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3. Etnografisch onderzoek

Author

Felder, M., Wallenburg, I., Kuijper, S. C., Bal, R. A., Eskes, Anne M., editor, and van Oostveen, Catharina J., editor

Published
2021
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6. Diagenetic controls on dryland clastic reservoirs from the Buntsandstein Subgroup in the Netherlands

Author

Cecchetti, E. (author), Felder, M. (author), Martinius, A.W. (author), Abels, H.A. (author), Cecchetti, E. (author), Felder, M. (author), Martinius, A.W. (author), and Abels, H.A. (author)

Abstract

The Buntsandstein subgroup in the southeastern part of the Netherlands represents one of the most promising, but risky, geothermal plays. To understand the main controls on Buntsandstein reservoir quality, we combine petrophysical (porosity and permeability) and petrographic (point counting) data derived from different wells and different depth levels. Results show that porosity ranges from 2 to 18.5 and permeability from 0.001 to 285 mD. Dolomite represents the most abundant cement and show an inverse correlation with porosity. Illite occurs in higher concentrations in samples with values of permeability below 20 mD, while kaolinite becomes the most dominant phyllosilicate cement in samples with higher permeability. By looking at the main cement distribution over the sedimentary facies, it appears that dolomite is strongly related to depositional facies and has a positive correlation with grain size, while illite and kaolinite yield a negative correlation with grain size. Pedogenic dolomite nodules are often reworked as detrital grain into the channel scour deposits and are the main source for dolomite cementation. The current study has shown how diagenesis makes Buntsandstein reservoir complex and heterogeneous, and how reservoir quality is strongly related to the depositional environment., Applied Geology

Published
2023
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7. Health care reform and financial crisis in the Netherlands:consequences for the financial arena of health care organizations

Author

Van Dijk, T. S., Van Der Scheer, W. K., Felder, M., Janssen, R. T.J.M., Van Dijk, T. S., Van Der Scheer, W. K., Felder, M., and Janssen, R. T.J.M.

Abstract

Over the past decade, many health care systems across the Global North have implemented elements of market mechanisms while also dealing with the consequences of the financial crisis. Although effects of these two developments have been researched separately, their combined impact on the governance of health care organizations has received less attention. The aim of this study is to understand how health care reforms and the financial crisis together shaped new roles and interactions within health care. The Netherlands - where dynamics between health care organizations and their financial stakeholders (i.e., banks and health insurers) were particularly impacted - provides an illustrative case. Through semi-structured interviews, additional document analysis and insights from institutional change theory, we show how banks intensified relationship management, increased demands on loan applications and shifted financial risks onto health care organizations, while health insurers tightened up their monitoring and accountability practices towards health care organizations. In return, health care organizations were urged to rearrange their operations and become more risk-minded. They became increasingly dependent on banks and health insurers for their existence. Moreover, with this study, we show how institutional arenas come about through both the long-term efforts of institutional agents and unpredictable implications of economic and societal crises.

Published
2023

10. Depositional and Diagenetic Heterogeneity Control on Aquifer Quality: a Case Study of the Lower Triassic Sandstones in the Southeastern Part of Netherlands

Author

Cecchetti, E. (author), Martinius, A.W. (author), Felder, M (author), Abels, H.A. (author), Cecchetti, E. (author), Martinius, A.W. (author), Felder, M (author), and Abels, H.A. (author)

Abstract

A combined study of depositional facies and diagenesis variation was carried out to understand the main controls on aquifer quality of the Middle Buntsandstein in the southeastern part of the Netherlands. Heterogeneities in continental sandstone bodies occur at different spatial scales, ranging from micrometers to hundreds of meters. Commonly, such heterogeneities result from the interaction of depositional processes at various spatial and time scales. These processes partially also influence subsequent diagenetic evolution, hence present-day aquifer properties. Understanding the role of the resulting architectural heterogeneities in controlling the dynamic reservoir behavior is key in determining aquifer properties and improving pre-drilling prediction. The sandstones of the Main Buntsandstein subgroup in the southeastern part of the Netherlands provide an excellent example where different detrital compositions, internal sedimentary architectures, and diverse burial histories have resulted in a wide range of present-day aquifer properties. In the study area, the aquifers are composed of stacked heterogenous alluvial sandstones bodies intercalated with mud-prone intervals deposited in arid to semi-arid conditions. Differences in sediment sources, transport mechanisms, and intrabasinal conditions resulted in a wide distribution of composition and texture. Additionally, the effect of post-depositional burial diagenesis in a basin with complex tectonic history created diverse burial histories across the basin. The study aims to investigate the variation of present-day aquifer hydraulic parameters about changes in aquifer facies and architecture, detrital composition, as well as compaction and cementation during burial. Core sample analysis unfolded a diverse spectrum of sedimentary facies and lithic fragments, which differ between formations. Thin section analysis provides insights about mechanical compaction, cementations, and authigenic phases. By combining these res, Applied Geology

Published
2022

11. Depositional and Diagenetic Heterogeneity Control on Aquifer Quality: a Case Study of the Lower Triassic Sandstones in the Southeastern Part of Netherlands

Author

Cecchetti, E., Martinius, A.W., Felder, M, and Abels, H.A.

Abstract

A combined study of depositional facies and diagenesis variation was carried out to understand the main controls on aquifer quality of the Middle Buntsandstein in the southeastern part of the Netherlands. Heterogeneities in continental sandstone bodies occur at different spatial scales, ranging from micrometers to hundreds of meters. Commonly, such heterogeneities result from the interaction of depositional processes at various spatial and time scales. These processes partially also influence subsequent diagenetic evolution, hence present-day aquifer properties. Understanding the role of the resulting architectural heterogeneities in controlling the dynamic reservoir behavior is key in determining aquifer properties and improving pre-drilling prediction. The sandstones of the Main Buntsandstein subgroup in the southeastern part of the Netherlands provide an excellent example where different detrital compositions, internal sedimentary architectures, and diverse burial histories have resulted in a wide range of present-day aquifer properties. In the study area, the aquifers are composed of stacked heterogenous alluvial sandstones bodies intercalated with mud-prone intervals deposited in arid to semi-arid conditions. Differences in sediment sources, transport mechanisms, and intrabasinal conditions resulted in a wide distribution of composition and texture. Additionally, the effect of post-depositional burial diagenesis in a basin with complex tectonic history created diverse burial histories across the basin. The study aims to investigate the variation of present-day aquifer hydraulic parameters about changes in aquifer facies and architecture, detrital composition, as well as compaction and cementation during burial. Core sample analysis unfolded a diverse spectrum of sedimentary facies and lithic fragments, which differ between formations. Thin section analysis provides insights about mechanical compaction, cementations, and authigenic phases. By combining these results with petrophysical data on permeability and porosity of core samples, the major controls on present-day aquifer quality can be assessed.

Published
2022

12. Hepatocellular carcinoma recurrence in patients with curative resection or ablation: impact of HCV eradication does not depend on the use of interferon

Author

Petta, S., Cabibbo, G., Barbara, M., Attardo, S., Bucci, L., Farinati, F., Giannini, E. G., Tovoli, F., Ciccarese, F., Rapaccini, G. L., Di Marco, M., Caturelli, E., Zoli, M., Borzio, F., Sacco, R., Virdone, R., Marra, F., Felder, M., Morisco, F., Benvegnù, L., Gasbarrini, A., Svegliati‐Baroni, G., Foschi, F. G., Olivani, A., Masotto, A., Nardone, G., Colecchia, A., Persico, M., Boccaccio, V., Craxì, A., Bruno, S., Trevisani, F., Cammà, C., Biselli, Maurizio, Caraceni, Paolo, Cucchetti, Alessandro, Domenicali, Marco, Piscaglia, Fabio, Gramenzi, Annagiulia, Granito, Alessandro, Magalotti, Donatella, Serra, Carla, Negrini, Giulia, Napoli, L., Napoli, Lucia, Salvatore, Veronica, Benevento, Francesca, Gazzola, Alessia, Murer, Francesca, Pozzan, Caterina, Vanin, Veronica, Moscatelli, Alessandro, Pellegatta, Gaia, Picciotto, Antonino, Savarino, Vincenzo, Poggio, Paolo Del, Olmi, Stefano, de Matthaeis, Nicoletta, Balsamo, Claudia, Vavassori, Elena, Roselli, Paola, DellʼIsola, Serena, Ialungo, Anna Maria, Rastrelli, Elena, Rini, Francesca, Costantino, Andrea, Affronti, Andrea, Affronti, Marco, Mascari, Marta, Mega, Andrea, Pompili, Maurizio, Rinninella, Emanuele, Mismas, Valeria, DallʼAglio, Anna Chiara, Feletti, Valentina, Lanzi, Arianna, Cappa, Federica Mirici, Neri, Elga, Stefanini, Giuseppe Francesco, Tamberi, Stefano, Biasini, Elisabetta, Missale, Gabriele, Guarino, Maria, Ortolani, Alessio, Chiaramonte, Maria, Marchetti, Fabiana, Valerio, Matteo, Aburas, Sami, Inghilesi, Andrea L., Cappelli, Alberta, Golfieri, Rita, Mosconi, Cristina, Renzulli, Matteo, Coccoli, Piero, and Zamparelli, Marco Sanduzzi

Published
2017
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13. Years of life that could be saved from prevention of hepatocellular carcinoma

Author

Cucchetti, A., Trevisani, F., Bucci, L., Ravaioli, M., Farinati, F., Giannini, E. G., Ciccarese, F., Piscaglia, F., Rapaccini, G. L., Di Marco, M., Caturelli, E., Zoli, M., Borzio, F., Sacco, R., Maida, M., Felder, M., Morisco, F., Gasbarrini, A., Gemini, S., Foschi, F. G., Missale, G., Masotto, A., Affronti, A., Bernardi, M., Pinna, A. D., Bolondi, Luigi, Biselli, Maurizio, Caraceni, Paolo, Domenicali, Marco, Gramenzi, Annagiulia, Magalotti, Donatella, Pecorelli, Anna, Serra, Carla, Venerandi, Laura, Gazzola, Alessia, Murer, Francesca, Pozzan, Caterina, Vanin, Veronica, Poggio, Paolo Del, Olmi, Stefano, Balsamo, Claudia, Vavassori, Elena, Benvegnù, Luisa, Cappelli, Alberta, Golfieri, Rita, Mosconi, Cristina, Renzulli, Matteo, Bosco, Giulia, Roselli, Paola, DellʼIsola, Serena, Lalungo, Anna Maria, Rastrelli, Elena, Moscatelli, Alessandro, Pellegatta, Gaia, Picciotto, Antonino, Savarino, Vincenzo, Barcellona, Maria Rosa, Virdone, Roberto, Mega, Andrea, Rinninella, Emanuele, Mismas, Valeria, DallʼAglio, Anna Chiara, Feletti, Valentina, Lanzi, Arianna, Cappa, Federica Mirici, Neri, Elga, Stefanini, Giuseppe Francesco, Tamberi, Stefano, Guarino, Maria, Baroni, Gianluca Svegliati, Schiadà, Laura, Chiaramonte, Maria, Marchetti, Fabiana, and Valerio, Matteo

Published
2016
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14. Comparison between alcohol- and hepatitis C virus-related hepatocellular carcinoma: clinical presentation, treatment and outcome

Author

Bucci, L., Garuti, F., Camelli, V., Lenzi, B., Farinati, F., Giannini, E. G., Ciccarese, F., Piscaglia, F., Rapaccini, G. L., Di Marco, M., Caturelli, E., Zoli, M., Borzio, F., Sacco, R., Maida, M., Felder, M., Morisco, F., Gasbarrini, A., Gemini, S., Foschi, F. G., Missale, G., Masotto, A., Affronti, A., Bernardi, M., Trevisani, F., Bolondi, Luigi, Biselli, Maurizio, Caraceni, Paolo, Cucchetti, Alessandro, Domenicali, Marco, Gramenzi, Annagiulia, Magalotti, Donatella, Pecorelli, Anna, Serra, Carla, Venerandi, Laura, Gazzola, Alessia, Murer, Francesca, Pozzan, Caterina, Vanin, Veronica, Poggio, Paolo Del, Olmi, Stefano, Balsamo, Claudia, Vavassori, Elena, Benvegnù, Luisa, Capelli, Alberta, Golfieri, Rita, Mosconi, Cristina, Renzulli, Matteo, Roselli, Paola, Isola, Serena, Ialungo, Anna Maria, Rastrelli, Elena, Moscatelli, Alessandro, Pelagatta, Gaia, Picciotto, Antonino, Savarino, Vincenzo, Barcellona, Maria Rosa, Cammà, Calogero, Cabibbo, Giuseppe, Costantino, Andrea, Virdone, Roberto, Mega, Andrea, Rinninella, Emanuele, Mismas, Valeria, DallʼAglio, Anna Chiara, Feletti, Valentina, Lanzi, Arianna, Cappa, Federica Mirici, Neri, Elga, Stefanini, Giuseppe Francesco, Tamberi, Stefano, Biasini, Elisabetta, Porro, Emanuela, Guarino, Maria, Baroni, Gianluca Svegliati, Schiadà, Laura, Chiaramonte, Maria, Marchetti, Fabiana, and Valerio, Matteo

Published
2016
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15. Daclatasvir-based regimens in HCV cirrhosis: experience from the Italian early access program

Author

Calvaruso, V, Mazzarelli, C, Milazzo, L, Badia, L, Pasulo, L, Guaraldi, G, Lionetti, R, Villa, E, Borghi, V, Carrai, P, Alberti, A, Biolato, M, Piai, G, Persico, M, Santantonio, T, Felder, M, Angelico, M, Montalbano, M, Mancusi, R, Grieco, A, Angeli, E, D'Offizi, G, Fagiuoli, S, Belli, L, Verucchi, G, Puoti, M, Craxi, A, Calvaruso V., Mazzarelli C., Milazzo L., Badia L., Pasulo L., Guaraldi G., Lionetti R., Villa E., Borghi V., Carrai P., Alberti A., Biolato M., Piai G., Persico M., Santantonio T., Felder M., Angelico M., Montalbano M., Mancusi R. L., Grieco A., Angeli E., D'Offizi G., Fagiuoli S., Belli L., Verucchi G., Puoti M., Craxi A., Calvaruso, V, Mazzarelli, C, Milazzo, L, Badia, L, Pasulo, L, Guaraldi, G, Lionetti, R, Villa, E, Borghi, V, Carrai, P, Alberti, A, Biolato, M, Piai, G, Persico, M, Santantonio, T, Felder, M, Angelico, M, Montalbano, M, Mancusi, R, Grieco, A, Angeli, E, D'Offizi, G, Fagiuoli, S, Belli, L, Verucchi, G, Puoti, M, Craxi, A, Calvaruso V., Mazzarelli C., Milazzo L., Badia L., Pasulo L., Guaraldi G., Lionetti R., Villa E., Borghi V., Carrai P., Alberti A., Biolato M., Piai G., Persico M., Santantonio T., Felder M., Angelico M., Montalbano M., Mancusi R. L., Grieco A., Angeli E., D'Offizi G., Fagiuoli S., Belli L., Verucchi G., Puoti M., and Craxi A.

