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2. Cardiomyocyte-stromal cell interplay modulates the pathogenesis of arrhythmogenic cardiomyopathy

Author

Maione, A S, primary, Iengo, L, additional, Sala, L, additional, Massaiu, I, additional, Chiesa, M, additional, Ghilardi, S, additional, Florindi, C, additional, Lodola, F, additional, Zaza, A, additional, Tondo, C, additional, Schiavone, M, additional, Banfi, C, additional, Pompilio, G, additional, Poggio, P, additional, and Sommariva, E, additional

Published
2024
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5. Impact of Sacubitril/Valsartan on Circulating microRNA in Patients with Heart Failure

Author

Brioschi, M, D'Alessandra, Y, Mapelli, M, Mattavelli, I, Salvioni, E, Eligini, S, Mallia, A, Ricci, V, Gianazza, E, Ghilardi, S, Agostoni, P, Banfi, C, Brioschi, Maura, D'Alessandra, Yuri, Mapelli, Massimo, Mattavelli, Irene, Salvioni, Elisabetta, Eligini, Sonia, Mallia, Alice, Ricci, Veronica, Gianazza, Erica, Ghilardi, Stefania, Agostoni, Piergiuseppe, Banfi, Cristina, Brioschi, M, D'Alessandra, Y, Mapelli, M, Mattavelli, I, Salvioni, E, Eligini, S, Mallia, A, Ricci, V, Gianazza, E, Ghilardi, S, Agostoni, P, Banfi, C, Brioschi, Maura, D'Alessandra, Yuri, Mapelli, Massimo, Mattavelli, Irene, Salvioni, Elisabetta, Eligini, Sonia, Mallia, Alice, Ricci, Veronica, Gianazza, Erica, Ghilardi, Stefania, Agostoni, Piergiuseppe, and Banfi, Cristina

Abstract

Sacubitril/Valsartan, used for the treatment of heart failure (HF), is a combination of two drugs, an angiotensin receptor inhibitor, and a neprilysin inhibitor, which activates vasoactive peptides. Even though its beneficial effects on cardiac functions have been demonstrated, the mechanisms underpinning these effects remain poorly understood. To achieve more mechanistic insights, we analyzed the profiles of circulating miRNAs in plasma from patients with stable HF with reduced ejection function (HFrEF) and treated with Sacubitril/Valsartan for six months. miRNAs are short (22–24 nt) non-coding RNAs, which are not only emerging as sensitive and stable biomarkers for various diseases but also participate in the regulation of several biological processes. We found that in patients with high levels of miRNAs, specifically miR-29b-3p, miR-221-3p, and miR-503-5p, Sacubitril/Valsartan significantly reduced their levels at follow-up. We also found a significant negative correlation of miR-29b-3p, miR-221-3p, and miR-503-5p with VO2 at peak exercise, whose levels decrease with HF severity. Furthermore, from a functional point of view, miR-29b-3p, miR-221-3p, and miR-503-5p all target Phosphoinositide-3-Kinase Regulatory Subunit 1, which encodes regulatory subunit 1 of phosphoinositide-3-kinase. Our findings support that an additional mechanism through which Sacubitril/Valsartan exerts its functions is the modulation of miRNAs with potentially relevant roles in HFrEF pathophysiology.

Published
2023

7. Prenylcysteine oxidase 1, an emerging player in atherosclerosis

Author

Banfi, C, Baetta, R, Barbieri, S, Brioschi, M, Guarino, A, Ghilardi, S, Sandrini, L, Eligini, S, Polvani, G, Bergman, O, Eriksson, P, Tremoli, E, Banfi C., Baetta R., Barbieri S. S., Brioschi M., Guarino A., Ghilardi S., Sandrini L., Eligini S., Polvani G., Bergman O., Eriksson P., Tremoli E., Banfi, C, Baetta, R, Barbieri, S, Brioschi, M, Guarino, A, Ghilardi, S, Sandrini, L, Eligini, S, Polvani, G, Bergman, O, Eriksson, P, Tremoli, E, Banfi C., Baetta R., Barbieri S. S., Brioschi M., Guarino A., Ghilardi S., Sandrini L., Eligini S., Polvani G., Bergman O., Eriksson P., and Tremoli E.

Abstract

The research into the pathophysiology of atherosclerosis has considerably increased our understanding of the disease complexity, but still many questions remain unanswered, both mechanistically and pharmacologically. Here, we provided evidence that the pro-oxidant enzyme Prenylcysteine Oxidase 1 (PCYOX1), in the human atherosclerotic lesions, is both synthesized locally and transported within the subintimal space by proatherogenic lipoproteins accumulating in the arterial wall during atherogenesis. Further, Pcyox1 deficiency in Apoe-/- mice retards atheroprogression, is associated with decreased features of lesion vulnerability and lower levels of lipid peroxidation, reduces plasma lipid levels and inflammation. PCYOX1 silencing in vitro affects the cellular proteome by influencing multiple functions related to inflammation, oxidative stress, and platelet adhesion. Collectively, these findings identify the pro-oxidant enzyme PCYOX1 as an emerging player in atherogenesis and, therefore, understanding the biology and mechanisms of all functions of this unique enzyme is likely to provide additional therapeutic opportunities in addressing atherosclerosis.

Published
2021

10. Prenylcysteine oxidase 1, A novel player in atherosclerosis

Author

Banfi, C., primary, Baetta, R., additional, Barbieri, S.S., additional, Brioschi, M., additional, Guarino, A., additional, Ghilardi, S., additional, Sandrini, L., additional, Polvani, G., additional, Bergman, O., additional, Eriksson, P., additional, and Tremoli, E., additional

Published
2021
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11. D-dimer is associated with arterial and venous coronary artery bypass graft occlusion

Author

Parolari, A, Cavallotti, L, Andreini, D, Myasoedova, V, Banfi, C, Camera, M, Poggio, P, Barili, F, Pontone, G, Mussoni, L, Centenaro, C, Alamanni, F, Tremoli, E, Zanobini, M, Roberto, M, Porqueddu, M, Naliato, M, Kassem, S, Mushtaq, S, Bertella, E, Pepi, M, Annoni, A, Formenti, A, Brambilla, M, Ghilardi, S, Brioschi, M, Barbieri, S, Parolari A., Cavallotti L., Andreini D., Myasoedova V., Banfi C., Camera M., Poggio P., Barili F., Pontone G., Mussoni L., Centenaro C., Alamanni F., Tremoli E., Zanobini M., Roberto M., Porqueddu M., Naliato M., Kassem S., Mushtaq S., Bertella E., Pepi M., Annoni A., Formenti A., Brambilla M., Ghilardi S., Brioschi M., Barbieri S., Parolari, A, Cavallotti, L, Andreini, D, Myasoedova, V, Banfi, C, Camera, M, Poggio, P, Barili, F, Pontone, G, Mussoni, L, Centenaro, C, Alamanni, F, Tremoli, E, Zanobini, M, Roberto, M, Porqueddu, M, Naliato, M, Kassem, S, Mushtaq, S, Bertella, E, Pepi, M, Annoni, A, Formenti, A, Brambilla, M, Ghilardi, S, Brioschi, M, Barbieri, S, Parolari A., Cavallotti L., Andreini D., Myasoedova V., Banfi C., Camera M., Poggio P., Barili F., Pontone G., Mussoni L., Centenaro C., Alamanni F., Tremoli E., Zanobini M., Roberto M., Porqueddu M., Naliato M., Kassem S., Mushtaq S., Bertella E., Pepi M., Annoni A., Formenti A., Brambilla M., Ghilardi S., Brioschi M., and Barbieri S.

Abstract

Objective In this observational prospective study, we assessed the role of clinical variables and circulating biomarkers in graft occlusion at 18 months to identify a signature for graft occlusion. Methods A total of 330 patients undergoing primary elective coronary artery bypass grafting were enrolled. Blood collection for biomarker assessment was performed before surgery and discharge. Patients were then scheduled to undergo coronary computed tomography angiography at 18 months follow-up, and 179 patients underwent coronary computed tomography angiography 18 ± 2 months postoperatively. Results There were 46 of 503 (9.1%) occluded grafts; of these, 29 (63%) were venous and 17 (37%) were arterial grafts; overall, 43 of 179 patients (24%) had at least 1 occluded graft. Logistic mixed effects model assessing independent factors associated with graft occlusion identified that lower D-dimer levels at baseline (odds ratio [OR], 2.58; 95% confidence interval [CI], 1.36-4.89; P =.00) and total protein content at discharge (OR, 1.09; 95% CI, 1.01-1.19; P =.028) were related to overall graft occlusion at follow-up, along with an arterial graft other than the left internal thoracic artery (OR, 2.92; 95% CI, 1.24-6.9; P =.078); moreover, a venous graft emerged was possibly associated with graft occlusion (OR, 1.51; 95% CI, 0.95-2.39; P =.078). By separately analyzing saphenous vein and arterial grafts, D-dimer levels (OR, 2.67; 95% CI, 1.15-6.2; P =.022 and OR, 2.5; 95% CI, 1.01-7.0; P =.05 for venous and arterial graft, respectively) were still associated with arterial and venous graft occlusion at follow-up. Conclusions We identified D-dimer as a biomarker associated with arterial and venous grafts occlusion. This may help stratify patients at risk of graft failure and identify new molecular targets to prevent this complication.

Published
2018

12. Identification of DKK-1 as a novel mediator of statin effects in human endothelial cells

Author

Pontremoli, M, Brioschi, M, Baetta, R, Ghilardi, S, Banfi, C, Pontremoli M., Brioschi M., Baetta R., Ghilardi S., Banfi C., Pontremoli, M, Brioschi, M, Baetta, R, Ghilardi, S, Banfi, C, Pontremoli M., Brioschi M., Baetta R., Ghilardi S., and Banfi C.

Abstract

This study shows that DKK-1, a member of the Dickkopf family and a regulator of the Wnt pathways, represents a novel target of statins which, through the inhibition of HMG-CoA reductase and of non-steroidal isoprenoid intermediates, exert extra-beneficial effect in preventing atherosclerosis beyond their effect on the lipid profile. We found that atorvastatin downregulates DKK-1 protein (−88.3 ± 4.1%) and mRNA expression (−90 ± 4.2%) through the inhibition of Cdc42, Rho and Rac geranylgeranylated proteins. Further, a combined approach based on the integration of label-free quantitative mass spectrometry based-proteomics and gene silencing allowed us to demonstrate that DKK-1 itself mediates, at least in part, statin effects on human endothelial cells. Indeed, DKK-1 is responsible for the regulation of the 21% of the statin-modulated proteins, which include, among others, clusterin/apoJ, plasminogen activator inhibitor type 1 (PAI-1), myristoylated alanine-rich C-kinase substrate (MARCKS), and pentraxin 3 (PTX3). The Gene Ontology enrichment annotation revealed that DKK-1 is also a potential mediator of the extracellular matrix organization, platelet activation and response to wounding processes induced by statin. Finally, we found that plasma level of DKK-1 from cholesterol-fed rabbits treated with atorvastatin (2.5 mg/kg/day for 8 weeks) was lower (−42 ± 23%) than that of control animals. Thus, DKK-1 is not only a target of statin but it directly regulates the expression of molecules involved in a plethora of biological functions, thus expanding its role, which has been so far restricted mainly to cancer.

Published
2018

14. Optimized protocol for the extraction of proteins from the human mitral valve

Author

Banfi, C, Guarino, A, Brioschi, M, Ghilardi, S, Mastrullo, V, Tremoli, E, Polvani, G, Banfi C., Guarino A., Brioschi M., Ghilardi S., Mastrullo V., Tremoli E., Polvani G., Banfi, C, Guarino, A, Brioschi, M, Ghilardi, S, Mastrullo, V, Tremoli, E, Polvani, G, Banfi C., Guarino A., Brioschi M., Ghilardi S., Mastrullo V., Tremoli E., and Polvani G.

Abstract

Analysis of the cellular proteome can help to elucidate the molecular mechanisms underlying diseases due to the development of technologies that permit the large-scale identification and quantification of the proteins present in complex biological systems. The knowledge gained from a proteomic approach can potentially lead to a better understanding of the pathogenic mechanisms underlying diseases, allowing for the identification of novel diagnostic and prognostic disease markers, and, hopefully, of therapeutic targets. However, the cardiac mitral valve represents a very challenging sample for proteomic analysis because of the low cellularity in proteoglycan and collagen-enriched extracellular matrix. This makes it challenging to extract proteins for a global proteomic analysis. This work describes a protocol that is compatible with subsequent protein analysis, such as quantitative proteomics and immunoblotting. This can allow for the correlation of data concerning protein expression with data on quantitative mRNA expression and non-quantitative immunohistochemical analysis. Indeed, these approaches, when performed together, will lead to a more comprehensive understanding of the molecular mechanisms underlying diseases, from mRNA to posttranslational protein modification. Thus, this method can be relevant to researchers interested in the study of cardiac valve physiopathology.

Published
2017

15. Normal human mitral valve proteome: A preliminary investigation by gel-based and gel-free proteomic approaches

Author

Brioschi M., Baetta R., Ghilardi S., Gianazza E., Guarino A., Parolari A., Polvani G., Tremoli E., Banfi C., Brioschi, M, Baetta, R, Ghilardi, S, Gianazza, E, Guarino, A, Parolari, A, Polvani, G, Tremoli, E, and Banfi, C

Subjects
Adult, Male, Proteomics, Proteome, Valvular interstitial cells&lt, LC/MS, Middle Aged, Immunohistochemistry, Liquid-phase IEF, Human normal mitral valve, Humans, Mitral Valve, 2-dimensional electrophoresis (2-DE), Electrophoresis, Gel, Two-Dimensional, Female
Abstract

The mitral valve is a highly complex structure which regulates blood flow from the left atrium to the left ventricle (LV) avoiding a significant forward gradient during diastole or regurgitation during systole. The integrity of the mitral valve is also essential for the maintenance of normal LV size, geometry, and function. Significant advances in the comprehension of the biological, functional, and mechanical behavior of the mitral valve have recently been made. However, current knowledge of protein components in the normal human mitral valve is still limited and complicated by the low cellularity of this tissue and the presence of high abundant proteins from the extracellular matrix. We employed here an integrated proteomic approach to analyse the protein composition of the normal human mitral valve and reported confident identification of 422 proteins, some of which have not been previously described in this tissue. In particular, we described the ability of pre-MS separation technique based on liquid-phase IEF and SDS-PAGE to identify the largest number of proteins. We also demonstrated that some of these proteins, e.g. αB-Crystallin, septin-11, four-and-a-half LIM domains protein 1, and dermatopontin, are synthesised by interstitial cells isolated from human mitral valves. These initial results provide a valuable basis for future studies aimed at analysing in depth the mitral valve protein composition and at investigating potential pathogenetic molecular mechanisms. Data are available via ProteomeXchange with identifier PXD004397.

Published
2016

16. Plasma immature form of surfactant protein type B correlates with prognosis in patients with chronic heart failure. A pilot single-center prospective study

Author

Magri, D, Banfi, C, Maruotti, A, Farina, S, Vignati, C, Salvioni, E, Morosin, M, Brioschi, M, Ghilardi, S, Tremoli, E, Agostoni, P, Magri D., Banfi C., Maruotti A., Farina S., Vignati C., Salvioni E., Morosin M., Brioschi M., Ghilardi S., Tremoli E., Agostoni P., Magri, D, Banfi, C, Maruotti, A, Farina, S, Vignati, C, Salvioni, E, Morosin, M, Brioschi, M, Ghilardi, S, Tremoli, E, Agostoni, P, Magri D., Banfi C., Maruotti A., Farina S., Vignati C., Salvioni E., Morosin M., Brioschi M., Ghilardi S., Tremoli E., and Agostoni P.

