanelli, F, Amoroso, A, Molfino, A, Petrillo, E, Zuccala, G, Franceschi, F, De Marco, G, Chiara, C, Marta, S, Romanelli, G, Amolini, C, Chiesa, D, Picardi, A, Gentilucci, U, Gallo, P, Annoni, G, Corsi, M, Zazzetta, S, Bellelli, G, Arturi, F, Succurro, E, Rubino, M, Sesti, G, Loria, P, Becchi, M, Martucci, G, Fantuzzi, A, Maurantonio, M, Carta, S, Atzori, S, Serra, M, Bleve, M, Gasbarrone, L, Sajeva, M, Brucato, A, Ghidoni, S, Di Corato, P, Agnelli, G, Marchesini, E, Fabris, F, Carlon, M, Turatto, F, Baritusso, A, Manfredini, R, Molino, C, Pala, M, Fabbian, F, Boari, B, De Giorgi, A, Paolisso, G, Rizzo, M, Laieta, M, Rini, G, Mansueto, P, Pepe, I, Borghi, C, Strocchi, E, De Sando, V, Sabba, C, Vella, F, Suppressa, P, Valerio, R, Capobianco, C, Fenoglio, L, Bracco, C, Giraudo, A, Testa, E, Serraino, C, Fargion, S, Bonara, P, Periti, G, Porzio, M, Peyvandi, F, Tedeschi, A, Rossio, R, Monzani, V, Savojardo, V, Folli, C, Magnini, M, Conca, A, Gobbo, G, Balduini, C, Bertolino, G, Provini, S, Quaglia, F, Dallegri, F, Ottonello, L, Liberale, L, Chin, W, Carassale, L, Caporotundo, S, Traisci, G, De Feudis, L, Di Carlo, S, Liberato, N, Buratti, A, Tognin, T, Bianchi, G, Giaquinto, S, Purrello, F, Di Pino, A, Piro, S, Rozzini, R, Falanga, L, Montrucchio, G, Greco, E, Tizzani, P, Petitti, P, Perciccante, A, Coralli, A, Salmi, R, Gaudenzi, P, Gamberini, S, Semplicini, A, Gottardo, L, Vendemiale, G, Serviddio, G, Forlano, R, Masala, C, Mammarella, A, Raparelli, V, Basili, S, Perri, L, Landolfi, R, Montalto, M, Mirijello, A, Vallone, C, Bellusci, M, Setti, D, Pedrazzoli, F, Guasti, L, Castiglioni, L, Maresca, A, Squizzato, A, Molaro, M, Bertolotti, M, Mussi, C, Libbra, M, Miceli, A, Pellegrini, E, Carulli, L, Sciacqua, A, Quero, M, Bagnato, C, Corinaldesi, R, De Giorgio, R, Grasso, V, Ruggeri, E, Salvi, A, Leonardi, R, Grassini, C, Mascherona, I, Minelli, G, Maltese, F, Gabrielli, A, Mattioli, M, Capeci, W, Martino, G, Messina, S, Ghio, R, Favorini, S, Dal Col, A, Minisola, S, Colangelo, L, Afeltra, A, Alemanno, P, Marigliano, B, Castellino, P, Blanco, J, Zanoli, L, Cattaneo, M, Fracasso, P, Amoruso, M, Saracco, V, Fogliati, M, Bussolino, C, Durante, V, Eusebi, G, Tirotta, D, Mete, F, Gino, M, Cittadini, A, Arcopinto, M, Salzano, A, Bobbio, E, Sirico, D, Moreo, G, Scopelliti, F, Gasparini, F, Cocca, M, Nieves, R, Alberto, M, Pedro, A, Vanessa, L, Lara, T, Xavier, C, Francesc, F, Jesus, D, Esperanza, B, Esther, D, Maria, S, Romero, M, Blanca, P, Cristina, L, Victoria, V, Saez, L, Bosco, J, Susana, S, Marta, A, Concepcion, G, Antonio, F, Hernandez, M, Borrego, M, Raquel, P, Florencia, P, Beatriz, G, Sara, C, Alfonso, G, Marta, P, Alberto, R, Antonio, A, Montserrat, G, Angel, B, Manuel, M, Ignacio, N, Lucia, A, Alfonso, L, David, R, Iria, I, and Monica, R
Subjects: Background: Because frailty is a complex phenomenon associated with poor outcomes, the identification of patient profiles with different care needs might be of greater practical help than to look for a unifying definition. This study aimed at identifying aging phenotypes and their related outcomes in order to recognize frailty in hospitalized older patients. Methods: Patients aged 65 or older enrolled in internal medicine and geriatric wards participating in the REPOSI registry. Relationships among variables associated to sociodemographic, physical, cognitive, functional, and medical status were explored using a multiple correspondence analysis. The hierarchical cluster analysis was then performed to identify possible patient profiles. Multivariable logistic regression was used to verify the association between clusters and outcomes (in-hospital mortality and 3-month postdischarge mortality and rehospitalization). Results: 2,841 patients were included in the statistical analyses. Four clusters were identified: the healthiest (I), those with multimorbidity (II), the functionally independent women with osteoporosis and arthritis (III), and the functionally dependent oldest old patients with cognitive impairment (IV). There was a significantly higher in-hospital mortality in Cluster II (odds ratio [OR] = 2.27, 95% confidence interval [CI] = 1.15-4.46) and Cluster IV (OR = 5.15, 95% CI = 2.58-10.26) and a higher 3-month mortality in Cluster II (OR = 1.66, 95% CI = 1.13-2.44) and Cluster IV (OR = 1.86, 95% CI = 1.15-3.00) than in Cluster I. Conclusions: Using alternative analytical techniques among hospitalized older patients, we could distinguish different frailty phenotypes, differently associated with adverse events. The identification of different patient profiles can help defining the best care strategy according to specific patient needs, Male, Aging, Osteoporosis, we could distinguish different frailty phenotypes, 030204 cardiovascular system & hematology, Logistic regression, 0302 clinical medicine, Internal medicine and geriatric wards, Aging phenotype, 80 and over, Medicine, Cluster analysi, LS4_4, 95% CI = 1.15-3.00) than in Cluster I. Conclusions: Using alternative analytical techniques among hospitalized older patients, 030212 general & internal medicine, Hospital Mortality, Prospective Studies, Prospective cohort study, physical, Outcome, 95% CI = 2.58-10.26) and a higher 3-month mortality in Cluster II (OR = 1.66, Aged, 80 and over, Frailty, 95% confidence interval [CI] = 1.15-4.46) and Cluster IV (OR = 5.15, Cognition, Hospitalization, Phenotype, aging phenotypes, cluster analysis, frailty, internal medicine and geriatric wards, outcomes, Female, 841 patients were included in the statistical analyses. Four clusters were identified: the healthiest (I), Human, medicine.medical_specialty, the identification of patient profiles with different care needs might be of greater practical help than to look for a unifying definition. This study aimed at identifying aging phenotypes and their related outcomes in order to recognize frailty in hospitalized older patients. Methods: Patients aged 65 or older enrolled in internal medicine and geriatric wards participating in the REPOSI registry. Relationships among variables associated to sociodemographic, Frail Elderly, Socio-culturale, Aging phenotypes, Cluster analysis, Outcomes, Aged, Humans, Geriatric Assessment, cognitive, 03 medical and health sciences, Multiple correspondence analysis, Internal medicine, differently associated with adverse events. The identification of different patient profiles can help defining the best care strategy according to specific patient needs, Adverse effect, Background: Because frailty is a complex phenomenon associated with poor outcomes, Aging phenotypes, Cluster analysis, Frailty, Internal medicine and geriatric wards, Outcomes, 95% CI = 1.13-2.44) and Cluster IV (OR = 1.86, business.industry, and the functionally dependent oldest old patients with cognitive impairment (IV). There was a significantly higher in-hospital mortality in Cluster II (odds ratio [OR] = 2.27, Settore MED/09 - MEDICINA INTERNA, and medical status were explored using a multiple correspondence analysis. The hierarchical cluster analysis was then performed to identify possible patient profiles. Multivariable logistic regression was used to verify the association between clusters and outcomes (in-hospital mortality and 3-month postdischarge mortality and rehospitalization). Results: 2, Odds ratio, medicine.disease, Confidence interval, Internal medicine and geriatric ward, Prospective Studie, functional, Physical therapy, Geriatrics and Gerontology, business
Abstract: Background Because frailty is a complex phenomenon associated with poor outcomes, the identification of patient profiles with different care needs might be of greater practical help than to look for a unifying definition. This study aimed at identifying aging phenotypes and their related outcomes in order to recognize frailty in hospitalized older patients. Methods Patients aged 65 or older enrolled in internal medicine and geriatric wards participating in the REPOSI registry. Relationships among variables associated to sociodemographic, physical, cognitive, functional, and medical status were explored using a multiple correspondence analysis. The hierarchical cluster analysis was then performed to identify possible patient profiles. Multivariable logistic regression was used to verify the association between clusters and outcomes (in-hospital mortality and 3-month postdischarge mortality and rehospitalization). Results 2,841 patients were included in the statistical analyses. Four clusters were identified: the healthiest (I); those with multimorbidity (II); the functionally independent women with osteoporosis and arthritis (III); and the functionally dependent oldest old patients with cognitive impairment (IV). There was a significantly higher in-hospital mortality in Cluster II (odds ratio [OR] = 2.27, 95% confidence interval [CI] = 1.15-4.46) and Cluster IV (OR = 5.15, 95% CI = 2.58-10.26) and a higher 3-month mortality in Cluster II (OR = 1.66, 95% CI = 1.13-2.44) and Cluster IV (OR = 1.86, 95% CI = 1.15-3.00) than in Cluster I. Conclusions Using alternative analytical techniques among hospitalized older patients, we could distinguish different frailty phenotypes, differently associated with adverse events. The identification of different patient profiles can help defining the best care strategy according to specific patient needs.
Published: 2017

31. Mechanisms of Drug Resistance in Melanoma

Author: Matthew Winder and Amaya Viros
Subjects: 0301 basic medicine, MAPK/ERK pathway, business.industry, medicine.medical_treatment, MEK inhibitor, Melanoma, Immunotherapy, Drug resistance, medicine.disease, Immune checkpoint, Targeted therapy, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, Immune system, 030220 oncology & carcinogenesis, medicine, Cancer research, business
Abstract: Metastatic melanoma is associated with poor outcome and is largely refractory to the historic standard of care. In recent years, the development of targeted small-molecule inhibitors and immunotherapy has revolutionised the care and improved the overall survival of these patients. Therapies targeting BRAF and MEK to block the mitogen-activated protein kinase (MAPK) pathway were the first to show unprecedented clinical responses. Following these encouraging results, antibodies targeting immune checkpoint inhibition molecules cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), programmed cell death (PD)-1, and PD-ligand1(PD-L1) demonstrated sustained tumour regression in a significant subset of patients by enabling an anti-tumour immunologic response. Despite these landmark changes in practice, the majority of patients are either intrinsically resistant or rapidly acquire resistance to MAPK pathway inhibitors and immune checkpoint blockade treatment. The lack of response can be driven by mutations and non-mutational events in tumour cells, as well as by changes in the surrounding tumour microenvironment. Common resistance mechanisms bypass the dependence of tumour cells on initial MAPK pathway driver mutations during targeted therapy, and permit evasion of the host immune system to allow melanoma growth and survival following immunotherapy. This highlights the requirement for personalised treatment regimens that take into account patient-specific genetic and immunologic characteristics. Here we review the mechanisms by which melanomas display intrinsic resistance or acquire resistance to targeted therapy and immunotherapy.
Published: 2017
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32. Pattern of in-hospital changes in drug use in the older people from 2010 to 2016