Abstract

We reported the efficacy and safety data for daclatasvir (DCV)-based all-oral antiviral therapy in patients treated in the Italian compassionate-use program. 275 patients were included (202 male-73.5%, mean age: 57.4 years, 62 HIV-coinfected, 94 with recurrence of hepatitis C post-OLT). Forty-nine patients (17.8%) had Child-Pugh B, Genotype(G) distribution was: G1a:72 patients (26.2%), G1b:137 (49.8%); G3:40 (14.5%) and G4:26 (9.5%). Patients received DCV with sofosbuvir(SOF) (n = 221, 129 with ribavirin(RBV) or with simeprevir (SMV) or asunaprevir (ASU) (n = 54, 19 with RBV) for up to 24 weeks. Logistic regression was used to identify baseline characteristics associated with sustained virological response at week 12 post-treatment (SVR12). Liver function changes between baseline and follow up were assessed in 228 patients. 240 patients achieved SVR12 (87.3%), post transplant and HIV co-infected patients were equally distributed among SVR and no SVR (35% vs 34.3%; p = 0.56 and 24.2% vs 11.4%, p = 0.13, respectively). SVR rate was significantly higher with the combination DCV + SOF compared with DCV + SIM or ASU (93.2% vs 63.0%, p < 0.0001). Bilirubin value (OR: 0.69, CI95%: 0.54–0.87, p = 0.002) and regimen containing SOF (OR: 9.99, CI95%: 4.09–24.40; p < 0.001) were independently related with SVR. Mean albumin and bilirubin values significantly improved between baseline and follow-up week 12. DCV-based antiviral therapy was well tolerated and resulted in a high SVR when combined with SOF either in pre-transplant and in OLT patients and in “difficult to treat” HCV genotypes. Regimens containing DCV in combination with NS3 protease inhibitors obtained suboptimal results.

Published
2019

16. Who contextualises clinical epidemiological evidence?: A political analysis of the problem of evidence-based medicine in the layered Dutch healthcare system

Author

Felder, M., van de Bovenkamp, H., Meerding, J.W., de Bont, A.A., Felder, M., van de Bovenkamp, H., Meerding, J.W., and de Bont, A.A.

Abstract

We critically examine the discussion on the role of evidence-based medicine (EBM) in healthcare governance. We take the institutionally layered Dutch healthcare system as our case study. Here, different actors are involved in the regulation, provision and financing of healthcare services. Over the last decades, these actors have related to EBM to inform their actor specific roles. At the same time, EBM has increasingly been problematised. To better understand this problematisation, we organised focus groups and interviews. We noticed that particularly EBM’s reductionist epistemology and its uncritical use by ‘professional others’ are considered problematic. However, our analysis also reveals that something else seems to be at stake. In fact, all the actors involved underwrite EBM’s reductionist epistemology and emphasise that evidence should be contextualised. They however do so in different ways and with different contexts in mind. Moreover, the ways in which some actors contextualise evidence has consequences for the ways in which others can do the same. We therefore emphasise that behind EBM’s scientific problematisation lurks a political issue. A dispute over who should contextualise evidence how, in a layered healthcare system with interdependent actors that cater to both individual patients and the public. We urge public administration scholars and policymakers to open-up the political confrontation between healthcare actors and their sometimes irreconcilable, yet evidence-informed perspectives.

Published
2021

17. Patients with advanced hepatocellular carcinoma need a personalized management: A lesson from clinical practice

Author

Giannini E. G., Bucci L., Garuti F., Brunacci M., Lenzi B., Valente M., Caturelli E., Cabibbo G., Piscaglia F., Virdone R., Felder M., Ciccarese F., Foschi F. G., Sacco R., Svegliati Baroni G., Farinati F., Rapaccini G. L., Olivani A., Gasbarrini A., Di Marco M., Morisco F., Zoli M., Masotto A., Borzio F., Benvegnu L., Marra F., Colecchia A., Nardone G., Bernardi M., Trevisani F, Olmi S, on behalf of Italian Liver Cancer (ITA. LI. CA) group, Giannini, E. G., Bucci, L., Garuti, F., Brunacci, M., Lenzi, B., Valente, M., Caturelli, E., Cabibbo, G., Piscaglia, F., Virdone, R., Felder, M., Ciccarese, F., Foschi, F. G., Sacco, R., Svegliati Baroni, G., Farinati, F., Rapaccini, G. L., Olivani, A., Gasbarrini, A., Di Marco, M., Morisco, F., Zoli, M., Masotto, A., Borzio, F., Benvegnu, L., Marra, F., Colecchia, A., Nardone, G., Bernardi, M., Trevisani, F, Olmi, S, on behalf of Italian Liver Cancer (ITA. LI., CA) group, Giannini EG, Bucci L, Garuti F, Brunacci M, Lenzi B, Valente M, Caturelli E, Cabibbo G, Piscaglia F, Virdone R, Felder M, Ciccarese F, Foschi FG, Sacco R, Svegliati Baroni G, Farinati F, Rapaccini GL, Olivani A, Gasbarrini A, Di Marco M, Morisco F, Zoli M, Masotto A, Borzio F, Benvegnù L, Marra F, Colecchia A, Nardone G, Bernardi M, Trevisani F, Giannini, Edoardo G, Bucci, Laura, Garuti, Francesca, Brunacci, Matteo, Lenzi, Barbara, Valente, Matteo, Caturelli, Eugenio, Cabibbo, Giuseppe, Piscaglia, Fabio, Virdone, Roberto, Felder, Martina, Ciccarese, Francesca, Foschi, Francesco Giuseppe, Sacco, Rodolfo, Baroni, Gianluca Svegliati, Farinati, Fabio, Rapaccini, Gian Lodovico, Olivani, Andrea, Gasbarrini, Antonio, Di Marco, Maria, Morisco, Filomena, Zoli, Marco, Masotto, Alberto, Borzio, Franco, Benvegnù, Luisa, Marra, Fabio, Colecchia, Antonio, Nardone, Gerardo, Bernardi, Mauro, and Trevisani, Franco

Subjects
Sorafenib, Male, medicine.medical_specialty, Carcinoma, Hepatocellular, Databases, Factual, Settore MED/12 - GASTROENTEROLOGIA, advanced stage, Gastroenterology, survival, 03 medical and health sciences, Liver disease, 0302 clinical medicine, Internal medicine, medicine, Carcinoma, Humans, Stage (cooking), Precision Medicine, Cancer staging, Aged, Neoplasm Staging, Retrospective Studies, Aged, 80 and over, therapy, Hepatology, Performance status, business.industry, Liver Neoplasms, Middle Aged, medicine.disease, Prognosis, Survival Analysis, Liver cancer, sorafenib, Liver cancer, advanced stage, sorafenib, survival, therapy, Treatment Outcome, Liver, 030220 oncology & carcinogenesis, Hepatocellular carcinoma, 030211 gastroenterology & hepatology, Female, alpha-Fetoproteins, business, medicine.drug
Abstract

The Barcelona Clinic Liver Cancer advanced stage (BCLC C) of hepatocellular carcinoma (HCC) includes a heterogeneous population, where sorafenib alone is the recommended treatment. In this study our aim was to assess treatment and overall survival (OS) of BCLC C patients sub-classified according to clinical features (Performance Status [PS], macro-vascular invasion [MVI], extra-hepatic spread [EHS] or MVI+EHS) determining their allocation to this stage. From the Italian Liver Cancer database, we analysed 835 consecutive BCLC C patients diagnosed between 2008 and 2014. Patients were sub-classified as: PS1 alone (n=385, 46.1%), PS2 alone (n=146, 17.5%), MVI (n=224, 26.8%), EHS (n=51, 6.1%) and MVI+EHS (n=29, 3.5%). MVI, EHS and MVI+EHS patients had larger and multifocal/massive HCCs and higher alpha-fetoprotein levels than PS1 and PS2 patients. Median OS significantly declined from PS1 (38.6 months) to PS2 (22.3 months), EHS (11.2 months), MVI (8.2 months) and MVI+EHS (3.1 months) (P

Published
2018

18. Safety and efficacy of ombitasvir/paritaprevir/ritonavir/dasabuvir plus ribavirin in patients over 65 years with HCV genotype 1 cirrhosis

Author

Ascione, A, De Luca, M, Melazzini, M, Montilla, S, Trotta, M, Petta, S, Puoti, M, Sangiovanni, V, Messina, V, Bruno, S, Izzi, A, Villa, E, Aghemo, A, Zignego, A, Orlandini, A, Fontanella, L, Gasbarrini, A, Marzioni, M, Giannini, E, Craxi, A, Abbati, G, Alberti, A, Andreone, P, Andreoni, M, Angeli, P, Angelico, M, Angarano, G, Angrisani, D, Antinori, A, Antonini, C, Avancini, I, Barone, M, Bruno, R, Benedetti, A, Bernabucci, V, Blanc, P, Boarini, C, Boffa, N, Boglione, L, Borghi, V, Borgia, G, Brancaccio, G, Brunetto, M, Cacciola, I, Calabrese, P, Calvaruso, V, Campagnolo, D, Canovari, B, Caporaso, N, Capra, F, Carolo, G, Cassola, G, Castelli, F, Cauda, R, Silberstein, F, Cecere, R, Chessa, L, Chiodera, A, Chirianni, A, Ciancio, A, Cima, S, Coco, B, Colombo, M, Coppola, N, Corti, G, Cosco, L, Corradori, S, Cozzolongo, R, Cristaudo, A, Danieli, E, Monforte, A, Monache, M, Del Poggio, P, de Luca, A, Dentone, C, Di Biagio, A, Di Leo, A, Di Perri, G, Di Stefano, M, D'Offizi, G, Donato, F, Durante, E, Erne, E, Fagiuoli, S, Falasca, K, Federico, A, Felder, M, Ferrari, C, Gaeta, G, Ganga, R, Gatti, P, Giacomet, V, Giacometti, A, Gianstefani, A, Giordani, M, Giorgini, A, Grieco, A, Guerra, M, Gulminetti, R, Ieluzzi, D, Imparato, M, Iodice, V, La Monica, S, Lazzarin, A, Lenzi, M, Levrero, M, Lichtner, M, Lionetti, R, Guercio, C, Madonna, S, Magnani, S, Maida, I, Marignani, M, Marrone, A, Marsetti, F, Martini, S, Masarone, M, Maserati, R, Mastroianni, C, Memoli, M, Menzaghi, B, Merli, M, Miele, L, Milella, M, Mondelli, M, Montalbano, M, Monti, M, Morelli, O, Morisco, F, Nardone, G, Novara, S, Onnelli, G, Onofrio, M, Paganin, S, Pani, L, Parisi, M, Parruti, G, Pasquazzi, C, Pasulo, L, Perno, C, Persico, M, Piai, G, Picciotto, A, Pigozzi, G, Piovesan, S, Piras, M, Pirisi, M, Piscaglia, A, Ponti, L, Potenza, D, Pravadelli, C, Quartini, M, Quirino, T, Raimondo, G, Rapaccini, G, Rendina, M, Rizzardini, G, Rizzetto, M, Rizzo, S, Romagnoli, D, Romano, A, Rossi, C, Rumi, M, Russello, M, Russo, F, Russo, M, Sansonno, D, Santantonio, T, Saracco, G, Schimizzi, A, Serviddio, G, Simeone, F, Solinas, A, Soria, A, Tabone, M, Taliani, G, Tarantino, G, Tarquini, P, Tavio, M, Termite, A, Teti, E, Toniutto, P, Torti, C, Tundi, P, Vecchiet, G, Verucchi, G, Gentilucci, U, Vinci, M, Vullo, V, Zolfino, T, Zuin, M, Ascione A., De Luca M., Melazzini M., Montilla S., Trotta M. P., Petta S., Puoti M., Sangiovanni V., Messina V., Bruno S., Izzi A., Villa E., Aghemo A., Zignego A. L., Orlandini A., Fontanella L., Gasbarrini A., Marzioni M., Giannini E. G., Craxi A., Abbati G., Alberti A., Andreone P., Andreoni M., Angeli P., Angelico M., Angarano G., Angrisani D., Antinori A., Antonini C., Avancini I., Barone M., Bruno R., Benedetti A., Bernabucci V., Blanc P., Boarini C., Boffa N., Boglione L., Borghi V., Borgia G., Brancaccio G., Brunetto M., Cacciola I., Calabrese P., Calvaruso V., Campagnolo D., Canovari B., Caporaso N., Capra F., Carolo G., Cassola G., Castelli F., Cauda R., Silberstein F. C., Cecere R., Chessa L., Chiodera A., Chirianni A., Ciancio A., Cima S., Coco B., Colombo M., Coppola N., Corti G., Cosco L., Corradori S., Cozzolongo R., Cristaudo A., Danieli E., Monforte A. D. A., Monache M., Del Poggio P., de Luca A., Dentone C., Di Biagio A., Di Leo A., Di Perri G., Di Stefano M., D'Offizi G., Donato F., Durante E., Erne E., Fagiuoli S., Falasca K., Federico A., Felder M., Ferrari C., Gaeta G. B., Ganga R., Gatti P., Giacomet V., Giacometti A., Gianstefani A., Giordani M., Giorgini A., Grieco A., Guerra M., Gulminetti R., Ieluzzi D., Imparato M., Iodice V., La Monica S., Lazzarin A., Lenzi M., Levrero M., Lichtner M., Lionetti R., Guercio C. L., Madonna S., Magnani S., Maida I., Marignani M., Marrone A., Marsetti F., Martini S., Masarone M., Maserati R., Mastroianni C. M., Memoli M., Menzaghi B., Merli M., Miele L., Milella M., Mondelli M., Montalbano M., Monti M., Morelli O., Morisco F., Nardone G., Novara S., Onnelli G., Onofrio M., Paganin S., Pani L., Parisi M. R., Parruti G., Pasquazzi C., Pasulo L., Perno C. F., Persico M., Piai G., Picciotto A., Pigozzi G. M., Piovesan S., Piras M. C., Pirisi M., Piscaglia A. M., Ponti L., Potenza D., Pravadelli C., Quartini M., Quirino T., Raimondo G., Rapaccini G. L., Rendina M., Rizzardini G., Rizzetto M., Rizzo S., Romagnoli D., Romano A., Rossi C., Rumi M. G., Russello M., Russo F. P., Russo M. L., Sansonno D. E., Santantonio T. A., Saracco G., Schimizzi A. M., Serviddio G., Simeone F., Solinas A., Soria A., Tabone M., Taliani G., Tarantino G., Tarquini P., Tavio M., Termite A., Teti E., Toniutto P., Torti C., Tundi P., Vecchiet G., Verucchi G., Gentilucci U. V., Vinci M., Vullo V., Zolfino T., Zuin M., Ascione, A, De Luca, M, Melazzini, M, Montilla, S, Trotta, M, Petta, S, Puoti, M, Sangiovanni, V, Messina, V, Bruno, S, Izzi, A, Villa, E, Aghemo, A, Zignego, A, Orlandini, A, Fontanella, L, Gasbarrini, A, Marzioni, M, Giannini, E, Craxi, A, Abbati, G, Alberti, A, Andreone, P, Andreoni, M, Angeli, P, Angelico, M, Angarano, G, Angrisani, D, Antinori, A, Antonini, C, Avancini, I, Barone, M, Bruno, R, Benedetti, A, Bernabucci, V, Blanc, P, Boarini, C, Boffa, N, Boglione, L, Borghi, V, Borgia, G, Brancaccio, G, Brunetto, M, Cacciola, I, Calabrese, P, Calvaruso, V, Campagnolo, D, Canovari, B, Caporaso, N, Capra, F, Carolo, G, Cassola, G, Castelli, F, Cauda, R, Silberstein, F, Cecere, R, Chessa, L, Chiodera, A, Chirianni, A, Ciancio, A, Cima, S, Coco, B, Colombo, M, Coppola, N, Corti, G, Cosco, L, Corradori, S, Cozzolongo, R, Cristaudo, A, Danieli, E, Monforte, A, Monache, M, Del Poggio, P, de Luca, A, Dentone, C, Di Biagio, A, Di Leo, A, Di Perri, G, Di Stefano, M, D'Offizi, G, Donato, F, Durante, E, Erne, E, Fagiuoli, S, Falasca, K, Federico, A, Felder, M, Ferrari, C, Gaeta, G, Ganga, R, Gatti, P, Giacomet, V, Giacometti, A, Gianstefani, A, Giordani, M, Giorgini, A, Grieco, A, Guerra, M, Gulminetti, R, Ieluzzi, D, Imparato, M, Iodice, V, La Monica, S, Lazzarin, A, Lenzi, M, Levrero, M, Lichtner, M, Lionetti, R, Guercio, C, Madonna, S, Magnani, S, Maida, I, Marignani, M, Marrone, A, Marsetti, F, Martini, S, Masarone, M, Maserati, R, Mastroianni, C, Memoli, M, Menzaghi, B, Merli, M, Miele, L, Milella, M, Mondelli, M, Montalbano, M, Monti, M, Morelli, O, Morisco, F, Nardone, G, Novara, S, Onnelli, G, Onofrio, M, Paganin, S, Pani, L, Parisi, M, Parruti, G, Pasquazzi, C, Pasulo, L, Perno, C, Persico, M, Piai, G, Picciotto, A, Pigozzi, G, Piovesan, S, Piras, M, Pirisi, M, Piscaglia, A, Ponti, L, Potenza, D, Pravadelli, C, Quartini, M, Quirino, T, Raimondo, G, Rapaccini, G, Rendina, M, Rizzardini, G, Rizzetto, M, Rizzo, S, Romagnoli, D, Romano, A, Rossi, C, Rumi, M, Russello, M, Russo, F, Russo, M, Sansonno, D, Santantonio, T, Saracco, G, Schimizzi, A, Serviddio, G, Simeone, F, Solinas, A, Soria, A, Tabone, M, Taliani, G, Tarantino, G, Tarquini, P, Tavio, M, Termite, A, Teti, E, Toniutto, P, Torti, C, Tundi, P, Vecchiet, G, Verucchi, G, Gentilucci, U, Vinci, M, Vullo, V, Zolfino, T, Zuin, M, Ascione A., De Luca M., Melazzini M., Montilla S., Trotta M. P., Petta S., Puoti M., Sangiovanni V., Messina V., Bruno S., Izzi A., Villa E., Aghemo A., Zignego A. L., Orlandini A., Fontanella L., Gasbarrini A., Marzioni M., Giannini E. G., Craxi A., Abbati G., Alberti A., Andreone P., Andreoni M., Angeli P., Angelico M., Angarano G., Angrisani D., Antinori A., Antonini C., Avancini I., Barone M., Bruno R., Benedetti A., Bernabucci V., Blanc P., Boarini C., Boffa N., Boglione L., Borghi V., Borgia G., Brancaccio G., Brunetto M., Cacciola I., Calabrese P., Calvaruso V., Campagnolo D., Canovari B., Caporaso N., Capra F., Carolo G., Cassola G., Castelli F., Cauda R., Silberstein F. C., Cecere R., Chessa L., Chiodera A., Chirianni A., Ciancio A., Cima S., Coco B., Colombo M., Coppola N., Corti G., Cosco L., Corradori S., Cozzolongo R., Cristaudo A., Danieli E., Monforte A. D. A., Monache M., Del Poggio P., de Luca A., Dentone C., Di Biagio A., Di Leo A., Di Perri G., Di Stefano M., D'Offizi G., Donato F., Durante E., Erne E., Fagiuoli S., Falasca K., Federico A., Felder M., Ferrari C., Gaeta G. B., Ganga R., Gatti P., Giacomet V., Giacometti A., Gianstefani A., Giordani M., Giorgini A., Grieco A., Guerra M., Gulminetti R., Ieluzzi D., Imparato M., Iodice V., La Monica S., Lazzarin A., Lenzi M., Levrero M., Lichtner M., Lionetti R., Guercio C. L., Madonna S., Magnani S., Maida I., Marignani M., Marrone A., Marsetti F., Martini S., Masarone M., Maserati R., Mastroianni C. M., Memoli M., Menzaghi B., Merli M., Miele L., Milella M., Mondelli M., Montalbano M., Monti M., Morelli O., Morisco F., Nardone G., Novara S., Onnelli G., Onofrio M., Paganin S., Pani L., Parisi M. R., Parruti G., Pasquazzi C., Pasulo L., Perno C. F., Persico M., Piai G., Picciotto A., Pigozzi G. M., Piovesan S., Piras M. C., Pirisi M., Piscaglia A. M., Ponti L., Potenza D., Pravadelli C., Quartini M., Quirino T., Raimondo G., Rapaccini G. L., Rendina M., Rizzardini G., Rizzetto M., Rizzo S., Romagnoli D., Romano A., Rossi C., Rumi M. G., Russello M., Russo F. P., Russo M. L., Sansonno D. E., Santantonio T. A., Saracco G., Schimizzi A. M., Serviddio G., Simeone F., Solinas A., Soria A., Tabone M., Taliani G., Tarantino G., Tarquini P., Tavio M., Termite A., Teti E., Toniutto P., Torti C., Tundi P., Vecchiet G., Verucchi G., Gentilucci U. V., Vinci M., Vullo V., Zolfino T., and Zuin M.