Abstract

Background Gas exchange abnormalities are part of the heart failure (HF) syndrome and growing interest raised on possible biomarkers of alveolar-capillary unit damage. The present pilot single-center study sought to investigate the prognostic values of circulating surfactant protein type B (SP-B) in a cohort of systolic HF patients. Methods One hundred and fifty-one HF stable outpatients and 37 healthy subjects underwent a full clinical assessment, including pulmonary function and lung diffusion for carbon monoxide (DLco), maximal cardiopulmonary exercise test and measurements for both circulating immature and mature forms of SP-B. Study end-points were hospitalization due to HF worsening and cardiovascular mortality. Results Immature SP-B, but not the mature form, was significantly higher in HF patients than in controls and was independently related to DLco, peak oxygen uptake and ventilatory efficiency. During the follow-up (median: 995 days; interquartile range: 739-1247 days), 97 patients experimented at least one HF hospitalization and 9 died for cardiovascular causes. At univariate analysis immature SP-B levels were significantly related to both cardiovascular death (p = 0.033) and HF hospitalization (p < 0.001). At multivariate analysis, immature SP-B levels remained independently associated to HF hospitalization (hazard ratio: 2.304; 95% confidence interval 1.858-3.019; p < 0.001). Conclusions Present data confirm a strong relationship between circulating immature SP-B levels, gas exchange abnormalities and exercise limitations in stable HF as well as they are consistent with the use of immature SP-B in HF clinical risk assessment. Larger prospective studies are needed to confirm its prognostic role as well as to evaluate whether immature SP-B plasma concentration varies in response to specific treatment.

Published
2015

17. Proteomics of tissue factor silencing in cardiomyocytic cells reveals a new role for this coagulation factor in splicing machinery control

Author

Lento, S, Brioschi, M, Barcella, S, Nasim, M, Ghilardi, S, Barbieri, S, Tremoli, E, Banfi, C, Lento S., Brioschi M., Barcella S., Nasim M. T., Ghilardi S., Barbieri S. S., Tremoli E., Banfi C., Lento, S, Brioschi, M, Barcella, S, Nasim, M, Ghilardi, S, Barbieri, S, Tremoli, E, Banfi, C, Lento S., Brioschi M., Barcella S., Nasim M. T., Ghilardi S., Barbieri S. S., Tremoli E., and Banfi C.

Abstract

It has long been known that Tissue Factor (TF) plays a role in blood coagulation and has a direct thrombotic action that is closely related to cardiovascular risk, but it is becoming increasingly clear that it has a much wider range of biological functions that range from inflammation to immunity. It is also involved in maintaining heart haemostasis and structure, and the observation that it is down-regulated in the myocardium of patients with dilated cardiomyopathy suggests that it influences cell-to-cell contact stability and contractility, and thus contributes to cardiac dysfunction. However, the molecular mechanisms underlying these coagulation-independent functions have not yet been fully elucidated.In order to analyse the influence of TF on the cardiomyocitic proteome, we used functional biochemical approaches incorporating label-free quantitative proteomics and gene silencing, and found that this provided a powerful means of identifying a new role for TF in regulating splicing machinery together with the expression of several proteins of the spliceosome, and mRNA metabolism with a considerable impact on cell viability. Biological significance: In this study, using quantitative proteomics and functional biochemical approaches, we define for the first time that, in addition to its primary role in blood coagulation, Tissue Factor also plays a novel role in regulating cell splicing machinery, with a relevant impact on cell survival.This new function may help to explain the wide range of biological activities of TF, and thus provide fruitful clues for developing new strategies for treating human diseases in which TF is dysregulated.

Published
2015

18. Data for proteomic analysis of murine cardiomyocytic HL-1 cells treated with siRNA against tissue factor

Author

Brioschi, M, Lento, S, Barcella, S, Nasim, M, Ghilardi, S, Barbieri, S, Tremoli, E, Banfi, C, Brioschi M., Lento S., Barcella S., Nasim M. T., Ghilardi S., Barbieri S. S., Tremoli E., Banfi C., Brioschi, M, Lento, S, Barcella, S, Nasim, M, Ghilardi, S, Barbieri, S, Tremoli, E, Banfi, C, Brioschi M., Lento S., Barcella S., Nasim M. T., Ghilardi S., Barbieri S. S., Tremoli E., and Banfi C.

Abstract

This data article is related to the research article entitled Proteomics of Tissue Factor silencing in cardiomyocytic cells reveals a new role for this coagulation factor in splicing machinery control by Lento et al. [1].Tissue Factor (TF) is a key player in the coagulation cascade, but it has additional functions ranging from angiogenesis, tumour invasion and, in the heart, the maintenance of the integrity of cardiac cells. This article reports the nano-LC-MSE analysis of the cardiomyocytic HL-1 cell line proteome and describes the results obtained from a Gene Ontology analysis of those proteins affected by TF-gene silencing.

Published
2015

20. Italian cancer figures, report 2014: Prevalence and cure of cancer in Italy

Author

Adamo, M., Alessi, D., Aletta, P., Amodio, R., Andreone, S., Angelin, T., Anghinoni, E., Annulli, M., Arciprete, C., Artioli, M., Autelitano, M., Baili, P., Balducci, C., Baracco, M., Baracco, S., Battisti, W., Bella, F., Bellatalla, C., Bellini, A., Belluardo, C., Benatti, P., Benedetto, G., Benfatto, L., Bernazza, E., Bianconi, F., Biavati, P., Bidoli, E., Birri, S., Bizzoco, S., Bonelli, L., Bonini, A., Borciani, E., Bordini, M., Bovo, E., Bozzani, F., Braghiroli, B., Brucculeri, M., Brunori, V., Bucalo, G., Bucchi, L., Bugliarello, E., Bulatko, A., Busco, S., Busso, P., Buzzoni, C., Calabrese, A., Calabretta, L., Caldarella, A., Candela, G., Cannone, G., Canu, L., Caparelli, M., Capocaccia, R., Cappelletti, M., Caprara, L., Carboni, D., Carletti, N., Caroli, S., Cascio, M., Cascone, G., Casella, C., Castaing, M., Cavalieri, D., L, Cecconami, L., Celesia, M., Cena, T., Cercato, M., Cesaraccio, R., Chiesa, R., Cirilli, C., Cocchioni, M., Codazzi, T., Cogno, R., Colamartini, A., Colanino, Z., A, Cometti, I., Contiero, P., Contrino, M., Corbinelli, A., Cordaro, C., Corti, M., Costa, A., Costarelli, D., Coviello, V., Crapanzano, G., Cremone, L., Crocetti, E., Cuccaro, F., Curatella, S., Cusimano, R., D Alò, D., Dal, C., Dal, T., Cin, A., Dal, M., Davini, C., Dottori, D., De, M., Angelis, R., Santis, D., De, E., Valiere, E., Dei, T., Demurtas, G., Devigili, E., Felice, D., Di, E., Grazia, L., Gregorio, D., Di, C., Norcia, R., Prima, D., Dinaro, Y., Distefano, R., Doa, N., Domati, F., Fabiano, S., Facchinelli, G., Falcini, F., Falk, M., Fanetti, A., Fattoruso, S., Federico, M., Ferrari, F., Ferrari, L., Ferretti, S., Fidelbo, M., Filipazzi, L., Fiore, A., Fiori, G., Foca, F., Forgiarini, O., Foschi, R., Francisci, S., Frasca, G., Frassoldi, E., Fusco, M., Gada, D., Garrone, E., Gasparotti, C., Gatta, G., Gatti, L., Gaudiano, C., Gennaro, V., Gentilini, M., Gerevini, C., Ghilardi, S., Ghisleni, S., Giacomin, A., Giavazzi, L., Gigli, A., Gilardi, F., Giorgetti, S., Giorgi, R., P, Giubelli, C., Giuliani, O., Giurdanella, M., Gola, G., Goldoni, C., Golizia, M., Greco, A., Guarda, L., Guttadauro, A., Guzzinati, S., Iachetta, F., Iannelli, A., Ieni, A., Intrieri, T., Kaleci, S., Rosa, L., F, Lando, C., Lavecchia, A., Lazzarato, F., Rose, L., Leone, A., Leone, R., Lonati, F., Lucchi, S., Luminari, S., Macci, L., Macerata, V., Madeddu, A., Maffei, S., Maghini, A., Magnani, C., Magnani, G., Magoni, M., Mallone, S., Mameli, G., Mancini, S., Mancuso, P., Mangone, L., Manneschi, G., Mannino, R., Mannino, S., Marani, E., Marchesi, C., Mariani, F., Martorana, C., Marzola, L., Maspero, S., Maule, M., Mazzei, A., Mazzoleni, G., Mazzucco, G., Melcarne, A., Merletti, F., Merlo, E., Michiara, M., Migliari, E., Minerba, S., Minicuzzi, A., Mizzi, M., Monetti, D., Morana, G., Moroni, E., Mosso, M., Muni, A., Mura, F., Natali, M., Negrino, L., Nemcova, L., Nicita, C., Ocello, C., Pala, F., Palumbo, M., Panciroli, E., Panico, M., Pannozzo, F., Pascucci, C., Pasolini, A., Pastore, G., Patriarca, S., Pedroni, M., Perrotta, C., Pesce, P., Petrinelli, A., Petrucci, C., Pezzarossi, A., Pezzuto, L., Piffer, S., Pinon, M., Antonio Pinto, Pintori, N., Pirani, M., Pirino, D., Pironi, V., Ponz, D., Leon, M., Prandi, R., Prazzoli, R., Puleio, M., Puppo, A., Quarta, F., Quattrocchi, M., Ramazzotti, V., Rashid, I., Ravaioli, A., Ravazzolo, B., Ravegnani, M., Reggiani Bonetti, L., Ricci, P., Rinaldi, E., Rizzello, R., Rognoni, M., Rollo, P., Roncaglia, F., Roncucci, L., Rosano, A., Rossi, F., Rossi, G., Rossi, M., Rossi, S., Rossini, S., Rosso, S., Rudisi, G., Ruggeri, M., Russo, A., Russo, M., Sacchettini, C., Sacchetto, L., Sacco, G., Sacerdote, C., Salvatore, S., Salvi, O., Sampietro, G., Santucci, C., Scheibel, M., Sciacca, S., Sciacchitano, C., Sciacchitano, S., Scuderi, T., Sechi, O., Seghini, P., Senatore, G., Serafini, G., Serraino, D., Sgargi, P., Sini, G., Sobrato, I., Soddu, M., Solimene, C., Spano, F., Spata, E., Sperduti, I., Spinosa, S., Staiti, R., Stocco, C., Stracci, F., Sunseri, R., Sutera, S., Tagliabue, G., Tamburo, L., Tamburrino, S., Taranto, V., Terracini, B., Tisano, F., Tittarelli, A., Tognazzo, S., Torrisi, A., Traina, A., Trama, A., Trapani, C., Tschugguel, B., Tumino, R., Usala, M., Vacirca, S., Valerio, O., Valla, K., Varvarà, M., Vasquez, E., Vassante, B., Vattiato, R., Vercelli, M., Vercellino, P., Vicentini, M., Villa, M., Virdone, S., Francesco Vitale, Vitale, M., Vitali, B., Vitali, M., Vitarelli, S., Zanchi, A., Zanetti, R., Zani, G., Zanier, L., Zappa, M., Zarcone, M., Zevola, A., Zorzi, M., Zucchetto, A., Zucchi, A., Adamo, MS, Alessi, D, Aletta, P, Amodio, R, Andreone, S, Angelin, T, Anghinoni, E, Annulli, ML, Arciprete, C, Artioli, ME, Autelitano, M, Baili, P, Balducci, C, Baracco, M, Baracco, S, Battisti, W, Bella, F, Bellatalla, C, Bellini, A, Belluardo, C, Benatti, P, Benedetto, G, Benfatto, L, Bernazza, E, Bianconi, F, Biavati, P, Bidoli, E, Birri, S, Bizzoco, S, Bonelli, L, Bonini, A, Borciani, E, Bordini, M, Bovo, E, Bozzani, F, Braghiroli, B, Brucculeri, MA, Brunori, V, Bucalo, G, Bucchi, L, Bugliarello, E, Bulatko, A, Busco, S, Busso, P, Buzzoni, C, Calabrese, A, Calabretta, L, Caldarella, A, Candela, G, Cannone, G, Canu, L, Caparelli, M, Capocaccia, R, Cappelletti, M, Caprara, L, Carboni, D, Carletti, N, Caroli, S, Cascio, MA, Cascone, G, Casella, C, Castaing, M, Cavalieri, d'Oro, L, Cecconami, L, Celesia, MV, Cena, T, Cercato, MC, Cesaraccio, R, Chiesa, R, Cirilli, C, Cocchioni, M, Codazzi, T, Cogno, R, Colamartini, A, Colanino, Ziino, A, Cometti, I, Contiero, P, Contrino, ML, Corbinelli, A, Cordaro, C, Corti, M, Costa, A, Costarelli, D, Coviello, V, Crapanzano, G, Cremone, L, Crocetti, E, Cuccaro, F, Curatella, S, Cusimano, R, D'Alò, D, Dal, Cappello, T, Dal, Cin, A, Dal, Maso, L, Davini, C, De, Dottori, M, De, Angelis, R, De, Santis, E, De, Valiere, E, Dei, Tos, AP, Demurtas, G, Devigili, E, Di, Felice, E, di, Grazia, L, Di, Gregorio, C, di, Norcia, R, Di, Prima, A, Dinaro, Y, Distefano, R, Doa, N, Domati, F, Fabiano, S, Facchinelli, G, Falcini, F, Falk, M, Fanetti, AC, Fattoruso, S, Federico, M, Ferrari, F, Ferrari, L, Ferretti, S, Fidelbo, M, Filipazzi, L, Fiore, AR, Fiori, G, Foca, F, Forgiarini, O, Foschi, R, Francisci, S, Frasca, G, Frassoldi, E, Fusco, M, Gada, D, Garrone, E, Gasparotti, C, Gatta, G, Gatti, L, Gaudiano, C, Gennaro, V, Gentilini, MA, Gerevini, C, Ghilardi, S, Ghisleni, S, Giacomin, A, Giavazzi, L, Gigli, A, Gilardi, F, Giorgetti, S, Giorgi, Rossi, P, Giubelli, C, Giuliani, O, Giurdanella, MC, Gola, G, Goldoni, CA, Golizia, MG, Greco, A, Guarda, L, Guttadauro, A, Guzzinati, S, Iachetta, F, Iannelli, A, Ieni, A, Intrieri, T, Kaleci, S, La, Rosa, F, Lando, C, Lavecchia, AM, Lazzarato, F, Le, Rose, L, Leone, A, Leone, R, Lonati, F, Lucchi, S, Luminari, S, Macci, L, Macerata, V, Madeddu, A, Maffei, S, Maghini, A, Magnani, C, Magnani, G, Magoni, M, Mallone, S, Mameli, G, Mancini, S, Mancuso, P, Mangone, L, Manneschi, G, Mannino, R, Mannino, S, Marani, E, Marchesi, C, Mariani, F, Martorana, C, Marzola, L, Maspero, S, Maule, M, Mazzei, A, Mazzoleni, G, Mazzucco, G, Melcarne, A, Merletti, F, Merlo, E, Michiara, M, Migliari, E, Minerba, S, Minicuzzi, A, Mizzi, M, Monetti, D, Morana, G, Moroni, E, Mosso, ML, Muni, A, Mura, F, Natali, M, Negrino, L, Nemcova, L, Nicita, C, Ocello, C, Pala, F, Palumbo, M, Panciroli, E, Panico, M, Pannozzo, F, Pascucci, C, Pasolini, A, Pastore, G, Patriarca, S, Pedroni, M, Perrotta, C, Pesce, P, Petrinelli, AM, Petrucci, C, Pezzarossi, A, Pezzuto, L, Piffer, S, Pinon, M, Pinto, A, Pintori, N, Pirani, M, Pirino, D, Pironi, V, Ponz, de, Leon, M, Prandi, R, Prazzoli, R, Puleio, M, Puppo, A, Quarta, F, Quattrocchi, M, Ramazzotti, V, Rashid, I, Ravaioli, A, Ravazzolo, B, Ravegnani, M, Reggiani-Bonetti, L, Ricci, P, Rinaldi, E, Rizzello, R, Rognoni, M, Rollo, PC, Roncaglia, F, Roncucci, L, Rosano, A, Rossi, F, Rossi, G, Rossi, M, Rossi, S, Rossini, S, Rosso, S, Rudisi, G, Ruggeri, MG, Russo, AG, Russo, M, Sacchettini, C, Sacchetto, L, Sacco, G, Sacerdote, C, Salvatore, S, Salvi, O, Sampietro, G, Santucci, C, Scheibel, M, Sciacca, S, Sciacchitano, C, Sciacchitano, S, Scuderi, T, Sechi, O, Seghini, P, Senatore, G, Serafini, G, Serraino, D, Sgargi, P, Sini, GM, Sobrato, I, Soddu, M, Solimene, C, Spano, F, Spata, E, Sperduti, I, Spinosa, S, Staiti, R, Stocco, C, Stracci, F, Sunseri, R, Sutera, Sardo, A, Tagliabue, G, Tamburo, L, Tamburrino, S, Taranto, V, Terracini, B, Tisano, F, Tittarelli, A, Tognazzo, S, Torrisi, A, Traina, A, Trama, A, Trapani, C, Tschugguel, B, Tumino, R, Usala, M, Vacirca, S, Valerio, O, Valla, K, Varvarà, M, Vasquez, E, Vassante, B, Vattiato, R, Vercelli, M, Vercellino, PC, Vicentini, M, Villa, M, Virdone, S, Vitale, F, Vitale, MF, Vitali, B, Vitali, ME, Vitarelli, S, Zanchi, A, Zanetti, R, Zani, G, Zanier, L, Zappa, M, Zarcone, M, Zevola, A, Zorzi, M, Zucchetto, A, and Zucchi, A