Author: Carlotta, Franchi, Ilaria, Ardoino, Alessandro, Nobili, Luca, Pasina, Pier Mannuccio Mannucci, Alessandra, Marengoni, Francesco, Perticone, Mauro, Tettamanti, Francesco, Salerno, Salvatore, Corrao, Giuseppe, Licata, Francesco, Violi, Gino Roberto Corazza, Marcucci, Maura, Tarek Kamal Eldin, Maria Pia Donatella Di Blanca, Giovanna, Lanzo, Sarah, Astuto, Laura, Cortesi, Prisco, Domenico, Elena, Silvestri, Caterina, Cenci, Giacomo, Emmi, Gianni, Biolo, Gianfranco, Guarnieri, Michela, Zanetti, Giovanni, Fernandes, Massimiliano, Chiuch, Massimo, Vanoli, Giulia, Grignani, Gianluca, Casella, Edoardo Alessandro Pulixi, Mauro, Bernardi, Silvia Li Bassi, Luca, Santi, Giacomo, Zaccherini, Mannarino, Elmo, Lupattelli, Graziana, Bianconi, Vanessa, Paciullo, Francesco, Ranuccio, Nuti, Roberto, Valenti, Martina, Ruvio, Silvia, Cappelli, Alberto, Palazzuoli, Teresa, Salvatore, Ferdinando Carlo Sasso, Domenico, Girelli, Oliviero, Olivieri, Thomas, Matteazzi, Mario, Barbagallo, Lidia, Plances, Roberta, Alcamo, Luigi, Calvo, Maria, Valenti, Marco, Zoli, Raffaella, Arnò, Franco Laghi Pasini, Pier Leopoldo Capecchi, Maurizio, Bicchi, Giuseppe, Palasciano, Maria Ester Modeo, Maria, Peragine, Fabrizio, Pappagallo, Stefania, Pugliese, Carla Di Gennaro, Alfredo, Postiglione, Maria Rosaria Barbella, Francesco De Stefano, Cappellini, MARIA DOMENICA, Giovanna, Fabio, Sonia, Seghezzi, Margherita Migone De Amicis, Marta, Mancarella, Daniela, Mari, Paolo Dionigi Rossi, Sarah, Damanti, Barbara Brignolo Ottolini, Giulia, Bonini, Emanuela, Miceli, Marco Vincenzo Lenti, Donatella, Padula, Giovanni, Murialdo, Alessio, Marra, Federico, Cattaneo, Maria Beatrice Secchi, Davide, Ghelfi, Luigi, Anastasio, Lucia, Sofia, Carbone, LUIGI MARIA, Giovanni, Davì, Maria Teresa Guagnano, Simona, Sestili, Gerardo, Mancuso, Daniela, Calipari, Mosè, Bartone, Maria Rachele Meroni, Paolo Cavallo Perin, Bartolomeo, Lorenzati, Gabriella, Gruden, Graziella, Bruno, Cristina, Amione, Paolo, Fornengo, Rodolfo, Tassara, Deborah, Melis, Lara, Rebella, Giuseppe, Delitala, Vincenzo, Pretti, Maristella Salvatora Masala, Chiara, Pes, Luigi, Bolondi, Leonardo, Rasciti, Ilaria, Serio, Filippo Rossi Fanelli, Antonio, Amoroso, Alessio, Molfino, Enrico, Petrillo, Giuseppe, Zuccalà, Francesco, Franceschi, Guido De Marco, Cordischi, Chiara, Sabbatini, Marta, Gabriella, D’Aurizio, Giuseppe, Romanelli, Claudia, Amolini, Deborah, Chiesa, Antonio, Picardi, Umberto Vespasiani Gentilucci, Paolo, Gallo, Giorgio, Annoni, Maurizio, Corsi, Sara, Zazzetta, Giuseppe, Bellelli, Hajnalka, Szabo, Franco, Arturi, Elena, Succurro, Mariangela, Rubino, Giorgio, Sesti, Paola, Loria, Maria Angela Becchi, Gianfranco, Martucci, Alessandra, Fantuzzi, Mauro, Maurantonio, Maria Grazia Serra, Maria Antonietta Bleve, Laura, Gasbarrone, Maria Rosaria Sajeva, Antonio, Brucato, Silvia, Ghidoni, Paola Di Corato, Agnelli, Giancarlo, Marchesini, Emanuela, Fabrizio, Fabris, Michela, Carlon, Francesca, Turatto, Aldo, Baritusso, Annalisa, Amabile, Elisabetta, Omenetto, Paolo, Scarinzi, Roberto, Manfredini, Christian, Molino, Marco, Pala, Fabio, Fabbian, Benedetta, Boari, Alfredo De Giorgi, Giuseppe, Paolisso, Maria Rosaria Rizzo, Maria Teresa Laieta, Giovanbattista, Rini, Pasquale, Mansueto, Ilenia, Pepe, Claudio, Borghi, Enrico, Strocchi, Valeria De Sando, Ilaria, Pareo, Carlo, Sabbà, Francesco Saverio Vella, Patrizia, Suppressa, Raffaella, Valerio, Pasquale, Agosti, Flavia, Fontana, Francesca, Loparco, Caterina, Capobianco, Luigi, Fenoglio, Christian, Bracco, Alessia Valentina Giraudo, Elisa, Testa, Cristina, Serraino, Silvia, Fargion, Paola, Bonara, Giulia, Periti, Marianna, Porzio, Slivia, Tiraboschi, Flora, Peyvandi, Alberto, Tedeschi, Raffaella, Rossio, Valter, Monzani, Valeria, Savojardo, Christian, Folli, Maria, Magnini, Alessio, Conca, Giulia, Gobbo, Giada, Pallini, Miriam, Valenti, Balduini, Carlo L., Giampiera, Bertolino, Stella, Provini, Federica, Quaglia, Franco, Dallegri, Luciano, Ottonello, Luca, Liberale, Wu Sheng Chin, Laura, Carassale, Silvia, Caporotundo, Giancarlo, Traisci, Lucrezia De Feudis, Silvia Di Carlo, Nicola Lucio Liberato, Alberto, Buratti, Tiziana, Tognin, Giovanni Battista Bianchi, Sabrina, Giaquinto, Francesco, Purrello, Antonino Di Pino, Salvatore, Piro, Renzo, Rozzini, Lina, Falanga, Elena, Spazzini, Giuseppe, Montrucchio, Elisabetta, Greco, Pietro, Tizzani, Paolo, Petitti, Antonio, Perciccante, Alessia, Coralli, Raffaella, Salmi, Piergiorgio, Gaudenzi, Susanna, Gamberini, Andrea, Semplicini, Lucia, Gottardo, Gianluigi, Vendemiale, Gaetano, Serviddio, Roberta, Forlano, Cesare, Masala, Antonio, Mammarella, Valeria, Raparelli, Stefania, Basili, Ludovica, Perri, Raffaele, Landolfi, Massimo, Montalto, Antonio, Mirijello, Carla, Vallone, Martino, Bellusci, Donatella, Setti, Filippo, Pedrazzoli, Luigina, Guasti, Luana, Castiglioni, Andrea, Maresca, Alessandro, Squizzato, Marta, Molaro, Bertolotti, Marco, Chiara, Mussi, Maria Vittoria Libbra, DI MICELI, Andrea, Pellegrini, Elisa, Lucia, Carulli, Francesca, Veltri, Angela, Sciacqua, Michele, Quero, Chiara, Bagnato, Lidia, Colangelo, Tania, Falbo, Roberto De Giorgio, DALLA SERRA, Mauro, Valentina, Grasso, Eugenio, Ruggeri, Benzoni, Ilaria, Andrea, Salvi, Leonardi, Roberto, Chiara, Grassini, Ilenia, Mascherona, Minelli, Giorgio, Francesca, Maltese, Giampaolo, Damiani, William, Capeci, Mattioli, Massimo, Giuseppe Pio Martino, Biondi, Lorenzo, Monica, Ormas, Pietro, Pettinari, Roberto, Romiti, Silvia, Messina, Federica, Cavallaro, Riccardi, Ghio, Serena, Favorini, Anna Dal Col, Salvatore, Minisola, Luciano, Colangelo, Antonella, Afeltra, Pamela, Alemanno, Benedetta, Marigliano, Maria Elena Pipita, Pietro, Castellino, Julien, Blanco, Luca, Zanoli, Cattaneo, Marco Natale, Paola, Fracasso, Amoruso, MARIA VALENTINA, Valter, Saracco, Marisa, Fogliati, Carlo, Bussolino, Vittorio, Durante, Giovanna, Eusebi, Daniela, Tirotta, Francesca, Mete, Miriam, Gino, Antonio, Cittadini, Carlo, Vigorito, Michele, Arcopinto, Andrea, Salzano, Emanuele, Bobbio, Alberto Maria Marra, Domenico, Sirico, Guido, Moreo, Francesco, Scopelliti, Francesca, Gasparini, Melissa, Cocca, Alberto, Ballestrero, Fabio, Ferrando, Sergio, Berra, Simonetta, Dassi, Maria Cristina Nava, Bruno, Graziella, Stefano, Baldassarre, Salvatore, Fragapani, Giorgio, Galanti, Gabriele, Mascherini, Cristian, Petri, Laura, Stefani, Margherita, Girino, Valeria, Piccinelli, Francesco, Nasso, Vincenza, Gioffrè, Maria, Pasquale, Giuseppe, Scattolin, Sergio, Martinelli, Mauro, Turrin, Leonardo, Sechi, Cristina, Catena, Gianluca, Colussi, Ramirez Duque Nieves, Muela Molinero Alberto, Abad Requejo Pedro, Lopez Pelaez Vanessa, Tamargo, Lara, Corbella Viros Xavier, Formiga, Francesc, Diez Manglano Jesus, Bejarano Tello Esperanza, Del Corral Behamonte Esther, Sevil Puras Maria, Manuel, Romero, Pinilla Llorente Blanca, Lopez Gonzalez-Cobos Cristina, Victoria, Villalba Garcia M., Lopez, Saez, Juan, Bosco, Sanz Baena Susana, Arroyo Gallego Marta, Gonzalez Becerra Concepcion, Fernandez Moyano Antonio, Mercedes Gomez Hernandez, Manuel Poyato Borrego, Pacheco Cuadros Raquel, Perez Rojas Florencia, Garcia Olid Beatriz, Carrascosa Garcia Sara, Gonzalez-Cruz Cervellera Alfonso, Peinado Martinez Marta, Sara Carrascosa Garcia, Ruiz Cantero Alberto, Albarracín Arraigosa Antonio, Godoy Guerrero Montserrat, Barón Ramos Miguel Ángel, Machin Jose Manuel, Novo Veleiro Ignacio, Alvela Suarez Lucía, Lopez, Alfonso, Rubal Bran David, Iñiguez Vazquez Iria, Rios Prego Monica, Franchi C., Ardoino I., Nobili A., Pasina L., Mannucci P.M., Marengoni A., Perticone F., REPOSI investigators., Barbagallo M., Dominguez Rodríguez L.J., Franchi, C., Ardoino, I., Nobili, A., Pasina, L., Mannucci, P. M., Marengoni, A., Perticone, F., Tettamanti, M., Salerno, F., Corrao, S., Licata, G., Violi, F., Corazza, G. R., Marcucci, M., Eldin, T. K., Donatella Di Blanca, M. P., Lanzo, G., Astuto, S., Cortesi, L., Prisco, D., Silvestri, E., Cenci, C., Emmi, G., Biolo, G., Guarnieri, G., Zanetti, M., Fernandes, G., Chiuch, M., Vanoli, M., Grignani, G., Casella, G., Pulixi, E. A., Bernardi, M., Li Bassi, S., Santi, L., Zaccherini, G., Mannarino, E., Lupattelli, G., Bianconi, V., Paciullo, F., Nuti, R., Valenti, R., Ruvio, M., Cappelli, S., Palazzuoli, A., Salvatore, T., Sasso, F. C., Girelli, D., Olivieri, O., Matteazzi, T., Barbagallo, M., Plances, L., Alcamo, R., Calvo, L., Valenti, M., Zoli, M., Arno, R., Pasini, F. L., Capecchi, P. L., Bicchi, M., Palasciano, G., Modeo, M. E., Peragine, M., Pappagallo, F., Pugliese, S., Di Gennaro, C., Postiglione, A., Barbella, M. R., De Stefano, F., Cappellini, M. D., Fabio, G., Seghezzi, S., De Amicis, M. M., Mancarella, M., Mari, D., Rossi, P. D., Damanti, S., Ottolini, B. B., Bonini, G., Miceli, E., Lenti, M. V., Padula, D., Murialdo, G., Marra, A., Cattaneo, F., Secchi, M. B., Ghelfi, D., Anastasio, L., Sofia, L., Carbone, M., Davi, G., Guagnano, M. T., Sestili, S., Mancuso, G., Calipari, D., Bartone, M., Meroni, M. R., Perin, P. C., Lorenzati, B., Gruden, G., Bruno, G., Amione, C., Fornengo, P., Tassara, R., Melis, D., Rebella, L., Delitala, G., Pretti, V., Masala, M. S., Pes, C., Bolondi, L., Rasciti, L., Serio, I., Fanelli, F. R., Amoroso, A., Molfino, A., Petrillo, E., Zuccala, G., Franceschi, F., De Marco, G., Chiara, C., Marta, S., D'Aurizio, G., Romanelli, G., Amolini, C., Chiesa, D., Picardi, A., Gentilucci, U. V., Gallo, P., Annoni, G., Corsi, M., Zazzetta, S., Bellelli, G., Szabo, H., Arturi, F., Succurro, E., Rubino, M., Sesti, G., Loria, P., Becchi, M. A., Martucci, G., Fantuzzi, A., Maurantonio, M., Serra, M. G., Bleve, M. A., Gasbarrone, L., Sajeva, M. R., Brucato, A., Ghidoni, S., Di Corato, P., Agnelli, G., Marchesini, E., Fabris, F., Carlon, M., Turatto, F., Baritusso, A., Amabile, A., Omenetto, E., Scarinzi, P., Manfredini, R., Molino, C., Pala, M., Fabbian, F., Boari, B., De Giorgi, A., Paolisso, G., Rizzo, M. R., Laieta, M. T., Rini, G., Mansueto, P., Pepe, I., Borghi, C., Strocchi, E., De Sando, V., Pareo, I., Sabba, C., Vella, F. S., Suppressa, P., Valerio, R., Agosti, P., Fontana, F., Loparco, F., Capobianco, C., Fenoglio, L., Bracco, C., Giraudo, A. V., Testa, E., Serraino, C., Fargion, S., Bonara, P., Periti, G., Porzio, M., Tiraboschi, S., Peyvandi, F., Tedeschi, A., Rossio, R., Monzani, V., Savojardo, V., Folli, C., Magnini, M., Conca, A., Gobbo, G., Pallini, G., Balduini, C. L., Bertolino, G., Provini, S., Quaglia, F., Dallegri, F., Ottonello, L., Liberale, L., Chin, W. S., Carassale, L., Caporotundo, S., Traisci, G., De Feudis, L., Di Carlo, S., Liberato, N. L., Buratti, A., Tognin, T., Bianchi, G. B., Giaquinto, S., Purrello, F., Di Pino, A., Piro, S., Rozzini, R., Falanga, L., Spazzini, E., Montrucchio, G., Greco, E., Tizzani, P., Petitti, P., Perciccante, A., Coralli, A., Salmi, R., Gaudenzi, P., Gamberini, S., Semplicini, A., Gottardo, L., Vendemiale, G., Serviddio, G., Forlano, R., Masala, C., Mammarella, A., Raparelli, V., Basili, S., Perri, L., Landolfi, R., Montalto, M., Mirijello, A., Vallone, C., Bellusci, M., Setti, D., Pedrazzoli, F., Guasti, L., Castiglioni, L., Maresca, A., Squizzato, A., Molaro, M., Bertolotti, M., Mussi, C., Libbra, M. V., Miceli, A., Pellegrini, E., Carulli, L., Veltri, F., Sciacqua, A., Quero, M., Bagnato, C., Colangelo, L., Falbo, T., De Giorgio, R., Serra, M., Grasso, V., Ruggeri, E., Ilaria, B., Salvi, A., Leonardi, R., Grassini, C., Mascherona, I., Minelli, G., Maltese, F., Damiani, G., Capeci, W., Mattioli, M., Martino, G. P., Biondi, L., Ormas, M., Pettinari, P., Romiti, R., Messina, S., Cavallaro, F., Ghio, R., Favorini, S., Dal Col, A., Minisola, S., Afeltra, A., Alemanno, P., Marigliano, B., Pipita, M. E., Castellino, P., Blanco, J., Zanoli, L., Cattaneo, M., Fracasso, P., Amoruso, M. V., Saracco, V., Fogliati, M., Bussolino, C., Durante, V., Eusebi, G., Tirotta, D., Mete, F., Gino, M., Cittadini, A., Vigorito, C., Arcopinto, M., Salzano, A., Bobbio, E., Marra, A. M., Sirico, D., Moreo, G., Scopelliti, F., Gasparini, F., Cocca, M., Ballestrero, A., Ferrando, F., Berra, S., Dassi, S., Nava, M. C., Graziella, B., Baldassarre, S., Fragapani, S., Galanti, G., Mascherini, G., Petri, C., Stefani, L., Girino, M., Piccinelli, V., Nasso, F., Gioffre, V., Pasquale, M., Scattolin, G., Martinelli, S., Turrin, M., Sechi, L., Catena, C., Colussi, G., Nieves, R. D., Alberto, M. M., Pedro, A. R., Vanessa, L. P., Lara, T., Xavier, C. V., Francesc, F., Jesus, D. M., Esperanza, B. T., Esther, D. C. B., Maria, S. P., Romero, M., Blanca, P. L., Cristina, L. G. -C., Victoria, V. G. M., Saez, L., Bosco, J., Susana, S. B., Marta, A. G., Concepcion, G. B., Antonio, F. M., Hernandez, M. G., Borrego, M. P., Raquel, P. C., Florencia, P. R., Beatriz, G. O., Sara, C. G., Alfonso, G. -C. C., Marta, P. M., Garcia, S. C., Alberto, R. C., Antonio, A. A., Montserrat, G. G., Angel, B. R. M., Manuel, M. J., Ignacio, N. V., Lucia, A. S., Alfonso, L., David, R. B., Iria, I. V., Monica, R. P., Franchi, C, Ardoino, I, Nobili, A, Pasina, L, Mannucci, P, Marengoni, A, Perticone, F, Tettamanti, M, Salerno, F, Corrao, S, Licata, G, Violi, F, Corazza, G, Marcucci, M, Eldin, T, Donatella Di Blanca, M, Lanzo, G, Astuto, S, Cortesi, L, Prisco, D, Silvestri, E, Cenci, C, Emmi, G, Biolo, G, Guarnieri, G, Zanetti, M, Fernandes, G, Chiuch, M, Vanoli, M, Grignani, G, Casella, G, Pulixi, E, Bernardi, M, Li Bassi, S, Santi, L, Zaccherini, G, Mannarino, E, Lupattelli, G, Bianconi, V, Paciullo, F, Nuti, R, Valenti, R, Ruvio, M, Cappelli, S, Palazzuoli, A, Salvatore, T, Sasso, F, Girelli, D, Olivieri, O, Matteazzi, T, Barbagallo, M, Plances, L, Alcamo, R, Calvo, L, Valenti, M, Zoli, M, Arno, R, Pasini, F, Capecchi, P, Bicchi, M, Palasciano, G, Modeo, M, Peragine, M, Pappagallo, F, Pugliese, S, Di Gennaro, C, Postiglione, A, Barbella, M, De Stefano, F, Cappellini, M, Fabio, G, Seghezzi, S, De Amicis, M, Mancarella, M, Mari, D, Rossi, P, Damanti, S, Ottolini, B, Bonini, G, Miceli, E, Lenti, M, Padula, D, Murialdo, G, Marra, A, Cattaneo, F, Secchi, M, Ghelfi, D, Anastasio, L, Sofia, L, Carbone, M, Davi, G, Guagnano, M, Sestili, S, Mancuso, G, Calipari, D, Bartone, M, Meroni, M, Perin, P, Lorenzati, B, Gruden, G, Bruno, G, Amione, C, Fornengo, P, Tassara, R, Melis, D, Rebella, L, Delitala, G, Pretti, V, Masala, M, Pes, C, Bolondi, L, Rasciti, L, Serio, I, Fanelli, F, Amoroso, A, Molfino, A, Petrillo, E, Zuccala, G, Franceschi, F, De Marco, G, Chiara, C, Marta, S, D'Aurizio, G, Romanelli, G, Amolini, C, Chiesa, D, Picardi, A, Gentilucci, U, Gallo, P, Annoni, G, Corsi, M, Zazzetta, S, Bellelli, G, Szabo, H, Arturi, F, Succurro, E, Rubino, M, Sesti, G, Loria, P, Becchi, M, Martucci, G, Fantuzzi, A, Maurantonio, M, Serra, M, Bleve, M, Gasbarrone, L, Sajeva, M, Brucato, A, Ghidoni, S, Di Corato, P, Agnelli, G, Marchesini, E, Fabris, F, Carlon, M, Turatto, F, Baritusso, A, Amabile, A, Omenetto, E, Scarinzi, P, Manfredini, R, Molino, C, Pala, M, Fabbian, F, Boari, B, De Giorgi, A, Paolisso, G, Rizzo, M, Laieta, M, Rini, G, Mansueto, P, Pepe, I, Borghi, C, Strocchi, E, De Sando, V, Pareo, I, Sabba, C, Vella, F, Suppressa, P, Valerio, R, Agosti, P, Fontana, F, Loparco, F, Capobianco, C, Fenoglio, L, Bracco, C, Giraudo, A, Testa, E, Serraino, C, Fargion, S, Bonara, P, Periti, G, Porzio, M, Tiraboschi, S, Peyvandi, F, Tedeschi, A, Rossio, R, Monzani, V, Savojardo, V, Folli, C, Magnini, M, Conca, A, Gobbo, G, Pallini, G, Balduini, C, Bertolino, G, Provini, S, Quaglia, F, Dallegri, F, Ottonello, L, Liberale, L, Chin, W, Carassale, L, Caporotundo, S, Traisci, G, De Feudis, L, Di Carlo, S, Liberato, N, Buratti, A, Tognin, T, Bianchi, G, Giaquinto, S, Purrello, F, Di Pino, A, Piro, S, Rozzini, R, Falanga, L, Spazzini, E, Montrucchio, G, Greco, E, Tizzani, P, Petitti, P, Perciccante, A, Coralli, A, Salmi, R, Gaudenzi, P, Gamberini, S, Semplicini, A, Gottardo, L, Vendemiale, G, Serviddio, G, Forlano, R, Masala, C, Mammarella, A, Raparelli, V, Basili, S, Perri, L, Landolfi, R, Montalto, M, Mirijello, A, Vallone, C, Bellusci, M, Setti, D, Pedrazzoli, F, Guasti, L, Castiglioni, L, Maresca, A, Squizzato, A, Molaro, M, Bertolotti, M, Mussi, C, Libbra, M, Miceli, A, Pellegrini, E, Carulli, L, Veltri, F, Sciacqua, A, Quero, M, Bagnato, C, Colangelo, L, Falbo, T, De Giorgio, R, Grasso, V, Ruggeri, E, Ilaria, B, Salvi, A, Leonardi, R, Grassini, C, Mascherona, I, Minelli, G, Maltese, F, Damiani, G, Capeci, W, Mattioli, M, Martino, G, Biondi, L, Ormas, M, Pettinari, P, Romiti, R, Messina, S, Cavallaro, F, Ghio, R, Favorini, S, Dal Col, A, Minisola, S, Afeltra, A, Alemanno, P, Marigliano, B, Pipita, M, Castellino, P, Blanco, J, Zanoli, L, Cattaneo, M, Fracasso, P, Amoruso, M, Saracco, V, Fogliati, M, Bussolino, C, Durante, V, Eusebi, G, Tirotta, D, Mete, F, Gino, M, Cittadini, A, Vigorito, C, Arcopinto, M, Salzano, A, Bobbio, E, Sirico, D, Moreo, G, Scopelliti, F, Gasparini, F, Cocca, M, Ballestrero, A, Ferrando, F, Berra, S, Dassi, S, Nava, M, Graziella, B, Baldassarre, S, Fragapani, S, Galanti, G, Mascherini, G, Petri, C, Stefani, L, Girino, M, Piccinelli, V, Nasso, F, Gioffre, V, Pasquale, M, Scattolin, G, Martinelli, S, Turrin, M, Sechi, L, Catena, C, Colussi, G, Nieves, R, Alberto, M, Pedro, A, Vanessa, L, Lara, T, Xavier, C, Francesc, F, Jesus, D, Esperanza, B, Esther, D, Maria, S, Romero, M, Blanca, P, Cristina, L, Victoria, V, Saez, L, Bosco, J, Susana, S, Marta, A, Concepcion, G, Antonio, F, Hernandez, M, Borrego, M, Raquel, P, Florencia, P, Beatriz, G, Sara, C, Alfonso, G, Marta, P, Garcia, S, Alberto, R, Antonio, A, Montserrat, G, Angel, B, Manuel, M, Ignacio, N, Lucia, A, Alfonso, L, David, R, Iria, I, and Monica, R
Subjects: Registrie, Male, pharmacoepidemiology, Epidemiology, Discharged alive, 030204 cardiovascular system & hematology, internal medicine and geriatric ward, drug use, excessive polypharmacy, internal medicine and geriatric wards, older people, polypharmacy, 0302 clinical medicine, Drug Prescription, Risk Factors, 80 and over, Pharmacology (medical), 030212 general & internal medicine, Registries, At-Risk Population, media_common, Aged, 80 and over, Overtime, drug use, excessive polypharmacy, internal medicine and geriatric wards, older people, pharmacoepidemiology, polypharmacy, Pharmacoepidemiology, Hospitalization, Italy, Female, Medical emergency, Human, Drug, medicine.medical_specialty, media_common.quotation_subject, Socio-culturale, Drug Prescriptions, 03 medical and health sciences, Hospital discharge, medicine, Internal Medicine, Humans, Aged, Polypharmacy, Inpatients, business.industry, Risk Factor, medicine.disease, Emergency medicine, Older people, business
Abstract: Purpose: To assess the pattern of in-hospital changes in drug use in older patients from 2010 to 2016. Methods: People aged 65years or more acutely hospitalized in those internal medicine and geriatric wards that did continuously participate to the REgistro POliterapie Società Italiana di Medicina Interna register from 2010 to 2016 were selected. Drugs use were categorized as 0 to 1 drug (very low drug use), 2 to 4 drugs (low drug use), 5 to 9 drugs (polypharmacy), and 10 or more drugs (excessive polypharmacy). To assess whether or not prevalence of patients in relation to drug use distribution changed overtime, adjusted prevalence ratios (PRs) was estimated with log-binomial regression models. Results: Among 2120 patients recruited in 27 wards continuously participating to data collection, 1882 were discharged alive and included in this analysis. The proportion of patients with very low drug use (0-1 drug) at hospital discharge increased overtime, from 2.7% in 2010 to 9.2% in 2016. Results from a log-logistic adjusted model confirmed the increasing PR of these very low drug users overtime (particularly in 2014 vs 2012, PR 1.83 95% CI 1.14-2.95). Moreover, from 2010 to 2016, there was an increasing number of patients who, on polypharmacy at hospital admission, abandoned it at hospital discharge, switching to the very low drug use group. Conclusion: This study shows that in internal medicine and geriatric wards continuously participating to the REgistro POliterapie Società Italiana di Medicina Interna register, the proportion of patients with a very low drug use at hospital discharge increased overtime, thus reducing the therapeutic burden in this at risk population.
Published: 2017