Abstract

Purpose: To analyse safety and efficacy of treatment based on ombitasvir/paritaprevir/ritonavir/dasabuvir plus ribavirin in the sub-group of GT1 patients older than 65 years. Methods: We collected data extracted from the ABACUS compassionate-use nationwide Italian programme, in patients with cirrhosis due to hepatitis C virus (HCV) Genotype-1 (GT1) or 4 and at high risk of decompensation. GT1-HCV-infected patients received once-daily ombitasvir/paritaprevir, with the pharmacokinetic enhancer ritonavir (25/150/100 mg) and twice-daily dasabuvir (250 mg) plus Ribavirin (RBV) (OBV/PTV/r + DSV + RBV) for 12 (GT1b) or 24 (GT1a) weeks. Endpoints were to evaluate safety and efficacy, the latter defined as HCV RNA negative 12 weeks after the end of treatment (SVR12). Results: Patients who suffered any adverse event (AE) were 74/240 (30.8%); 13/240 (5.4%) discontinued the treatment. A multivariate analysis found albumin < 3.5 g/dL (OR 2.04: 95% CI 1.0–4.2, p < 0.05) and hypertension (OR 4.6: 95% CI 2.3–9.2, p < 0.001) as variables independently associated with AE occurrence. The SVR12 was 95% (228/240). Multivariate analysis identified baseline bilirubin < 2 mg/dL (OR 4.9: 95% CI 1.17–20.71, p = 0.029) as the only variable independently associated with SVR12. Conclusion: Our findings suggest that OBV/PTV/r + DSV + RBV is safe and effective in real-life use in patients with compensated cirrhosis, HCV-GT1 infection, and age over 65.

Published
2018

19. The Italian compassionate use of sofosbuvir in HCV patients waitlisted for liver transplantation: A national real-life experience

Author

Martini, S, Donato, M, Mazzarelli, C, Rendina, M, Visco-Comandini, U, Fili, D, Gianstefani, A, Fagiuoli, S, Melazzini, M, Montilla, S, Pani, L, Petraglia, S, Russo, P, Trotta, M, Carrai, P, Caraceni, P, Angeli, P, Ballardini, G, Bernabucci, V, Bhoori, S, Burra, P, Civolani, A, D'Offizi, G, Felder, M, Gaeta, G, Ganga, R, Ginanni Corradini, S, Iemmolo, R, Lenci, I, Lionetti, R, Montalbano, M, Morelli, M, Picciotto, A, Sapere, C, Serviddio, G, Tame, M, Verucchi, G, Zignego, A, Martini S., Donato M. F., Mazzarelli C., Rendina M., Visco-Comandini U., Fili D., Gianstefani A., Fagiuoli S., Melazzini M., Montilla S., Pani L., Petraglia S., Russo P., Trotta M. P., Carrai P., Caraceni P., Angeli P., Ballardini G., Bernabucci V., Bhoori S., Burra P., Civolani A., D'Offizi G., Felder M., Gaeta G. B., Ganga R., Ginanni Corradini S., Iemmolo R. M., Lenci I., Lionetti R., Montalbano M., Morelli M. C., Picciotto A., Sapere C., Serviddio G., Tame M., Verucchi G., Zignego A. L., Martini, S, Donato, M, Mazzarelli, C, Rendina, M, Visco-Comandini, U, Fili, D, Gianstefani, A, Fagiuoli, S, Melazzini, M, Montilla, S, Pani, L, Petraglia, S, Russo, P, Trotta, M, Carrai, P, Caraceni, P, Angeli, P, Ballardini, G, Bernabucci, V, Bhoori, S, Burra, P, Civolani, A, D'Offizi, G, Felder, M, Gaeta, G, Ganga, R, Ginanni Corradini, S, Iemmolo, R, Lenci, I, Lionetti, R, Montalbano, M, Morelli, M, Picciotto, A, Sapere, C, Serviddio, G, Tame, M, Verucchi, G, Zignego, A, Martini S., Donato M. F., Mazzarelli C., Rendina M., Visco-Comandini U., Fili D., Gianstefani A., Fagiuoli S., Melazzini M., Montilla S., Pani L., Petraglia S., Russo P., Trotta M. P., Carrai P., Caraceni P., Angeli P., Ballardini G., Bernabucci V., Bhoori S., Burra P., Civolani A., D'Offizi G., Felder M., Gaeta G. B., Ganga R., Ginanni Corradini S., Iemmolo R. M., Lenci I., Lionetti R., Montalbano M., Morelli M. C., Picciotto A., Sapere C., Serviddio G., Tame M., Verucchi G., and Zignego A. L.

Abstract

Background & Aims: This study aimed to assess the real-life clinical and virological outcomes of HCV waitlisted patients for liver transplantation (LT) who received sofosbuvir/ribavirin (SOF/R) within the Italian compassionate use program. Methods: Clinical and virological data were collected in 224 patients with decompensated cirrhosis and/or hepatocellular carcinoma (HCC) receiving daily SOF/R until LT or up a maximum of 48 weeks. Results: Of 100 transplanted patients, 51 were HCV-RNA negative for >4 weeks before LT (SVR12: 88%) and 49 negative for <4 weeks or still viraemic at transplant: 34 patients continued treatment after LT (bridging therapy) (SVR12: 88%), while 15 stopped treatment (SVR12: 53%). 98 patients completed SOF/R without LT (SVR12: 73%). In patients with advanced decompensated cirrhosis (basal MELD ≥15 and/or C-P ≥B8), a marked improvement of the scores occurred in about 50% of cases and almost 20% of decompensated patients without HCC reached a condition suitable for inactivation and delisting. Conclusions: These real-life data indicate that in waitlisted patients: (i) bridging antiviral therapy can be an option for patients still viraemic or negative <4 weeks at LT; and (ii) clinical improvement to a condition suitable for delisting can occur even in patients with advanced decompensated cirrhosis.

Published
2018

20. Who contextualises clinical epidemiological evidence?

Author

Felder, M. (Martijn), Bovenkamp, H.M. (Hester) van de, Meerding, W.J. (Willem Jan), Bont, A.A. (Antoinette) de, Felder, M. (Martijn), Bovenkamp, H.M. (Hester) van de, Meerding, W.J. (Willem Jan), and Bont, A.A. (Antoinette) de

Abstract

We critically examine the discussion on the role of evidence-based medicine (EBM) in healthcare governance. We take the institutionally layered Dutch healthcare system as our case study. Here, different actors are involved in the regulation, provision and financing of healthcare services. Over the last decades, these actors have related to EBM to inform their actor specific roles. At the same time, EBM has increasingly been problematised. To better understand this problematisation, we organised focus groups and interviews. We noticed that particularly EBM’s reductionist epistemology and its uncritical use by ‘professional others’ are considered problematic. However, our analysis also reveals that something else seems to be at stake. In fact, all the actors involved underwrite EBM’s reductionist epistemology and emphasise that evidence should be contextualised. They however do so in different ways and with different contexts in mind. Moreover, the ways in which some actors contextualise evidence has consequences for the ways in which others can do the same. We therefore emphasise that behind EBM’s scientific problematisation lurks a political issue. A dispute over who should contextualise evidence how, in a layered healthcare system with interdependent actors that cater to both individual patients and the public. We urge public administration scholars and policymakers to open-up the political confrontation between healthcare actors and their sometimes irreconcilable, yet evidence-informed perspectives.

Published
2020

21. Taking the relationship between populism and healthcare seriously

Author

Felder, M. (Martijn), Wallenburg, I. (Iris), Kuijper, S. (Syb), Bal, R.A. (Roland), Felder, M. (Martijn), Wallenburg, I. (Iris), Kuijper, S. (Syb), and Bal, R.A. (Roland)

Abstract

In this commentary, we reflect on Rinaldi and Bekker’s scoping review of the literature on populist radical right (PRR) parties and welfare policies. We argue that their review provides political scientists and healthcare scholars with a firm basis to further explore the relationships between populism and welfare policies in different political systems. In line with the authors, we furthermore (re)emphasize the need for additional empirical inquiries into the relationship between populism and healthcare. But instead of expanding the research agenda suggested – for instance by adding categories or niches in which this relationship can be observed – we would like to challenge some of the premises of the studies conducted and reviewed thus far. We do so by identifying two concerns and by illustrating these concerns with two examples from the Netherlands.

Published
2020
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22. Together Alone: An analysis of policy experimentation in Dutch healthcare governance

Author

Felder, M. (Martijn) and Felder, M. (Martijn)

Abstract

In this book, Martijn Felder critically examines whether and how policy experimentation contributes to overcoming tensions amongst actors involved in Dutch healthcare governance. He does so by analyzing different policy experiments aimed at moving beyond vested interests and improving collaboration be

Published
2020

23. 'Ich glaube...': theologische Überlegungen zum Glauben nach dem Apostolikum

Author

Felder, Matthias, Mathwig, Frank, Felder, M ( Matthias ), Mathwig, F ( Frank ), Wüthrich, Matthias D; https://orcid.org/0000-0002-1063-5267, Felder, Matthias, Mathwig, Frank, Felder, M ( Matthias ), Mathwig, F ( Frank ), and Wüthrich, Matthias D; https://orcid.org/0000-0002-1063-5267

Published
2020

24. Curative therapies are superior to standard of care (transarterial chemoembolization) for intermediate stage hepatocellular carcinoma