Subjects
Aged, 80 and over, Male, Medicine (all), Aged, Female, Humans, Italy, Middle Aged, Neoplasms, Prevalence, Registries, Survival Rate, Socio-culturale, Settore MED/42 - Igiene Generale E Applicata, 80 and over, cancer prevalence, cancer incidence, cancer in Italy
Abstract

This Report intends to estimate the total number of people still alive in 2010 after cancer diagnosis in Italy, regardless of the time since diagnosis, and to project these estimates to 2015. This study is also aimed to estimate the number of already cured cancer patients, whose mortality rates have become undistinguishable from that of the general population of the same age and sex.The study took advantage of the information from the AIRTUM database, which included 29 Cancer Registries (covering 21 million people, 35% of the Italian population). A total of 1,624,533 cancer cases diagnosed between 1976 and 2009 contributed to the study. For each registry, the observed prevalence was calculated. Prevalence for lengths of time exceeding the maximum duration of the registration and of the complete prevalence were derived by applying an estimated correction factor, the completeness index. This index was estimated by means of statistical regression models using cancer incidence and survival data available in registries with 18 years of observation or more. For 50 types or combinations of neoplasms, complete prevalence was estimated at 1.1.2010 as an absolute number and as a proportion per 100,000 inhabitants by sex, age group, area of residence, and years since diagnosis. Projections of complete prevalence for 1.1.2015 were computed under the assumption of a linear trend of the complete prevalence observed until 2010. Validated mixture cure models were used to estimate: the cure fraction, that is the proportion of patients who, starting from the time of diagnosis, are expected to reach the same mortality rate of the general population; the conditional relative survival (CRS), that is the cumulative probability of surviving some additional years, given that patients already survived a certain number of years; the time to cure, that is the number of years necessary so that conditional survival in the following five years (5-year CRS) exceeds the conventional threshold of 95% (i.e., mortality rates in cancer patients become undistinguishable compared to those of the general population); the proportion of patients already cured, i.e., people alive since a number of years exceeding time to cure.As of 1.1.2010, it was estimated that 2,587,347 people were alive after a cancer diagnosis, corresponding to 4.4% of the Italian population. A relevant geographical heterogeneity emerged, with a prevalence above 5% in northern registries and below 4% in southern areas. Men were 45% of the total (1,154,289) and women 55% (1,433,058). In the population aged 75 years or more, the proportions of prevalent cases were 20% in males and 13% in females, 11% between 60 and 74 years of age in both sexes. Nearly 600,000 Italian women were alive after a breast cancer diagnosis (41% of all women with this neoplasm), followed by women with cancers of the colon rectum (12%), corpus uteri (7%), and thyroid (6%). In men, 26% of prevalent cases (295,624) were patients with prostate cancer, 16% with either bladder or colon rectum cancer. The projections for 1.1.2015 are of three million (3,036,741) people alive after a cancer diagnosis, 4.9% of the Italian population; with a 20% increase for males and 15% for females, compared to 2010. The cure fractions were heterogeneous according to cancer type and age. Estimates obtained as the sum of cure fractions for all cancer types showed that more than 60% of patients diagnosed below the age of 45 years will reach the same mortality rate of the general population. This proportion decreased with increasing age and it was30% for cancer diagnosed after the age of 74 years. It was observed that 60% of all prevalent cases (1,543,531 people or 2.6% of overall Italian population) had been diagnosed5 years earlier (long-term survivors). Time to cure (5-year CRS95%) was reached in10 years by patients with cancers of the stomach, colon rectum, pancreas, corpus and cervix uteri, brain, and Hodgkin lymphoma. Mortality rates similar to the ones reported by the general population were reached after approximately 20 years for breast and prostate cancer patients. Five-year CRS remained95% for25 years after cancer diagnosis in patients with liver and larynx cancers, non-Hodgkin lymphoma, myeloma, and leukaemia. Time to cure was reached by 27% (20% in men and 33% in women) of all people living after a cancer diagnosis, defined as already cured.The study showed a steady increase over time (nearly +3% per year) of prevalent cases in Italy. A quarter of Italian cancer patients alive in 2010 can be considered as already cured. The AIRTUM Report 2014 describes characteristics of cancer patients and former-patients for 50 cancer types or combinations by sex and age. This detailed information promotes the conduction of studies aimed at expanding the current knowledge on the quality of life of these patients during and after the active phase of treatments (prevalence according to health status), on the long-term effects of treatments (in particular for paediatric patients), on the cost profile of cancer patients, and on rare tumours. All these observations have a high potential impact on health planning, clinical practice, and, most of all, patients' perspective.

Published
2014

21. ITALIAN CANCER FIGURES - REPORT 2015: The burden of rare cancers in Italy = I TUMORI IN ITALIA - RAPPORTO 2015: I tumori rari in Italia

Author

Busco, Susanna, Buzzoni, Carlotta, Mallone, Sandra, Trama, Annalisa, Castaing, Marine, Bella, Francesca, Amodio, Rosalba, Bizzoco, Sabrina, Cassetti, Tiziana, Cirilli, Claudia, Cusimano, Rosanna, De Angelis, Roberta, Fusco, Mario, Gatta, Gemma, Gennaro, Valerio, Giacomin, Adriano, Giorgi Rossi, Paolo, Mangone, Lucia, Mannino, Salvatore, Rossi, Silvia, Pierannunzio, Daniela, Tavilla, Andrea, Tognazzo, Sandro, Tumino, Rosario, Vicentini, Massimo, Vitale, Maria Francesca, Crocetti, Emanuele, Dal Maso, Luigino, Mazzoleni, G, Bulatko, A, Devigili, E, Tschugguel, B, De Valiere, E, Facchinelli, G, Falk, M, Vittadello, F, Coviello, V, Cuccaro, F, Calabrese, A, Pinto, A, Cannone, G, Vitali, Me, Sampietro, G, Ghisleni, S, Giavazzi, L, Zanchi, A, Zucchi, A, Giacomin, A, Vercellino, Pc, Andreone, S, Fedele, M, Barale, A, Germinetti, F, Magoni, M, Zani, G, Salvi, O, Puleio, M, Gerevini, C, Adorni, A, Chiesa, R, Lonati, F, Tumino, R, Cascone, G, Frasca, G, Giurdanella, Mc, Martorana, C, Morana, G, Nicita, C, Rollo, Pc, Ruggeri, Mg, Spata, E, Vacirca, S, Sciacca, S, Sciacchitano, C, Fidelbo, M, Paderni, F, Benedetto, G, Vasquez, E, Bella, F, Calabretta, L, Castaing, M, Di Prima, A, Ieni, A, Leone, A, Pesce, P, Sciacchitano, S, Torrisi, A, Varvarà, M, Sutera Sardo, A, Mazzei, A, Lavecchia, Am, Mancuso, P, Nocera, V, Gola, G, Corti, M, Grandi, L, Caparelli, M, Mannino, S, Belluardo, C, Bizzoco, S, Davini, C, Lucchi, S, Villa, M, Anghinoni, E, Di Norcia, R, Ferretti, S, Biavati, P, Marzola, L, Migliari, E, Carletti, N, Petrucci, C, Brosio, F, Piccinni, L, Valente, N, Barchielli, A, Buzzoni, C, Caldarella, A, Corbinelli, A, Di Dia PP, Intrieri, T, Manneschi, G, Nemcova, L, Susini, N, Visoli, C, Zappa, M, Serraino, D, Angelin, T, Bidoli, E, Birri, S, Dal Maso, L, De Dottori, M, De Santis, E, Forgiarini, O, Zucchetto, A, Zanier, L, Filiberti, Ra, Casella, C, Marani, E, Puppo, A, Celesia, Mv, Cogno, R, Garrone, E, Pannozzo, F, Busco, S, Rashid, I, Ramazzotti, V, Cercato, Mc, Natali, M, Battisti, W, Sperduti, I, Macci, L, Bugliarello, E, Bernazza, E, Tamburo, L, Rossi, M, Curatella, S, Tamburrino, S, Fattoruso, S, Valerio, O, Melcarne, A, Quarta, F, Golizia, Mg, Raho, Am, De Maria, V, Vitarelli, S, Ricci, P, Guarda, L, Gatti, L, Pironi, V, Pasolini, A, Bordini, M, Autelitano, M, Ghilardi, S, Leone, R, Filipazzi, L, Bonini, A, Giubelli, C, Russo, Ag, Quattrocchi, M, Distefano, R, Panciroli, E, Bellini, A, Pinon, M, Spinosa, S, Spagnoli, G, Goldoni, Ca, Valla, K, Braghiroli, B, Cirilli, C, Donini, M, Amendola, V, Cavalieri d'Oro, L, Rognoni, M, Le Rose, L, Merlo, E, Negrino, L, Pezzuto, L, Fusco, M, Bellatalla, C, Panico, M, Perrotta, C, Vassante, B, Vitale, Mf, Usala, M, Pala, F, Sini, Gm, Pintori, N, Canu, L, Demurtas, G, Doa, N, Vitale, F, Cusimano, R, Traina, A, Guttadauro, A, Cascio, Ma, Mannino, R, Ravazzolo, B, Brucculeri, Ma, Rudisi, G, Adamo, Ms, Amodio, R, Costa, A, Zarcone, M, Sunseri, R, Bucalo, G, Trapani, C, Staiti, R, Michiara, M, Bozzani, F, Sgargi, P, Borciani, E, Seghini, P, Faccini, F, Prazzoli, R, Mangone, L, Di Felice, E, Pezzarossi, A, Caroli, S, Sacchettini, C, Ferrari, F, Roncaglia, F, Vicentini, M, Falcini, F, Colamartini, A, Bucchi, L, Balducci, C, Ravegnani, M, Vitali, B, Cordaro, C, Caprara, L, Giuliani, O, Giorgetti, S, Palumbo, M, Vattiato, R, Ravaioli, A, Mancini, S, Caiazzo, Al, Cavallo, R, Colavolpe, Af, D'Alessandro, A, Iannelli, A, Lombardo, C, Senatore, G, Sensi, F, Cesaraccio, R, Sechi, O, Pirino, D, Mura, F, Contrino, Ml, Madeddu, A, Tisano, F, Muni, A, Dinaro, Y, Mizzi, M, Sacco, G, Aletta, P, Ziino, Ac, Maspero, S, Fanetti, Ac, Moroni, E, Cometti, I, Annulli, Ml, Cecconami, L, Minerba, S, Minicuzzi, A, Zanetti, R, Rosso, S, Patriarca, S, Prandi, R, Sobrato, I, Gilardi, F, Busso, P, Sacchetto, L, Candela, G, Scuderi, T, Crapanzano, G, Taranto, V, Piffer, S, Gentilini, Ma, Rizzello, R, Cappelletti, M, Stracci, F, D'Alò, D, Scheibel, M, Costarelli, D, Spano, F, Rossini, S, Santucci, C, Petrinelli, Am, Solimene, C, Bianconi, F, Brunori, V, Tagliabue, G, Contiero, P, Tittarelli, A, Fabiano, S, Maghini, A, Codazzi, T, Frassoldi, E, Gada, D, di Grazia, L, Ruzza, Mr, Dei Tos AP, Baracco, M, Baracco, S, Bovo, E, Dal Cin, A, Fiore, Ar, Greco, A, Guzzinati, S, Monetti, D, Rosano, A, Stocco, C, Tognazzo, S, Zorzi, M, Merletti, F, Magnani, C, Pastore, G, Terracini, B, Alessi, D, Cena, T, Lazzarato, F, Macerata, V, Maule, M, Mosso, Ml, Sacerdote, C, Cocchioni, M, Pascucci, C, Ponz de Leon, M, Domati, F, Rossi, G, Kaleci, S, Rossi, F, Benatti, P, Roncucci, L, Di Gregorio, C, Magnani, G, Pedroni, M, Maffei, S, Mariani, F, Reggiani-Bonetti, L, Gennaro, V, Benfatto, L, Lando, C, Mazzucco, G, Romanelli, A, Storchi, C, Sala, O, Gabbi, C, and Buzzoni, C.

Published
2016

22. Characteristics of the colorectal cancers diagnosed in the early 2000s in Italy. Figures from the IMPATTO study on colorectal cancer screening [Caratteristiche dei tumori del colon retto diagnosticati in Italia nei primi anni Duemila. Dati dello studio IMPATTO sdelo screening colorettale]

Author

Zorzi, Manuel, Mangone, Lucia, Anghinoni, Emanuela, Baracco, Susanna, Borciani, Elisabetta, Caldarella, Adele, Falcini, Fabio, Fanetti, Anna Clara, Ferretti, Stefano, Rossi, Paolo Giorgi, Michiara, Maria, Randi, Giorgia, Stracci, Fabrizio, Vicentini, Massimo, Zucchetto, Antonella, Zappa, Marco, Giacomin, A., Azzoni, A., Baldazzi, P., Collina, N., Pandolfi, P., Biavati, P., Gualandi, G., Sciacca, S., Pesce, P., Torrisi, A., Sciacchitano, C., Fidelbo, M., Finarelli, A. C., Naldoni, C., De'Bianchi, P. Sassoli, Landi, P., Matarese, V., De Togni, A., Palmonari, C., Crocetti, E., Grazzini, G., Manneschi, G., Mantellini, P., Serraino, D., Bidoli, E., Taborelli, M., Gini, A., Virdone, S., Puppo, A., Casella, C., Celesia, M., Cogno, R., Marani, E., Bugliarello, E., Fattoruso, S., Tamburo, L., Tamburrino, S., Bellardini, P., Autelitano, M., Frammartino, B., Bisanti, L., Ghilardi, S., Leone, R., Corradini, R., De Girolamo, F., Valla, K., Palombino, R., Gigli, L., Spena, S. Russo, Vitale, M. F., Cascio, M. A., Mannino, R., Mazzucco, W., Mistretta, A., Ravazzolo, B., Sgarzi, P., Bozzani, F., Zatelli, M., Zurlini, C., Caruana, P., Seghini, P., Gatti, G., Prazzoli, R., Campari, C., Paterlini, L., Cassetti, T., Sassatelli, R., Imolesi, C., Casale, C., Serafini, M., Vattiato, R., Giuliani, O., Cesaraccio, R., Sechi, O., Budroni, M., Madeddu, A., Contrino, M. L., Ziino, A. Colanino, Russo, M., Tisano, F., Fanetti, A. C., Maspero, S., Moroni, E., Cometti, I., Gentilini, M., Piffer, S., De Pretis, G., Caciagli, P., Pertile, R., Bianconi, F., Bucchi, D., Galeotti, M. E., Malaspina, M., Greco, A., Fiore, A. R., Stocco, C. F., and Fedato, C.