33. Use of non-steroidal anti-inflammatory drugs and analgesics in a cohort of hospitalized elderly patients: Results from the REPOSI study

Author: Pasina, L, Cortesi, L, Tettamanti, M, Nobili, A, Mannucci, Pm, Franchi, F, Salerno, F, Corrao, S, Marengoni, A, Licata, G, Violi, F, Corazza, Gr, Marcucci, M, Prisco, D, Silvestri, E, Cenci, C, Emmi, G, Biolo, G, Guarnieri, G, Zanetti, M, Fernandes, G, Vanoli, M, Grignani, G, Casella, G, Bernardi, M, Li Bassi, S, Santi, L, Zaccherini, G, Mannarino, E, Lupattelli, G, Bianconi, V, Paciullo, F, Nuti, R, Valenti, R, Ruvio, R, Cappelli, S, Palazzuoli, A, Salvatore, T, Sasso, Fc, Girelli, G, Olivieri, O, Matteazzi, T, Barbagallo, M, Plances, L, Alcamo, R, Calvo, G, Valenti, V, Zoli, M, Arnò, A, Laghi Pasini, F, Capecchi, Pl, Bicchi, M, Palasciano, P, Modeo, Me, Peragine, M, Pappagallo, F, Pugliese, S, Di Gennaro, C, Postiglione, A, Barbella, Mr, De Stefano, F, Cappellini, Md, Fabio, G, Seghezzi, S, Migone De Amicis, M, Mari, D, Dionigi Rossi, P, Damanti, S, Brignolo Ottolini, B, Miceli, M, Lenti, Mv, Padula, D, Murialdo, G, Marra, A, Cattaneo, F, Secchi, Mb, Ghelfi, D, Anastasio, A, Sofia, L, Carbone, M, Davì, G, Guagnano, Mt, Sestili, S, Mancuso, G, Calipari, D, Bartone, M, Meroni, Mr, Cavallo Perin, P, Lorenzati, B, Gruden, G, Bruno, G, Amione, C, Fornengo, P, Tassara, T, Melis, D, Rebella, L, Delitala, D, Pretti, V, Masala, Ms, Bolondi, L, Rasciti, L, Serio, I, Rossi Fanelli, F, Amoroso, A, Molfino, A, Petrillo, E, Zuccalà, G, Franceschi, F, De Marco, G, Cordischi, C, Sabbatini, M, Romanelli, G, Amolini, C, Chiesa, D, Picardi, A, Vespasiani Gentilucci, U, Gallo, P, Annoni, G, Corsi, M, Zazzetta, S, Bellelli, G, Arturi, F, Succurro, E, Rubino, M, Sesti, G, Loria, P, Becchi, Ma, Martucci, G, Fantuzzi, A, Maurantonio, M, Delitala, G, Carta, S, Atzori, S, Serra, Mg, Bleve, Ma, Gasbarrone, L, Sajeva, Mr, Brucato, A, Ghidoni, S, Di Corato, P, Agnelli, G, Marchesini, E, Fabris, F, Carlon, M, Turatto, F, Baritusso, A, Manfredini, Roberto, Molino, C, Pala, M, Fabbian, Fabio, Boari, B, De Giorgi, A, Paolisso, G, Rizzo, Mr, Laieta, Mt, Rini, G, Mansueto, P, Pepe, I, Borghi, C, Strocchi, E, De Sando, V, Sabbà, C, Vella, Fs, Suppressa, P, Valerio, R, Capobianco, C, Fenoglio, L, Bracco, C, Giraudo, Av, Testa, E, Serraino, C, Fargion, S, Bonara, P, Periti, G, Porzio, M, Peyvandi, F, Tedeschi, A, Rossio, R, Monzani, V, Savojardo, V, Folli, C, Magnini, M, Conca, A, Gobbo, G, Balduini, Cl, Bertolino, G, Provini, S, Quaglia, F, Dallegri, F, Ottonello, L, Liberale, L, Chin, Ws, Carassale, L, Caporotundo, S, Traisci, G, De Feudis, L, Di Carlo, S, Liberato, Nl, Buratti, A, Tiziana Tognin, T, Bianchi, Gb, Giaquinto, S, Purrello, F, Di Pino, A, Piro, S, Rozzini, R, Falanga, L, Montrucchio, G, Greco, E, Tizzani, P, Petitti, P, Perciccante, A, Coralli, A, Salmi, R, Gaudenzi, P, Gamberini, S, Semplicini, A, Gottardo, L, Vendemiale, G, Serviddio, G, Forlano, R, Masala, C, Mammarella, A, Raparelli, V, Basili, S, Ludovica Perri, P, Landolfi, R, Montalto, M, Mirijello, A, Vallone, C, Bellusci, M, Setti, D, Pedrazzoli, F, Guasti, L, Castiglioni, L, Maresca, A, Squizzato, A, Molaro, M, Bertolotti, M, Mussi, C, Libbra, Mv, Miceli, A, Pellegrini, E, Carulli, L, Perticone, F, Sciacqua, A, Quero, M, Bagnato, C, Corinaldesi, R, DE GIORGIO, Roberto, Serra, M, Grasso, V, Ruggeri, E, Salvi, A, Leonardi, R, Grassini, C, Mascherona, I, Minelli, G, Maltese, F, Gabrielli, A, Mattioli, M, Capeci, W, Martino, Gp, Messina, S, Ghio, R, Favorini, S, Dal Col, A, Minisola, S, Colangelo, L, Afeltra, A, Alemanno, P, Marigliano, B, Castellino, P, Blanco, J, Zanoli, L, Cattaneo, M, Fracasso, P, Amoruso, Mv, Saracco, V, Fogliati, M, Bussolino, C, Durante, V, Eusebi, G, Tirotta, D, Mete, F, Gino, M, Cittadini, A, Arcopinto, M, Salzano, A, Bobbio, E, Marra, Am, Sirico, D, Moreo, M, Scopelliti, F, Gasparini, F, Cocca, M, Ramirez Duque, N, Muela Molinero, A, Abad Requejo, P, Lopez Pelaez, V, Tamargo, L, Corbella Viros, X, Formiga, F, Diez Manglano, J, Bejarano Tello, E, Del Corral Behamonte, E, Sevil Puras, M, Manuel, R, Pinilla Llorente, B, Lopez Gonzalez Cobos, C, Villalba Garcia, Mv, Sanz Baena, S, Arroyo Gallego, M, Gonzalez Becerra, C, Fernandez Moyano, A, Mercedes Gomez, H, Poyato Borrego, M, Pacheco Cuadros, R, Perez Rojas, F, Garcia Olid, B, Carrascosa Garcia, S, Gonzalez Cruz, C, Peinado Martinez, M, Ruiz Cantero, A, Albarracín Arraigosa, A, Godoy Guerrero, M, Barón Ramos, Ma, Machin, Jm, Novo Veleiro, I, Alvela Suarez, L, Lopez, A, Rubal Bran, D, Iñiguez Vazquez, I, and Rios Prego, M.
Subjects: Male, medicine.medical_specialty, Phamacoepidemiology, Socio-culturale, Pain, Comorbidity, 030204 cardiovascular system & hematology, 03 medical and health sciences, 0302 clinical medicine, Elderly, Internal medicine, Internal Medicine, medicine, Humans, Pain Management, 030212 general & internal medicine, Aged, Aged, 80 and over, Analgesics, business.industry, Anti-Inflammatory Agents, Non-Steroidal, Drug Utilization, Hospitalization, Non steroidal anti inflammatory, Italy, Cohort, Polypharmacy, Female, business, Elderly, Non-steroidal anti-inflammatory drugs, Phamacoepidemiology, Non-steroidal anti-inflammatory drugs
Published: 2016