Author

Pecorelli A, Lenzi B, Gramenzi A, Garuti F, Farinati F, Giannini EG, Ciccarese F, Piscaglia F, Rapaccini GL, Di Marco M, Caturelli E, Zoli M, Borzio F, Sacco R, Cabibbo G, Felder M, Morisco F, Gasbarrini A, Baroni GS, Foschi FG, Biasini E, Masotto A, Virdone R, Bernardi M, Trevisani F, Bolondi L, Biselli M, Bucci L, Caraceni P, Cucchetti A, Domenicali M, Venerandi L, Giacomin A, Maddalo G, Pozzan C, Vani V, Poggio PD, Olmi S, Balsamo C, Vavassori E, Benvegnù L, Cappelli A, Golfieri R, Mosconi C, Renzulli M, Bosco G, Roselli P, Dell'Isola S, Ialungo AM, Bruzzone L, Picciotto A, Marenco S, Risso D, Sammito G, Savarino V, Cammà C, Maida M, Costantino A, Barcellona MR, Affronti A, Mega A, Rinninella E, Mismas V, Cappa FM, Dall'Aglio AC, Feletti V, Lanzi A, Neri E, Stefanini GF, Tamberi S, Missale G, Porro E, Guarino M, Gemini S, Schiadà L, for the Italian LiverCancer (ITA. LI. CA) group, Donatella Magalotti, Carla Serra, Pecorelli A, Lenzi B, Gramenzi A, Garuti F, Farinati F, Giannini EG, Ciccarese F, Piscaglia F, Rapaccini GL, Di Marco M, Caturelli E, Zoli M, Borzio F, Sacco R, Cabibbo G, Felder M, Morisco F, Gasbarrini A, Baroni GS, Foschi FG, Biasini E, Masotto A, Virdone R, Bernardi M, Trevisani F, Bolondi L, Biselli M, Bucci L, Caraceni P, Cucchetti A, Domenicali M, Magalotti D, Serra C, Venerandi L, Giacomin A, Maddalo G, Pozzan C, Vani V, Poggio PD, Olmi S, Balsamo C, Vavassori E, Benvegnù L, Cappelli A, Golfieri R, Mosconi C, Renzulli M, Bosco G, Roselli P, Dell'Isola S, Ialungo AM, Bruzzone L, Picciotto A, Marenco S, Risso D, Sammito G, Savarino V, Cammà C, Maida M, Costantino A, Barcellona MR, Affronti A, Mega A, Rinninella E, Mismas V, Cappa FM, Dall'Aglio AC, Feletti V, Lanzi A, Neri E, Stefanini GF, Tamberi S, Missale G, Porro E, Guarino M, Gemini S, Schiadà L, Pecorelli, A., Lenzi, B., Gramenzi, A., Garuti, F., Farinati, F., Giannini, E. G., Ciccarese, F., Piscaglia, F., Rapaccini, G. L., Di Marco, M., Caturelli, E., Zoli, M., Borzio, F., Sacco, R., Cabibbo, G., Felder, M., Morisco, F., Gasbarrini, A., Baroni, G. S., Foschi, F. G., Biasini, E., Masotto, A., Virdone, R., Bernardi, M., Trevisani, F., Bolondi, L., Biselli, M., Bucci, L., Caraceni, P., Cucchetti, A., Domenicali, M., Magalotti, D., Serra, C., Venerandi, L., Giacomin, A., Maddalo, G., Pozzan, C., Vani, V., Poggio, P. D., Olmi, S., Balsamo, C., Vavassori, E., Benvegnu, L., Cappelli, A., Golfieri, R., Mosconi, C., Renzulli, M., Bosco, G., Roselli, P., Dell'Isola, S., Ialungo, A. M., Bruzzone, L., Picciotto, A., Marenco, S., Risso, D., Sammito, G., Savarino, V., Camma, C., Maida, M., Costantino, A., Barcellona, M. R., Affronti, A., Mega, A., Rinninella, E., Mismas, V., Cappa, F. M., Dall'Aglio, A. C., Feletti, V., Lanzi, A., Neri, E., Stefanini, G. F., Tamberi, S., Missale, G., Porro, E., Guarino, M., Gemini, S., Schiada, L., Pecorelli, Anna, Lenzi, Barbara, Gramenzi, Annagiulia, Garuti, Francesca, Farinati, Fabio, Giannini, Edoardo G, Ciccarese, Francesca, Piscaglia, Fabio, Rapaccini, Gian Lodovico, Di Marco, Maria, Caturelli, Eugenio, Zoli, Marco, Borzio, Franco, Sacco, Rodolfo, Cabibbo, Giuseppe, Felder, Martina, Morisco, Filomena, Gasbarrini, Antonio, Baroni, Gianluca Svegliati, Foschi, Francesco G, Biasini, Elisabetta, Masotto, Alberto, Virdone, Roberto, Bernardi, Mauro, and Trevisani, Franco

Subjects
Sorafenib, Male, Niacinamide, medicine.medical_specialty, Standard of care, Carcinoma, Hepatocellular, Antineoplastic Agents, Gastroenterology, Intermediate stage, 03 medical and health sciences, 0302 clinical medicine, HCC, BCLC-B, Treatment, Hepatology, Internal medicine, medicine, Humans, Chemoembolization, Therapeutic, Propensity Score, Aged, Neoplasm Staging, Retrospective Studies, intermediate stage, treatment, business.industry, Patient Selection, Phenylurea Compounds, Liver Neoplasms, Settore MED/09 - MEDICINA INTERNA, Standard of Care, Middle Aged, medicine.disease, Survival Analysis, Treatment Outcome, Italy, 030220 oncology & carcinogenesis, Hepatocellular carcinoma, Propensity score matching, Multivariate Analysis, 030211 gastroenterology & hepatology, Female, Liver function, Liver cancer, business, medicine.drug
Abstract

Background and aims the Barcelona Clinic Liver Cancer intermediate stage (BCLC-B) of hepatocellular carcinoma (HCC) includes extremely heterogeneous patients in terms of tumor burden and liver function. Transarterial-chemoembolization (TACE) is the first-line treatment for these patients although it may be risky/useless for someone, while others could undergo curative treatments. This study assesses the treatment type performed in a large cohort of BCLC-B patients and its outcome. Methods retrospective analysis of 485 consecutive BCLC-B patients from the ITA.LI.CA database diagnosed with naive HCC after 1999. Patients were stratified by treatment. Results 29 patients (6%) were lost to follow-up before receiving treatment. Treatment distribution was: TACE (233, 51.1%), curative treatments (145 patients, 31.8%), sorafenib (18, 3.9%), other (39, 8.5%), best supportive care (BSC) (21, 4.6%). Median survival (95% CI) was 45 months (37.4-52.7) for curative treatments, 30 (24.7-35.3) for TACE, 14 (10.5-17.5) for sorafenib, 14 (5.2-22.7) for other treatments and 10 (6.0-14.2) for BSC (p

Published
2017

25. Laser ablation is superior to TACE in large-sized hepatocellular carcinoma: A pilot case-control study

Author

Morisco, Filomena, Camera, Silvia, Guarino, Maria, Tortora, Raffaella, Cossiga, Valentina, Vitiello, Anna, Cordone, Gabriella, Caporaso, Nicola, Di Costanzo, Giovan Giuseppe, Zoli, M., Garuti, F., Neri, A., Piscaglia, F., Lenzi, B., Valente, M., Trevisani, F., Bolondi, L., Biselli, M., Caraceni, P., Cucchetti, A., Domenicali, M., Gramenzi, A., Magalotti, D., Serra, C., Venerandi, L., Cappelli, A., Golfieri, R., Mosconi, C., Renzulli, M., Giannini, E. G., Brunacci, M., Moscatelli, A., Pellegatta, G., Savarino, V., Caturelli, E., Roselli, P., Lauria, V., Pelecca, G., Dell'Isola, S., Ialungo, A. M., Rastrelli, E., Cabibbo, G., Cammà, C., Attardo, S., Rossi, M., Cavani, G., Virdone, R., Affronti, A., Nardone, G., Felder, M., Mega, A., Ciccarese, F., Del Poggio, P., Olmi, S., Foschi, F. G., Bevilacqua, V., Dall'Aglio, A. C., Ercolani, G., Fiorini, E., Casadei Gardini, A., Lanzi, A., Mirici Cappa, F., Sacco, R., Mismas, V., Svegliati Barone, G., Schiadà, L., Farinati, F., Gazzola, A., Murer, F., Pozzan, C., Vanin, V., Rapaccini, G. L., de Matthaeis, N., Gasbarrini, A., Rinninella, E., Olivani, A., Missale, G., Biasini, E., Di Marco, M., Balsamo, C., Vavassori, E., Masotto, A., Marchetti, F., Valerio, M., Marra, F., Aburas, S., Campani, C., Dragoni, G., Borzio, F., Benvegnù, L., Festi, D., Marasco, Giovanni, Ravaioli, Federico, Morisco, Filomena, Camera, Silvia, Guarino, Maria, Tortora, Raffaella, Cossiga, Valentina, Vitiello, Anna, Cordone, Gabriella, Caporaso, Nicola, Di Costanzo, Giovan Giuseppe, Zoli, M., Garuti, F., Neri, A., Piscaglia, F., Lenzi, B., Valente, M., Trevisani, F., Bolondi, L., Biselli, M., Caraceni, P., Cucchetti, A., Domenicali, M., Gramenzi, A., Magalotti, D., Serra, C., Venerandi, L., Cappelli, A., Golfieri, R., Mosconi, C., Renzulli, M., Giannini, E.G., Brunacci, M., Moscatelli, A., Pellegatta, G., Savarino, V., Caturelli, E., Roselli, P., Lauria, V., Pelecca, G., Dell'Isola, S., Ialungo, A.M., Rastrelli, E., Cabibbo, G., Cammà, C., Attardo, S., Rossi, M., Cavani, G., Virdone, R., Affronti, A., Nardone, G., Felder, M., Mega, A., Ciccarese, F., Del Poggio, P., Olmi, S., Foschi, F.G., Bevilacqua, V., Dall'Aglio, A.C., Ercolani, G., Fiorini, E., Casadei Gardini, A., Lanzi, A., Mirici Cappa, F., Sacco, R., Mismas, V., Svegliati Barone, G., Schiadà, L., Farinati, F., Gazzola, A., Murer, F., Pozzan, C., Vanin, V., Rapaccini, G.L., de Matthaeis, N., Gasbarrini, A., Rinninella, E., Olivani, A., Missale, G., Biasini, E., Di Marco, M., Balsamo, C., Vavassori, E., Masotto, A., Marchetti, F., Valerio, M., Marra, F., Aburas, S., Campani, C., Dragoni, G., Borzio, F., Benvegnù, L., Festi, D., Marasco, Giovanni, Ravaioli, Federico, Giannini, E. G., Ialungo, A. M., Foschi, F. G., Dall'Aglio, A. C., Rapaccini, G. L., Garuti, Franca, Venerandi, Laura, Mega, Angela, Fiorini, Elisabetta, Lanzi, Andrea, and Balsamo, Carlo

Subjects
medicine.medical_specialty, Large HCC, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Survival rate, Laser ablation, TACE, Univariate analysis, business.industry, Standard treatment, Large HCC, Laser ablation, TACE, Oncology, Cancer, Hepatology, medicine.disease, BCLC Stage, Oncology, 030220 oncology & carcinogenesis, Hepatocellular carcinoma, 030211 gastroenterology & hepatology, Liver cancer, business, Research Paper
Abstract

// Filomena Morisco 1 , Silvia Camera 1 , Maria Guarino 1 , Raffaella Tortora 2 , Valentina Cossiga 1 , Anna Vitiello 1 , Gabriella Cordone 2 , Nicola Caporaso 1 , Giovan Giuseppe Di Costanzo 2 and Italian Liver Cancer (ITA.LI.CA) group 1 Gastroenterology Unit, Department of Clinical Medicine and Surgery, University of Naples “Federico II”, Naples, Italy 2 Hepatology Unit, “Cardarelli” Hospital, Naples, Italy Correspondence to: Filomena Morisco, email: filomena.morisco@unina.it Keywords: large HCC; laser ablation; TACE Received: December 13, 2017 Accepted: February 27, 2018 Published: April 03, 2018 ABSTRACT Background: Limited therapies are available for large (≥40 mm) unresectable hepatocellular carcinoma (HCC). Currently, the standard treatment with transarterial chemoembolisation (TACE) is unsatisfactory with high recurrence rate and limited effect on survival. Laser Ablation (LA) has emerged as a relatively new technique characterized by high efficacy and good safety. This study is aimed to evaluate the efficacy of LA in comparison to TACE in patients with large HCC. Methods: Eighty-two patients with a single HCC nodule ≥40 mm (BCLC stage A or B) were enrolled in this case-control study. Forty-one patients were treated with LA and 41 patients were treated with TACE. Response to therapy was evaluated according to the mRECIST criteria. Survival was calculated with Kaplan-Meier from the time of cancer diagnosis to death with values censored at the date of the last follow-up. Results: Twenty-six (63.4%) and 8 (19.5%) patients had a complete response after LA and TACE, respectively ( p 60 mm. LA resulted superior to TACE especially in nodules ranging between 51 and 60 mm in diameter, with a complete response rate post-LA and post-TACE of 75% and 14.3%, respectively ( p = 0.0133). The 36 months cumulative survival rate in patients treated with LA and TACE was 55.4% and 48.8%, respectively. The disease recurrence rates after LA and TACE were 19.5% and 75.0%, respectively. Conclusions: LA is a more effective therapeutic option than TACE in patients with solitary large HCC.

Published
2018

26. The Italian compassionate use of sofosbuvir in HCV patients waitlisted for liver transplantation: A national real-life experience

Author

Martini, Silvia, Donato, Maria Francesca, Mazzarelli, Chiara, Rendina, Maria, Visco-Comandini, Ubaldo, Filì, Daniela, Gianstefani, Alice, Fagiuoli, Stefano, Melazzini, Mario, Montilla, Simona, Pani, Luca, Petraglia, Sandra, Russo, Pierluigi, Trotta, Maria Paola, Carrai, Paola, Caraceni, Paolo, ITACOPS study group, Angeli, P, Ballardini, G, Bernabucci, V, Bhoori, S, Burra, P, Civolani, A, D'Offizi, G, Felder, M, Gaeta, Gb, Ganga, R, Ginanni Corradini, S, Iemmolo, Rm, Lenci, I, Lionetti, R, Montalbano, M, Morelli, Mc, Picciotto, A, Sapere, C, Serviddio, G, Tamè, M, Verucchi, G, Zignego, A. L., Martini, Silvia, Donato, Maria Francesca, Mazzarelli, Chiara, Rendina, Maria, Visco-Comandini, Ubaldo, Filì, Daniela, Gianstefani, Alice, Fagiuoli, Stefano, Melazzini, Mario, Montilla, Simona, Pani, Luca, Petraglia, Sandra, Russo, Pierluigi, Trotta, Maria Paola, Carrai, Paola, Caraceni, Paolo, Martini, S, Donato, M, Mazzarelli, C, Rendina, M, Visco-Comandini, U, Fili, D, Gianstefani, A, Fagiuoli, S, Melazzini, M, Montilla, S, Pani, L, Petraglia, S, Russo, P, Trotta, M, Carrai, P, Caraceni, P, Angeli, P, Ballardini, G, Bernabucci, V, Bhoori, S, Burra, P, Civolani, A, D'Offizi, G, Felder, M, Gaeta, G, Ganga, R, Ginanni Corradini, S, Iemmolo, R, Lenci, I, Lionetti, R, Montalbano, M, Morelli, M, Picciotto, A, Sapere, C, Serviddio, G, Tame, M, Verucchi, G, and Zignego, A

Subjects
Compassionate Use Trials, Liver Cirrhosis, Male, Cirrhosis, Sofosbuvir, bridging therapy, decompensated cirrhosis, delisting, direct-acting antivirals, hepatitis C, liver transplantation, Adult, Aged, Antiviral Agents, Carcinoma, Hepatocellular, Drug Therapy, Combination, Female, Hepacivirus, Hepatitis C, Chronic, Humans, Italy, Kaplan-Meier Estimate, Liver Neoplasms, Middle Aged, Prospective Studies, Ribavirin, Liver Transplantation, Waiting Lists, Hepatology, medicine.medical_treatment, Liver transplantation, chemistry.chemical_compound, 0302 clinical medicine, Chronic, Hepatitis C, 030220 oncology & carcinogenesis, Combination, 030211 gastroenterology & hepatology, medicine.drug, medicine.medical_specialty, 03 medical and health sciences, Drug Therapy, Internal medicine, medicine, direct-acting antiviral, business.industry, decompensated cirrhosi, Carcinoma, Hepatocellular, medicine.disease, Surgery, Transplantation, chemistry, business
Abstract

Background & aims This study aimed to assess the real-life clinical and virological outcomes of HCV waitlisted patients for liver transplantation (LT) who received sofosbuvir/ribavirin (SOF/R) within the Italian compassionate use program. Methods Clinical and virological data were collected in 224 patients with decompensated cirrhosis and/or hepatocellular carcinoma (HCC) receiving daily SOF/R until LT or up a maximum of 48 weeks. Results Of 100 transplanted patients, 51 were HCV-RNA negative for >4 weeks before LT (SVR12: 88%) and 49 negative for