Subjects
Colorectal cancer, Colorectal cancer screening, Italy, Epidemiology, Public Health, Environmental and Occupational Health, Environmental and Occupational Health, Socio-culturale, Public Health
Published
2015

23. Multiple-conclusion rules, hypersequent syntax and step frames

Author

Bezhanishvili, N., Ghilardi, S., Goré, R., Kooi, B., Kurucz, A., Logic and Computation (ILLC, FNWI/FGw), and ILLC (FNWI)

Subjects
Computer Science::Logic in Computer Science
Abstract

We investigate proof theoretic properties of logical systems via algebraic methods. We introduce a calculus for deriving multiple-conclusion rules and show that it is a Hilbert style counterpart of hypersequent calculi. Using step-algebras we develop a criterion establishing the bounded proof property and finite model property for these systems. Finally, we show how this criterion can be applied to universal classes axiomatized by certain canonical rules, thus recovering and extending known results from both semantically and proof-theoretically inspired modal literature.

Published
2014

24. Free modal algebras revisited: the step-by-step method

Author

Bezhanishvili, N., Ghilardi, S., Jibladze, M., Bezhanishvili, G., Logic and Computation (ILLC, FNWI/FGw), and ILLC (FNWI)

Subjects
Rank (linear algebra), 010102 general mathematics, Duality (mathematics), 02 engineering and technology, 01 natural sciences, Dual (category theory), Algebra, Interior algebra, Modal, 0202 electrical engineering, electronic engineering, information engineering, 020201 artificial intelligence & image processing, Finitely-generated abelian group, 0101 mathematics, Mathematics, Step method
Abstract

We review the step-by-step method of constructing finitely generated free modal algebras. First we discuss the global step-by-step method, which works well for rank one modal logics. Next we refine the global step-by-step method to obtain the local step-by-step method, which is applicable beyond rank one modal logics. In particular, we show that it works well for constructing the finitely generated free algebras for such well-known modal systems as T, K4 and S4. This yields the notions of one-step algebras and of one-step frames, as well as of universal one-step extensions of one-step algebras and of one-step frames. We show that finitely generated free algebras for T, K4 and S4 and their dual spaces can be obtained by iterating the universal one-step extensions of one-step algebras and of one-step frames. In the final part of the chapter we compare our construction with recent literature, especially with [11] which undertakes a very similar approach.

Published
2014

26. I TUMORI IN ITALIA - RAPPORTO 2013: Tumori multipli = ITALIAN CANCER FIGURES - REPORT 2013: Multiple tumours

Author

Adamo, Ms, Alessi, D, Aletta, P, Amodio, R, Andreone, S, Angelin, T, Anghinoni, E, Annulli, Ml, Antonini, S, Artioli, Me, Autelitano, M, Balducci, C, Balottari, P, Baracco, M, Battisti, W, Bella, F, Bellatalla, C, Belluardo, C, Benatti, P, Benedetto, G, Benfatto, L, Bernazza, E, Bianconi, F, Biavati, P, Bidoli, E, Birri, S, Bizzoco, S, Bonelli, L, Bonini, A, Borciani, E, Bovo, E, Bozzani, F, Bozzeda, A, Braghiroli, B, Brucculeri, Ma, Brunori, V, Bucalo, G, Bucchi, L, Bugliarello, E, Bulatko, A, Busco, S, Busso, P, Buzzoni, C, Calabretta, L, Caldarella, A, Candela, G, Canu, L, Cappelletti, M, Caprara, L, Carboni, D, Carletti, N, Caroli, S, Carone, S, Cascio, Ma, Cascone, G, Casella, C, Castaing, M, Cecconami, L, Celesia, Mv, Cena, T, Cercato, Mc, Cesaraccio, R, Chiesa, R, Cirilli, C, Civaschi, A, Cocchioni, Mario, Codazzi, T, Cogno, R, Colamartini, A, Colanino Ziino, A, Cometti, I, Contiero, P, Contrino, Ml, Corbinelli, A, Cordaro, C, Corti, M, Costa, A, Costarelli, D, Cremone, L, Crocetti, E, Curatella, S, Cusimano, R, D'Alò, D, D'Angelo, S, Dal Cappello, T, Dal Cin, A, Dal Maso, L, Dall'Acqua, M, Dalsasso, F, Davini, C, De Dottori, M, De Maria, V, De Santis, E, De Valiere, E, Dei Tos AP, Demurtas, G, Devigli, E, Di Felice, E, di Grazia, L, Di Gregorio, C, Di Prima, A, Distefano, R, Doa, N, Domati, F, Fabiano, S, Facchinelli, G, Falcini, F, Falk, M, Fanetti, Ac, Fattoruso, S, Federico, M, Ferrari, L, Ferretti, S, Fidelbo, M, Filipazzi, L, Fiore, Ar, Fiori, G, Foca, F, Forgiarini, O, Frasca, G, Frassoldi, E, Frizza, J, Fusco, M, Gada, D, Garrone, E, Gasparotti, C, Gatti, L, Gaudiano, C, Gennaro, V, Gentilini, M, Gerevini, C, Ghilardi, S, Ghisleni, S, Giacomin, A, Giavazzi, L, Gilardi, F, Giorgetti, S, Giubelli, C, Giuliani, O, Giurdanella, Mc, Gola, G, Goldoni, Ca, Golizia, Mg, Grandi, L, Greco, A, Guarda, L, Guttadauro, A, Guzzinati, S, Iachetta, F, Iannelli, A, Ieni, A, Intrieri, T, Kaleci, S, La Rosa, F, Lando, C, Lavecchia, Am, Lazzarato, F, Leone, A, Leone, R, Lonati, F, Lottero, B, Lucchi, S, Luminari, S, Macci, L, Macerata, V, Madeddu, A, Maffei, S, Maghini, A, Magnani, C, Magnani, G, Magoni, M, Mameli, G, Mancini, S, Mancuso, P, Mangone, L, Manneschi, G, Mannino, R, Mannino, S, Marani, E, Mariani, F, Martorana, C, Marzola, L, Maspero, S, Maule, M, Mazzei, A, Mazzoleni, G, Mazzucco, G, Melcarne, A, Merletti, F, Michiara, M, Migliari, E, Minerba, S, Minicuzzi, A, Mizzi, M, Monetti, D, Morana, G, Moroni, E, Mosso, Ml, Muni, A, Mura, F, Natali, M, Nemcova, L, Nicita, C, Ocello, C, Paci, E, Pala, F, Palumbo, M, Panico, M, Pannozzo, F, Pascucci, Cristiana, Pastore, G, Patriarca, S, Pedroni, M, Pellegri, C, Perrotta, C, Pesce, P, Petrinelli, Am, Petrucci, C, Pezzarossi, A, Piffer, S, Pintori, N, Pirani, M, Pirino, D, Pironi, V, Ponz de Leon, M, Prandi, R, Prazzoli, R, Preto, L, Puleio, M, Puppo, A, Quaglia, A, Quarta, F, Quattrocchi, M, Raho, Am, Ramazzotti, V, Rashid, I, Ravaioli, A, Ravazzolo, B, Ravegnani, M, Reggiani Bonetti, L, Ribaudo, M, Rinaldi, E, Ricci, P, Rizzello, R, Rollo, Pc, Roncucci, L, Rosano, A, Rossi, F, Rossi, G, Rossi, M, Rossini, S, Rosso, S, Rudisi, G, Ruggeri, Mg, Russo, Ag, Russo, M, Sacchettini, C, Sacco, G, Sacerdote, C, Salvatore, S, Salvi, O, Sampietro, G, Sandrini, M, Santucci, C, Scheibel, M, Schiacchitano, S, Sciacca, S, Sciacchitano, C, Scuderi, T, Sechi, O, Seghini, P, Senatore, G, Serafini, G, Serraino, D, Sgargi, P, Sigona, A, Sini, Gm, Sobrato, I, Soddu, M, Solimene, C, Spano, F, Spata, E, Sperduti, I, Staiti, R, Stocco, C, Stracci, F, Sunseri, R, Sardo, As, Tagliabue, G, Tamburo, L, Tamburrino, S, Tanzarella, M, Terracini, B, Tessandori, R, Tisano, F, Tittarelli, A, Tognazzo, S, Torrisi, A, Traina, A, Trapani, C, Tschugguel, B, Tumino, R, Usala, M, Vacirca, S, Valerio, O, Valla, K, Varvarà, M, Vasquez, E, Vassante, B, Vattiato, R, Vercelli, M, Vercellino, Pc, Vicentini, M, Villa, M, Vitale, F, Vitale, Mf, Vitali, B, Vitarelli, Susanna, Zanchi, A, Zanetti, R, Zani, G, Zanier, L, Zappa, M, Zarcone, M, Zevola, A, Zucchetto, A, and Zucchi, A.

Published
2013

27. Evidence Logic: A New Look at Neighborhood Structures

Author

van Benthem, J., Fernández-Duque, D., Pacuit, E., Bolander, T., Braüner, T., Ghilardi, S., Moss, L., ILLC (FNWI), and Logic and Computation (ILLC, FNWI/FGw)

Subjects
Computer Science::Logic in Computer Science
Abstract

Two of the authors (van Benthem and Pacuit) recently introduced evidence logic as a way to model epistemic agents faced with possibly contradictory evidence from different sources. For this the authors used neighborhood semantics, where a neighborhood N indicates that the agent has reason to believe that the true state of the world lies in N. A normal belief modality is defined in terms of the neighborhood structure. In this paper we consider four variants of evidence logic which hold for different classes of evidence models. For each of these logics we give a representation theorem using extended evidence models, where the belief operator is replaced by a standard relational modality. With this, we axiomatize all four logics, and determine whether each has the finite model property.

Published
2012

28. Topological Completeness of First-Order Modal Logic

Author

Awodey, S., Kishida, K., Bolander, T., Braüner, T., Ghilardi, S., Moss, L., Logic and Language (ILLC, FNWI/FGw), Faculty of Science, and ILLC (FNWI)

Subjects
TheoryofComputation_MATHEMATICALLOGICANDFORMALLANGUAGES, Computer Science::Logic in Computer Science
Abstract

As McKinsey and Tarski [20] showed, the Stone representation theorem for Boolean algebras extends to algebras with operators to give topological semantics for (classical) propositional modal logic, in which the "necessity" operation is modeled by taking the interior of an arbitrary subset of a topological space. This topological interpretation was recently extended in a natural way to arbitrary theories of full first-order logic by Awodey and Kishida [3], using topological sheaves to interpret domains of quantification. This paper proves the system of full first-order S4 modal logic to be deductively complete with respect to such extended topological semantics. The techniques employed are related to recent work in topos theory, but are new to systems of modal logic. They are general enough to also apply to other modal systems.

Published
2012

30. Italian cancer figures, report 2011: Survival of cancer patients in Italy

Author

Fusco, M, Buzzoni, C, Coviello, E, Rashid, I, Bianconi, F, Cuccaro, F, Castaing, M, De Angelis, R, Giacomin, A, Guzzinati, S, Mosso, Ml, Pisani, P, Quaglia, A, Randi, G, Ramazzotti, V, Russo, A, Senatore, G, Stracci, F, Traina, A, Vercelli, M, Zarcone, M, Ferretti, S, Mazzoleni, G, Bellú, F, Tschugguel, B, De Valiere, E, Facchinelli, G, Falk, M, Dal Cappello, T, Vercellino, Pc, Andreone, S, Busato, A, Marzola, L, Migliari, E, Carletti, N, Nenci, I, Crocetti, E, Caldarella, A, Corbinelli, A, Giusti, F, Intrieri, T, Manneschi, G, Nemcova, L, Romeo, G, Sacchettini, C, Zappa, M, Paci, E, Serraino, D, Angelin, T, Bidoli, E, Dal Maso, L, de Dottori, M, De Paoli, A, De Santis, E, Forgiarini, O, Lise, M, Zucchetto, A, Zanier, L, Orengo, Ma, Casella, C, Marani, E, Puppo, A, Celesia, Mv, Cogno, R, Manenti, S, Garrone, E, Pannozzo, F, Busco, S, Cercato, Mc, Battisti, W, Sperduti, I, Macci, L, Bugliarello, E, Bernazza, E, Tamburo, L, Rossi, M, Curatella, S, De Francesco, C, Tamburrino, S, Bisanti, L, Autelitano, M, Ghilardi, S, Leone, R, Filipazzi, L, Bonini, A, Giubelli, C, Federico, M, Artioli, Me, Valla, K, Braghiroli, B, Cirilli, C, Luminari, S, Pirani, M, Ferrari, L, Bellatalla, C, Panico, M, Perrotta, C, Vassante, B, Vitale, Mf, Michiara, M, Bozzani, F, Sgargi, P, Tumino, R, La Rosa MG, Cascone, G, Frasca, G, Giurdanella, Mc, Martorana, C, Morana, G, Nicita, C, Rollo, Pc, Ruggeri, Mg, Sigona, A, Spata, E, Vacirca, S, Mangone, L, Di Felice, E, Pezzarossi, A, Caroli, S, Pellegri, C, Vicentini, M, Storchi, C, Cavuto, S, Costa, J, Falcini, F, Colamartini, A, Bucchi, L, Balducci, C, Ravegnani, M, Vitali, B, Cordaro, C, Caprara, L, Giuliani, O, Giorgetti, S, Salvatore, S, Palumbo, M, Vattiato, R, Ravaioli, A, Foca, F, Rinaldi, E, Mancini, S, Tonelli, C, Amadori, M, Cremone, L, Iannelli, A, Zevola, A, Budroni, M, Cesaraccio, R, Pirino, D, Carboni, D, Fiori, G, Soddu, M, Mameli, G, Mura, F, Contrino, Ml, Madeddu, A, Tisano, F, Sciacca, S, Muni, A, Mizzi, M, Russo, M, Sacco, G, Aletta, P, Colanino Ziino, A, Tessandori, R, Fanetti, Ac, Maspero, S, Annulli, Ml, Moroni, E, Sanoja Gonzalez ME, Zanetti, R, Rosso, S, Patriarca, S, Prandi, R, Sobrato, I, Gilardi, F, Busso, P, Piffer, S, Gentilini, Ma, Battisti, L, Rizzello, R, Cappelletti, M, Moser, M, La Rosa, F, D'Alò, D, Scheibel, M, Costarelli, D, Spano, F, Rossini, S, Santucci, C, Petrinelli, Am, Solimene, C, Brunori, V, Crosignani, P, Tagliabue, G, Contiero, P, Preto, L, Tittarelli, A, Maghini, A, Codazzi, T, Frassoldi, E, Gada, D, Costa, E, di Grazia, L, Zambon, P, Baracco, M, Bovo, E, Dal Cin, A, Fiore, Ar, Greco, A, Monetti, D, Rosano, A, Stocco, C, Tognazzo, S, Donato, Francesco, Limina, Rosa Maria, Adorni, A, Andreis, P, Zani, G, Piovani, F, Salvi, O, Puleio, M, Vitarelli, S, Antonini, S, Candela, G, Pappalardo, G, Scuderi, T, Lottero, B, Ribaudo, M, Ricci, P, Guarda, L, Gatti, L, Bozzeda, A, Dall'Acqua, M, Pironi, V, Sutera Sardo, A, Mazzei, A, Sirianni, N, Lavecchia, Am, Mancuso, P, Usala, M, Pala, F, Sini, Gm, Pintori, N, Canu, L, Demurtas, G, Doa, N, Ponz de Leon, M, Domati, F, Rossi, G, Goldoni, Ca, Rossi, F, De Gaetani, C, Benatti, P, Roncucci, L, Di Gregorio, C, Pedroni, M, Pezzi, A, Maffei, S, Mariani, F, Borsi, E, Carruba, G, Cusimano, R, Amodio, R, Dolcemascolo, C, Staiti, R, Pastore, G, Magnani, C, Terracini, B, Cena, T, Alessi, D, Baussano, I, Merletti, F, Maule, M, Macerata, V, Cocchioni, M, Pascucci, C, Gennaro, V, Lazzarotto, A, Benfatto, L, Mazzucco, G, and Montanaro, F.