34. RASMutations in Cutaneous Squamous-Cell Carcinomas in Patients Treated with BRAF Inhibitors

Author: Holly Hilton, Nicholas Otte, Julie S. Hang, Ion Niculescu-Duvaz, Felipe C. Geyer, Lidia Robert, K. B. Nolop, Jorge S. Reis-Filho, Luc Andries, Alfonso Zambon, Gideon Bollag, Rene Gonzalez, Natasha Preece, Paul B. Chapman, Damien Kee, Min Jung Kim, Kerstin Trunzer, Dan Niculescu-Duvaz, Stephen Mok, Brian Lestini, Roger S. Lo, Gaston Habets, Amaya Viros, James L. Troy, Caroline J. Springer, Mark M. Kockx, Yan Ma, Igor Puzanov, Carla Milagre, Robert Hayward, Elizabeth A. Burton, Antoni Ribas, Xiangju Kong, Chao Zhang, Matthew J. Martin, Maryou B K Lambros, Andrew K. Joe, Richard C. Koya, Jeffrey A. Sosman, Olivia Spleiss, Johannes Noe, Bartosz Chmielowski, Hoa Nguyen, Richard J. Lee, Keith T. Flaherty, Richard Marais, Nathalie Dhomen, Hong Yang, Bernice Wong, Qiongqing Wang, Grant A. McArthur, Fei Su, and Thomas E. Hutson
Subjects: Male, Proto-Oncogene Proteins B-raf, Neuroblastoma RAS viral oncogene homolog, Indoles, Skin Neoplasms, Gene Expression, medicine.disease_cause, Mice, chemistry.chemical_compound, CDKN2A, Animals, Humans, Medicine, HRAS, Vemurafenib, Protein Kinase Inhibitors, Aged, Aged, 80 and over, Mitogen-Activated Protein Kinase Kinases, Cobimetinib, Sulfonamides, business.industry, Melanoma, General Medicine, Middle Aged, medicine.disease, Gene Expression Regulation, Neoplastic, Genes, ras, chemistry, Mutation, Carcinoma, Squamous Cell, Cancer research, Female, KRAS, business, Carcinogenesis, medicine.drug
Abstract: Cutaneous squamous-cell carcinomas and keratoacanthomas are common findings in patients treated with BRAF inhibitors.We performed a molecular analysis to identify oncogenic mutations (HRAS, KRAS, NRAS, CDKN2A, and TP53) in the lesions from patients treated with the BRAF inhibitor vemurafenib. An analysis of an independent validation set and functional studies with BRAF inhibitors in the presence of the prevalent RAS mutation was also performed.Among 21 tumor samples, 13 had RAS mutations (12 in HRAS). In a validation set of 14 samples, 8 had RAS mutations (4 in HRAS). Thus, 60% (21 of 35) of the specimens harbored RAS mutations, the most prevalent being HRAS Q61L. Increased proliferation of HRAS Q61L-mutant cell lines exposed to vemurafenib was associated with mitogen-activated protein kinase (MAPK)-pathway signaling and activation of ERK-mediated transcription. In a mouse model of HRAS Q61L-mediated skin carcinogenesis, the vemurafenib analogue PLX4720 was not an initiator or a promoter of carcinogenesis but accelerated growth of the lesions harboring HRAS mutations, and this growth was blocked by concomitant treatment with a MEK inhibitor.Mutations in RAS, particularly HRAS, are frequent in cutaneous squamous-cell carcinomas and keratoacanthomas that develop in patients treated with vemurafenib. The molecular mechanism is consistent with the paradoxical activation of MAPK signaling and leads to accelerated growth of these lesions. (Funded by Hoffmann-La Roche and others; ClinicalTrials.gov numbers, NCT00405587, NCT00949702, NCT01001299, and NCT01006980.).
Published: 2012
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35. Publisher Correction: Ultraviolet radiation–induced DNA damage is prognostic for outcome in melanoma

Author: Amaya Viros, Martin G. Cook, Franziska Baenke, Pablo Garcia-Martinez, Caroline Gaudy-Marqueste, Nicolas Macagno, Donald Allan, Berta Sanchez-Laorden, Clare McManus, Richard Marais, Nathalie Dhomen, Piyushkumar A. Mundra, Kate Hogan, A. Mandal, and Lucas D Trucco
Subjects: 0301 basic medicine, Oncology, medicine.medical_specialty, business.industry, DNA damage, Published Erratum, Melanoma, General Medicine, medicine.disease, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, 030220 oncology & carcinogenesis, Internal medicine, Medicine, business, Ultraviolet radiation
Abstract: In the version of this article originally published, Extended Data Fig. 3 was incorrect. A duplicate of Extended Data Fig. 4 was uploaded in place of Extended Data Fig. 3. Extended Data Fig. 3 has now been uploaded. The error has been fixed in the PDF and HTML versions of this article.
Published: 2018
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36. Adherence to antithrombotic therapy guidelines improves mortality among elderly patients with atrial fibrillation: insights from the REPOSI study