Published
2018

27. Metabolic disorders across hepatocellular carcinoma in Italy

Author

Morisco, F., Guarino, M., Valvano, M. R., Auriemma, F., Farinati, F., Giannini, E. G., Ciccarese, F., Tovoli, F., Rapaccini, Gian Ludovico, Di Marco, M., Caturelli, E., Zoli, M., Borzio, F., Sacco, R., Cabibbo, G., Felder, M., Benvengu, L., Gasbarrini, Antonio, Svegliati Baroni, G., Foschi, F. G., Biasini, E., Masotto, A., Virdone, R., Marra, F., Caporaso, N., Trevisani, F., Sessa, A., Marafatto, F., Peserico, G., Pozzan, C., Brunacci, M., Moscatelli, A., Pellegatta, G., Savarino, V., Del Poggio, P., Olmi, S., De Matthaeis, Nicoletta, Balsamo, C., Vavassori, E., Roselli, P., Lauria, V., Pelecca, G., Mismas, V., Rossi, M., Attardo, S., Cavani, G., Mega, A., Rinninella, Emanuele, Ortolani, A., Bevilacqua, V., Chiara Dall'Aglio, A., Ercolani, G., Fiorini, Carlo Ettore, Casadei Gardini, A., Lanzi, Alessio, Mirici Cappa, F., Missale, G., Porro, E., Marchetti, F., Valerio, M., Affronti, A., Orlando, E., Rosa Barcellona, M., Aburas, S., Dragoni, G., Campani, C., Biselli, M., Bucci, L., Caraceni, P., Cucchetti, A., Domenicali, M., Garuti, F., Gramenzi, A., Magalotti, D., Serra, C., Granito, A., Negrini, G., Napoli, L., Piscaglia, F., Morisco, F., Guarino, M., Valvano, M. R., Auriemma, F., Farinati, F., Giannini, E. G., Ciccarese, F., Tovoli, F., Rapaccini, G. L., Di Marco, M., Caturelli, E., Zoli, M., Borzio, F., Sacco, R., Cabibbo, G., Felder, M., Benvengu, L., Gasbarrini, A., Svegliati Baroni, G., Foschi, F. G., Biasini, E., Masotto, A., Virdone, R., Marra, F., Caporaso, N., Trevisani, F., Sessa, A., Marafatto, F., Peserico, G., Pozzan, C., Brunacci, M., Moscatelli, A., Pellegatta, G., Savarino, V., Del Poggio, P., Olmi, S., de Matthaeis, N., Balsamo, C., Vavassori, E., Roselli, P., Lauria, V., Pelecca, G., Mismas, V., Rossi, M., Attardo, S., Cavani, G., Mega, A., Rinninella, E., Ortolani, A., Bevilacqua, V., Chiara Dall'Aglio, A., Ercolani, G., Fiorini, E., Casadei Gardini, A., Lanzi, A., Mirici Cappa, F., Missale, G., Porro, E., Marchetti, F., Valerio, M., Affronti, A., Orlando, E., Rosa Barcellona, M., Aburas, S., Dragoni, G., Campani, C., Biselli, M., Bucci, L., Caraceni, P., Cucchetti, A., Domenicali, M., Garuti, F., Gramenzi, A., Magalotti, D., Serra, C., Granito, A., Negrini, G., Napoli, L., Piscaglia, F., Morisco, Filomena, Guarino, Maria, Valvano, Maria R., Auriemma, Francesco, Farinati, Fabio, Giannini, Edoardo G., Ciccarese, Francesca, Tovoli, Francesco, Rapaccini, Gian Ludovico, Di Marco, Maria, Caturelli, Eugenio, Zoli, Marco, Borzio, Franco, Sacco, Rodolfo, Cabibbo, Giuseppe, Felder, Martina, Benvengù, Luisa, Gasbarrini, Antonio, Svegliati Baroni, Gianluca, Foschi, Francesco G., Biasini, Elisabetta, Masotto, Alberto, Virdone, Roberto, Marra, Fabio, Caporaso, Nicola, Trevisani, Franco, Sessa, Anna, Marafatto, Filippo, Peserico, Giulia, Pozzan, Caterina, Brunacci, Matteo, Moscatelli, Alessandro, Pellegatta, Gaia, Savarino, Vincenzo, Del Poggio, Paolo, Olmi, Stefano, de Matthaeis, Nicoletta, Balsamo, Claudia, Vavassori, Elena, Roselli, Paola, Lauria, Valentina, Pelecca, Giorgio, Mismas, Valeria, Rossi, Margherita, Attardo, Simona, Cavani, Giulia, Mega, Andrea, Rinninella, Emanuele, Ortolani, Alessio, Bevilacqua, Vittoria, Chiara Dall'Aglio, Anna, Ercolani, Giorgio, Fiorini, Erica, Casadei Gardini, Andrea, Lanzi, Arianna, Mirici Cappa, Federica, Missale, Gabriele, Porro, Emanuela, Marchetti, Fabiana, Valerio, Matteo, Affronti, Andrea, Orlando, Emanuele, Rosa Barcellona, Maria, Aburas, Sami, Dragoni, Gabriele, Campani, Claudia, Biselli, Maurizio, Bucci, Laura, Caraceni, Paolo, Cucchetti, Alessandro, Domenicali, Marco, Garuti, Francesca, Gramenzi, Annagiulia, Magalotti, Donatella, Serra, Carla, Granito, Alessandro, Negrini, Giulia, Napoli, Lucia, Piscaglia, Fabio, Valvano, Maria R, Giannini, Edoardo G, and Foschi, Francesco G

Subjects
Oncology, Male, obesity, Databases, Factual, Hepatocellular carcinoma, 0302 clinical medicine, Risk Factors, Prospective cohort study, diabetes, Metabolic disorder, Liver Neoplasms, Diabetes, hepatocellular carcinoma, Middle Aged, Metabolic syndrome, Portal vein thrombosis, Italy, 030220 oncology & carcinogenesis, 030211 gastroenterology & hepatology, Female, medicine.medical_specialty, Carcinoma, Hepatocellular, Settore MED/12 - GASTROENTEROLOGIA, Obesity, metabolic syndrome, 03 medical and health sciences, Databases, Metabolic Diseases, Internal medicine, medicine, Diabetes Mellitus, Humans, Factual, Aged, Neoplasm Staging, Retrospective Studies, Hepatology, business.industry, Carcinoma, Hepatocellular, medicine.disease, Survival Analysis, BCLC Stage, Multivariate Analysis, diabete, Liver function, business
Abstract

Background: Metabolic disorders are well-known risk factors for HCC. Conversely, their impact on the natural history of HCC is not established. This study aimed at evaluating the impact of metabolic disorders on clinical features, treatment and survival of HCC patients regardless of its aetiology. Methods: We analysed the ITA.LI.CA database regarding 839 HCC patients prospectively collected. The following metabolic features were analysed: BMI, diabetes, arterial hypertension, hypercholesterolaemia and hypertriglyceridaemia. According to these features, patients were divided into 3 groups: 0-1, 2 and 3-5 metabolic features. Results: As compared with patients with 0-1 metabolic features, patients with 3-5 features showed lower percentage of HCC diagnosis on surveillance (P=.021), larger tumours (P=.038), better liver function (higher percentage of Child-Pugh class A [P=.007] and MELD&nbsp

Published
2018

28. The Italian compassionate use of sofosbuvir observational cohort study for the treatment of recurrent hepatitis C: clinical and virological outcomes

Author

Carrai, P, Morelli, C, Cordone, G, Romano, A, Tame, M, Lionetti, R, Pietrosi, G, Lenci, I, Piai, G, Russo, F, Coppola, C, Melazzini, M, Montilla, S, Pani, L, Petraglia, S, Russo, P, Trotta, M, Martini, S, Toniutto, P, Bandiera, F, Bhoori, S, Brillanti, S, Burra, P, Corsale, S, De Luca, A, Fagiuoli, S, Fattovich, G, Fava, G, Felder, M, Forte, P, Galeota-Lanza, A, Gitto, S, Grieco, A, Grossi, P, Ialungo, A, Iemmolo, R, Loiacono, L, Mangia, A, Merli, M, Piacentini, A, Pellicelli, A, Rigamonti, C, Gabriella, V, Zignego, A, Carrai P., Morelli C., Cordone G., Romano A., Tame M., Lionetti R., Pietrosi G., Lenci I., Piai G., Russo F. P., Coppola C., Melazzini M., Montilla S., Pani L., Petraglia S., Russo P., Trotta M. P., Martini S., Toniutto P., Bandiera F., Bhoori S., Brillanti S., Burra P., Corsale S., De Luca A., Fagiuoli S., Fattovich G., Fava G., Felder M., Forte P., Galeota-Lanza A., Gitto S., Grieco A., Grossi P., Ialungo A. M., Iemmolo R. M., Loiacono L., Mangia A., Merli M., Piacentini A., Pellicelli A., Rigamonti C., Gabriella V., Zignego A. L., Carrai, P, Morelli, C, Cordone, G, Romano, A, Tame, M, Lionetti, R, Pietrosi, G, Lenci, I, Piai, G, Russo, F, Coppola, C, Melazzini, M, Montilla, S, Pani, L, Petraglia, S, Russo, P, Trotta, M, Martini, S, Toniutto, P, Bandiera, F, Bhoori, S, Brillanti, S, Burra, P, Corsale, S, De Luca, A, Fagiuoli, S, Fattovich, G, Fava, G, Felder, M, Forte, P, Galeota-Lanza, A, Gitto, S, Grieco, A, Grossi, P, Ialungo, A, Iemmolo, R, Loiacono, L, Mangia, A, Merli, M, Piacentini, A, Pellicelli, A, Rigamonti, C, Gabriella, V, Zignego, A, Carrai P., Morelli C., Cordone G., Romano A., Tame M., Lionetti R., Pietrosi G., Lenci I., Piai G., Russo F. P., Coppola C., Melazzini M., Montilla S., Pani L., Petraglia S., Russo P., Trotta M. P., Martini S., Toniutto P., Bandiera F., Bhoori S., Brillanti S., Burra P., Corsale S., De Luca A., Fagiuoli S., Fattovich G., Fava G., Felder M., Forte P., Galeota-Lanza A., Gitto S., Grieco A., Grossi P., Ialungo A. M., Iemmolo R. M., Loiacono L., Mangia A., Merli M., Piacentini A., Pellicelli A., Rigamonti C., Gabriella V., and Zignego A. L.

Abstract

Direct antivirals are available for treating recurrent hepatitis C (RHC). This study reported outcomes of 424 patients with METAVIR F3–F4 RHC who were treated for 24 weeks with sofosbuvir/ribavirin and followed for 12 weeks within the Italian sofosbuvir compassionate use program. In 55 patients, daclatasvir or simeprevir were added. Child–Pugh class and model of end stage liver disease (MELD) scores were evaluated at baseline and 36 weeks after the start of therapy. The sustained viral response (SVR) was 86.7% (316/365) in patients who received sofosbuvir/ribavirin and 98.3% (58/59) in patients who received a second antiviral (P < 0.01). In patients treated with sofosbuvir/ribavirin, a significant difference in SVR was observed between patients diagnosed with METAVIR F4 (211/250; 84.4%), METAVIR F3 (95/105; 90.5%) and fibrosing cholestatic hepatitis (10/10; 100%) (P = 0.049). A significant association was found between patients who worsened from Child–Pugh class A and who experienced viral relapse (4/26 vs. 8/189, P = 0.02). In patients with a baseline MELD score <15, a significant association was found between maintaining a final MELD score <15 and the achievement of SVR (187/219 vs. 6/10, P = 0.031). This real-world study indicates that sofosbuvir/ribavirin treatment for 24 weeks was effective, and the achievement of SVR was associated with a reduced probability of developing worsening liver function.

Published
2017

30. Comparison between alcohol- and hepatitis C virus-related hepatocellular carcinoma: clinical presentation, treatment and outcome

Author

BUCCI, LAURA, GARUTI, FRANCESCA, LENZI, BARBARA, PISCAGLIA, FABIO, ZOLI, MARCO, BERNARDI, MAURO, TREVISANI, FRANCO, BOLONDI, LUIGI, BISELLI, MAURIZIO, CARACENI, PAOLO, CUCCHETTI, ALESSANDRO, DOMENICALI, MARCO, GRAMENZI, ANNAGIULIA, Camelli, V, Farinati, F, Giannini, E, Ciccarese, F, Rapaccini, G, Di Marco, M, Caturelli, E, Borzio, F, Sacco, R, Maida, M, Felder, M, Morisco, F, Gasbarrini, A, Gemini, S, Foschi, F, Missale, G, Masotto, A, Affronti, A, Italian Liver Cancer Group, Bucci, L., Garuti, F., Camelli, V., Lenzi, B., Farinati, F., Giannini, E. G., Ciccarese, F., Piscaglia, F., Rapaccini, G. L., Di Marco, M., Caturelli, E., Zoli, M., Borzio, F., Sacco, R., Maida, M., Felder, M., Morisco, F., Gasbarrini, A., Gemini, S., Foschi, F. G., Missale, G., Masotto, A., Affronti, A., Bernardi, M., Trevisani, F, Olmi, S, on behalf of Italian Liver Cancer, (ITA. LI. CA) Group., Bucci, L, Garuti, F, Camelli, V, Lenzi, B, Farinati, F, Giannini, E, Ciccarese, F, Piscaglia, F, Rapaccini, G, Di Marco, M, Caturelli, E, Zoli, M, Borzio, F, Sacco, R, Maida, M, Felder, M, Morisco, F, Gasbarrini, A, Gemini, S, Foschi, F, Missale, G, Masotto, A, Affronti, A, Bernardi, M, Italian Liver Cancer (ITA.LI.CA.) Group, Bolondi, L, Biselli, M, Caraceni, P, Cucchetti, A, Domenicali, M, Gramenzi, A, Giannini, E. G, Rapaccini, G. L, Morisco, Filomena, Foschi, F. G, and Trevisani, F.

Subjects
Male, Sex Factor, Gastroenterology, Hepatitis, 0302 clinical medicine, alcoholic cirrhosi, Liver Function Tests, Retrospective Studie, Risk Factors, Esophageal and Gastric Varice, 80 and over, Age Factor, Pharmacology (medical), Age Factors, Aged, Aged, 80 and over, Carcinoma, Hepatocellular, Esophageal and Gastric Varices, Female, Hepatitis C, Hepatitis, Alcoholic, Humans, Liver Neoplasms, Middle Aged, Neoplasm Staging, Prognosis, Proportional Hazards Models, Retrospective Studies, Sex Factors, Treatment Outcome, Venous Thrombosis, alpha-Fetoproteins, Medicine (all), medicine.diagnostic_test, Liver Function Test, Alcoholic, Liver Neoplasm, Hepatocellualr carinoma, 030220 oncology & carcinogenesis, Hepatocellular carcinoma, epidemiology, 030211 gastroenterology & hepatology, Liver cancer, Viral hepatitis, Human, medicine.medical_specialty, Prognosi, 03 medical and health sciences, Internal medicine, medicine, Venous Thrombosi, Hepatology, business.industry, Risk Factor, Carcinoma, Cancer, Hepatocellular, medicine.disease, digestive system diseases, BCLC Stage, Proportional Hazards Model, Liver function, business, Liver function tests, HCV-related cirrhosi
Abstract

Summary Background Hepatitis C virus (HCV) and alcohol abuse are the main risk factors for hepatocellular carcinoma (HCC) in Western countries. Aim To investigate the role of alcoholic aetiology on clinical presentation, treatment and outcome of HCC as well as on each Barcelona Clinic Liver Cancer (BCLC) stage, as compared to HCV-related HCCs. Methods A total of 1642 HCV and 573 alcoholic patients from the Italian Liver Cancer (ITA.LI.CA) database, diagnosed with HCC between January 2000 and December 2012 were compared for age, gender, type of diagnosis, tumour burden, portal vein thrombosis (PVT), oesophageal varices, liver function tests, alpha-fetoprotein, BCLC, treatment and survival. Aetiology was tested as predictor of survival in multivariate Cox regression models and according to HCC stages. Results Cirrhosis was present in 96% of cases in both groups. Alcoholic patients were younger, more likely male, with HCC diagnosed outside surveillance, in intermediate/terminal BCLC stage and had worse liver function. After adjustment for the lead-time, median (95% CI) overall survival (OS) was 27.4 months (21.5–33.2) in alcoholic and 33.6 months (30.7–36.5) in HCV patients (P = 0.021). The prognostic role of aetiology disappeared when survival was assessed in each BCLC stage and in the Cox regression multivariate models. Conclusions Alcoholic aetiology affects survival of HCC patients through its negative effects on secondary prevention and cancer presentation but not through a greater cancer aggressiveness or worse treatment result. In fact, survival adjusted for confounding factors was similar in alcoholic and HCV patients.