Subjects
Survival, Italy, cancer patients
Published
2011

31. I tumori in Italia. Rapporto 2011: La sopravvivenza dei pazienti oncologici in Italia

Author

Fusco M, Airtum Working G. R. O. U. P., Buzzoni, C., Coviello, E., Rashid, I., Bianconi, F., Cuccaro, F., Castaing, M., Angelis, R., Giacomin, A., Guzzinati, S., Mosso, Ml, Pisani, P., Quaglia, A., Randi, G., Ramazzotti, V., Russo, A., Senatore, G., Stracci, F., Traina, A., Vercelli, M., Zarcone, M., Ferretti, S., Mazzoleni, G., Bellú, F., Tschugguel, B., Valiere, E., Facchinelli, G., Falk, M., Dal Cappello, T., Vercellino, Pc, Andreone, S., Busato, A., Marzola, L., Migliari, E., Carletti, N., Nenci, I., Crocetti, E., Caldarella, A., Corbinelli, A., Giusti, F., Intrieri, T., Manneschi, G., Nemcova, L., Romeo, G., Sacchettini, C., Zappa, M., Paci, E., Serraino, D., Angelin, T., Bidoli, E., Dal Maso, L., Dottori, M., Paoli, A., Santis, E., Forgiarini, O., Lise, M., Zucchetto, A., Zanier, L., Orengo, Ma, Casella, C., Marani, E., Puppo, A., Celesia, Mv, Cogno, R., Manenti, S., Garrone, E., Pannozzo, F., Busco, S., Cercato, Mc, Battisti, W., Sperduti, I., Macci, L., Bugliarello, E., Bernazza, E., Tamburo, L., Rossi, M., Curatella, S., Francesco, C., Tamburrino, S., Bisanti, L., Autelitano, M., Ghilardi, S., Leone, R., Filipazzi, L., Bonini, A., Giubelli, C., Federico, Massimo, Artioli, Me, Valla, K., Braghiroli, B., Cirilli, C., stefano luminari, Pirani, M., Ferrari, L., Bellatalla, C., Fusco, M., Panico, M., Perrotta, C., Vassante, B., Vitale, Mf, Michiara, M., Bozzani, F., Sgargi, P., Tumino, R., La Rosa MG, Cascone, G., Frasca, G., Giurdanella, Mc, Martorana, C., Morana, G., Nicita, C., Rollo, Pc, Ruggeri, Mg, Sigona, A., Spata, E., Vacirca, S., Mangone, L., Di Felice, E., Pezzarossi, A., Caroli, S., Pellegri, C., Vicentini, M., Storchi, C., Cavuto, S., Costa, J., Falcini, F., Colamartini, A., Bucchi, L., Balducci, C., Ravegnani, M., Vitali, B., Cordaro, C., Caprara, L., Giuliani, O., Giorgetti, S., Salvatore, S., Palumbo, M., Vattiato, R., Ravaioli, A., Foca, F., Rinaldi, E., Mancini, S., Tonelli, C., Amadori, M., Cremone, L., Iannelli, A., Zevola, A., Budroni, M., Cesaraccio, R., Pirino, D., Carboni, D., Fiori, G., Soddu, M., Mameli, G., Mura, F., Contrino, Ml, Madeddu, A., Tisano, F., Sciacca, S., Muni, A., Mizzi, M., Russo, M., Sacco, G., Aletta, P., Colanino Ziino, A., Tessandori, R., Fanetti, Ac, Maspero, S., Annulli, Ml, Moroni, E., Sanoja Gonzalez ME, Zanetti, R., Rosso, S., Patriarca, S., Prandi, R., Sobrato, I., Gilardi, F., Busso, P., Piffer, S., Gentilini, Ma, Battisti, L., Rizzello, R., Cappelletti, M., Moser, M., La Rosa, F., D Alò, D., Scheibel, M., Costarelli, D., Spano, F., Rossini, S., Santucci, C., Petrinelli, Am, Solimene, C., Brunori, V., Crosignani, P., Tagliabue, G., Contiero, P., Preto, L., Tittarelli, A., Maghini, A., Codazzi, T., Frassoldi, E., Gada, D., Costa, E., Di Grazia, L., Zambon, P., Baracco, M., Bovo, E., Dal Cin, A., Fiore, Ar, Greco, A., Monetti, D., Rosano, A., Stocco, C., Tognazzo, S., Donato, F., Limina, Rm, Adorni, A., Andreis, P., Zani, G., Piovani, F., Salvi, O., Puleio, M., Vitarelli, S., Antonini, S., Candela, G., Pappalardo, G., Scuderi, T., Lottero, B., Ribaudo, M., Ricci, P., Guarda, L., Gatti, L., Bozzeda, A., Dall Acqua, M., Pironi, V., Sutera Sardo, A., Mazzei, A., Sirianni, N., Lavecchia, Am, Mancuso, P., Usala, M., Pala, F., Sini, Gm, Pintori, N., Canu, L., Demurtas, G., Doa, N., Maurizio Ponz de Leon, Domati, Federica, Rossi, Giuseppina, Goldoni, Ca, Rossi, F., Gaetani, C., Piero Benatti, Luca Roncucci, Di Gregorio, C., Pedroni, Monica, Pezzi, A., Maffei, Stefania, Mariani, Francesco, Borsi, E., Carruba, G., Cusimano, R., Amodio, R., Dolcemascolo, C., Staiti, R., Pastore, G., Magnani, C., Terracini, B., Cena, T., Alessi, D., Baussano, I., Merletti, F., Maule, M., Macerata, V., Cocchioni, M., Pascucci, C., Gennaro, V., Lazzarotto, A., Benfatto, L., Mazzucco, G., and Montanaro, F.

Subjects
Survival, cancer
Published
2011

36. Italian cancer figures, report 2012: Cancer in children and adolescents

Author

Pisani, P, Buzzoni, C, Crocetti, E, Maso, L, Rondelli, R, Alessi, D, Aricò, M, Bidoli, E, Ferrari, A, Fusco, M, Gatta, G, Guzzinati, S, Jankovic, M, Locatelli, F, Maule, M, Mosso, M, Pastore, G, Pession, A, Rashid, I, Sacerdote, C, Terracini, B, Tognazzo, S, Trama, A, Ferretti, S, Porta, F, Mazzoleni, G, Tschugguel, B, De Valiere, E, Facchinelli, G, Falk, M, Cappello, T, Giacomin, A, Vercellino, P, Andreone, S, Marzola, L, Migliari, E, Carletti, N, Nenci, I, Caldarella, A, Corbinelli, A, Intrieri, T, Manneschi, G, Nemcova, L, Ocello, C, Sacchettini, C, Zappa, M, Paci, E, Serraino, D, Angelin, T, Birri, S, De Dottori, M, De Santis, E, Forgiarini, O, Zucchetto, A, Zanier, L, Vercelli, M, Orengo, M, Casella, C, Marani, E, Puppo, A, Celesia, M, Cogno, R, Levrieri, I, Manenti, S, Garrone, E, Quaglia, A, Pannozzo, F, Busco, S, Ramazzotti, V, Cercato, M, Battisti, W, Sperduti, I, Macci, L, Bugliarello, E, Valerio, O, Bernazza, E, Tamburo, L, Rossi, M, Curatella, S, Tamburrino, S, Fattoruso, S, Bisanti, L, Autelitano, M, Cuccaro, F, Randi, G, Ghilardi, S, Leone, R, Filipazzi, L, Bonini, A, Giubelli, C, Federico, M, Artioli, M, Valla, K, Braghiroli, B, Cirilli, C, Luminari, S, Pirani, M, Ferrari, L, Bellatalla, C, Panico, M, Perrotta, C, Vassante, B, Vitale, M, Michiara, M, Bozzani, F, Sgargi, P, Tumino, R, Rosa, M, Cascone, G, Frasca, G, Giurdanella, M, Martorana, C, Morana, G, Nicita, C, Rollo, P, Ruggeri, M, Sigona, A, Spata, E, Vacirca, S, Mangone, L, Di Felice, E, Pezzarossi, A, Caroli, S, Pellegri, C, Vicentini, M, D'Angelo, S, Balottari, P, Romagna, R, Falcini, F, Colamartini, A, Bucchi, L, Balducci, C, Ravegnani, M, Vitali, B, Cordaro, C, Caprara, L, Giuliani, O, Giorgetti, S, Palumbo, M, Vattiato, R, Ravaioli, A, Mancini, S, Tonelli, C, Amadori, M, Cremone, L, Iannelli, A, Senatore, G, Zevola, A, Sechi, O, Budroni, M, Cesaraccio, R, Pirino, D, Carboni, D, Fiori, G, Soddu, M, Mameli, G, Mura, F, Contrino, M, Madeddu, A, Tisano, F, Sciacca, S, Muni, A, Mizzi, M, Russo, M, Sacco, G, Aletta, P, Ziino, A, Tessandori, R, Fanetti, A, Maspero, S, Cecconami, L, Annulli, M, Moroni, E, Gonzalez, M, Zanetti, R, Rosso, S, Patriarca, S, Prandi, R, Sobrato, I, Gilardi, F, Busso, P, Piffer, S, Rizzello, R, Gentilini, M, Cappelletti, M, Rosa, F, Stracci, F, D'Alò, D, Scheibel, M, Costarelli, D, Spano, F, Rossini, S, Santucci, C, Petrinelli, A, Solimene, C, Bianconi, F, Brunori, V, Crosignani, P, Tagliabue, G, Contiero, P, Preto, L, Tittarelli, A, Maghini, A, Codazzi, T, Frassoldi, E, Gada, D, Costa, E, Grazia, L, Zambon, P, Baracco, M, Bovo, E, Cin, A, Fiore, A, Greco, A, Monetti, D, Rosano, A, Stocco, C, Donato, F, Limina, R, Adorni, A, Andreis, P, Zani, G, Piovani, F, Salvi, O, Puleio, M, Vitarelli, S, Candela, G, Pappalardo, G, Scuderi, T, Lottero, B, Ribaudo, M, Ricci, P, Guarda, L, Gatti, L, Bozzeda, A, Dall'Acqua, M, Pironi, V, Sardo, A, Mazzei, A, Sirianni, N, Lavecchia, A, Mancuso, P, Vitale, F, Cusimano, R, Amodio, R, Guttadauro, A, Ravazzolo, B, Bucalo, G, Trapani, C, Sunseri, R, Cascio, M, Brucculeri, M, Adamo, M, Mannino, R, Mistretta, A, Costa, A, Rudisi, G, Gola, G, Corti, M, Prosperini, E, Grandi, L, Sciacchitano, S, Fidelbo, M, Benedetto, G, Vasquez, E, Torrisi, A, Pesce, P, Calabretta, L, Bella, F, Leone, A, Ieni, A, Varvarà, M, Castaing, M, Di Prima, A, Benedetto, A, Paderni, F, Usala, M, Pala, F, Sini, G, Pintori, N, Canu, L, Demurtas, G, Doa, N, Lazzarato, F, Magnani, C, Merletti, F, Sarcerdote, C, Macerata, V, de Leon, M, Domati, F, Rossi, G, Goldoni, C, Rossi, F, De Gaetani, C, Benatti, P, Roncucci, L, Di Gregorio, C, Pedroni, M, Pezzi, A, Maffei, S, Mariani, F, Borsi, E, Cocchioni, M, Pascucci, C, Gennaro, V, Lazzarotto, A, Benfatto, L, Mazzucco, G, Montanaro, F, Traina, A, Carruba, G, Dolcemascolo, C, Staiti, R, Zarcone, M, Bisogno, G, Cuttini, M, De Rosa, M, Haupt, R, Soresina, A, Valsecchi, M, Fagioli, F, Bona, G, Dini, G, Conter, V, Biondi, A, Zecca, M, Fedeli, F, Massimino, M, Nespoli, L, Roncarolo, M, Basso, G, Cesaro, S, Memo, L, Bellettato, M, Tamaro, P, Mascarin, M, Rosolen, A, Izzi, G, Paolucci, P, Borgna Pignatti, C, Vecchi, V, Abate, M, D'Ambrosio, A, Favre, C, Caniglia, M, Pierani, P, Felici, L, Visani, G, Fioritoni, G, Foà, R, Riccardi, R, Frega, G, Clerico, A, Casale, F, Poggi, V, Amendola, G, Filosa, A, Ladogana, S, Presta, G, Tornesello, A, De Mattia, D, Consarino, C, Nobile, F, Sperlì, D, D'Angelo, P, Marino, S, Cosmi, C, Mura, R, Battisti, L, Maso, LD, Mosso, ML, Cappello, TD, Vercellino, PC, Orengo, MA, Celesia, MV, Cercato, MC, Artioli, ME, Vitale, MF, Rosa, MG, Giurdanella, MC, Rollo, PC, Ruggeri, MG, Romagna, Rt, Contrino, ML, Ziino, AC, Fanetti, AC, Annulli, ML, Gonzalez, ME, Gentilini, MA, Rosa, FL, Petrinelli, AM, Grazia, Ld, Cin, AD, Fiore, AR, Limina, RM, Sardo, AS, Lavecchia, AM, Cascio, MA, Brucculeri, MA, Adamo, MS, Sini, GM, de Leon, MP, Goldoni, CA, VALSECCHI, MARIA GRAZIA, BIONDI, ANDREA, Roncarolo, MG, Abate, ME, Mura, RM, Battisti, L., Pisani, P, Buzzoni, C, Crocetti, E, Maso, L, Rondelli, R, Alessi, D, Aricò, M, Bidoli, E, Ferrari, A, Fusco, M, Gatta, G, Guzzinati, S, Jankovic, M, Locatelli, F, Maule, M, Mosso, M, Pastore, G, Pession, A, Rashid, I, Sacerdote, C, Terracini, B, Tognazzo, S, Trama, A, Ferretti, S, Porta, F, Mazzoleni, G, Tschugguel, B, De Valiere, E, Facchinelli, G, Falk, M, Cappello, T, Giacomin, A, Vercellino, P, Andreone, S, Marzola, L, Migliari, E, Carletti, N, Nenci, I, Caldarella, A, Corbinelli, A, Intrieri, T, Manneschi, G, Nemcova, L, Ocello, C, Sacchettini, C, Zappa, M, Paci, E, Serraino, D, Angelin, T, Birri, S, De Dottori, M, De Santis, E, Forgiarini, O, Zucchetto, A, Zanier, L, Vercelli, M, Orengo, M, Casella, C, Marani, E, Puppo, A, Celesia, M, Cogno, R, Levrieri, I, Manenti, S, Garrone, E, Quaglia, A, Pannozzo, F, Busco, S, Ramazzotti, V, Cercato, M, Battisti, W, Sperduti, I, Macci, L, Bugliarello, E, Valerio, O, Bernazza, E, Tamburo, L, Rossi, M, Curatella, S, Tamburrino, S, Fattoruso, S, Bisanti, L, Autelitano, M, Cuccaro, F, Randi, G, Ghilardi, S, Leone, R, Filipazzi, L, Bonini, A, Giubelli, C, Federico, M, Artioli, M, Valla, K, Braghiroli, B, Cirilli, C, Luminari, S, Pirani, M, Ferrari, L, Bellatalla, C, Panico, M, Perrotta, C, Vassante, B, Vitale, M, Michiara, M, Bozzani, F, Sgargi, P, Tumino, R, Rosa, M, Cascone, G, Frasca, G, Giurdanella, M, Martorana, C, Morana, G, Nicita, C, Rollo, P, Ruggeri, M, Sigona, A, Spata, E, Vacirca, S, Mangone, L, Di Felice, E, Pezzarossi, A, Caroli, S, Pellegri, C, Vicentini, M, D'Angelo, S, Balottari, P, Romagna, R, Falcini, F, Colamartini, A, Bucchi, L, Balducci, C, Ravegnani, M, Vitali, B, Cordaro, C, Caprara, L, Giuliani, O, Giorgetti, S, Palumbo, M, Vattiato, R, Ravaioli, A, Mancini, S, Tonelli, C, Amadori, M, Cremone, L, Iannelli, A, Senatore, G, Zevola, A, Sechi, O, Budroni, M, Cesaraccio, R, Pirino, D, Carboni, D, Fiori, G, Soddu, M, Mameli, G, Mura, F, Contrino, M, Madeddu, A, Tisano, F, Sciacca, S, Muni, A, Mizzi, M, Russo, M, Sacco, G, Aletta, P, Ziino, A, Tessandori, R, Fanetti, A, Maspero, S, Cecconami, L, Annulli, M, Moroni, E, Gonzalez, M, Zanetti, R, Rosso, S, Patriarca, S, Prandi, R, Sobrato, I, Gilardi, F, Busso, P, Piffer, S, Rizzello, R, Gentilini, M, Cappelletti, M, Rosa, F, Stracci, F, D'Alò, D, Scheibel, M, Costarelli, D, Spano, F, Rossini, S, Santucci, C, Petrinelli, A, Solimene, C, Bianconi, F, Brunori, V, Crosignani, P, Tagliabue, G, Contiero, P, Preto, L, Tittarelli, A, Maghini, A, Codazzi, T, Frassoldi, E, Gada, D, Costa, E, Grazia, L, Zambon, P, Baracco, M, Bovo, E, Cin, A, Fiore, A, Greco, A, Monetti, D, Rosano, A, Stocco, C, Donato, F, Limina, R, Adorni, A, Andreis, P, Zani, G, Piovani, F, Salvi, O, Puleio, M, Vitarelli, S, Candela, G, Pappalardo, G, Scuderi, T, Lottero, B, Ribaudo, M, Ricci, P, Guarda, L, Gatti, L, Bozzeda, A, Dall'Acqua, M, Pironi, V, Sardo, A, Mazzei, A, Sirianni, N, Lavecchia, A, Mancuso, P, Vitale, F, Cusimano, R, Amodio, R, Guttadauro, A, Ravazzolo, B, Bucalo, G, Trapani, C, Sunseri, R, Cascio, M, Brucculeri, M, Adamo, M, Mannino, R, Mistretta, A, Costa, A, Rudisi, G, Gola, G, Corti, M, Prosperini, E, Grandi, L, Sciacchitano, S, Fidelbo, M, Benedetto, G, Vasquez, E, Torrisi, A, Pesce, P, Calabretta, L, Bella, F, Leone, A, Ieni, A, Varvarà, M, Castaing, M, Di Prima, A, Benedetto, A, Paderni, F, Usala, M, Pala, F, Sini, G, Pintori, N, Canu, L, Demurtas, G, Doa, N, Lazzarato, F, Magnani, C, Merletti, F, Sarcerdote, C, Macerata, V, de Leon, M, Domati, F, Rossi, G, Goldoni, C, Rossi, F, De Gaetani, C, Benatti, P, Roncucci, L, Di Gregorio, C, Pedroni, M, Pezzi, A, Maffei, S, Mariani, F, Borsi, E, Cocchioni, M, Pascucci, C, Gennaro, V, Lazzarotto, A, Benfatto, L, Mazzucco, G, Montanaro, F, Traina, A, Carruba, G, Dolcemascolo, C, Staiti, R, Zarcone, M, Bisogno, G, Cuttini, M, De Rosa, M, Haupt, R, Soresina, A, Valsecchi, M, Fagioli, F, Bona, G, Dini, G, Conter, V, Biondi, A, Zecca, M, Fedeli, F, Massimino, M, Nespoli, L, Roncarolo, M, Basso, G, Cesaro, S, Memo, L, Bellettato, M, Tamaro, P, Mascarin, M, Rosolen, A, Izzi, G, Paolucci, P, Borgna Pignatti, C, Vecchi, V, Abate, M, D'Ambrosio, A, Favre, C, Caniglia, M, Pierani, P, Felici, L, Visani, G, Fioritoni, G, Foà, R, Riccardi, R, Frega, G, Clerico, A, Casale, F, Poggi, V, Amendola, G, Filosa, A, Ladogana, S, Presta, G, Tornesello, A, De Mattia, D, Consarino, C, Nobile, F, Sperlì, D, D'Angelo, P, Marino, S, Cosmi, C, Mura, R, Battisti, L, Maso, LD, Mosso, ML, Cappello, TD, Vercellino, PC, Orengo, MA, Celesia, MV, Cercato, MC, Artioli, ME, Vitale, MF, Rosa, MG, Giurdanella, MC, Rollo, PC, Ruggeri, MG, Romagna, Rt, Contrino, ML, Ziino, AC, Fanetti, AC, Annulli, ML, Gonzalez, ME, Gentilini, MA, Rosa, FL, Petrinelli, AM, Grazia, Ld, Cin, AD, Fiore, AR, Limina, RM, Sardo, AS, Lavecchia, AM, Cascio, MA, Brucculeri, MA, Adamo, MS, Sini, GM, de Leon, MP, Goldoni, CA, VALSECCHI, MARIA GRAZIA, BIONDI, ANDREA, Roncarolo, MG, Abate, ME, Mura, RM, and Battisti, L.