Author: Proietti, Marco, Nobili, Alessandro, Raparelli, Valeria, Napoleone, Laura, Mannucci, Pier o, Lip, Gregory Y, Tettamanti, Mauro, Pasina, Luca, Franchi, Carlotta, Perticone, Francesco, Salerno, Francesco, Corrao, Salvatore, Marengoni, Alessandra, Licata, Giuseppe, Violi, Francesco, Corazza, Gino Roberto, Marcucci, Maura, Prisco, Domenico, Silvestri, Elena, Cenci, Caterina, Emmi, Giacomo, Biolo, Gianni, Guarnieri, Gianfranco, Zanetti, Michela, Fernandes, Giovanni, Vanoli, Massimo, Grignani, Giulia, Casella, Gianluca, Bernardi, Mauro, Bassi, Silvia Li, Santi, Luca, Zaccherini, Giacomo, Mannarino, Elmo, Lupattelli, Graziana, Bianconi, Vanessa, Paciullo, Francesco, Nuti, Ranuccio, Valenti, Roberto, Ruvio, Martina, Cappelli, Silvia, Palazzuoli, Alberto, Salvatore, Teresa, Sasso, Ferdinando Carlo, Girelli, Domenico, Olivieri, Oliviero, Matteazzi, Thomas, Barbagallo, Mario, Plances, Lidia, Alcamo, Roberta, Calvo, Luigi, Valenti, Maria, Zoli, Marco, Arnò, Raffaella, Pasini, Franco Laghi, Capecchi, Pier Leopoldo, Bicchi, Maurizio, Palasciano, Giuseppe, Modeo, Maria Ester, Peragine, Maria, Pappagallo, Fabrizio, Pugliese, Stefania, Gennaro, Carla Di, Postiglione, Alfredo, Barbella, Maria Rosaria, Stefano, Francesco De, Cappellini, Maria Domenica, Fabio, Giovanna, Seghezzi, Sonia, Amicis, Margherita Migone De, Mari, Daniela, Rossi, Paolo Dionigi, Damanti, Sarah, Ottolini, Barbara Brignolo, Miceli, Emanuela, Lenti, Marco Vincenzo, Padula, Donatella, Murialdo, Giovanni, Marra, Alessio, Cattaneo, Federico, Secchi, Maria Beatrice, Ghelfi, Davide, Anastasio, Luigi, Sofia, Lucia, Carbone, Maria, Davì, Giovanni, Guagnano, Maria Teresa, Sestili, Simona, Mancuso, Gerardo, Calipari, Daniela, Bartone, Mosè, Meroni, Maria Rachele, Perin, Paolo Cavallo, Lorenzati, Bartolomeo, Gruden, Gabriella, Bruno, Graziella, Amione, Cristina, Fornengo, Paolo, Tassara, Rodolfo, Melis, Deborah, Rebella, Lara, Delitala, Giuseppe, Pretti, Vincenzo, Masala, Maristella Salvatora, Bolondi, Luigi, Rasciti, Leonardo, Serio, Ilaria, Fanelli, Filippo Rossi, Amoroso, Antonio, Molfino, Alessio, Petrillo, Enrico, Zuccalà, Giuseppe, Franceschi, Francesco, Marco, Guido De, Chiara, Cordischi, Marta, Sabbatini, Romanelli, Giuseppe, Amolini, Claudia, Chiesa, Deborah, Picardi, Antonio, Gentilucci, Umberto Vespasiani, Gallo, Paolo, Annoni, Giorgio, Corsi, Maurizio, Zazzetta, Sara, Bellelli, Giuseppe, Arturi, Franco, Succurro, Elena, Rubino, Mariangela, Sesti, Giorgio, Loria, Paola, Becchi, Maria Angela, Martucci, Gianfranco, Fantuzzi, Alessandra, Maurantonio, Mauro, Carta, Stefano, Atzori, Sebastiana, Serra, Maria Grazia, Bleve, Maria Antonietta, Gasbarrone, Laura, Sajeva, Maria Rosaria, Brucato, Antonio, Ghidoni, Silvia, Corato, Paola Di, Agnelli, Giancarlo, Marchesini, Emanuela, Fabris, Fabrizio, Carlon, Michela, Turatto, Francesca, Baritusso, Aldo, Manfredini, Roberto, Molino, Christian, Pala, Marco, Fabbian, Fabio, Boari, Benedetta, Giorgi, Alfredo De, Paolisso, Giuseppe, Rizzo, Maria Rosaria, Laieta, Maria Teresa, Rini, Giovanbattista, Mansueto, Pasquale, Pepe, Ilenia, Borghi, Claudio, Strocchi, Enrico, Sando, Valeria De, Sabbà, Carlo, Vella, Francesco Saverio, Suppressa, Patrizia, Valerio, Raffaella, Capobianco, Caterina, Fenoglio, Luigi, Bracco, Christian, Giraudo, Alessia Valentina, Testa, Elisa, Serraino, Cristina, Fargion, Silvia, Bonara, Paola, Periti, Giulia, Porzio, Marianna, Peyvandi, Flora, Tedeschi, Alberto, Rossio, Raffaella, Monzani, Valter, Savojardo, Valeria, Folli, Christian, Magnini, Maria, Conca, Alessio, Gobbo, Giulia, Balduini, Carlo L., Bertolino, Giampiera, Provini, Stella, Quaglia, Federica, Dallegri, Franco, Ottonello, Luciano, Liberale, Luca, Chin, Wu Sheng, Carassale, Laura, Caporotundo, Silvia, Traisci, Giancarlo, Feudis, Lucrezia De, Carlo, Silvia Di, Liberato, Nicola Lucio, Buratti, Alberto, Tognin, Tiziana, Bianchi, Giovanni Battista, Giaquinto, Sabrina, Purrello, Francesco, Pino, Antonino Di, Piro, Salvatore, Rozzini, Renzo, Falanga, Lina, Montrucchio, Giuseppe, Greco, Elisabetta, Tizzani, Pietro, Petitti, Paolo, Perciccante, Antonio, Coralli, Alessia, Salmi, Raffaella, Gaudenzi, Piergiorgio, Gamberini, Susanna, Semplicini, Andrea, Gottardo, Lucia, Vendemiale, Gianluigi, Serviddio, Gaetano, Forlano, Roberta, Masala, Cesare, Mammarella, Antonio, Basili, Stefania, Perri, Ludovica, Landolfi, Raffaele, Montalto, Massimo, Mirijello, Antonio, Vallone, Carla, Bellusci, Martino, Setti, Donatella, Pedrazzoli, Filippo, Guasti, Luigina, Castiglioni, Luana, Maresca, Andrea, Squizzato, Alessandro, Molaro, Marta, Bertolotti, Marco, Mussi, Chiara, Libbra, Maria Vittoria, Miceli, Andrea, Pellegrini, Elisa, Carulli, Lucia, Sciacqua, Angela, Quero, Michele, Bagnato, Chiara, Corinaldesi, Roberto, Giorgio, Roberto De, Serra, Mauro, Grasso, Valentina, Ruggeri, Eugenio, Salvi, Andrea, Leonardi, Roberto, Grassini, Chiara, Mascherona, Ilenia, Minelli, Giorgio, Maltese, Francesca, Gabrielli, Armando, Mattioli, Massimo, Capeci, William, Martino, Giuseppe Pio, Messina, Silvia, Ghio, Riccardi, Favorini, Serena, Anna Dal Col, Minisola, Salvatore, Colangelo, Luciano, Afeltra, Antonella, Alemanno, Pamela, Marigliano, Benedetta, Castellino, Pietro, Blanco, Julien, Zanoli, Luca, Cattaneo, Marco, Fracasso, Paola, Amoruso, Maria Valentina, Saracco, Valter, Fogliati, Marisa, Bussolino, Carlo, Durante, Vittorio, Eusebi, Giovanna, Tirotta, Daniela, Mete, Francesca, Gino, Miriam, Cittadini, Antonio, Arcopinto, Michele, Salzano, Andrea, Bobbio, Emanuele, Marra, Alberto Maria, Sirico, Domenico, Moreo, Guido, Scopelliti, Francesco, Gasparini, Francesca, Cocca, Melissa, Nieves, Ramirez Duque, Alberto, Muela Molinero, Pedro, Abad Requejo, Vanessa, Lopez Pelaez, Lara, Tamargo, Xavier, Corbella Viros, Francesc, Formiga, Jesus, Diez Manglano, Esperanza, Bejarano Tello, Esther, Del Corral Behamonte, Maria, Sevil Puras, Romero, Manuel, Blanca, Pinilla Llorente, Cristina, Lopez Gonzalez Cobos, Victoria, Villalba Garcia M., Saez, Lopez, Bosco, Juan, Susana, Sanz Baena, Marta, Arroyo Gallego, Concepcion, Gonzalez Becerra, Antonio, Fernandez Moyano, Hernandez, Mercedes Gomez, Borrego, Manuel Poyato, Raquel, Pacheco Cuadros, Florencia, Perez Rojas, Beatriz, Garcia Olid, Sara, Carrascosa Garcia, Alfonso, Gonzalez Cruz Cervellera, Marta, Peinado Martinez, Alberto, Ruiz Cantero, Antonio, Albarracín Arraigosa, Montserrat, Godoy Guerrero, Ángel, Barón Ramos Miguel, Manuel, Machin Jose, Ignacio, Novo Veleiro, Lucía, Alvela Suarez, Alfonso, Lopez, David, Rubal Bran, Iria, Iñiguez Vazquez, Monica, Rios Prego ., Proietti, M, Nobili, A, Raparelli, V, Napoleone, L, Mannucci, P, Lip, G, Pasina, L, Franchi, C, Tettamanti, M, Eldin, T, Di Blanca, M, Djade, C, Ardoino, I, Cortesi, L, Marengoni, A, Licata, G, Violi, F, Corazza, G, Biolo, G, Guarnieri, G, Zanetti, M, Fernandes, G, Vanoli, M, Grignani, G, Casella, G, Bernardi, M, Bassi, S, Santi, L, Zaccherini, G, Mannarino, E, Lupattelli, G, Bianconi, V, Paciullo, F, Nuti, R, Valenti, R, Ruvio, M, Cappelli, S, Palazzuoli, A, Salvatore, T, Sasso, F, Girelli, D, Olivieri, O, Matteazzi, T, Barbagallo, M, Plances, L, Alcamo, R, Calvo, L, Valenti, M, Zoli, M, Arno, R, Pasini, F, Capecchi, P, Bicchi, M, Palasciano, G, Modeo, M, Peragine, M, Pappagallo, F, Di Gennaro, C, Postiglione, A, Barbella, M, De Stefano, F, Cappellini, M, Fabio, G, Seghezzi, S, De Amicis, M, Mari, D, Rossi, P, Ottolini, B, Miceli, E, Lenti, M, Padula, D, Murialdo, G, Marra, A, Cattaneo, F, Secchi, M, Ghelfi, D, Anastasio, L, Sofia, L, Carbone, M, Damanti, S, Guagnano, M, Sestili, S, Mancuso, G, Calipari, D, Bartone, M, Meroni, M, Perin, P, Lorenzati, B, Gruden, G, Bruno, G, Amione, C, Fornengo, P, Tassara, R, Melis, D, Rebella, L, Pretti, V, Masala, M, Bolondi, L, Rasciti, L, Serio, I, Fanelli, F, Amoroso, A, Molfino, A, Petrillo, E, Zuccala, G, Franceschi, F, De Marco, G, Chiara, C, Marta, S, Romanelli, G, Amolini, C, Chiesa, D, Picardi, A, Gentilucci, U, Gallo, P, Annoni, G, Corsi, M, Zazzetta, S, Bellelli, G, Arturi, F, Succurro, E, Rubino, M, Sesti, G, Loria, P, Becchi, M, Martucci, G, Fantuzzi, A, Maurantonio, M, Carta, S, Atzori, S, Serra, M, Bleve, M, Gasbarrone, L, Sajeva, M, Brucato, A, Ghidoni, S, Di Corato, P, Agnelli, G, Marchesini, E, Fabris, F, Carlon, M, Baritusso, A, Manfredini, R, Molino, C, Pala, M, Fabbian, F, Boari, B, De Giorgi, A, Paolisso, G, Rizzo, M, Laieta, M, Rini, G, Mansueto, P, Pepe, I, Borghi, C, Strocchi, E, De Sando, V, Sabba, C, Vella, F, Turatto, F, Valerio, R, Capobianco, C, Fenoglio, L, Bracco, C, Giraudo, A, Testa, E, Serraino, C, Fargion, S, Bonara, P, Periti, G, Porzio, M, Peyvandi, F, Tedeschi, A, Rossio, R, Monzani, V, Savojardo, V, Folli, C, Magnini, M, Gobbo, G, Balduini, C, Bertolino, G, Provini, S, Quaglia, F, Dallegri, F, Ottonello, L, Liberale, L, Chin, W, Carassale, L, Caporotundo, S, Traisci, G, De Feudis, L, Di Carlo, S, Liberato, N, Buratti, A, Tognin, T, Bianchi, G, Giaquinto, S, Purrello, F, Di Pino, A, Piro, S, Conca, A, Falanga, L, Montrucchio, G, Greco, E, Tizzani, P, Petitti, P, Perciccante, A, Coralli, A, Salmi, R, Gaudenzi, P, Gamberini, S, Semplicini, A, Gottardo, L, Vendemiale, G, Serviddio, G, Forlano, R, Masala, C, Mammarella, A, Basili, S, Perri, L, Landolfi, R, Montalto, M, Mirijello, A, Vallone, C, Bellusci, M, Setti, D, Pedrazzoli, F, Guasti, L, Castiglioni, L, Maresca, A, Squizzato, A, Molaro, M, Bertolotti, M, Mussi, C, Libbra, M, Miceli, A, Pellegrini, E, Carulli, L, Sciacqua, A, Quero, M, Bagnato, C, Corinaldesi, R, De Giorgio, R, Grasso, V, Ruggeri, E, Salvi, A, Leonardi, R, Grassini, C, Mascherona, I, Minelli, G, Maltese, F, Gabrielli, A, Mattioli, M, Capeci, W, Martino, G, Messina, S, Ghio, R, Favorini, S, Col, A, Minisola, S, Colangelo, L, Afeltra, A, Alemanno, P, Marigliano, B, Castellino, P, Blanco, J, Zanoli, L, Cattaneo, M, Fracasso, P, Amoruso, M, Saracco, V, Fogliati, M, Bussolino, C, Durante, V, Eusebi, G, Tirotta, D, Mete, F, Gino, M, Cittadini, A, Arcopinto, M, Salzano, A, Bobbio, E, Sirico, D, Moreo, G, Scopelliti, F, Gasparini, F, Cocca, M, Nieves, R, Alberto, M, Pedro, A, Vanessa, L, Lara, T, Xavier, C, Francesc, F, Jesus, D, Esperanza, B, Behamonte Esther, D, Maria, S, Romero, M, Blanca, P, Cristina, L, Victoria, V, Saez, L, Bosco, J, Susana, S, Marta, A, Concepcion, G, Antonio, F, Hernandez, M, Borrego, M, Raquel, P, Florencia, P, Beatriz, G, Sara, C, Cervellera Alfonso, G, Marta, P, Alberto, R, Antonio, A, Montserrat, G, Miguel Angel, B, Manuel, M, Ignacio, N, Lucia, A, Alfonso, L, David, R, Iria, I, Monica, R, Proietti, M., Nobili, A., Raparelli, V., Napoleone, L., Mannucci P., M., Lip, G., Y., H., Pasina, L., Franchi, C., Tettamanti, M., Eldin T., K., Di Blanca, M., P., D., Djade C., D., Ardoino, I., Cortesi, L., Marengoni, A., Licata, G., Violi, F., Corazza G., R., Biolo, G., Guarnieri, G., Zanetti, M., Fernandes, G., Vanoli, M., Grignani, G., Casella, G., Bernardi, M., Bassi S., L., Santi, L., Zaccherini, G., Mannarino, E., Lupattelli, G., Bianconi, V., Paciullo F., Nuti R., Valenti, R., Ruvio, M., Cappelli, S., Palazzuoli, A., Salvatore, T., Sasso F., C., Girelli, D., Olivieri, O., Matteazzi, T., Barbagallo, M., Plances, L., Alcamo, R., Calvo, L., Valenti, M., Zoli, M., Arnò, R., Pasini F., L., Capecchi P., L., Bicchi, M., Palasciano, G., Modeo M., E., Peragine, M., Pappagallo, F., Di Gennaro, C., Barbella M., R., De Stefano, F., Cappellini M., D., Fabio, G., Seghezzi, S., De Amicis M., M., Mari, D., Rossi P., D., Ottolini, B., Miceli, E., Lenti M., V., Padula, D., Murialdo, G., Marra, A., Cattaneo, F., Secchi M., B., Ghelfi, D., Anastasio, L., Sofia, L., Carbone, M., Damanti, S., Guagnano M., T., Sestili, S., Mancuso G., Calipari D., Bartone, M., Meroni M., R., Perin P., C., Lorenzati, B., Gruden, G., Bruno, G., Amione, C., Fornengo, P., Tassara, R., Melis, D., Rebella, L., Pretti, V., Masala M., S., Bolondi, L., Rasciti, L., Serio, I., Fanelli F., R., Amoroso, A., Molfino, A., Petrillo, E., Zuccalà, G., Franceschi, F., De Marco, G., Chiara, C., Marta, S., Romanelli, G., Amolini, C., Chiesa, D., Picardi, A., Gentilucci U., V., Gallo, P., Annoni, G., Corsi, M., Zazzetta, S., Bellelli, G., Arturi, F., Succurro, E., Rubino, M., Sesti, G., Loria, P., Becchi, M., Martucci, G., Fantuzzi, A., Maurantonio, M., Carta, S., Atzori, S., Serra, M., Bleve, M., Gasbarrone, L., Sajeva, M., Brucato, A., Ghidoni, S., Di Corato, P., Agnelli, G., Marchesini, E., Fabris, F., Carlon, M., Baritusso, A., Manfredini, R., Molino, C., Pala, M., Fabbian, F., Boari, B., bc De Giorgi, A., Paolisso, G., Rizzo, M., Laieta, M., Rini, G., Mansueto, P., Pepe, I., Borghi, C., Strocchi, E., De Sando, V., Sabbà, C., Vella, F., Turatto, F., Valerio, R., Capobianco, C., Fenoglio, L., Bracco, C., Giraudo, A., Testa, E., Serraino, C., Fargion, S., Bonara, P., Periti, G., Porzio, M., Peyvandi, F., Tedeschi, A., Rossio, R., Monzani, V., Savojardo, V., Folli, C., Magnini, M., Gobbo, G., Balduini, C., Bertolino, G., Provini, S., Quaglia, F., Dallegri, F., Ottonello, L., Liberale, L., Chin, W., Carassale, L., Caporotundo, S., Traisci, G., De Feudis, L., Di Carlo, S., Liberato, N., Buratti, A., Tognin, T., Bianchi, G., Giaquinto, S., Purrello, F., Di Pino, A., Piro, S., Conca, A., Falanga, L., Montrucchio, G., Greco, E., Tizzani, P., Petitti, P., Perciccante, A., Coralli, A., Salmi, R., Gaudenzi, P., Gamberini, S., Semplicini, A., Gottardo, L., Vendemiale, G., Serviddio, G., Forlano, R., Masala, C., Mammarella, A., Basili, S., Perri, L., Landolfi, R., Montalto, M., Mirijello, A., Vallone, C., Bellusci, M., cc Setti, D., cc Pedrazzoli, F., Guasti, L., Castiglioni, L., Maresca, A., Squizzato, A., Molaro, M., Bertolotti, M., Mussi, C., Libbra, M., Miceli, A., Pellegrini, E., Carulli, L., Sciacqua, A., Quero, M., Bagnato, C., Corinaldesi, R., De Giorgio, R., Grasso, V., Ruggeri, E., Salvi, A., Leonardi, R., Grassini, C., Mascherona, I., Minelli, G., Maltese, F., Gabrielli, A., Mattioli, M., Capeci, W., Martino, G., Messina, S., Ghio, R., Favorini, S., Col, A., Minisola, S., Colangelo, L., Afeltra, A., Alemanno, P., Marigliano, B., Castellino, P., Blanco, J., Zanoli, L., Cattaneo, M., Fracasso, P., Amoruso, M., Saracco, V., Fogliati, M., Bussolino, C., Durante, V., Eusebi, G., Tirotta, D., Mete, F., Gino, M., Cittadini, A., Arcopinto, M., Salzano, A., Bobbio, E., Sirico, D., On behalf of REPOSI, Investigators, Corrao, S, Mannucci, P. M., Lip, G. Y. H., Eldin, T. K., Di Blanca, M. P. D., Djade, C. D., Corazza, G. R., Bassi, S. L., Paciullo, F., Nuti, R., Sasso, F. C., Arno, R., Pasini, F. L., Capecchi, P. L., Modeo, M. E., Postiglione, A., Barbella, M. R., Cappellini, M. D., De