Published
2015

31. Utility of Tumor Burden Score to Stratify Prognosis of Patients with Hepatocellular Cancer: Results of 4759 Cases from ITA.LI.CA Study Group

Author

Vitale, A, Lai, Q, Farinati, F, Bucci, L, Giannini, Eg, Napoli, L, Ciccarese, F, Rapaccini, Gl, Di Marco, M, Caturelli, E, Zoli, M, Borzio, F, Sacco, R, Cabibbo, G, Virdone, R, Marra, F, Felder, M, Morisco, F, Benvegnù, L, Gasbarrini, A, Svegliati-Baroni, G, Foschi, Fg, Missale, G, Masotto, A, Nardone, G, Colecchia, A, Bernardi, M, Trevisani, F, Pawlik, Tm, Italian Liver Cancer, (ITA. LI. CA) group., Vitale, Alessandro, Lai, Quirino, Farinati, Fabio, Bucci, Laura, Giannini, Edoardo G., Napoli, Lucia, Ciccarese, Francesca, Rapaccini, Gian Lodovico, Di Marco, Maria, Caturelli, Eugenio, Zoli, Marco, Borzio, Franco, Sacco, Rodolfo, Cabibbo, Giuseppe, Virdone, Roberto, Marra, Fabio, Felder, Martina, Morisco, Filomena, Benvegnù, Luisa, Gasbarrini, Antonio, Svegliati-Baroni, Gianluca, Foschi, Francesco Giuseppe, Missale, Gabriele, Masotto, Alberto, Nardone, Gerardo, Colecchia, Antonio, Bernardi, Mauro, Trevisani, Franco, Pawlik, Timothy M., and D'Alessandro, Vitale

Subjects
Oncology, Male, Hepatocellular carcinoma, Tumor burden, Disease, Severity of Illness Index, Milan Criteria, Outcomes, Prognosis, 0302 clinical medicine, Risk Factors, Outcome, education.field_of_study, Liver Neoplasms, Gastroenterology, Middle Aged, Survival Rate, 030220 oncology & carcinogenesis, 030211 gastroenterology & hepatology, Female, alpha-Fetoproteins, medicine.medical_specialty, Carcinoma, Hepatocellular, Prognosi, Settore MED/12 - GASTROENTEROLOGIA, Population, Milan criteria, End Stage Liver Disease, 03 medical and health sciences, Internal medicine, medicine, Humans, Neoplasm Invasiveness, Risk factor, education, Survival analysis, Aged, Proportional Hazards Models, Retrospective Studies, Hepatocellular carcinoma, Milan Criteria, Outcomes, Prognosis, Tumor burden, Surgery, Gastroenterology, business.industry, Proportional hazards model, medicine.disease, Blood Vessels, Surgery, business
Abstract

Background: Dichotomous models like Milan Criteria represent the routinely used tools for predicting the outcome of patients with hepatocellular carcinoma (HCC). However, a paradigm shift from a dichotomous to continuous prognostic stratification should represent a good strategy for improving the prediction process. Recently, the tumor burden score (TBS) has been proposed for selecting patients with colorectal liver metastases. To date, TBS has not been validated in a large HCC population. The main objective of this study was to evaluate the prognostic power of TBS in an HCC population treated with different curative and palliative modalities. Methods: Prospectively collected data from consecutive HCC patients managed in 24 institutions participating in the ITA.LI.CA group between Jan 2002 and Mar 2015 were analyzed (n = 4759). A sub-analysis focused on 3909 patients with the radiological evidence of vascular invasion or metastatic disease was also performed. Results: TBS demonstrated the best discriminative ability when compared to MC and other tumor-specific scores. At multivariable Cox regression analysis, TBS was an independent risk factor of overall survival, with a 6% increased risk for patient death for each point increase in TBS. At survival analysis, when TBS ≥ 8 was connected with MELD ≥ 15 and alpha-fetoprotein ≥ 1000 ng/mL, patients presenting all these three risk factors presented the worst results (p value < 0.0001). Conclusions: Survival prediction of HCC patients was very well done using TBS model, even stratifying the population in relation to the presence of metastases and/or vascular invasion. TBS model was the best in terms of discriminatory ability and goodness of fit when compared with other continuous or binary variables. Its incorporation in a model composed by tumor- and liver function-related variables further increases its survival prediction.

Published
2018

32. Restaging Patients With Hepatocellular Carcinoma Before Additional Treatment Decisions: A Multicenter Cohort Study

Author

Vitale, A, Farinati, F, Noaro, G, Burra, P, Pawlik, Tm, Bucci, L, Giannini, Eg, Faggiano, C, Ciccarese, F, Rapaccini, Gl, Di Marco, M, Caturelli, E, Zoli, M, Borzio, F, Sacco, R, Cabibbo, G, Virdone, R, Marra, F, Felder, M, Morisco, F, Benvegnù, L, Gasbarrini, A, Svegliati-Baroni, G, Foschi, Fg, Olivani, A, Masotto, A, Nardone, G, Colecchia, A, Fornari, F, Marignani, M, Vicari, S, Bortolini, E, Cozzolongo, R, Grasso, A, Aliberti, C, Bernardi, M, Frigo, Ac, Borzio, M, Trevisani, F, Cillo, U, CA) group, Italian Liver Cancer (ITA. LI., Vitale, Alessandro, Farinati, Fabio, Noaro, Giulia, Burra, Patrizia, Pawlik, Timothy M., Bucci, Laura, Giannini, Edoardo G., Faggiano, Chiara, Ciccarese, Francesca, Rapaccini, Gian Lodovico, Di Marco, Maria, Caturelli, Eugenio, Zoli, Marco, Borzio, Franco, Sacco, Rodolfo, Cabibbo, Giuseppe, Virdone, Roberto, Marra, Fabio, Felder, Martina, Morisco, Filomena, Benvegnù, Luisa, Gasbarrini, Antonio, Svegliati-Baroni, Gianluca, Foschi, Francesco Giuseppe, Olivani, Andrea, Masotto, Alberto, Nardone, Gerardo, Colecchia, Antonio, Fornari, Fabio, Marignani, Massimo, Vicari, Susanna, Bortolini, Emanuela, Cozzolongo, Raffaele, Grasso, Alessandro, Aliberti, Camillo, Bernardi, Mauro, Frigo, Anna Chiara, Borzio, Mauro, Trevisani, Franco, and Cillo, Umberto

Subjects
Male, Oncology, Databases, Factual, Liver cancer, non surgical therapy, prognostic system, surgical therapy, survival, hepatocellular carcinoma, stage, treatment, Kaplan-Meier Estimate, Cohort Studies, Liver disease, 0302 clinical medicine, Middle Aged, Sorafenib, Prognosis, Italy, 030220 oncology & carcinogenesis, Catheter Ablation, Disease Progression, Female, 030211 gastroenterology & hepatology, medicine.drug, Cohort study, medicine.medical_specialty, Carcinoma, Hepatocellular, Settore MED/12 - GASTROENTEROLOGIA, Clinical Decision-Making, Risk Assessment, Disease-Free Survival, Statistics, Nonparametric, 03 medical and health sciences, Internal medicine, medicine, Hepatectomy, Humans, Infusions, Intra-Arterial, Neoplasm Invasiveness, Survival analysis, Aged, Neoplasm Staging, Retrospective Studies, Analysis of Variance, Hepatology, business.industry, Reproducibility of Results, Cancer, Retrospective cohort study, medicine.disease, Survival Analysis, business, Progressive disease
Abstract

Prognostic assessment of patients with hepatocellular carcinoma (HCC) at the time of diagnosis remains controversial and becomes even more complex at the time of restaging when new variables need to be considered. The aim of the current study was to evaluate the prognostic utility of restaging patients before proceeding with additional therapies for HCC. Two independent Italian prospective databases were used to identify 1,196 (training cohort) and 648 (validation cohort) consecutive patients with HCC treated over the same study period (2008-2015) who had complete restaging before decisions about additional therapies. The performance of the Italian Liver Cancer (ITA.LI.CA) prognostic score at restaging was compared with that of the Barcelona Clinic Liver Cancer, Hong Kong Liver Cancer, and Cancer of the Liver Italian Program systems. A multivariable Cox survival analysis was performed to identify baseline, restaging, or dynamic variables that were able to improve the predictive performance of the prognostic systems. At restaging, 35.3% of patients maintained stable disease; most patients were either down-staged by treatment (27.2%) or had disease progression (37.5%). The ITA.LI.CA scoring system at restaging demonstrated the best prognostic performance in both the training and validation cohorts (c-index 0.707 and 0.722, respectively) among all systems examined. On multivariable analysis, several variables improved the prognostic ability of the ITA.LI.CA score at restaging, including progressive disease after the first treatment, Model for End-Stage Liver Disease at restaging, and choice of nonsurgical treatment as additional therapy. A new ITA.LI.CA restaging model was created that demonstrated high discriminative power in both the training and validation cohorts (c-index 0.753 and 0.745, respectively). Conclusion: Although the ITA.LI.CA score demonstrated the best prognostic performance at restaging, other variables should be considered to improve the prognostic assessment of patients at the time of deciding additional therapies for HCC.

Published
2018

34. Together alone: organizing integrated, patient-centered primary care in the layered institutional context of Dutch healthcare governance

Author

Felder, M. (Martijn), Bovenkamp, H.M. (Hester) van de, Maaijen, M.H. (Marlies), Bont, A.A. (Antoinette) de, Felder, M. (Martijn), Bovenkamp, H.M. (Hester) van de, Maaijen, M.H. (Marlies), and Bont, A.A. (Antoinette) de

Abstract

We aim to better understand the dynamic between professionals and institutions by scrutinizing how professionals conduct institutional work in a layered institutional context. To date, institutional scholars have either studied professionals or institutions as objects of maintenance or change. Here, we suggest an alternative ‘relational’ and ‘evolutionary’ interpretation of the relation between institutions and professionals. We do so by introducing a two-dimensional analytical framework. We illustrate the relevance of this framework by analyzing a policy implementation program called ‘Primary Focus’. This program sought to improve the provision of integrated and patient-centered primary care by organizing multidisciplinary collaboration. Progress

Published
2018
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35. Shifting the limits in wheat research and breeding using a fully annotated reference genome

Author

Appels, R., Eversole, K., Feuillet, C., Keller, B., Rogers, J., Stein, N., Pozniak, C.J., Choulet, F., Distelfeld, A., Poland, J., Ronen, G., Barad, O., Baruch, K., Keeble-Gagnère, G., Mascher, M., Sharpe, A.G., Ben-Zvi, G., Josselin, A-A, Himmelbach, A., Balfourier, F., Gutierrez-Gonzalez, J., Hayden, M., Koh, C., Muehlbauer, G., Pasam, R.K., Paux, E., Rigault, P., Tibbits, J., Tiwari, V., Spannagl, M., Lang, D., Gundlach, H., Haberer, G., Mayer, K.F.X., Ormanbekova, D., Prade, V., Šimková, H., Wicker, T., Swarbreck, D., Rimbert, H., Felder, M., Guilhot, N., Kaithakottil, G., Keilwagen, J., Leroy, P., Lux, T., Twardziok, S., Venturini, L., Juhász, A., Abrouk, M., Fischer, I., Uauy, C., Borrill, P., Ramirez-Gonzalez, R.H., Arnaud, D., Chalabi, S., Chalhoub, B., Cory, A., Datla, R., Davey, M.W., Jacobs, J., Robinson, S.J., Steuernagel, B., van Ex, F., Wulff, B.B.H., Benhamed, M., Bendahmane, A., Concia, L., Latrasse, D., Alaux, M., Bartoš, J., Bellec, A., Berges, H., Doležel, J., Frenkel, Z., Gill, B., Korol, A., Letellier, T., Olsen, O-A, Singh, K., Valárik, M., van der Vossen, E., Vautrin, S., Weining, S., Fahima, T., Glikson, V., Raats, D., Číhalíková, J., Toegelová, H., Vrána, J., Sourdille, P., Darrier, B., Barabaschi, D., Cattivelli, L., Hernandez, P., Galvez, S., Budak, H., Jones, J.D.G., Witek, K., Yu, G., Small, I., Melonek, J., Zhou, R., Belova, T., Kanyuka, K., King, R., Nilsen, K., Walkowiak, S., Cuthbert, R., Knox, R., Wiebe, K., Xiang, D., Rohde, A., Gold, T., Čížková, J., Akpinar, B.A., Biyiklioglu, S., Gao, L., N’Daiye, A., Kubaláková, M., Šafář, J., Alfama, F., Adam-Blondon, A-F, Flores, R., Guerche, C., Loaec, M., Quesneville, H., Condie, J., Ens, J., Koh, C.S., Maclachlan, R., Tan, Y., Alberti, A., Aury, J-M, Barbe, V., Couloux, A., Cruaud, C., Labadie, K., Mangenot, S., Wincker, P., Kaur, G., Luo, M., Sehgal, S., Chhuneja, P., Gupta, O.P., Jindal, S., Kaur, P., Malik, P., Sharma, P., Yadav, B., Singh, N.K., Khurana, J.P., Chaudhary, C., Khurana, P., Kumar, V., Mahato, A., Mathur, S., Sevanthi, A., Sharma, N., Tomar, R.S., Holušová, K., Plíhal, O., Clark, M.D., Heavens, D., Kettleborough, G., Wright, J., Balcárková, B., Hu, Y., Salina, E., Ravin, N., Skryabin, K., Beletsky, A., Kadnikov, V., Mardanov, A., Nesterov, M., Rakitin, A., Sergeeva, E., Handa, H., Kanamori, H., Katagiri, S., Kobayashi, F., Nasuda, S., Tanaka, T., Wu, J., Cattonaro, F., Jiumeng, M., Kugler, K.G., Pfeifer, M., Sandve, S., Xun, X., Zhan, B., Batley, J., Bayer, P.E., Edwards, D., Hayashi, S., Tulpová, Z., Visendi, P., Cui, L., Du, X., Feng, K., Nie, X., Tong, W., Wang, L., Appels, R., Eversole, K., Feuillet, C., Keller, B., Rogers, J., Stein, N., Pozniak, C.J., Choulet, F., Distelfeld, A., Poland, J., Ronen, G., Barad, O., Baruch, K., Keeble-Gagnère, G., Mascher, M., Sharpe, A.G., Ben-Zvi, G., Josselin, A-A, Himmelbach, A., Balfourier, F., Gutierrez-Gonzalez, J., Hayden, M., Koh, C., Muehlbauer, G., Pasam, R.K., Paux, E., Rigault, P., Tibbits, J., Tiwari, V., Spannagl, M., Lang, D., Gundlach, H., Haberer, G., Mayer, K.F.X., Ormanbekova, D., Prade, V., Šimková, H., Wicker, T., Swarbreck, D., Rimbert, H., Felder, M., Guilhot, N., Kaithakottil, G., Keilwagen, J., Leroy, P., Lux, T., Twardziok, S., Venturini, L., Juhász, A., Abrouk, M., Fischer, I., Uauy, C., Borrill, P., Ramirez-Gonzalez, R.H., Arnaud, D., Chalabi, S., Chalhoub, B., Cory, A., Datla, R., Davey, M.W., Jacobs, J., Robinson, S.J., Steuernagel, B., van Ex, F., Wulff, B.B.H., Benhamed, M., Bendahmane, A., Concia, L., Latrasse, D., Alaux, M., Bartoš, J., Bellec, A., Berges, H., Doležel, J., Frenkel, Z., Gill, B., Korol, A., Letellier, T., Olsen, O-A, Singh, K., Valárik, M., van der Vossen, E., Vautrin, S., Weining, S., Fahima, T., Glikson, V., Raats, D., Číhalíková, J., Toegelová, H., Vrána, J., Sourdille, P., Darrier, B., Barabaschi, D., Cattivelli, L., Hernandez, P., Galvez, S., Budak, H., Jones, J.D.G., Witek, K., Yu, G., Small, I., Melonek, J., Zhou, R., Belova, T., Kanyuka, K., King, R., Nilsen, K., Walkowiak, S., Cuthbert, R., Knox, R., Wiebe, K., Xiang, D., Rohde, A., Gold, T., Čížková, J., Akpinar, B.A., Biyiklioglu, S., Gao, L., N’Daiye, A., Kubaláková, M., Šafář, J., Alfama, F., Adam-Blondon, A-F, Flores, R., Guerche, C., Loaec, M., Quesneville, H., Condie, J., Ens, J., Koh, C.S., Maclachlan, R., Tan, Y., Alberti, A., Aury, J-M, Barbe, V., Couloux, A., Cruaud, C., Labadie, K., Mangenot, S., Wincker, P., Kaur, G., Luo, M., Sehgal, S., Chhuneja, P., Gupta, O.P., Jindal, S., Kaur, P., Malik, P., Sharma, P., Yadav, B., Singh, N.K., Khurana, J.P., Chaudhary, C., Khurana, P., Kumar, V., Mahato, A., Mathur, S., Sevanthi, A., Sharma, N., Tomar, R.S., Holušová, K., Plíhal, O., Clark, M.D., Heavens, D., Kettleborough, G., Wright, J., Balcárková, B., Hu, Y., Salina, E., Ravin, N., Skryabin, K., Beletsky, A., Kadnikov, V., Mardanov, A., Nesterov, M., Rakitin, A., Sergeeva, E., Handa, H., Kanamori, H., Katagiri, S., Kobayashi, F., Nasuda, S., Tanaka, T., Wu, J., Cattonaro, F., Jiumeng, M., Kugler, K.G., Pfeifer, M., Sandve, S., Xun, X., Zhan, B., Batley, J., Bayer, P.E., Edwards, D., Hayashi, S., Tulpová, Z., Visendi, P., Cui, L., Du, X., Feng, K., Nie, X., Tong, W., and Wang, L.