Abstract

This study describes up-to-date cancer incidence and survival in Italian paediatric and adolescent patients, based on data collected by the network of Italian cancer registries (AIRTUM). It updates the monograph published on the same topic in 2008. The main objective of this monograph is to present the statistics according to standard rigorous epidemiological methods and disseminate them to a wide range of readers, including the lay public. Given the deep impact of the 2008 monograph on the general public, in this update we complement descriptive statistics with additional data and commentaries on issues of importance for public health, in order to provide unambiguous criteria on how to interpret the statistics. The study is the result of the collaboration between AIRTUM and AIEOP (Italian Association of Paediatric Haematology and Oncology) with contributions from interested parties, including representatives of parent associations. The monograph is divided into three parts. The first part presents incidence rates, survival probabilities, and time trends, by sex, age, geographical area, and cancer site or type, by means of tables and graphs as in the previous monograph, to facilitate direct comparisons. Four articles summarize and comment the results. The second part uses data from AIRTUM and AIEOP to outline patient management and health care issues; it includes estimates of the number of new cases in the next decade and of young adults living after a paediatric cancer diagnosis. Health organizational aspects of treatment services for paediatric patients, based on the AIEOP database, are also discussed, along with long-term complications in cured patients. The third section describes the changes in mortality trends due to improving therapies and healthcare services, and discusses risk factors and prevention of childhood cancer, late adverse events in cured patients, and other related issues.

Published
2013

38. Trends in Lung Cancer and Smoking Behavior in Italy: An Alarm Bell for Women

Author

Trama, Annalisa, Boffi, Roberto, Contiero, Paolo, Buzzoni, Carlotta, Pacifici, Roberta, Mangone, Lucia, Coviello, V, Buzzoni, C, Fusco, M, Barchielli, A, Cuccaro, F, De Angelis, R, Giacomin, A, Luminari, S, Randi, G, Mangone, L, Mazzoleni, G, Bulatko, A, Devigili, E, Tschugguel, B, De Valiere, E, Facchinelli, G, Falk, M, Vittadello, F, Coviello, V, Cuccaro, F, Calabrese, A, Pinto, A, Cannone, G, Vitali, ME, Galasso, R, Del Riccio, L, Napolitano, D, Sampietro, G, Ghisleni, S, Giavazzi, L, Zanchi, A, Zucchi, A, Giacomin, A, Vercellino, PC, Andreone, S, Fedele, M, Barale, A, Germinetti, F, Magoni, M, Salvi, O, Puleio, M, Gerevini, C, Chiesa, R, Lonati, F, Cavalieri d'Oro, L, Rognoni, M, Le Rose, L, Merlo, E, Bracchi, A, Negrino, L, Pezzuto, L, Ardizzone, A, Spagnolo, G, Cozzi, E, De Lorenzism, L, Lotti, F, Pagliara, MC, D'Argenzio, A, D'Abronzo, M, De Francesco, D, Pereira da Silva, MCM, Menditto, V, Perrotta, E, Pesce, MT, Sessa, A, Sciacca, S, Sciacchitano, S, Fidelbo, M, Benedetto, G, Benedetto, A, Calabretta, LMR, Caruso, AM, Castaing, M, Di Prima, AA, Dinaro, YM, Fidelbo, P, Grosso, G, Ippolito, A, Irato, E, Leone, A, Paderni, F, Pesce, PNR, Pollina Addario, S, Savasta, A, Sciacchitano, CG, Torrisi, AAM, Torrisi, A, Varvarà, M, Viscosi, C, Sutera Sardo, A, Sia, A, Scalzi, S, Lavecchia, AM, Mancuso, P, Nocera, V, Mancusi, F, Del Duca, S, Gola, G, Corti, M, Caparelli, M, Ferretti, S, Marzola, L, Migliari, E, Carletti, N, Biavati, P, Petrucci, C, Serraino, D, Angelin, T, Bidoli, E, Birri, S, Dal Maso, L, De Dottori, M, De Santis, E, Forgiarini, O, Zucchetto, A, Zanier, L, Pannozzo, F, Busco, S, Rossi, M, Curatella, S, Bugliarello, E, Macci, L, Bernazza, E, Calabretta, F, Tamburrino, S, Sperduti, I, Tamburo, L, Serafini, G, Quarta, F, Melcarne, A, Golizia, MG, Arciprete, C, De Maria, V, Filiberti, RA, Casella, C, Marani, E, Puppo, A, Celesia, MV, Cogno, R, Vitarelli, S, Ricci, P, Autelitano, M, Ghilardi, S, Leone, R, Filipazzi, L, Bonini, A, Giubelli, C, Russo, AG, Quattrocchi, M, Distefano, R, Panciroli, E, Bellini, A, Pinon, M, Spinosa, S, Spagnoli, G, Carrozzi, G, Cirilli, C, Valla, K, Amendola, V, Fusco, M, Bellatalla, C, Ciullo, V, Di Buono, M, Fusco, M, Panico, M, Perrotta, C, Vitale, MF, Usala, M, Pala, F, Sini, GM, Pintori, N, Canu, L, Demurtas, G, Doa, N, Vitale, F, Cusimano, R, Traina, A, Guttadauro, A, Cascio, MA, Mannino, R, Ravazzolo, B, Brucculeri, MA, Rudisi, G, Adamo, MS, Amodio, R, Costa, A, Zarcone, M, Sunseri, R, Bucalo, G, Trapani, C, Staiti, R, Michiara, M, Bozzani, F, Sgargi, P, Boschetti, L, Migliazza, S, Reggiani, E, Incardona, N, Borciani, E, Seghini, P, Prazzoli, R, Zanetti, R, Rosso, S, Patriarca, S, Prandi, R, Sobrato, I, Gilardi, F, Busso, P, Sacchetto, L, Tumino, R, Cascone, G, Frasca, G, Giurdanella, MC, Martorana, C, Morana, G, Nicita, C, Rollo, PC, Ruggeri, MG, Spata, E, Vacirca, S, Mangone, L, Vicentini, M, Di Felice, E, Pezzarossi, A, Ferrari, F, Roncaglia, F, Sacchettini, C, Caroli, S, Falcini, F, Colamartini, A, Bucchi, L, Balducci, C, Ravegnani, M, Vitali, B, Cordaro, C, Caprara, L, Giuliani, O, Giorgetti, S, Palumbo, M, Vattiato, R, Ravaioli, A, Mancini, S, Caiazzo, AL, Cavallo, R, Colavolpe, AFG, D'Alessandro, A, Iannelli, A, Lombardo, C, Senatore, G, Sensi, F, Cesaraccio, R, Pirino, D, Mura, F, Contrino, ML, Madeddu, A, Tisano, F, Dinaro, Y, Muni, A, Mizzi, M, Bella, F, Rossitto, L, Sacco, G, Aletta, P, Colanino Ziino, A, Maspero, S, Fanetti, AC, Cometti, I, Cecconami, L, Minerba, S, Mincuzzi, A, Carone, S, Tanzarella, M, Galluzzo, C, Barchielli, A, Buzzoni, C, Caldarella, A, Corbinelli, A, Intrieri, T, Di Dia, PP, Manneschi, G, Nemcova, L, Visioli, C, Zappa, M, Candela, G, Scuderi, T, Crapanzano, G, Taranto, V, Piffer, S, Gentilini, M, Rizzello, R, Bombarda, L, Pedron, M, Clivati, E, Stracci, F, D'Alò, D, Scheibel, M, Costarelli, D, Spano, F, Rossini, S, Santucci, C, Petrinelli, AM, Solimene, C, Bianconi, F, Brunori, V, Tagliabue, G, Contiero, P, Tittarelli, A, Fabiano, S, Maghini, A, Codazzi, T, Barigelletti, G, D'Agostino, A, Modonesi, C, Rugge, M, Baracco, M, Baracco, S, Bovo, E, Dal Cin, A, Fiore, AR, Greco, A, Guzzinati, S, Martin, G, Memo, L, Monetti, D, Rizzato, S, Rosano, A, Stocco, C, Tognazzo, S, Zorzi, M, Brustolin, A, Beggiato, S, Aniceti, S, Fiocchetti, L, Schirra, G, Galeotti, P, Capati, A, Nami, A, Montanaro, M, Verrico, G, Poleggi, F, Rashid, I, Grappasonni, I, Pascucci, C, Merletti, F, Magnani, C, Pastore, G, Terracini, B, Alessi, D, Cena, T, Lazzarato, F, Macerata, V, Maule, M, Mosso, ML, Sacerdote, C, Romanelli, A, Mangone, L, Storchi, C, Sala, O, Gabbi, C, Gennaro, V, Benfatto, L, Malacarne, D, Lando, C, Campi, MG, Mazzucco, G, Ponz de Leon, M, Domati, F, Rossi, G, Goldoni, CA, Kaleci, S, Rossi, F, Benatti, P, Roncucci, L, Di Gregorio, C, Magnani, G, Pedroni, M, Maffei, S, Mariani, F, Reggiani-Bonetti, L, Sassatelli, R, Cassetti, T, Giorgi Rossi, P, and Vicentini, M

Abstract

Introduction The epidemiology of lung cancer is changing worldwide, with smoking being the key driver of lung cancer incidence and mortality. Our aim is to analyze the incidence, survival and mortality trends in Italy in the framework of the 2017 survey on smoking behavior in Italy.Methods AIRTUM 2017 reports on cancer survival and incidence; 2017 survey on smoking behavior in Italy.Results Men achieved progress in lung cancer control characterized by a decrease in incidence and mortality and an increase in survival. The decreasing use of tobacco in men (from 60% in the 1960s to 24% in 2017) was most likely responsible for the decreasing incidence and mortality. Women showed no progress: although survival improved slightly, the incidence and mortality were both on the rise. This was most likely due to the increasing smoking rates in women in the 1970s and 80s. Of major concern is the accelerated rise in the number of smoking women from 4.6 million in 2016 to 5.7 million in 2017 compared to the decrease observed in men (from 6.9 to 6 million).Conclusions The incidence and mortality trends in males clearly demonstrate that primary prevention is the most effective way to reduce lung cancer mortality. By contrast, a 24% increase in the prevalence of smoking among women in just 1 year is extremely worrying for the future, and calls for immediate action by targeted strategies to reduce tobacco consumption in women and avert the dreadful prospect of a lung cancer epidemic in Italy.