Amicis, M. M., Rossi, P. D., Ottolini, B. B., Lenti, M. V., Secchi, M. B., Guagnano, M. T., Mancuso, G., Calipari, D., Meroni, M. R., Perin, P. C., Masala, M. S., Fanelli, F. R., Zuccala, G., Gentilucci, U. V., Becchi, M. A., Serra, M. G., Bleve, M. A., Sajeva, M. R., De Giorgi, A., Rizzo, M. R., Laieta, M. T., Sabba, C., Vella, F. S., Giraudo, A. V., Balduini, C. L., Chin, W. S., Liberato, N. L., Bianchi, G. B., Setti, D., Pedrazzoli, F., Libbra, M. V., Martino, G. P., Col, A. D., Amoruso, M. V., Marra, A. M., Moreo, G., Scopelliti, F., Gasparini, F., Cocca, M., Nieves, R. D., Alberto, M. M., Pedro, A. R., Vanessa, L. P., Lara, T., Xavier, C. V., Francesc, F., Jesus, D. M., Esperanza, B. T., Behamonte Esther, D. C., Maria, S. P., Romero, M., Blanca, P. L., Cristina, L. G. -C., Victoria, V. G. M., Saez, L., Bosco, J., Susana, S. B., Marta, A. G., Concepcion, G. B., Antonio, F. M., Hernandez, M. G., Borrego, M. P., Raquel, P. C., Florencia, P. R., Beatriz, G. O., Sara, C. G., Cervellera Alfonso, G. -C., Marta, P. M., Alberto, R. C., Antonio, A. A., Montserrat, G. G., Miguel Angel, B. R., Manuel, M. J., Ignacio, N. V., Lucia, A. S., Alfonso, L., David, R. B., Iria, I. V., Monica, R. P., Proietti M., Nobili A., Raparelli V., Napoleone L., Mannucci P.M., Lip G.Y.H., Pasina L., Franchi C., Tettamanti M., Eldin T.K., Di Blanca M.P.D., Djade C.D., Ardoino I., Cortesi L., Marengoni A., Licata G., Violi F., Corazza G.R., Biolo G., Guarnieri G., Zanetti M., Fernandes G., Vanoli M., Grignani G., Casella G., Bernardi M., Bassi S.L., Santi L., Zaccherini G., Mannarino E., Lupattelli G., Bianconi V., Paciullo F., Nuti R., Valenti R., Ruvio M., Cappelli S., Palazzuoli A., Salvatore T., Sasso F.C., Girelli D., Olivieri O., Matteazzi T., Barbagallo M., Plances L., Alcamo R., Calvo L., Valenti M., Zoli M., Arno R., Pasini F.L., Capecchi P.L., Bicchi M., Palasciano G., Modeo M.E., Peragine M., Pappagallo F., Di Gennaro C., Postiglione A., Barbella M.R., De Stefano F., Cappellini M.D., Fabio G., Seghezzi S., De Amicis M.M., Mari D., Rossi P.D., Ottolini B.B., Miceli E., Lenti M.V., Padula D., Murialdo G., Marra A., Cattaneo F., Secchi M.B., Ghelfi D., Anastasio L., Sofia L., Carbone M., Damanti S., Guagnano M.T., Sestili S., Mancuso G., Calipari D., Bartone M., Meroni M.R., Perin P.C., Lorenzati B., Gruden G., Bruno G., Amione C., Fornengo P., Tassara R., Melis D., Rebella L., Pretti V., Masala M.S., Bolondi L., Rasciti L., Serio I., Fanelli F.R., Amoroso A., Molfino A., Petrillo E., Zuccala G., Franceschi F., De Marco G., Chiara C., Marta S., Romanelli G., Amolini C., Chiesa D., Picardi A., Gentilucci U.V., Gallo P., Annoni G., Corsi M., Zazzetta S., Bellelli G., Arturi F., Succurro E., Rubino M., Sesti G., Loria P., Becchi M.A., Martucci G., Fantuzzi A., Maurantonio M., Carta S., Atzori S., Serra M.G., Bleve M.A., Gasbarrone L., Sajeva M.R., Brucato A., Ghidoni S., Di Corato P., Agnelli G., Marchesini E., Fabris F., Carlon M., Baritusso A., Manfredini R., Molino C., Pala M., Fabbian F., Boari B., De Giorgi A., Paolisso G., Rizzo M.R., Laieta M.T., Rini G., Mansueto P., Pepe I., Borghi C., Strocchi E., De Sando V., Sabba C., Vella F.S., Turatto F., Valerio R., Capobianco C., Fenoglio L., Bracco C., Giraudo A.V., Testa E., Serraino C., Fargion S., Bonara P., Periti G., Porzio M., Peyvandi F., Tedeschi A., Rossio R., Monzani V., Savojardo V., Folli C., Magnini M., Gobbo G., Balduini C.L., Bertolino G., Provini S., Quaglia F., Dallegri F., Ottonello L., Liberale L., Chin W.S., Carassale L., Caporotundo S., Traisci G., De Feudis L., Di Carlo S., Liberato N.L., Buratti A., Tognin T., Bianchi G.B., Giaquinto S., Purrello F., Di Pino A., Piro S., Conca A., Falanga L., Montrucchio G., Greco E., Tizzani P., Petitti P., Perciccante A., Coralli A., Salmi R., Gaudenzi P., Gamberini S., Semplicini A., Gottardo L., Vendemiale G., Serviddio G., Forlano R., Masala C., Mammarella A., Basili S., Perri L., Landolfi R., Montalto M., Mirijello A., Vallone C., Bellusci M., Setti D., Pedrazzoli F., Guasti L., Castiglioni L., Maresca A., Squizzato A., Molaro M., Bertolotti M., Mussi C., Libbra M.V., Miceli A., Pellegrini E., Carulli L., Sciacqua A., Quero M., Bagnato C., Corinaldesi R., De Giorgio R., Serra M., Grasso V., Ruggeri E., Salvi A., Leonardi R., Grassini C., Mascherona I., Minelli G., Maltese F., Gabrielli A., Mattioli M., Capeci W., Martino G.P., Messina S., Ghio R., Favorini S., Col A.D., Minisola S., Colangelo L., Afeltra A., Alemanno P., Marigliano B., Castellino P., Blanco J., Zanoli L., Cattaneo M., Fracasso P., Amoruso M.V., Saracco V., Fogliati M., Bussolino C., Durante V., Eusebi G., Tirotta D., Mete F., Gino M., Cittadini A., Arcopinto M., Salzano A., Bobbio E., Marra A.M., Sirico D., Moreo G., Scopelliti F., Gasparini F., Cocca M., Nieves R.D., Alberto M.M., Pedro A.R., Vanessa L.P., Lara T., Xavier C.V., Francesc F., Jesus D.M., Esperanza B.T., Behamonte Esther D.C., Maria S.P., Romero M., Blanca P.L., Cristina L.G.-C., Victoria V.G.M., Saez L., Bosco J., Susana S.B., Marta A.G., Concepcion G.B., Antonio F.M., Hernandez M.G., Borrego M.P., Raquel P.C., Florencia P.R., Beatriz G.O., Sara C.G., Cervellera Alfonso G.-C., Marta P.M., Alberto R.C., Antonio A.A., Montserrat G.G., Miguel Angel B.R., Manuel M.J., Ignacio N.V., Lucia A.S., Alfonso L., David R.B., Iria I.V., Monica R.P., On behalf of REPOSI investigators, Proietti, Marco, Nobili, Alessandro, Raparelli, Valeria, Napoleone, Laura, Mannucci, Pier Mannuccio, Lip, Gregory Y. H., Pasina, Luca, Franchi, Carlotta, Marcucci, Maura, Eldin, Tarek Kamal, Di Blanca, Maria Pia Donatella, Perticone, Francesco, Salerno, Francesco, Corrao, Salvatore, Prisco, Domenico, Silvestri, Elena, Cenci, Caterina, Emmi, Giacomo, Biolo, Gianni, Guarnieri, Gianfranco, Zanetti, Michela, Fernandes, Giovanni, Vanoli, Massimo, Grignani, Giulia, Casella, Gianluca, Bernardi, Mauro, Bassi, Silvia Li, Santi, Luca, Zaccherini, Giacomo, Mannarino, Elmo, Lupattelli, Graziana, Bianconi, Vanessa, Paciullo, Francesco, Nuti, Ranuccio, Valenti, Roberto, Ruvio, Martina, Cappelli, Silvia, Palazzuoli, Alberto, Salvatore, Teresa, Sasso, Ferdinando Carlo, Girelli, Domenico, Olivieri, Oliviero, Matteazzi, Thoma, Barbagallo, Mario, Plances, Lidia, Alcamo, Roberta, Licata, Giuseppe, Calvo, Luigi, Valenti, Maria, Zoli, Marco, Arnò, Raffaella, Pasini, Franco Laghi, Capecchi, Pier Leopoldo, Bicchi, Maurizio, Palasciano, Giuseppe, Modeo, Maria Ester, Peragine, Maria, Pappagallo, Fabrizio, Di Gennaro, Carla, Postiglione, Alfredo, Barbella, Maria Rosaria, De Stefano, Francesco, Cappellini, Maria Domenica, Fabio, Giovanna, Seghezzi, Sonia, De Amicis, Margherita Migone, Mari, Daniela, Rossi, Paolo Dionigi, Ottolini, Barbara Brignolo, Pugliese, Stefania, Lenti, Marco Vincenzo, Padula, Donatella, Murialdo, Giovanni, Marra, Alessio, Cattaneo, Federico, Secchi, Maria Beatrice, Ghelfi, Davide, Anastasio, Luigi, Sofia, Lucia, Carbone, Maria, Davì, Giovanni, Guagnano, Maria Teresa, Sestili, Simona, Mancuso, Gerardo, Calipari, Daniela, Bartone, Mosè, Meroni, Maria Rachele, Perin, Paolo Cavallo, Lorenzati, Bartolomeo, Gruden, Gabriella, Bruno, Graziella, Amione, Cristina, Fornengo, Paolo, Tassara, Rodolfo, Melis, Deborah, Rebella, Lara, Pretti, Vincenzo, Masala, Maristella Salvatora, Bolondi, Luigi, Rasciti, Leonardo, Serio, Ilaria, Fanelli, Filippo Rossi, Amoroso, Antonio, Molfino, Alessio, Petrillo, Enrico, Zuccalà, Giuseppe, Franceschi, Francesco, De Marco, Guido, Chiara, Cordischi, Marta, Sabbatini, Romanelli, Giuseppe, Delitala, Giuseppe, Chiesa, Deborah, Picardi, Antonio, Gentilucci, Umberto Vespasiani, Gallo, Paolo, Annoni, Giorgio, Corsi, Maurizio, Zazzetta, Sara, Bellelli, Giuseppe, Arturi, Franco, Succurro, Elena, Rubino, Mariangela, Sesti, Giorgio, Loria, Paola, Becchi, Maria Angela, Martucci, Gianfranco, Fantuzzi, Alessandra, Maurantonio, Mauro, Carta, Stefano, Atzori, Sebastiana, Serra, Maria Grazia, Bleve, Maria Antonietta, Gasbarrone, Laura, Sajeva, Maria Rosaria, Brucato, Antonio, Ghidoni, Silvia, Di Corato, Paola, Agnelli, Giancarlo, Marchesini, Emanuela, Fabris, Fabrizio, Carlon, Michela, Baritusso, Aldo, Manfredini, Roberto, Molino, Christian, Pala, Marco, Fabbian, Fabio, Boari, Benedetta, De Giorgi, Alfredo, Paolisso, Giuseppe, Rizzo, Maria Rosaria, Laieta, Maria Teresa, Rini, Giovanbattista, Mansueto, Pasquale, Pepe, Ilenia, Borghi, Claudio, Strocchi, Enrico, De Sando, Valeria, Sabbà, Carlo, Vella, Francesco Saverio, Suppressa, Patrizia, Valerio, Raffaella, Capobianco, Caterina, Fenoglio, Luigi, Bracco, Christian, Giraudo, Alessia Valentina, Testa, Elisa, Serraino, Cristina, Fargion, Silvia, Bonara, Paola, Periti, Giulia, Porzio, Marianna, Peyvandi, Flora, Tedeschi, Alberto, Rossio, Raffaella, Monzani, Valter, Savojardo, Valeria, Folli, Christian, Magnini, Maria, Gobbo, Giulia, Balduini, Carlo L., Bertolino, Giampiera, Provini, Stella, Quaglia, Federica, Dallegri, Franco, Ottonello, Luciano, Liberale, Luca, Chin, Wu Sheng, Carassale, Laura, Caporotundo, Silvia, Traisci, Giancarlo, De Feudis, Lucrezia, Di Carlo, Silvia, Liberato, Nicola Lucio, Buratti, Alberto, Tognin, Tiziana, Bianchi, Giovanni Battista, Giaquinto, Sabrina, Purrello, Francesco, Di Pino, Antonino, Piro, Salvatore, Rozzini, Renzo, Falanga, Lina, Montrucchio, Giuseppe, Greco, Elisabetta, Tizzani, Pietro, Petitti, Paolo, Perciccante, Antonio, Coralli, Alessia, Salmi, Raffaella, Gaudenzi, Piergiorgio, Gamberini, Susanna, Semplicini, Andrea, Gottardo, Lucia, Vendemiale, Gianluigi, Serviddio, Gaetano, Forlano, Roberta, Masala, Cesare, Mammarella, Antonio, Basili, Stefania, Perri, Ludovica, Landolfi, Raffaele, Montalto, Massimo, Mirijello, Antonio, Vallone, Carla, Bellusci, Martino, Setti, Donatella, Pedrazzoli, Filippo, Guasti, Luigina, Castiglioni, Luana, Maresca, Andrea, Squizzato, Alessandro, Molaro, Marta, Bertolotti, Marco, Mussi, Chiara, Libbra, Maria Vittoria, Miceli, Andrea, Pellegrini, Elisa, Carulli, Lucia, Sciacqua, Angela, Quero, Michele, Bagnato, Chiara, Corinaldesi, Roberto, De Giorgio, Roberto, Serra, Mauro, Grasso, Valentina, Ruggeri, Eugenio, Salvi, Andrea, Leonardi, Roberto, Grassini, Chiara, Mascherona, Ilenia, Minelli, Giorgio, Maltese, Francesca, Gabrielli, Armando, Mattioli, Massimo, Capeci, William, Martino, Giuseppe Pio, Messina, Silvia, Ghio, Riccardi, Favorini, Serena, Col, Anna Dal, Minisola, Salvatore, Colangelo, Luciano, Afeltra, Antonella, Alemanno, Pamela, Marigliano, Benedetta, Castellino, Pietro, Blanco, Julien, Zanoli, Luca, Cattaneo, Marco, Fracasso, Paola, Amoruso, Maria Valentina, Saracco, Valter, Fogliati, Marisa, Bussolino, Carlo, Durante, Vittorio, Eusebi, Giovanna, Tirotta, Daniela, Mete, Francesca, Gino, Miriam, Cittadini, Antonio, Arcopinto, Michele, Salzano, Andrea, Bobbio, Emanuele, Marra, Alberto Maria, Sirico, Domenico, Moreo, Guido, Scopelliti, Francesco, Gasparini, Francesca, Cocca, Melissa, Nieves, Ramirez Duque, Alberto, Muela Molinero, Pedro, Abad Requejo, Vanessa, Lopez Pelaez, Lara, Tamargo, Xavier, Corbella Viro, Francesc, Formiga, Jesus, Diez Manglano, Esperanza, Bejarano Tello, Behamonte Esther, Del Corral, Maria, Sevil Pura, Romero, Manuel, Blanca, Pinilla Llorente, Cristina, Lopez Gonzalez Cobo, Victoria, Villalba Garcia M., Saez, Lopez, Bosco, Juan, Susana, Sanz Baena, Marta, Arroyo Gallego, Concepcion, Gonzalez Becerra, Antonio, Fernandez Moyano, Hernandez, Mercedes Gomez, Borrego, Manuel Poyato, Raquel, Pacheco Cuadro, Florencia, Perez Roja, Beatriz, Garcia Olid, Sara, Carrascosa Garcia, Cervellera Alfonso, Gonzalez Cruz, Marta, Peinado Martinez, Alberto, Ruiz Cantero, Antonio, Albarracín Arraigosa, Montserrat, Godoy Guerrero, Miguel Ángel, Barón Ramo, Manuel, Machin Jose, Ignacio, Novo Veleiro, Lucía, Alvela Suarez, Alfonso, Lopez, David, Rubal Bran, Iria, Iñiguez Vazquez, and Monica, Rios Prego
Subjects: Antithrombotic therapy, Atrial fibrillation, Elderly, Guidelines, Outcomes, Cardiology and Cardiovascular Medicine, Male, Registrie, Time Factors, antithrombotic therapy, atrial fibrillation, elderly, guidelines, outcomes, Atrial fibrillation (AF), Practice Patterns, Kaplan-Meier Estimate, 030204 cardiovascular system & hematology, Guideline, Coronary artery disease, 0302 clinical medicine, Risk Factors, Atrial Fibrillation, Antithrombotic, 80 and over, Age Factor, 030212 general & internal medicine, Registries, Antithrombotic therapy, Atrial fibrillation, Elderly, Guidelines, Outcomes, Practice Patterns, Physicians', Outcome, Aged, 80 and over, Fibrinolytic Agent, Age Factors, General Medicine, Treatment Outcome, Italy, Atrial fibrillation (AF) ,thromboembolism ,antithrombotic prophylaxis, Practice Guidelines as Topic, Cardiology, Female, Guideline Adherence, Human, Aged, Chi-Square Distribution, Fibrinolytic Agents, Humans, Logistic Models, Proportional Hazards Models, Risk Assessment, Thromboembolism, medicine.medical_specialty, Logistic Model, Time Factor, Socio-culturale, Lower risk, 03 medical and health sciences, Internal medicine, medicine, Physicians', business.industry, Proportional hazards model, Risk Factor, Settore MED/09 - MEDICINA INTERNA, thromboembolism, medicine.disease, Proportional Hazards Model, antithrombotic prophylaxis, business, Chi-squared distribution, Fibrinolytic agent
Abstract: Background: Atrial fibrillation (AF) is associated with a substantial risk of thromboembolism and mortality, significantly reduced by oral anticoagulation. Adherence to guidelines may lower the risks for both all cause and cardiovascular (CV) deaths. Methods: Our objective was to evaluate if antithrombotic prophylaxis according to the 2012 European Society of Cardiology (ESC) guidelines is associated to a lower rate of adverse outcomes. Data were obtained from REPOSI; a prospective observational study enrolling inpatients aged ≥65years. Patients enrolled in 2012 and 2014 discharged with an AF diagnosis were analysed. Results: Among 2535 patients, 558 (22.0%) were discharged with a diagnosis of AF. Based on ESC guidelines, 40.9% of patients were on guideline-adherent thromboprophylaxis, 6.8% were overtreated, and 52.3% were undertreated. Logistic analysis showed that increasing age (p=0.01), heart failure (p=0.04), coronary artery disease (p=0.013), peripheral arterial disease (p=0.03) and concomitant cancer (p=0.003) were associated with non-adherence to guidelines. Specifically, undertreatment was significantly associated with increasing age (p=0.001) and cancer (p&nbsp
Published: 2016
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37. Keratosis lichenoides chronica masquerading as discoid lupus erythematosus