Abstract

Wheat is one of the major sources of food for much of the world. However, because bread wheat's genome is a large hybrid mix of three separate subgenomes, it has been difficult to produce a high-quality reference sequence. Using recent advances in sequencing, the International Wheat Genome Sequencing Consortium presents an annotated reference genome with a detailed analysis of gene content among subgenomes and the structural organization for all the chromosomes. Examples of quantitative trait mapping and CRISPR-based genome modification show the potential for using this genome in agricultural research and breeding. Ramírez-González et al. exploited the fruits of this endeavor to identify tissue-specific biased gene expression and coexpression networks during development and exposure to stress. These resources will accelerate our understanding of the genetic basis of bread wheat.

Published
2018

36. Mapmaking and the (re)organization of professional practice

Author

Maaijen, M.H. (Marlies), Felder, M. (Martijn), Bont, A.A. (Antoinette) de, Bal, R.A. (Roland), Maaijen, M.H. (Marlies), Felder, M. (Martijn), Bont, A.A. (Antoinette) de, and Bal, R.A. (Roland)

Abstract

Combining insights from sociology and geography, we examine how professionals organize professional relations, beyond the boundaries of their profess

Published
2018
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37. Genetic Factors of the Disease Course After Sepsis: Rare Deleterious Variants Are Predictive

Author

Taudien, S. Lausser, L. Giamarellos-Bourboulis, E.J. Sponholz, C. Schöneweck, F. Felder, M. Schirra, L.-R. Schmid, F. Gogos, C. Groth, S. Petersen, B.-S. Franke, A. Lieb, W. Huse, K. Zipfel, P.F. Kurzai, O. Moepps, B. Gierschik, P. Bauer, M. Scherag, A. Kestler, H.A. Platzer, M.

Abstract

Sepsis is a life-threatening organ dysfunction caused by dysregulated host response to infection. For its clinical course, host genetic factors are important and rare genomic variants are suspected to contribute. We sequenced the exomes of 59 Greek and 15 German patients with bacterial sepsis divided into two groups with extremely different disease courses. Variant analysis was focusing on rare deleterious single nucleotide variants (SNVs). We identified significant differences in the number of rare deleterious SNVs per patient between the ethnic groups. Classification experiments based on the data of the Greek patients allowed discrimination between the disease courses with estimated sensitivity and specificity > 75%. By application of the trained model to the German patients we observed comparable discriminatory properties despite lower population-specific rare SNV load. Furthermore, rare SNVs in genes of cell signaling and innate immunity related pathways were identified as classifiers discriminating between the sepsis courses. Sepsis patients with favorable disease course after sepsis, even in the case of unfavorable preconditions, seem to be affected more often by rare deleterious SNVs in cell signaling and innate immunity related pathways, suggesting a protective role of impairments in these processes against a poor disease course. © 2016 The Authors

Published
2016

38. Genetic Factors of the Disease Course after Sepsis: A Genome-Wide Study for 28 Day Mortality

Author

Scherag, A. Schöneweck, F. Kesselmeier, M. Taudien, S. Platzer, M. Felder, M. Sponholz, C. Rautanen, A. Hill, A.V.S. Hinds, C.J. Hossain, H. Suttorp, N. Kurzai, O. Slevogt, H. Giamarellos-Bourboulis, E.J. Armaganidis, A. Trips, E. Scholz, M. Brunkhorst, F.M.

Abstract

Sepsis is the dysregulated host response to an infection which leads to life-threatening organ dysfunction that varies by host genomic factors. We conducted a genome-wide association study (GWAS) in 740 adult septic patients and focused on 28 day mortality as outcome. Variants with suggestive evidence for an association (p ≤ 10− 5) were validated in two additional GWA studies (n = 3470) and gene coding regions related to the variants were assessed in an independent exome sequencing study (n = 74). In the discovery GWAS, we identified 243 autosomal variants which clustered in 14 loci (p ≤ 10− 5). The best association signal (rs117983287; p = 8.16 × 10− 8) was observed for a missense variant located at chromosome 9q21.2 in the VPS13A gene. VPS13A was further supported by additional GWAS (p = 0.03) and sequencing data (p = 0.04). Furthermore, CRISPLD2 (p = 5.99 × 10− 6) and a region on chromosome 13q21.33 (p = 3.34 × 10− 7) were supported by both our data and external biological evidence. We found 14 loci with suggestive evidence for an association with 28 day mortality and found supportive, converging evidence for three of them in independent data sets. Elucidating the underlying biological mechanisms of VPS13A, CRISPLD2, and the chromosome 13 locus should be a focus of future research activities. © 2016 The Authors

Published
2016

40. Construction of a map-based reference genome sequence for barley, Hordeum vulgare L

Author

Beier, S., Himmelbach, A., Colmsee, C., Zhang, X-Q, Barrero, R.A., Zhang, Q., Li, L., Bayer, M., Bolser, D., Taudien, S., Groth, M., Felder, M., Hastie, A., Šimková, H., Staňková, H., Vrána, J., Chan, S., Muñoz-Amatriaín, M., Ounit, R., Wanamaker, S., Schmutzer, T., Aliyeva-Schnorr, L., Grasso, S., Tanskanen, J., Sampath, D., Heavens, D., Cao, S., Chapman, B., Dai, F., Han, Y., Li, H., Li, X., Lin, C., McCooke, J.K., Tan, C., Wang, S., Yin, S., Zhou, G., Poland, J.A., Bellgard, M.I., Houben, A., Doležel, J., Ayling, S., Lonardi, S., Langridge, P., Muehlbauer, G.J., Kersey, P., Clark, M.D., Caccamo, M., Schulman, A.H., Platzer, M., Close, T.J., Hansson, M., Zhang, G., Braumann, I., Li, C., Waugh, R., Scholz, U., Stein, N., Mascher, M., Beier, S., Himmelbach, A., Colmsee, C., Zhang, X-Q, Barrero, R.A., Zhang, Q., Li, L., Bayer, M., Bolser, D., Taudien, S., Groth, M., Felder, M., Hastie, A., Šimková, H., Staňková, H., Vrána, J., Chan, S., Muñoz-Amatriaín, M., Ounit, R., Wanamaker, S., Schmutzer, T., Aliyeva-Schnorr, L., Grasso, S., Tanskanen, J., Sampath, D., Heavens, D., Cao, S., Chapman, B., Dai, F., Han, Y., Li, H., Li, X., Lin, C., McCooke, J.K., Tan, C., Wang, S., Yin, S., Zhou, G., Poland, J.A., Bellgard, M.I., Houben, A., Doležel, J., Ayling, S., Lonardi, S., Langridge, P., Muehlbauer, G.J., Kersey, P., Clark, M.D., Caccamo, M., Schulman, A.H., Platzer, M., Close, T.J., Hansson, M., Zhang, G., Braumann, I., Li, C., Waugh, R., Scholz, U., Stein, N., and Mascher, M.

Abstract

Barley (Hordeum vulgare L.) is a cereal grass mainly used as animal fodder and raw material for the malting industry. The map-based reference genome sequence of barley cv. ‘Morex’ was constructed by the International Barley Genome Sequencing Consortium (IBSC) using hierarchical shotgun sequencing. Here, we report the experimental and computational procedures to (i) sequence and assemble more than 80,000 bacterial artificial chromosome (BAC) clones along the minimum tiling path of a genome-wide physical map, (ii) find and validate overlaps between adjacent BACs, (iii) construct 4,265 non-redundant sequence scaffolds representing clusters of overlapping BACs, and (iv) order and orient these BAC clusters along the seven barley chromosomes using positional information provided by dense genetic maps, an optical map and chromosome conformation capture sequencing (Hi-C). Integrative access to these sequence and mapping resources is provided by the barley genome explorer (BARLEX).

Published
2017

41. A chromosome conformation capture ordered sequence of the barley genome

Author

Mascher, M., Gundlach, H., Himmelbach, A., Beier, S., Twardziok, S.O., Wicker, T., Radchuk, V., Dockter, C., Hedley, P.E., Russell, J., Bayer, M., Ramsay, L., Liu, H., Haberer, G., Zhang, X-Q, Zhang, Q., Barrero, R.A., Li, L., Taudien, S., Groth, M., Felder, M., Hastie, A., Šimková, H., Staňková, H., Vrána, J., Chan, S., Muñoz-Amatriaín, M., Ounit, R., Wanamaker, S., Bolser, D., Colmsee, C., Schmutzer, T., Aliyeva-Schnorr, L., Grasso, S., Tanskanen, J., Chailyan, A., Sampath, D., Heavens, D., Clissold, L., Cao, S., Chapman, B., Dai, F., Han, Y., Li, H., Li, X., Lin, C., McCooke, J.K., Tan, C., Wang, P., Wang, S., Yin, S., Zhou, G., Poland, J.A., Bellgard, M.I., Borisjuk, L., Houben, A., Doležel, J., Ayling, S., Lonardi, S., Kersey, P., Langridge, P., Muehlbauer, G.J., Clark, M.D., Caccamo, M., Schulman, A.H., Mayer, K.F.X., Platzer, M., Close, T.J., Scholz, U., Hansson, M., Zhang, G., Braumann, I., Spannagl, M., Li, C., Waugh, R., Stein, N., Mascher, M., Gundlach, H., Himmelbach, A., Beier, S., Twardziok, S.O., Wicker, T., Radchuk, V., Dockter, C., Hedley, P.E., Russell, J., Bayer, M., Ramsay, L., Liu, H., Haberer, G., Zhang, X-Q, Zhang, Q., Barrero, R.A., Li, L., Taudien, S., Groth, M., Felder, M., Hastie, A., Šimková, H., Staňková, H., Vrána, J., Chan, S., Muñoz-Amatriaín, M., Ounit, R., Wanamaker, S., Bolser, D., Colmsee, C., Schmutzer, T., Aliyeva-Schnorr, L., Grasso, S., Tanskanen, J., Chailyan, A., Sampath, D., Heavens, D., Clissold, L., Cao, S., Chapman, B., Dai, F., Han, Y., Li, H., Li, X., Lin, C., McCooke, J.K., Tan, C., Wang, P., Wang, S., Yin, S., Zhou, G., Poland, J.A., Bellgard, M.I., Borisjuk, L., Houben, A., Doležel, J., Ayling, S., Lonardi, S., Kersey, P., Langridge, P., Muehlbauer, G.J., Clark, M.D., Caccamo, M., Schulman, A.H., Mayer, K.F.X., Platzer, M., Close, T.J., Scholz, U., Hansson, M., Zhang, G., Braumann, I., Spannagl, M., Li, C., Waugh, R., and Stein, N.

Abstract

Cereal grasses of the Triticeae tribe have been the major food source in temperate regions since the dawn of agriculture. Their large genomes are characterized by a high content of repetitive elements and large pericentromeric regions that are virtually devoid of meiotic recombination. Here we present a high-quality reference genome assembly for barley (Hordeum vulgare L.). We use chromosome conformation capture mapping to derive the linear order of sequences across the pericentromeric space and to investigate the spatial organization of chromatin in the nucleus at megabase resolution. The composition of genes and repetitive elements differs between distal and proximal regions. Gene family analyses reveal lineage-specific duplications of genes involved in the transport of nutrients to developing seeds and the mobilization of carbohydrates in grains. We demonstrate the importance of the barley reference sequence for breeding by inspecting the genomic partitioning of sequence variation in modern elite germplasm, highlighting regions vulnerable to genetic erosion.

Published
2017

42. EFFICACY AND SAFETY OF RADIATION SYNOVECTOMY WITH YTTRIUM-90: A RETROSPECTIVE LONG-TERM ANALYSIS OF 164 APPLICATIONS IN 82 PATIENTS

Author

STUCKI, G., BOZZONE, P., TREUER, E., WASSMER, P., FELDER, M., STUCKI, G., BOZZONE, P., TREUER, E., WASSMER, P., and FELDER, M.