Published
2017
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44. Italian cancer figures, report 2012: Cancer in children and adolescents

Author

Pisani, P, Buzzoni, C, Crocetti, E, Maso, Ld, Rondelli, R, Alessi, D, Aricò, M, Bidoli, E, Ferrari, A, Fusco, M, Gatta, G, Guzzinati, S, Jankovic, M, Locatelli, F, Maule, M, Mosso, Ml, Pastore, G, Pession, A, Rashid, I, Sacerdote, C, Terracini, B, Tognazzo, S, Trama, A, Ferretti, S, Porta, F, Mazzoleni, G, Tschugguel, B, De Valiere, E, Facchinelli, G, Falk, M, Cappello, Td, Giacomin, A, Vercellino, Pc, Andreone, S, Marzola, L, Migliari, E, Carletti, N, Nenci, I, Caldarella, A, Corbinelli, A, Intrieri, T, Manneschi, G, Nemcova, L, Ocello, C, Sacchettini, C, Zappa, M, Paci, E, Serraino, D, Angelin, T, Birri, S, De Dottori, M, De Santis, E, Forgiarini, O, Zucchetto, A, Zanier, L, Vercelli, M, Orengo, Ma, Casella, C, Marani, E, Puppo, A, Celesia, Mv, Cogno, R, Levrieri, I, Manenti, S, Garrone, E, Quaglia, A, Pannozzo, F, Busco, S, Ramazzotti, V, Cercato, Mc, Battisti, W, Sperduti, I, Macci, L, Bugliarello, E, Valerio, O, Bernazza, E, Tamburo, L, Rossi, M, Curatella, S, Tamburrino, S, Fattoruso, S, Bisanti, L, Autelitano, M, Cuccaro, F, Randi, G, Ghilardi, S, Leone, R, Filipazzi, L, Bonini, A, Giubelli, C, Federico, M, Artioli, Me, Valla, K, Braghiroli, B, Cirilli, C, Luminari, S, Pirani, M, Ferrari, L, Bellatalla, C, Panico, M, Perrotta, C, Vassante, B, Vitale, Mf, Michiara, M, Bozzani, F, Sgargi, P, Tumino, R, Rosa, Mg, Cascone, G, Frasca, G, Giurdanella, Mc, Martorana, C, Morana, G, Nicita, C, Rollo, Pc, Ruggeri, Mg, Sigona, A, Spata, E, Vacirca, S, Mangone, L, Di Felice, E, Pezzarossi, A, Caroli, S, Pellegri, C, Vicentini, M, D'Angelo, S, Balottari, P, Romagna, Rt, Falcini, F, Colamartini, A, Bucchi, L, Balducci, C, Ravegnani, M, Vitali, B, Cordaro, C, Caprara, L, Giuliani, O, Giorgetti, S, Palumbo, M, Vattiato, R, Ravaioli, A, Mancini, S, Tonelli, C, Amadori, M, Cremone, L, Iannelli, A, Senatore, G, Zevola, A, Sechi, O, Budroni, M, Cesaraccio, R, Pirino, D, Carboni, D, Fiori, G, Soddu, M, Mameli, G, Mura, F, Contrino, Ml, Madeddu, A, Tisano, F, Sciacca, S, Muni, A, Mizzi, M, Russo, M, Sacco, G, Aletta, P, Ziino, Ac, Tessandori, R, Fanetti, Ac, Maspero, S, Cecconami, L, Annulli, Ml, Moroni, E, Gonzalez, Me, Zanetti, R, Rosso, S, Patriarca, S, Prandi, R, Sobrato, I, Gilardi, F, Busso, P, Piffer, S, Rizzello, R, Gentilini, Ma, Cappelletti, M, Rosa, Fl, Stracci, F, D'Alò, D, Scheibel, M, Costarelli, D, Spano, F, Rossini, S, Santucci, C, Petrinelli, Am, Solimene, C, Bianconi, F, Brunori, V, Crosignani, P, Tagliabue, G, Contiero, P, Preto, L, Tittarelli, A, Maghini, A, Codazzi, T, Frassoldi, E, Gada, D, Costa, E, Grazia, Ld, Zambon, P, Baracco, M, Bovo, E, Cin, Ad, Fiore, Ar, Greco, A, Monetti, D, Rosano, A, Stocco, C, Donato, F, Limina, Rm, Adorni, A, Andreis, P, Zani, G, Piovani, F, Salvi, O, Puleio, M, Vitarelli, S, Candela, G, Pappalardo, G, Scuderi, T, Lottero, B, Ribaudo, M, Ricci, P, Guarda, L, Gatti, L, Bozzeda, A, Dall'Acqua, M, Pironi, V, Sardo, As, Mazzei, A, Sirianni, N, Lavecchia, Am, Mancuso, P, Vitale, F, Cusimano, R, Amodio, R, Guttadauro, A, Ravazzolo, B, Bucalo, G, Trapani, C, Sunseri, R, Cascio, Ma, Brucculeri, Ma, Adamo, Ms, Mannino, R, Mistretta, A, Costa, A, Rudisi, G, Gola, G, Corti, M, Prosperini, E, Grandi, L, Sciacchitano, S, Fidelbo, M, Benedetto, G, Vasquez, E, Torrisi, A, Pesce, P, Calabretta, L, Bella, F, Leone, A, Ieni, A, Varvarà, M, Castaing, M, Di Prima, A, Benedetto, A, Paderni, F, Usala, M, Pala, F, Sini, Gm, Pintori, N, Canu, L, Demurtas, G, Doa, N, Lazzarato, F, Magnani, C, Merletti, F, Sarcerdote, C, Macerata, V, de Leon MP, Domati, F, Rossi, G, Goldoni, Ca, Rossi, F, De Gaetani, C, Benatti, P, Roncucci, L, Di Gregorio, C, Pedroni, M, Pezzi, A, Maffei, S, Mariani, F, Borsi, E, Cocchioni, M, Pascucci, C, Gennaro, V, Lazzarotto, A, Benfatto, L, Mazzucco, G, Montanaro, F, Traina, A, Carruba, G, Dolcemascolo, C, Staiti, R, Zarcone, M, Bisogno, G, Cuttini, M, De Rosa, M, Haupt, R, Soresina, A, Valsecchi, Mg, Fagioli, F, Bona, G, Dini, G, Conter, V, Biondi, A, Zecca, M, Fedeli, F, Massimino, M, Nespoli, L, Roncarolo, Mg, Basso, G, Cesaro, S, Memo, L, Bellettato, M, Tamaro, Paolo, Mascarin, M, Rosolen, A, Izzi, G, Paolucci, P, Borgna Pignatti, C, Vecchi, V, Abate, Me, D'Ambrosio, A, Favre, C, Caniglia, M, Pierani, P, Felici, L, Visani, G, Fioritoni, G, Foà, R, Riccardi, R, Frega, G, Clerico, A, Casale, F, Poggi, V, Amendola, G, Filosa, A, Ladogana, S, Presta, G, Tornesello, A, De Mattia, D, Consarino, C, Nobile, F, Sperlì, D, D'Angelo, P, Marino, S, Cosmi, C, Mura, Rm, Battisti, L., Pisani, P, Buzzoni, C, Crocetti, E, Maso, Ld, Rondelli, R, Alessi, D, Aricò, M, Bidoli, E, Ferrari, A, Fusco, M, Gatta, G, Guzzinati, S, Jankovic, M, Locatelli, F, Maule, M, Mosso, Ml, Pastore, G, Pession, A, Rashid, I, Sacerdote, C, Terracini, B, Tognazzo, S, Trama, A, Ferretti, S, Porta, F, Mazzoleni, G, Tschugguel, B, De Valiere, E, Facchinelli, G, Falk, M, Cappello, Td, Giacomin, A, Vercellino, Pc, Andreone, S, Marzola, L, Migliari, E, Carletti, N, Nenci, I, Caldarella, A, Corbinelli, A, Intrieri, T, Manneschi, G, Nemcova, L, Ocello, C, Sacchettini, C, Zappa, M, Paci, E, Serraino, D, Angelin, T, Birri, S, De Dottori, M, De Santis, E, Forgiarini, O, Zucchetto, A, Zanier, L, Vercelli, M, Orengo, Ma, Casella, C, Marani, E, Puppo, A, Celesia, Mv, Cogno, R, Levrieri, I, Manenti, S, Garrone, E, Quaglia, A, Pannozzo, F, Busco, S, Ramazzotti, V, Cercato, Mc, Battisti, W, Sperduti, I, Macci, L, Bugliarello, E, Valerio, O, Bernazza, E, Tamburo, L, Rossi, M, Curatella, S, Tamburrino, S, Fattoruso, S, Bisanti, L, Autelitano, M, Cuccaro, F, Randi, G, Ghilardi, S, Leone, R, Filipazzi, L, Bonini, A, Giubelli, C, Federico, M, Artioli, Me, Valla, K, Braghiroli, B, Cirilli, C, Luminari, S, Pirani, M, Ferrari, L, Bellatalla, C, Panico, M, Perrotta, C, Vassante, B, Vitale, Mf, Michiara, M, Bozzani, F, Sgargi, P, Tumino, R, Rosa, Mg, Cascone, G, Frasca, G, Giurdanella, Mc, Martorana, C, Morana, G, Nicita, C, Rollo, Pc, Ruggeri, Mg, Sigona, A, Spata, E, Vacirca, S, Mangone, L, Di Felice, E, Pezzarossi, A, Caroli, S, Pellegri, C, Vicentini, M, D'Angelo, S, Balottari, P, Romagna, Rt, Falcini, F, Colamartini, A, Bucchi, L, Balducci, C, Ravegnani, M, Vitali, B, Cordaro, C, Caprara, L, Giuliani, O, Giorgetti, S, Palumbo, M, Vattiato, R, Ravaioli, A, Mancini, S, Tonelli, C, Amadori, M, Cremone, L, Iannelli, A, Senatore, G, Zevola, A, Sechi, O, Budroni, M, Cesaraccio, R, Pirino, D, Carboni, D, Fiori, G, Soddu, M, Mameli, G, Mura, F, Contrino, Ml, Madeddu, A, Tisano, F, Sciacca, S, Muni, A, Mizzi, M, Russo, M, Sacco, G, Aletta, P, Ziino, Ac, Tessandori, R, Fanetti, Ac, Maspero, S, Cecconami, L, Annulli, Ml, Moroni, E, Gonzalez, Me, Zanetti, R, Rosso, S, Patriarca, S, Prandi, R, Sobrato, I, Gilardi, F, Busso, P, Piffer, S, Rizzello, R, Gentilini, Ma, Cappelletti, M, Rosa, Fl, Stracci, F, D'Alò, D, Scheibel, M, Costarelli, D, Spano, F, Rossini, S, Santucci, C, Petrinelli, Am, Solimene, C, Bianconi, F, Brunori, V, Crosignani, P, Tagliabue, G, Contiero, P, Preto, L, Tittarelli, A, Maghini, A, Codazzi, T, Frassoldi, E, Gada, D, Costa, E, Grazia, Ld, Zambon, P, Baracco, M, Bovo, E, Cin, Ad, Fiore, Ar, Greco, A, Monetti, D, Rosano, A, Stocco, C, Donato, F, Limina, Rm, Adorni, A, Andreis, P, Zani, G, Piovani, F, Salvi, O, Puleio, M, Vitarelli, S, Candela, G, Pappalardo, G, Scuderi, T, Lottero, B, Ribaudo, M, Ricci, P, Guarda, L, Gatti, L, Bozzeda, A, Dall'Acqua, M, Pironi, V, Sardo, A, Mazzei, A, Sirianni, N, Lavecchia, Am, Mancuso, P, Vitale, F, Cusimano, R, Amodio, R, Guttadauro, A, Ravazzolo, B, Bucalo, G, Trapani, C, Sunseri, R, Cascio, Ma, Brucculeri, Ma, Adamo, M, Mannino, R, Mistretta, A, Costa, A, Rudisi, G, Gola, G, Corti, M, Prosperini, E, Grandi, L, Sciacchitano, S, Fidelbo, M, Benedetto, G, Vasquez, E, Torrisi, A, Pesce, P, Calabretta, L, Bella, F, Leone, A, Ieni, A, Varvarà, M, Castaing, M, Di Prima, A, Benedetto, A, Paderni, F, Usala, M, Pala, F, Sini, Gm, Pintori, N, Canu, L, Demurtas, G, Doa, N, Lazzarato, F, Magnani, C, Merletti, F, Sarcerdote, C, Macerata, V, de Leon, Mp, Domati, F, Rossi, G, Goldoni, Ca, Rossi, F, De Gaetani, C, Benatti, P, Roncucci, L, Di Gregorio, C, Pedroni, M, Pezzi, A, Maffei, S, Mariani, F, Borsi, E, Cocchioni, M, Pascucci, C, Gennaro, V, Lazzarotto, A, Benfatto, L, Mazzucco, G, Montanaro, F, Traina, A, Carruba, G, Dolcemascolo, C, Staiti, R, Zarcone, M, Bisogno, G, Cuttini, M, De Rosa, M, Haupt, R, Soresina, A, Valsecchi, Mg, Fagioli, F, Bona, G, Dini, G, Conter, V, Biondi, A, Zecca, M, Fedeli, F, Massimino, M, Nespoli, L, Roncarolo, Mg, Basso, G, Cesaro, S, Memo, L, Bellettato, M, Tamaro, Paolo, Mascarin, M, Rosolen, A, Izzi, G, Paolucci, P, Borgna Pignatti, C, Vecchi, V, Abate, Me, D'Ambrosio, A, Favre, C, Caniglia, M, Pierani, P, Felici, L, Visani, G, Fioritoni, G, Foà, R, Riccardi, R, Frega, G, Clerico, A, Casale, F, Poggi, V, Amendola, G, Filosa, A, Ladogana, S, Presta, G, Tornesello, A, De Mattia, D, Consarino, C, Nobile, F, Sperlì, D, D'Angelo, P, Marino, S, Cosmi, C, Mura, Rm, Battisti, L., Maso, L, Mosso, M, Cappello, T, Vercellino, P, Orengo, M, Celesia, M, Cercato, M, Artioli, M, Vitale, M, Rosa, M, Giurdanella, M, Rollo, P, Ruggeri, M, Romagna, R, Contrino, M, Ziino, A, Fanetti, A, Annulli, M, Gonzalez, M, Gentilini, M, Rosa, F, Petrinelli, A, Grazia, L, Cin, A, Fiore, A, Limina, R, Lavecchia, A, Cascio, M, Brucculeri, M, Sini, G, de Leon, M, Goldoni, C, Valsecchi, M, Roncarolo, M, Tamaro, P, Abate, M, Mura, R, Battisti, L, AIRTUM Working Group[.., Enrica Borsi, ], CCM, and AIEOP Working Group

Subjects
Male, Parents, cancer incidence, Adolescent, Epidemiology, Aftercare, cancer in adolescents, Young Adult, children, Neoplasms, cancer in children, Italian population, cancer, Cluster Analysis, Humans, Registries, Survivors, Age of Onset, Mortality, Child, cancer survival, Incidence, Environmental and Occupational Health, Infant, Newborn, Disease Management, Infant, pediatric, Survival Rate, Italy, Child, Preschool, Public Health, Environmental and Occupational Health, Female, Public Health, Morbidity, Forecasting
Abstract