Author: L. Ffolkes, J. Natkunarajah, K. Misch, J. S. Wee, and Amaya Viros
Subjects: Male, medicine.medical_specialty, Pathology, Lichenoid Eruptions, Discoid lupus erythematosus, business.industry, Keratosis, Dermatology, Middle Aged, medicine.disease, Diagnosis, Differential, Lupus Erythematosus, Discoid, Chronic Disease, medicine, Humans, Keratosis lichenoides chronica, business
Published: 2013
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38. Síndrome esclerodermiforme por paclitaxel

Author: Jordi Mollet, R. Bartralot, Lucía Palacio, Amaya Viros, Vicente García-Patos, Antoni Castells, and Antonio Medina
Subjects: Gynecology, medicine.medical_specialty, business.industry, Toxicodermia, medicine, General Medicine, business, Toxicoderma
Abstract: Resumen —Los sindromes esclerodermiformes se han relacionado con una larga lista de medicamentos, a la que se han anadido en los ultimos anos los taxanos. Se presenta el caso de una mujer con una neoplasia de mama que recibio tratamiento ciclico con paclitaxel. Tras 17 sesiones presento edema y eritrodisestesia en ambos pies que, a pesar del tratamiento sintomatico y de reducir la dosis de paclitaxel, progresaron hacia un endurecimiento cutaneo en estas localizaciones. Diez meses despues de suspender el taxano las lesiones cutaneas se mantenian estables y no existian otras manifestaciones de esclerosis sistemica. Los taxanos pueden producir un sindrome esclerodermiforme que suele afectar a las extremidades inferiores y esta precedido por edema y/o eritrodisestesia; no se acompana de otras manifestaciones de esclerosis sistemica y tiende a estabilizarse o a involucionar al suspender el tratamiento.
Published: 2004
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39. Abstract 3704: Novel panRAF inhibitors active in melanomas that are resistant to BRAF-selective, or BRAF-selective/MEK inhibitor combinations

Author: Robert McLeary, Bart M. J. M. Suijkerbuijk, John Brognard, Paul Lorigan, Steven R. Whittaker, Natasha Preece, Dan Niculescu-Duvaz, Margaret C. Frame, Grazia Saturno, Alfonso Zambon, Laura Fish, Delphine Menard, Anna A. Marusiak, Filipa Lopes, Amaya Viros, Kenneth G. MacLeod, Maria Romina Girotti, Sarah Ejiama, Alberto Fusi, Neil O. Carragher, Richard Marais, Lawrence Davies, Malin Pedersen, Garry Ashton, Berta Sanchez-Laorden, Caroline J. Springer, and L. Johnson
Subjects: MAPK/ERK pathway, Neuroblastoma RAS viral oncogene homolog, Gerontology, Cancer Research, Mutation, business.industry, MEK inhibitor, Melanoma, Mutant, Cancer, medicine.disease, medicine.disease_cause, Oncology, Cancer research, medicine, Protein kinase A, business, neoplasms
Abstract: The protein kinase BRAF is mutated ∼40% of human melanomas. BRAF is a component of the RAS/RAF/MEK/ERK pathway and BRAF or MEK inhibitors increase progression-free and overall survival in melanoma patients with BRAF mutations. However, most patients relapse with acquired resistance and ∼20% of patients present intrinsic resistance and do not respond to these drugs. We describe here two novel compounds that target mutant BRAF and wild-type CRAF. Our compounds inhibited the growth of melanoma cells that were resistant to BRAF-selective inhibitors. ERK pathway reactivation is responsible for resistance to BRAF targeted therapies in ∼60% of the patients and in ∼25% of patients resistance is driven by acquisition of mutations in NRAS. We show that our compounds inhibited the growth of melanoma cells that were resistant to BRAF-selective inhibitors due to pathway reactivation mediated by different mechanisms. We show that the drugs were active against patient derived xenografts (PDXs) from patients with acquired or intrinsic resistance to BRAF-selective inhibitors and in whose tumors resistance was associated with ERK pathway reactivation. Further, our compounds are active in a PDX from a patient whose tumor developed acquired resistance to a combination of a BRAF-selective plus a MEK inhibitor and associated with acquisition of an NRAS mutation. Thus, our panRAF inhibitors can inhibit melanomas with different mechanisms of acquired or intrinsic resistance to BRAF-selective and BRAF-selective/MEK inhibitor combinations, potentially providing first-line treatment for naïve patients and second-line treatments for a range of relapsed patients. Citation Format: Maria R. Girotti, Filipa Lopes, Natasha Preece, Dan Niculescu-Duvaz, Alfonso Zambon, Lawrence Davies, Steven Whittaker, Grazia Saturno, Amaya Viros, Malin Pedersen, Bart MJM Suijkerbuijk, Delphine Menard, Robert Mcleary, Louise Johnson, Laura Fish, Sarah Ejiama, Berta Sanchez-Laorden, Neil Carragher, Kenneth Macleod, Garry Ashton, Anna Marusiak, Alberto Fusi, John Brognard, Margaret Frame, Paul Lorigan, Caroline J. Springer, Richard Marais. Novel panRAF inhibitors active in melanomas that are resistant to BRAF-selective, or BRAF-selective/MEK inhibitor combinations. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3704. doi:10.1158/1538-7445.AM2014-3704
Published: 2014

40. Abstract 2400: Mechanisms of resistance to immuno and targeted therapies in acral melanoma

Author: Caron Abbey, Matt Smith, Robert E. Hawkins, Rebecca Lee, Maria Romina Girotti, Milena Kalaitsidou, Alberto Fusi, Crispin J. Miller, Elena Galvani, A. Mandal, Richard Marais, Franziska Baenke, Garry Ashton, Amaya Viros, Jacqueline Swan, Garima Khandelwal, John S. Bridgeman, Gabriela Gremel, Kang Zeng, Paul Lorigan, Nathalie Dhomen, David E. Gilham, Isabel Peset, and Haoran Tang
Subjects: Cancer Research, Pathology, medicine.medical_specialty, business.industry, medicine.medical_treatment, Melanoma, Cancer, Dabrafenib, Immunotherapy, medicine.disease, Targeted therapy, Oncology, Cutaneous melanoma, Cancer research, Medicine, Nivolumab, business, Brain metastasis, medicine.drug
Abstract: Acral melanoma is a rare subtype of melanoma found on the non-hair bearing surfaces of the skin. It is associated with a worse prognosis than cutaneous melanoma, with higher proportions of patients developing metastatic disease. Combination treatments targeting the MAP kinase (MAPK) pathway and immune checkpoint inhibitors have improved overall survival in patients with stage IV disease. However, resistance to both modalities remains a challenge. This is exemplified by our comprehensive analysis of a patient presenting with acral melanoma that developed resistance to both immune and targeted therapy. The patient developed metastatic disease in multiple sites and we obtained fresh tumour tissue and generated cell lines from a skin metastasis at baseline prior to nivolumab. Following an initial complete response, the patient developed new mediastinal lymph node and brain metastases, which were also resected. On further relapse, the patient commenced dabrafenib with a partial response. Despite ongoing extra-cranial control, the brain lesion progressed and was therefore resected. To investigate resistance to immune therapy, we performed comprehensive genomic analysis and gene expression profiling on the lesions from the three sites, which identified common mutations in all three lesions and a low overall mutational burden consistent with acral melanoma. Heterogeneity of the MHC class I and II restricted antigen profile of the pre-treatment subcutaneous metastasis versus lymph node and brain progressions could not account for the development of resistance to immunotherapy. Gene expression profiling revealed up-regulation of known mechanisms of immune tolerance in both the lymph node and brain metastasis compared to the pre-treatment subcutaneous metastasis. To investigate resistance to targeted therapy, we compared patient-derived cell lines from brain lesions taken pre (DabS) and on progression on dabrafenib (DabR), and showed ongoing sensitivity to dabrafenib despite the patient having progressed in the brain. When cells from the DabR cell line were cultured in cerebrospinal fluid (CSF) in the presence of dabrafenib, we observed a reduction in cell death. Thus, extrinsic factors present in CSF may have resulted in the progression of the brain lesion in this patient. Using a combination of platforms to study patient derived tissues, we show that immune editing through selection of cells with an immune resistant phenotype may have resulted in the resistance of this patient's tumours to immune therapy whilst resistance to MAPK targeted therapy could have been mediated by extrinsic factors in the CSF. Citation Format: Rebecca J. Lee, Maria Romina Girotti, Amaya Viros, Franziska Baenke, Amit Mandal, Garima Khandelwal, John Bridgeman, Elena Galvani, Gabriela Gremel, Milena Kalaitsidou, Garry Ashton, Isabel Peset, Matthew Smith, Jacqueline Swan, Kang Zeng, Haoran Tang, Caron Abbey, Robert Hawkins, Alberto Fusi, Crispin Miller, David Gilham, Nathalie Dhomen, Paul Lorigan, Richard Marais. Mechanisms of resistance to immuno and targeted therapies in acral melanoma. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2400.
Published: 2016
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41. Abstract 470: Application of sequencing, liquid biopsies and patient derived xenografts for personalized medicine in melanoma

Author: Grazia Saturno, Deemesh Oudit, Simon J. Furney, Ged Brady, A. Mandal, Franziska Baenke, Jacqueline Swan, Nathalie Dhomen, Malin Pedersen, Richard Marais, Rebecca Lee, Dominic G. Rothwell, Elena Galvani, Amaya Viros, Alberto Fusi, Caroline Dive, Kok Haw Jonathan Lim, Gabriela Gremel, Jane Rogan, Matt Smith, and Maria Romina Girotti
Subjects: Oncology, Cancer Research, medicine.medical_specialty, business.industry, Melanoma, Cancer, medicine.disease, Bioinformatics, Patient care, Internal medicine, medicine, In patient, Personalized medicine, business, Exome sequencing, Median survival, Advanced melanoma
Abstract: BRAF/MEK inhibitors and immunotherapies have revolutionized care for patients with advanced melanoma, improving expected median survival from 9 months to 25-30 months, but the majority of patients still die of their disease. Personalized medicine strives to individualize and improve patient care. To individualize treatment decisions in advanced melanoma we analyzed 364 samples from 214 patients. We performed whole exome sequencing (WES) and circulating tumor DNA (ctDNA) analysis, and we developed patient derived xenografts (PDX). WES and targeted sequencing of ctDNA allowed us to predict responses to therapy and to identify and monitor mechanisms of resistance. WES of tumors revealed new therapeutic strategies in BRAF V600 wild-type and BRAF inhibitor-resistant melanoma and we validated these in patient derived xenografts (PDX). Thus, we describe a powerful combination of techniques for personalized medicine to improve the management of melanoma patients. Citation Format: Maria R. Girotti, Gabriela Gremel, Rebecca Lee, Elena Galvani, Dominic Rothwell, Amaya Viros, Amit Kumar Mandal, Kok Haw Jonathan Lim, Grazia Saturno, Simon J Furney, Franziska Baenke, Malin Pedersen, Jane Rogan, Jacqueline Swan, Matthew Smith, Alberto Fusi, Deemesh Oudit, Nathalie Dhomen, Ged Brady, Caroline Dive, Richard Marais. Application of sequencing, liquid biopsies and patient derived xenografts for personalized medicine in melanoma. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 470.
Published: 2016
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42. Abstract LB-212: Therapeutic efficacy of the paradox-breaking panRAF and SRC drug CCT3833/BAL3833 in KRAS-driven cancer models