OBJECTIVES: This study describes up-to-date cancer incidence and survival in Italian paediatric and adolescent patients, based on data collected by the network of Italian cancer registries (AIRTUM). It updates the monograph published on the same topic in 2008. The main objective of this monograph is to present the statistics according to standard rigorous epidemiological methods and disseminate them to a wide range of readers, including the lay public. Given the deep impact of the 2008 monograph on the general public, in this update we complement descriptive statistics with additional data and commentaries on issues of importance for public health, in order to provide unambiguous criteria on how to interpret the statistics. The study is the result of the collaboration between AIRTUM and AIEOP (Italian Association of Paediatric Haematology and Oncology) with contributions from interested parties, including representatives of parent associations. The monograph is divided into three parts. The first part presents incidence rates, survival probabilities, and time trends, by sex, age, geographical area, and cancer site or type, by means of tables and graphs as in the previous monograph, to facilitate direct comparisons. Four articles summarize and comment the results. The second part uses data from AIRTUM and AIEOP to outline patient management and health care issues; it includes estimates of the number of new cases in the next decade and of young adults living after a paediatric cancer diagnosis. Health organizational aspects of treatment services for paediatric patients, based on the AIEOP database, are also discussed, along with long-term complications in cured patients. The third section describes the changes in mortality trends due to improving therapies and healthcare services, and discusses risk factors and prevention of childhood cancer, late adverse events in cured patients, and other related issues. MATERIAL AND METHODS: Data herein presented were provided by AIRTUM population-based cancer registries, covering 47%of the Italian population below age 20 years, in the period 2003-2008. Quality of cancer registration in Italy is elevated, with high proportions of microscopically verified diagnoses (91%in the 0-14 years age group and 96% between 15 and 19 years of age) and a very small proportion of cases collected through death certificate only (0.1%).The proportion of cases in diagnostic groups XI (other malignant epithelial neoplasms) and XII (other and unspecified neoplasms) of the International Classification for Childhood Cancer (ICCC), based on the third revision of the International Classification of Diseases for Oncology (ICD-O-3), were 7.0% in the 0-14 years age group and 26.0%in the 15-19 years age group.The ratio between mortality and incidence was 17.7% in both children and adolescents. Detailed results are presented in 24 fact sheets for the 12 major ICCC-3 diagnostic groups and 10 sub-groups of special interest; the series is completed by a sheet on all malignant tumours and one on all tumours including non-malignant neoplasms of the central nervous system. All sheets include results for three age groups (0-14, 15-19, and 0-19 years) and are followed by two commentaries on incidence in the recent period, one on trends and the other on survival. Incidence rates were age-standardized on the European population and presented per million children. Incidence rates are also presented by age group, sex, and geographical area. Incidence trends were evaluated for two periods, 1988-2008 and 1998-2008, using estimated annual percent changes, and survival estimates were calculated by age and period. Indicators and corresponding 95% confidence intervals are shown in forms of graphics and tables at the end of the monograph and online at http://www.registri-tumori.it. Geographical analyses were conducted rearranging cancer registries into four macroareas (North-West, North-East, Centre, and South and Islands). Age groups were the same used in descriptive studies on children worldwide (0, 1-4, 5-9, 10- 14 years for paediatric tumours and 15-19 years for adolescents). Incidence trend analyses included cancer registries with three or more years of registration in the 5-year period, using Poisson regression models. Observed survival was computed according to the Kaplan-Meier method. The estimate of expected cases in the next decade was based on observed incidence rates in the most recent period, extended to the Italian estimated population of children and adolescents in the periods 2011-2015 and 2016-2020. The AIEOP database (Modello 1.01) allowed us to compare the number of patients treated and followed-up in specialized centres with expected cases based on AIRTUM estimates. The AIEOP database also provided information regarding health care migration throughout Italian regions and the number of foreign (immigrated) children treated in Italian AIEOP centres. RESULTS: In the period 2003-2008, 31 cancer registries reported 4,473 incident malignant neoplasms, 2,855 in children and 1,618 in adolescents. Cancer incidence rates were 164 cases per million in children aged 14 years or below and 269 cases per million in patients aged 15-19 years. Limited geographical variations emerged. In children (0-14 years) a significant increase in malignant cancer incidence was observed until 1997 (APC: +3.2%), followed by a plateau (APC: -1.1%not statistically significant).Until the late Nineties, a statistically significant increase was also observed in the incidence of all leukaemias in males (APC: +5.7%), lymphoid leukaemias (APC: +5.6%), representing 80% of all leukaemias, Hodgkin and non- Hodgkin lymphomas (APC: +6.3%). A significant decrease emerged for lymphoid leukaemia starting in 1995 (APC: -1.9%), while no substantial change in cancer incidence rates was observed in the last decade of observation for all malignant neoplasms and lymphomas. In addition, no variation emerged for malignant (according to the most recent classification) central nervous system (CNS) neoplasms, while an annual increase of 1.8% (significant) was observed in the period 1988-2008, when non-malignant tumours were included. Increases in cancer incidence were observed throughout the study period for neuroblastoma (APC: +1.9%) and epithelial tumours or melanoma (APC: +4.1%). In the period 1998-2008, in addition to lymphoid leukaemias, a significant decrease was observed for all malignant neoplasms, lymphomas in girls, CNS tumours (males and females), and renal tumours in girls, while no increases were observed in this age group. In adolescents (15-19 years) between 1988 and 2008, a significant increase in incidence rates was observed (APC: +2.0%) for all malignant neoplasms, all lymphomas (APC: +2.9%; in particular Hodgkin lymphoma, APC: +3.6%), thyroid cancer (APC: +6.1%), and melanoma (APC: +8.1%). Conversely, lymphoid leukaemia is the only neoplasm showing a long-term decrease in adolescents. Recent trends (1998-2008) confirm the long-term increases only for all malignant neoplasms in girls and thyroid cancer (APC: +7.9%, boys and girls), while a decrease in bone tumour incidence emerged in girls, albeit based only on 46 cases. Cancer mortality in children showed a persistent decrease for all neoplasms and even for more frequent cancer sites or types, and mortality rates for cancer were three-fold higher in the early Seventies than in 2008. In addition, five-year survival after cancer diagnosis increased in the last three decades and was still increasing in the period 2003- 2008, reaching 82% in children and 86% in adolescents. In the period 2008-2010, 4,488 children (0-14 years) were treated in one of the AIEOP clinical centres and we estimate, based on the above-presented incidence rates, that they represented 92% of all cancer cases in Italy. However, in adolescents, the proportion of patients treated in AIEOP centres was only 25%. A migration of patients living in the South of Italy to Central and Northern Italy emerged from AIEOP information. The expected number of cancer cases in children aged between 0 and 14 years of age is approximately 7,000 in the period 2016- 2020, while the corresponding figure for adolescents between 15 and 19 years of age is 4,000, with no relevant variation in comparison with the previous five-year period. COMMENTS: The present findings update descriptive cancer epidemiology in children and adolescents in Italy based on data provided by an extensive network of general and specialized population-based cancer registries. Data obtained from cancer registries are supplemented by additional information collected by specialized clinical AIEOP centres and mortality reports collected by the National Institute of Statistics (ISTAT). Incidence rates reported in Italy were slightly higher in comparison to other developed Countries, but relatively consistent between different Italian areas. Our results also showed that the significant increase in cancer incidence observed until the end of Nineties has halted, with the exception solely of thyroid cancer in adolescents. Efficacy of therapeutic protocols has improved constantly since the Seventies, and recent findings confirm this trend in all age groups and, in particular, for rarer tumours and cancer types that have very poor prognosis. Findings derived from cross-analysis with AIEOP data suggest that it is possible to further improve the efficiency of our healthcare system, in particular for adolescents; migration can be reduced with a more rational use of hospitals throughout Italy.

45. Characteristics of the colorectal cancers diagnosed in the early 2000s in Italy. Figures from the IMPATTO study on colorectal cancer screening

Author

Zorzi, M., Lucia Mangone, Anghinoni, E., Baracco, S., Borciani, E., Caldarella, A., Falcini, F., Fanetti, A. C., Ferretti, S., Rossi, P. G., Michiara, M., Randi, G., Stracci, F., Vicentini, M., Zucchetto, A., Zappa, M., Giacomin, A., Azzoni, A., Baldazzi, P., Collina, N., Pandolfi, P., Biavati, P., Gualandi, G., Sciacca, S., Pesce, P., Torrisi, A., Sciacchitano, C., Fidelbo, M., Finarelli, A. C., Naldoni, C., Bianchi, P. S., Landi, P., Matarese, V., Togni, A., Palmonari, C., Crocetti, E., Grazzini, G., Manneschi, G., Mantellini, P., Serraino, D., Bidoli, E., Taborelli, M., Gini, A., Virdone, S., Puppo, A., Casella, C., Celesia, M., Cogno, R., Marani, E., Bugliarello, E., Fattoruso, S., Tamburo, L., Tamburrino, S., Bellardini, P., Autelitano, M., Frammartino, B., Bisanti, L., Ghilardi, S., Leone, R., Corradini, R., Girolamo, F., Valla, K., Palombino, R., Gigli, L., Spena, S. R., Vitale, M. F., Cascio, M. A., Mannino, R., Mazzucco, W., Mistretta, A., Ravazzolo, B., Sgarzi, P., Bozzani, F., Zatelli, M., Zurlini, C., Caruana, P., Seghini, P., Gatti, G., Prazzoli, R., Campari, C., Paterlini, L., Cassetti, T., Sassatelli, R., Imolesi, C., Casale, C., Serafini, M., Vattiato, R., Giuliani, O., Cesaraccio, R., Sechi, O., Budroni, M., Madeddu, A., Contrino, M. L., Ziino, A. C., Russo, M., Tisano, F., Maspero, S., Moroni, E., Cometti, I., Gentilini, M., Piffer, S., Pretis, G., Caciagli, P., Pertile, R., Bianconi, F., Bucchi, D., Galeotti, M. E., Malaspina, M., Greco, A., Fiore, A. R., Stocco, C. F., Fedato, C., Zorzi, M., Mangone, L., Anghinoni, E., Baracco, S., Borciani, E., Caldarella, A., Falcini, F., Fanetti, A., Ferretti, S., Rossi, P., Michiara, M., Randi, G., Stracci, F., Vicentini, M., Zucchetto, A., Zappa, M., Giacomin, A., Azzoni, A., Baldazzi, P., Collina, N., Pandolfi, P., Biavati, P., Gualandi, G., Sciacca, S., Pesce, P., Torrisi, A., Sciacchitano, C., Fidelbo, M., Finarelli, A., Naldoni, C., De'Bianchi, P., Landi, P., Matarese, V., De Togni, A., Palmonari, C., Crocetti, E., Grazzini, G., Manneschi, G., Mantellini, P., Serraino, D., Bidoli, E., Taborelli, M., Gini, A., Virdone, S., Puppo, A., Casella, C., Celesia, M., Cogno, R., Marani, E., Bugliarello, E., Fattoruso, S., Tamburo, L., Tamburrino, S., Bellardini, P., Autelitano, M., Frammartino, B., Bisanti, L., Ghilardi, S., Leone, R., Corradini, R., De Girolamo, F., Valla, K., Palombino, R., Gigli, L., Spena, S., Vitale, M., Cascio, M., Mannino, R., Mazzucco, W., Mistretta, A., Ravazzolo, B., Sgarzi, P., Bozzani, F., Zatelli, M., Zurlini, C., Caruana, P., Seghini, P., Gatti, G., Prazzoli, R., Campari, C., Paterlini, L., Cassetti, T., Sassatelli, R., Imolesi, C., Casale, C., Serafini, M., Vattiato, R., Giuliani, O., Cesaraccio, R., Sechi, O., Budroni, M., Madeddu, A., Contrino, M., Ziino, A., Russo, M., Tisano, F., Maspero, S., Moroni, E., Cometti, I., Gentilini, M., Piffer, S., De Pretis, G., Caciagli, P., Pertile, R., Bianconi, F., Bucchi, D., Galeotti, M., Malaspina, M., Greco, A., Fiore, A., Stocco, C., and Fedato, C.

Subjects
Colorectal cancer, Colorectal cancer screening, Italy, Epidemiology, Public Health, Environmental and Occupational Health, Settore MED/42 - Igiene Generale E Applicata
Abstract

The impact of organized screening programmes on colorectal cancer (CRC) can be observed at a population level only several years after the implementation of screening. We compared CRC characteristics by diagnostic modality (screen-detected, non-screen-detected) as an early outcome to monitor screening programme effectiveness. Data on CRCs diagnosed in Italy from 2000 to 2008 were collected by several cancer registries. Linkage with screening datasets made it possible to divide the cases by geographic area, implementation of screening, and modality of diagnosis (screen-detected, non-screen-detected).We compared the main characteristics of the different subgroups of CRCs through multivariate logistic regression models. The study included 23,668 CRCs diagnosed in subjects aged 50-69 years, of which 11.9%were screendetected (N=2,806), all from the North-Centre of Italy. Among screen-detected CRCs, we observed a higher proportion of males, of cases in the distal colon, and a higher mean age of the patients. Compared with pre-screening cases, screen-detected CRCs showed a better distribution by stage at diagnosis (OR for stage III or IV: 0.40, 95%CI: 0.36-0.44) and grading (OR for poorly differentiated CRCs was 0.86, 95%CI: 0.75-1.00). Screen-detected CRCs have more favourable prognostic characteristics than non-screen-detected cases. A renewed effort to implement screening programmes throughout the entire country is recommended.

49. Impact of Sacubitril/Valsartan on Circulating microRNA in Patients with Heart Failure

Author

Maura Brioschi, Yuri D’Alessandra, Massimo Mapelli, Irene Mattavelli, Elisabetta Salvioni, Sonia Eligini, Alice Mallia, Veronica Ricci, Erica Gianazza, Stefania Ghilardi, Piergiuseppe Agostoni, Cristina Banfi, Brioschi, M, D'Alessandra, Y, Mapelli, M, Mattavelli, I, Salvioni, E, Eligini, S, Mallia, A, Ricci, V, Gianazza, E, Ghilardi, S, Agostoni, P, and Banfi, C

Subjects
heart failure, Medicine (miscellaneous), Sacubitril/Valsartan, miRNA, Settore MED/11 - Malattie dell'Apparato Cardiovascolare, General Biochemistry, Genetics and Molecular Biology
Abstract

Sacubitril/Valsartan, used for the treatment of heart failure (HF), is a combination of two drugs, an angiotensin receptor inhibitor, and a neprilysin inhibitor, which activates vasoactive peptides. Even though its beneficial effects on cardiac functions have been demonstrated, the mechanisms underpinning these effects remain poorly understood. To achieve more mechanistic insights, we analyzed the profiles of circulating miRNAs in plasma from patients with stable HF with reduced ejection function (HFrEF) and treated with Sacubitril/Valsartan for six months. miRNAs are short (22–24 nt) non-coding RNAs, which are not only emerging as sensitive and stable biomarkers for various diseases but also participate in the regulation of several biological processes. We found that in patients with high levels of miRNAs, specifically miR-29b-3p, miR-221-3p, and miR-503-5p, Sacubitril/Valsartan significantly reduced their levels at follow-up. We also found a significant negative correlation of miR-29b-3p, miR-221-3p, and miR-503-5p with VO2 at peak exercise, whose levels decrease with HF severity. Furthermore, from a functional point of view, miR-29b-3p, miR-221-3p, and miR-503-5p all target Phosphoinositide-3-Kinase Regulatory Subunit 1, which encodes regulatory subunit 1 of phosphoinositide-3-kinase. Our findings support that an additional mechanism through which Sacubitril/Valsartan exerts its functions is the modulation of miRNAs with potentially relevant roles in HFrEF pathophysiology.

Published
2023
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50. Impact of Sacubitril/Valsartan on surfactant binding proteins, central sleep apneas, lung function tests and heart failure biomarkers: Hemodynamic or pleiotropism?

Author

Massimo Mapelli, Irene Mattavelli, Elisabetta Salvioni, Cristina Banfi, Stefania Ghilardi, Fabiana De Martino, Paola Gugliandolo, Valentina Mantegazza, Valentina Volpato, Christian Basile, Maria Inês Fiuza Branco Pires, Valentina Sassi, Benedetta Nusca, Carlo Vignati, Mauro Contini, Chiarella Sforza, Maria Luisa Biondi, Pasquale Perrone Filardi, Piergiuseppe Agostoni, Mapelli, M., Mattavelli, I., Salvioni, E., Banfi, C., Ghilardi, S., De Martino, F., Gugliandolo, P., Mantegazza, V., Volpato, V., Basile, C., Branco Pires, M. I. F., Sassi, V., Nusca, B., Vignati, C., Contini, M., Sforza, C., Biondi, M. L., Perrone Filardi, P., and Agostoni, P.

Subjects
hemodynamic, pleiotropic, surfactant binding proteins, biomarkers, biomarker, heart failure, Settore MED/11 - Malattie dell'Apparato Cardiovascolare, hemodynamics, Sacubitril/Valsartan, Cardiology and Cardiovascular Medicine
Abstract

PurposeLittle is known about the mechanism underlying Sacubitril/Valsartan effects in patients with heart failure (HFrEF). Aim of the study is to assess hemodynamic vs. non-hemodynamic Sacubitril/Valsartan effects by analyzing several biological and functional parameters.MethodsSeventy-nine patients (86% males, age 66 ± 10 years) were enrolled. At baseline and 6 months after reaching the maximum Sacubitril/Valsartan tolerated dose, we assessed biomarkers, transthoracic echocardiography, polysomnography, spirometry, and carbon monoxide diffusing capacity of the lung (DLCO).ResultsMean follow-up was 8.7 ± 1.4 months with 83% of patients reaching Sacubitril/Valsartan maximum dose (97/103 mg b.i.d). Significant improvements were observed in cardiac performance and biomarkers: left ventricular ejection fraction increased (31 ± 5 vs. 37 ± 9 %; p < 0.001), end-diastolic and end-systolic volumes decreased; NT-proBNP decreased (1,196 [IQR 648–2891] vs. 958 [IQR 424-1,663] pg/ml; p < 0.001) in parallel with interleukin ST-2 (28.4 [IQR 19.4–36.6] vs. 20.4 [IQR 15.1–29.2] ng/ml; p < 0.001) and circulating surfactant binding proteins (proSP-B: 58.43 [IQR 40.42–84.23] vs. 50.36 [IQR 37.16–69.54] AU; p = 0.014 and SP-D: 102.17 [IQR 62.85–175.34] vs. 77.64 [IQR 53.55-144.70] AU; p < 0.001). Forced expiratory volume in 1 second and forced vital capacity improved. DLCO increased in the patients' subgroup (n = 39) with impaired baseline values (from 65.3 ± 10.8 to 70.3 ± 15.9 %predicted; p = 0.013). We also observed a significant reduction in central sleep apneas (CSA).ConclusionSacubitril/Valsartan effects share a double pathway: hemodynamic and systemic. The first is evidenced by NT-proBNP, proSP-B, lung mechanics, and CSA improvement. The latter is confirmed by an amelioration of DLCO, ST-2, SP-D as well as by reverse remodeling echocardiographic parameters.

Published
2022

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