Author: Alfonso Zambon, Filipa Lopes, Robert McLeary, Nathalie Dhomen, Malin Pedersen, Caroline J. Springer, Maria Romina Girotti, Natasha Preece, Rebecca Lee, L. Johnson, Richard Marais, Ruth Knight, Grazia Saturno, Lawrence Davies, Ion Niculescu-Duvaz, Denys Holovanchuk, Paul Lorigan, Dan Niculescu-Duvaz, and Amaya Viros
Subjects: 0301 basic medicine, Drug, Cancer Research, Pancreatic ductal adenocarcinoma, Colorectal cancer, media_common.quotation_subject, Pharmacology, medicine.disease_cause, 03 medical and health sciences, 0302 clinical medicine, Medicine, Lung cancer, neoplasms, media_common, business.industry, Cancer, medicine.disease, digestive system diseases, Clinical trial, 030104 developmental biology, Oncology, 030220 oncology & carcinogenesis, Cancer research, KRAS, business, Proto-oncogene tyrosine-protein kinase Src
Abstract: KRAS is mutated in ∼80% of pancreatic ductal adenocarcinoma (PDAC), ∼35% of colorectal cancer (CRC) and ∼20% of non-small-cell lung cancer (NSCLC). KRAS remains an intractable drug target and targeting the downstream pathway component is ineffective because feedback mechanisms or parallel pathways provide alternative routes to cell proliferation and/or survival. Here we show that a new panRAF/SRC inhibitor, CCT3833, is active in KRAS-mutant PDAC, CRC and NSCLC. We demonstrate that CCT3833 inhibits tumor growth in several KRAS-driven cancers via inhibition of RAF and SRC, eliciting therapeutic efficacy at well-tolerated doses in mouse models of human cancer. CCT3833 has already entered clinical trials (NCT02437227) for BRAF mutant and BRAF inhibitor-resistant melanomas and these new data show that it is also effective in KRAS mutant cancers, potentially providing a new therapeutic option for these patients. Citation Format: Grazia Saturno, Filipa Lopes, Maria Romina Girotti, Ion Niculescu-Duvaz, Dan Niculescu-Duvaz, Alfonso Zambon, Lawrence Davies, Louise Johnson, Natasha Preece, Amaya Viros, Malin Pedersen, Robert McLeary, Ruth Knight, Rebecca Lee, Denys Holovanchuk, Paul Lorigan, Nathalie Dhomen, Richard Marais, Caroline Springer. Therapeutic efficacy of the paradox-breaking panRAF and SRC drug CCT3833/BAL3833 in KRAS-driven cancer models. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr LB-212.
Published: 2016
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43. Abstract 3207: Influence of tumor mutation burden on response to anti-PD-1 treatment in murine models of melanoma

Author: Garry Ashton, A. Mandal, Matt Smith, Antonia Banyard, Gabriela Gremel, Kate Hogan, Nathalie Dhomen, Elena Galvani, Jacqueline Swan, Richard Marais, and Amaya Viros
Subjects: 0301 basic medicine, Cancer Research, Mutation, biology, business.industry, Melanoma, Cancer, medicine.disease_cause, medicine.disease, Blockade, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, Immune system, Oncology, 030220 oncology & carcinogenesis, biology.protein, Cancer research, medicine, Cytotoxic T cell, Antibody, business, Exome sequencing
Abstract: Therapeutic antibodies directed against immune checkpoints, such as cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) and programmed cell death-1 (PD-1), have recently shown remarkable clinical benefits, particularly in metastatic melanoma and non-small cell lung cancer (NSCLC), cancers largely caused by chronic exposure to mutagenic agents. Recent studies have focused on identifying genomic and immune predictors of response, but consistent, robust biomarkers have yet to be fully characterized. However, some data suggests a high non-synonymous tumour mutation burden is associated with clinical benefit in melanoma patients who received anti-CTLA-4 therapy. A similar correlation was also found in NSCLC patients treated with anti-PD-1. Using mouse models of BRAFV600E-driven melanoma, we examined the relationship between tumour mutation burden and response to the immune checkpoint inhibitor anti-PD-1. Chronic exposure to ultraviolet radiation (UVR) was used to increase the number of tumour non-synonymous single nucleotide variants (SNVs), and thus mutational load. Responses to PD-1 blockade were compared between tumours having low (∼10 SNVs) and high (>100 SNVs) mutation burden and tumours were subsequently subjected to comprehensive molecular and immune profiling using whole exome sequencing, immunohistochemistry, and flow cytometry. Our initial data suggest there is no significant correlation between tumour mutation burden and response in our model of BRAFV600E-driven melanoma, and we will present a detailed analysis of low- and high-mutation burden tumours in light of their response to PD-1 blockade. Consistent with previous studies, our results highlight that integrated molecular characterization of tumour tissue and associated microenvironment in larger cohorts is needed to identify robust determinants of response to immune checkpoint inhibitors. Citation Format: Elena Galvani, Kate Hogan, Gabriela Gremel, Amaya Viros, Amit K. Mandal, Matthew Smith, Jacqueline Swan, Antonia Banyard, Garry Ashton, Nathalie Dhomen, Richard Marais. Influence of tumor mutation burden on response to anti-PD-1 treatment in murine models of melanoma. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3207.
Published: 2016
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44. Assessing the interplay of RNA-fusion events with cancer driver mutations in melanoma patients

Author: Richard Marais, Nathalie Dhomen, Elena Galvani, A. Mandal, Gabriela Gremel, Rebecca Lee, Franziska Baenke, K.H.J. Lim, Paul Lorigan, Amaya Viros, and Maria Romina Girotti
Subjects: Oncology, Cancer Research, medicine.medical_specialty, business.industry, Internal medicine, Melanoma, medicine, RNA, Cancer, medicine.disease, business
Published: 2016
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45. Therapeutic efficacy of the paradox-breaking panRAF and SRC drug CCT3833/BAL3833 in KRAS-driven cancer models

Author: Richard Marais, Ruth Knight, Caroline J. Springer, Paul Lorigan, Natasha Preece, Robert McLeary, Ion Niculescu-Duvaz, L. Johnson, Alfonso Zambon, Rebecca Lee, Dan Niculescu-Duvaz, Alberto Fusi, Amaya Viros, Grazia Saturno, Nathalie Dhomen, Malin Pedersen, Linda Davies, Maria Romina Girotti, D. Holovanchuk, and Filipa Lopes
Subjects: 0301 basic medicine, Drug, Cancer Research, business.industry, media_common.quotation_subject, Cancer, Pharmacology, medicine.disease, medicine.disease_cause, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, Oncology, 030220 oncology & carcinogenesis, Cancer research, Medicine, KRAS, business, media_common, Proto-oncogene tyrosine-protein kinase Src
Published: 2016
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46. Impact of molecular prescreening for genomically-guided trials in head and neck cancer (HNC)

Author: Irene Brana, Margarita Alberola, Enriqueta Felip, Ana Vivancos, Rodrigo Dienstmann, Jordi Rodon, Juan Lorente, Jorge Pamias, Neus Baste, David Viros, Jordi Giralt, Josep Tabernero, Paolo Nuciforo, Josep M. del Campo, and Coro Bescos
Subjects: Oncology, Cancer Research, medicine.medical_specialty, Pathology, business.industry, Head and neck cancer, medicine.disease, stomatognathic diseases, 03 medical and health sciences, 0302 clinical medicine, 030220 oncology & carcinogenesis, Internal medicine, Medicine, 030223 otorhinolaryngology, business
Abstract: 6030Background: HNC encompass a group of highly heterogeneous diseases, including oral, oropharyngeal and laryngeal squamous cell carcinomas (SCC), nasopharyngeal (NP), nasosinusal (NS) and salivar...
Published: 2016
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47. Analysis of the efficacy and toxicity of sorafenib in thyroid cancer: a phase II study in a UK based population

Author: Richard Marais, Katie L. Newbold, Christopher M. Nutting, Jen Hickey, Angela Riddell, Amaya Viros, Merina Ahmed, Yolanda Barbachano, and Kevin J. Harrington
Subjects: Sorafenib, Adult, Male, Niacinamide, medicine.medical_specialty, Pyridines, Endocrinology, Diabetes and Metabolism, Population, Phases of clinical research, Antineoplastic Agents, Thyroid carcinoma, Young Adult, Endocrinology, Internal medicine, Clinical endpoint, Medicine, Humans, Thyroid Neoplasms, education, Thyroid cancer, Survival analysis, Aged, education.field_of_study, business.industry, Phenylurea Compounds, Benzenesulfonates, Carcinoma, General Medicine, Middle Aged, medicine.disease, Survival Analysis, United Kingdom, Treatment Outcome, Tolerability, Female, business, medicine.drug
Abstract: AimTo evaluate the tolerability and efficacy of sorafenib in patients with thyroid carcinoma.MethodsPatients with progressive locally advanced/metastatic medullary thyroid carcinoma (MTC), or differentiated thyroid carcinoma (DTC) with non-radioiodine-avid disease, were treated with sorafenib 400 mg twice daily until disease progression. The primary endpoint was the radiological response rate (RR) at 6 months. Secondary endpoints were RR at 3, 9 and 12 months, biochemical responses, toxicity, biomarker analyses and progression free and overall survival (OS).ResultsA total of 34 patients were recruited to the study (15 medullary and 19 differentiated). After 6 months, the RR rate was 15% and a further 74% of patients achieved stable disease in the first 6 months. After 12 months of treatment, the RR was 21%. In the MTC patients, the RR at 12 months was 25% and OS was 100%. In DTC patients corresponding rates were 18 and 79% respectively. Median overall and progression-free survival points were not reached at 19 months. Commonest adverse events included hand–foot syndrome, other skin toxicities, diarrhoea and alopecia. Dose reduction was required in 79% patients. Median time on treatment was 16.5 months.ConclusionThis study demonstrates that sorafenib is tolerable at reduced doses over prolonged periods of time in patients with thyroid cancer. Sorafenib leads to radiological and biochemical stabilisation of disease in the majority of these patients despite dose reductions.
Published: 2011

48. Hooked on UVR

Author: Richard Marais and Amaya Viros
Subjects: Oncology, business.industry, Medicine, Dermatology, business, General Biochemistry, Genetics and Molecular Biology
Published: 2014
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49. Abstract 2683: Simultaneous inactivation of TP53 and loss of PTEN diminish response to targeted therapy in V600EBRAF mutant melanoma

Author: Franziska Baenke, Elena Galvani, Kok Haw Jonathan Lim, Kelly Brooks, Matt Smith, Gabriela Gremel, Rebecca Lee, Amaya Viros, Clare McManus, Maria Romina Girotti, Paul Lorigan, Alberto Fusi, Richard Marais, and A. Mandal
Subjects: Cancer Research, biology, business.industry, Melanoma, medicine.medical_treatment, Mutant, medicine.disease, Targeted therapy, Oncology, medicine, biology.protein, Cancer research, PTEN, business
Abstract: Numerous cancers are driven by mutationally activated kinases, many of which can be employed to define subsets of cancers and therefore patients most likely to benefit from treatment with rationally designed targeted therapies. Defining the landscape of genetic alterations that participate in cancer transformation provides insight into the diversity of clinical responses observed to targeted treatments. Here, we identified concurrent mutational inactivation of the tumor suppressors TP53 and PTEN as a mechanism of resistance to BRAF inhibitors in melanomas harboring mutant V600EBRAF. Defects in TP53 function and PTEN loss occur in 17% and 12% of malignant melanomas respectively, rendering cells dependent on CHK1 to maintain normal cell cycle progression. We demonstrate that CHK1 inhibition increases sensitivity to a variety of alkylating agents and targeted therapies in V600EBRAF mutant, TP53/PTEN deficient cell lines and patient derived xenografts. Inhibition of CHK1 concurrently with the induction of either DNA damage or replication stress leads to ‘‘mitotic catastrophe’’ and cell death in our in vitro and in vivo models of TP53/PTEN deficient tumors. In the case of externally applied cellular stress from chemotherapeutics, our results suggest CHK1 inhibition may sensitise this genetically defined subset of melanomas to such treatments. Our results provide some insight into the heterogeneity of clinical outcomes observed when treating BRAF mutant melanomas with BRAF inhibitor and suggest a need for comprehensive screening of TP53 and PTEN inactivation in these patients. Citation Format: Elena Galvani, Kelly Brooks, Franziska Baenke, Maria Romina Girotti, Gabriela Gremel, Amit Kumar Mandal, Amaya Viros, Clare McManus, Matthew Smith, Kok Haw Jonathan Lim, Rebecca Lee, Alberto Fusi, Paul Lorigan, Richard Marais. Simultaneous inactivation of TP53 and loss of PTEN diminish response to targeted therapy in V600EBRAF mutant melanoma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2683. doi:10.1158/1538-7445.AM2015-2683
Published: 2015
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50. Abstract 5024: Implications of MAPK pathway inhibition on monocytes and tumor-associated macrophages in melanoma

Author: Elena Galvani, Paul Lorigan, Rebecca Lee, Helen Bradley, Richard Marais, Alberto Fusi, Amaya Viros, Gabriela Gremel, Maria Romina Girotti, and Garry Ashton
Subjects: MAPK/ERK pathway, Cancer Research, business.industry, medicine.medical_treatment, Monocyte, Melanoma, medicine.disease, Targeted therapy, Paracrine signalling, medicine.anatomical_structure, Oncology, Monocyte differentiation, Immunology, medicine, Macrophage, Tumor necrosis factor alpha, business
Abstract: Plasticity in T-cell populations during response and onset of resistance to targeted therapy has been well documented. More recently, macrophage-derived tumor necrosis factor has been described to drive resistance to MAPK pathway inhibition, yet little is known on the adaptation of tumor-associated macrophage populations to treatment and disease progression in human melanoma. To test for alterations in macrophage abundance following resistance to MAPK pathway inhibition, we applied a fluorescence-based co-staining strategy on melanoma specimens, representing tissue collected from patients before treatment and at relapse. In addition, we established in vitro co-culture systems to study the paracrine effects of melanoma cells on various aspects of monocyte differentiation and macrophage activation in the background of MAPK inhibition and resistance. Resistance to targeted therapy was found to be associated with an increase in the number of tumor-resident macrophages. In vitro co-culture of melanoma cell lines with monocytes isolated from the peripheral blood of healthy donors or with CSF1-differentiated macrophages in the presence or absence of MAPK inhibition led to profound changes in monocyte/macrophage marker expression, indicating a direct interplay between the two cell populations upon MAPK pathway inhibition. Our data show that macrophages play an integral role in the changing immune-microenvironment during the course of MAPK pathway inhibition. Elucidation of mechanisms driving these processes will result in strategies to optimize treatment combinations and consecutive treatment outcomes for melanoma patients. Note: This abstract was not presented at the meeting. Citation Format: Gabriela Gremel, Maria Romina Girotti, Amaya Viros, Garry Ashton, Helen Bradley, Elena Galvani, Rebecca Lee, Alberto Fusi, Paul Lorigan, Richard Marais. Implications of MAPK pathway inhibition on monocytes and tumor-associated macrophages in melanoma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5024. doi:10.1158/1538-7445.AM2015-5024
Published: 2015
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