Abstract

In this long term retrospective study of radiation synovectomy with Yttrium-90 (Y90), we evaluated the results of 164 applications in 82 patients with RA, OA with synovitis, ankylosing spondylitis and psoriatic arthritis. Radiation synovectomy with Y90 has an overall success rate of approximately 50% and is therefore an effective alternative to surgical synovectomy in chronic synovitis which fails to respond to conservative treatment. Elbow and knee responded significantly better than shoulder and ankle joints. Patients with radiological stages from 0 to 2 showed a significantly better success rate than those with stage 3 changes. In responders, repeat therapy for recurrence of symptoms or treatment of a symptomatic corresponding symmetrical joint is advisable. Repeat therapy in a previous non-responder is associated with an unacceptably high failure rate. Therefore, when a joint fails to respond after 6 months, arthroscopy should be performed to evaluate further treatment procedures. A successful result was found in only 11 of 25 joints treated with arthroscopic synovectomy followed by radiation synovectomy within 2 weeks, indicating no benefit of this combination

Published
2017

45. Years of life that could be saved from prevention of hepatocellular carcinoma

Author

Cucchetti, A, Trevisani, F., Bucci, L., Ravaioli, M., Farinati, F., Giannini, E. G., Ciccarese, F., Piscaglia, F., Rapaccini, Gian Ludovico, Di Marco, M., Caturelli, E., Zoli, M., Borzio, F., Sacco, R., Maida, M., Felder, M., Morisco, F., Gasbarrini, Antonio, Gemini, S., Foschi, F. G., Missale, G., Masotto, A., Affronti, A., Bernardi, M., Pinna, A. D., Bolondi, Luigi, Biselli, Maurizio, Caraceni, Paolo, Domenicali, Marco, Gramenzi, Annagiulia, Magalotti, Donatella, Pecorelli, Anna, Serra, Carla, Venerandi, Laura, Gazzola, Alessia, Murer, Francesca, Pozzan, Caterina, Vanin, Veronica, Del Poggio, Paolo, Olmi, Stefano, Balsamo, Claudia, Vavassori, Elena, Benvegnù, Luisa, Cappelli, Alberta, Golfieri, Rita, Mosconi, Cristina, Renzulli, Matteo, Bosco, Giulia, Roselli, Paola, Dell'Isola, Serena, Lalungo, Anna Maria, Rastrelli, Elena, Moscatelli, Alessandro, Pellegatta, Gaia, Picciotto, Antonino, Savarino, Vincenzo, Barcellona, Maria Rosa, Cammà, Calogero, Cabibbo, Giuseppe, Costantino, Andrea, Virdone, Roberto, Mega, Andrea, Rinninella, Emanuele, Mismas, Valeria, Dall'Aglio, Anna Chiara, Feletti, Valentina, Lanzi, Arianna, Cappa, Federica Mirici, Neri, Elga, Stefanini, Giuseppe Francesco, Tamberi, Stefano, Biasini, Elisabetta, Porro, Emanuela, Guarino, Maria, Baroni, Gianluca Svegliati, Schiadà, Laura, Chiaramonte, Maria, Marchetti, Fabiana, Valerio, Matteo, Rapaccini, Gian Ludovico (ORCID:0000-0002-6467-857X), Gasbarrini, Antonio (ORCID:0000-0002-7278-4823), Rinninella, Emanuele (ORCID:0000-0002-9165-2367), Cucchetti, A, Trevisani, F., Bucci, L., Ravaioli, M., Farinati, F., Giannini, E. G., Ciccarese, F., Piscaglia, F., Rapaccini, Gian Ludovico, Di Marco, M., Caturelli, E., Zoli, M., Borzio, F., Sacco, R., Maida, M., Felder, M., Morisco, F., Gasbarrini, Antonio, Gemini, S., Foschi, F. G., Missale, G., Masotto, A., Affronti, A., Bernardi, M., Pinna, A. D., Bolondi, Luigi, Biselli, Maurizio, Caraceni, Paolo, Domenicali, Marco, Gramenzi, Annagiulia, Magalotti, Donatella, Pecorelli, Anna, Serra, Carla, Venerandi, Laura, Gazzola, Alessia, Murer, Francesca, Pozzan, Caterina, Vanin, Veronica, Del Poggio, Paolo, Olmi, Stefano, Balsamo, Claudia, Vavassori, Elena, Benvegnù, Luisa, Cappelli, Alberta, Golfieri, Rita, Mosconi, Cristina, Renzulli, Matteo, Bosco, Giulia, Roselli, Paola, Dell'Isola, Serena, Lalungo, Anna Maria, Rastrelli, Elena, Moscatelli, Alessandro, Pellegatta, Gaia, Picciotto, Antonino, Savarino, Vincenzo, Barcellona, Maria Rosa, Cammà, Calogero, Cabibbo, Giuseppe, Costantino, Andrea, Virdone, Roberto, Mega, Andrea, Rinninella, Emanuele, Mismas, Valeria, Dall'Aglio, Anna Chiara, Feletti, Valentina, Lanzi, Arianna, Cappa, Federica Mirici, Neri, Elga, Stefanini, Giuseppe Francesco, Tamberi, Stefano, Biasini, Elisabetta, Porro, Emanuela, Guarino, Maria, Baroni, Gianluca Svegliati, Schiadà, Laura, Chiaramonte, Maria, Marchetti, Fabiana, Valerio, Matteo, Rapaccini, Gian Ludovico (ORCID:0000-0002-6467-857X), Gasbarrini, Antonio (ORCID:0000-0002-7278-4823), and Rinninella, Emanuele (ORCID:0000-0002-9165-2367)

Abstract

Background: Hepatocellular carcinoma (HCC) causes premature death and loss of life expectancy worldwide. Its primary and secondary prevention can result in a significant number of years of life saved. Aim: To assess how many years of life are lost after HCC diagnosis. Methods: Data from 5346 patients with first HCC diagnosis were used to estimate lifespan and number of years of life lost after tumour onset, using a semi-parametric extrapolation having as reference an age-, sex- and year-of-onset-matched population derived from national life tables. Results: Between 1986 and 2014, HCC lead to an average of 11.5 years-of-life lost for each patient. The youngest age-quartile group (18-61 years) had the highest number of years-of-life lost, representing approximately 41% of the overall benefit obtainable from prevention. Advancements in HCC management have progressively reduced the number of years-of-life lost from 12.6 years in 1986-1999, to 10.7 in 2000-2006 and 7.4 years in 2007-2014. Currently, an HCC diagnosis when a single tumour <2 cm results in 3.7 years-of-life lost while the diagnosis when a single tumour ≥2 cm or 2/3 nodules still within the Milan criteria, results in 5.0 years-of-life lost, representing the loss of only approximately 5.5% and 7.2%, respectively, of the entire lifespan from birth. Conclusions: Hepatocellular carcinoma occurrence results in the loss of a considerable number of years-of-life, especially for younger patients. In recent years, the increased possibility of effectively treating this tumour has improved life expectancy, thus reducing years-of-life lost.

Published
2016

46. Metabolic Disorders across Hepatocellular Carcinoma in Italy

Author

Morisco, F., primary, Guarino, M., additional, Valvano, R., additional, Caporaso, N., additional, Farinati, F., additional, Giannini, E.G., additional, Ciccarese, F., additional, Piscaglia, F., additional, Rapaccini, G.L., additional, Di Marco, M., additional, Caturelli, E., additional, Zoli, M., additional, Borzio, F., additional, Sacco, R., additional, Cammà, C., additional, Felder, M., additional, Gasbarrini, A., additional, Barone, G.S., additional, Foschi, F.G., additional, Missale, G., additional, Masotto, A., additional, Virdone, R., additional, and Trevisani, F., additional

Published
2016
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47. THU-078 - Metabolic Disorders across Hepatocellular Carcinoma in Italy

Author

Morisco, F., Guarino, M., Valvano, R., Caporaso, N., Farinati, F., Giannini, E.G., Ciccarese, F., Piscaglia, F., Rapaccini, G.L., Di Marco, M., Caturelli, E., Zoli, M., Borzio, F., Sacco, R., Cammà, C., Felder, M., Gasbarrini, A., Barone, G.S., Foschi, F.G., Missale, G., Masotto, A., Virdone, R., and Trevisani, F.

Published
2016
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48. Daclatasvir-based regimens in HCV cirrhosis: experience from the Italian early access program

Author

Stefano Fagiuoli, Mario Angelico, Paola Carrai, Marzia Montalbano, Marco Biolato, Teresa Santantonio, Luisa Pasulo, Luca S. Belli, Gabriella Verucchi, Gianpiero D'Offizi, Lorenzo Badia, Elena Angeli, Erica Villa, Marcello Persico, Chiara Mazzarelli, Guido Piai, Raffaella Lionetti, Giovanni Guaraldi, Vanni Borghi, Vincenza Calvaruso, Laura Milazzo, Martina Felder, Antonio Grieco, Massimo Puoti, Antonio Craxì, Alfredo Alberti, Rossella Letizia Mancusi, Calvaruso, Vincenza, Mazzarelli, Chiara, Milazzo, Laura, Badia, Lorenzo, Pasulo, Luisa, Guaraldi, Giovanni, Lionetti, Raffaella, Villa, Erica, Borghi, Vanni, Carrai, Paola, Alberti, Alfredo, Biolato, Marco, Piai, Guido, Persico, Marcello, Santantonio, Teresa, Felder, Martina, Angelico, Mario, Montalbano, Marzia, Mancusi, Rossella Letizia, Grieco, Antonio, Angeli, Elena, D'Offizi, Gianpiero, Fagiuoli, Stefano, Belli, Luca, Verucchi, Gabriella, Puoti, Massimo, Craxì, Antonio, Calvaruso V, Mazzarelli C, Milazzo L, Badia L, Pasulo L, Guaraldi G, Lionetti R, Villa E, Borghi V, Carrai P, Alberti A, Biolato M, Piai G, Persico M, Santantonio T, Felder M, Angelico M, Montalbano M, Mancusi RL, Grieco A, Angeli E, D'Offizi G, Fagiuoli S, Belli L, Verucchi G, Puoti M, Craxì A., Calvaruso, V, Mazzarelli, C, Milazzo, L, Badia, L, Pasulo, L, Guaraldi, G, Lionetti, R, Villa, E, Borghi, V, Carrai, P, Alberti, A, Biolato, M, Piai, G, Persico, M, Santantonio, T, Felder, M, Angelico, M, Montalbano, M, Mancusi, R, Grieco, A, Angeli, E, D'Offizi, G, Fagiuoli, S, Belli, L, Verucchi, G, Puoti, M, and Craxi, A

Subjects
0301 basic medicine, Simeprevir, Liver Cirrhosis, Male, Pyrrolidines, Sofosbuvir, Sustained Virologic Response, lcsh:Medicine, Settore MED/05, Gastroenterology, chemistry.chemical_compound, 0302 clinical medicine, Liver Function Tests, INFECTION, Medicine, PLUS SOFOSBUVIR, lcsh:Science, Sulfonamides, Multidisciplinary, Imidazoles, Valine, Hepatitis C, Middle Aged, Treatment Outcome, Italy, SAFETY, HCV, SUSTAINED VIROLOGICAL RESPONSE, Drug Therapy, Combination, Female, RIBAVIRIN, Settore BIO/19 - MICROBIOLOGIA GENERALE, CHRONIC HEPATITIS-C, medicine.drug, Adult, medicine.medical_specialty, Daclatasvir, Drug-Related Side Effects and Adverse Reactions, Antiviral Agents, Article, 03 medical and health sciences, Internal medicine, Humans, Aged, ADVANCED LIVER-DISEASE, business.industry, Ribavirin, VIRUS GENOTYPE 3, lcsh:R, Hepatitis C, Chronic, HCV HIV Daclatasvir, medicine.disease, Isoquinolines, EFFICACY, Regimen, 030104 developmental biology, chemistry, Asunaprevir, lcsh:Q, Liver function, Carbamates, business, 030217 neurology & neurosurgery
Abstract

We reported the efficacy and safety data for daclatasvir (DCV)-based all-oral antiviral therapy in patients treated in the Italian compassionate-use program. 275 patients were included (202 male-73.5%, mean age: 57.4 years, 62 HIV-coinfected, 94 with recurrence of hepatitis C post-OLT). Forty-nine patients (17.8%) had Child-Pugh B, Genotype(G) distribution was: G1a:72 patients (26.2%), G1b:137 (49.8%); G3:40 (14.5%) and G4:26 (9.5%). Patients received DCV with sofosbuvir(SOF) (n = 221, 129 with ribavirin(RBV) or with simeprevir (SMV) or asunaprevir (ASU) (n = 54, 19 with RBV) for up to 24 weeks. Logistic regression was used to identify baseline characteristics associated with sustained virological response at week 12 post-treatment (SVR12). Liver function changes between baseline and follow up were assessed in 228 patients. 240 patients achieved SVR12 (87.3%), post transplant and HIV co-infected patients were equally distributed among SVR and no SVR (35% vs 34.3%; p = 0.56 and 24.2% vs 11.4%, p = 0.13, respectively). SVR rate was significantly higher with the combination DCV + SOF compared with DCV + SIM or ASU (93.2% vs 63.0%, p

Published
2019
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49. The concept of therapeutic hierarchy for patients with hepatocellular carcinoma: A multicenter cohort study

Author

Antonio Colecchia, Antonio Gasbarrini, Francesco Giuseppe Foschi, Alessandro Vitale, Luisa Benvegnù, Gerardo Nardone, Gabriele Missale, Timothy M. Pawlik, Fabio Farinati, Umberto Cillo, Rodolfo Sacco, Edoardo G. Giannini, Gianluca Svegliati-Baroni, Filomena Morisco, Mauro Bernardi, Anna Chiara Frigo, Lucia Napoli, Marco Zoli, Franco Trevisani, Franco Borzio, Martina Felder, Gian Ludovico Rapaccini, Eugenio Caturelli, Maria Di Marco, Fabio Marra, Giuseppe Cabibbo, Alberto Masotto, Francesco Ciccarese, Roberto Virdone, Vitale A., Farinati F., Pawlik T.M., Frigo A.C., Giannini E.G., Napoli L., Ciccarese F., Rapaccini G.L., Di Marco M., Caturelli E., Zoli M., Borzio F., Sacco R., Cabibbo G., Virdone R., Marra F., Felder M., Morisco F., Benvegnu L., Gasbarrini A., Svegliati-Baroni G., Foschi F.G., Missale G., Masotto A., Nardone G., Colecchia A., Bernardi M., Trevisani F., Cillo U., Vitale, A., Farinati, F., Pawlik, T. M., Frigo, A. C., Giannini, E. G., Napoli, L., Ciccarese, F., Rapaccini, G. L., Di Marco, M., Caturelli, E., Zoli, M., Borzio, F., Sacco, R., Cabibbo, G., Virdone, R., Marra, F., Felder, M., Morisco, F., Benvegnu, L., Gasbarrini, A., Svegliati-Baroni, G., Foschi, F. G., Missale, G., Masotto, A., Nardone, G., Colecchia, A., Bernardi, M., Trevisani, F., and Cillo, U.

Subjects
Male, Oncology, Sorafenib, medicine.medical_specialty, Prognostic variable, Carcinoma, Hepatocellular, medicine.medical_treatment, treatment selection, Liver transplantation, hepatocellular carcinoma, prognostic variable, survival benefit, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Humans, Aged, Neoplasm Staging, Retrospective Studies, Aged, 80 and over, Hepatology, Performance status, business.industry, Liver Neoplasms, Hazard ratio, Middle Aged, medicine.disease, Confidence interval, Italy, 030220 oncology & carcinogenesis, Hepatocellular carcinoma, Female, 030211 gastroenterology & hepatology, Liver cancer, business, medicine.drug
Abstract

Background: The Italian Liver Cancer (ITA.LI.CA) prognostic system for patients with hepatocellular carcinoma (HCC) has recently been proposed and validated. We sought to explore the relationship among the ITA.LI.CA prognostic variables (ie tumour stage, functional score based on performance status and Child-Pugh score, and alpha-fetoprotein), treatment selection and survival outcome in HCC patients. Patients and Methods: We analysed 4,867 consecutive HCC patients undergoing six main treatment strategies (liver transplantation, LT; liver resection, LR; ablation, ABL; intra-arterial therapy, IAT; Sorafenib, SOR; and best supportive care, BSC) and enrolled during 2002-2015 in a multicenter Italian database. In order to control pretreatment imbalances in observed variables, a machine learning methodology was used and inverse probability of treatment weights (IPTW) was calculated. An IPTW-adjusted multivariate survival model that included ITA.LI.CA prognostic variables, treatment period and treatment strategy was then developed. The survival benefit of HCC treatments was described as a hazard ratio (95% confidence interval), using BSC as a reference value and as predicted median survival. Results: After the IPTW, the six treatment groups became well balanced for most baseline characteristics. In the IPTW-adjusted multivariate survival model, treatment strategy was found to be the strongest survival predictor, irrespective of ITA.LI.CA prognostic variables and treatment period. The survival benefit of different therapies over BSC was: LT=0.19 (0.18-0.20); RES=0.40 (0.37-0.42); ABL 0.42 (0.40-0.44); IAT=0.58 (0.55-0.61); SOR=0.92 (0.87-0.97). This multivariate model was then used to predict median survival for each therapy within each ITA.LI.CA stage. Conclusion: The concept of therapeutic hierarchy was established within each ITA.LI.CA stage.

Published
2019

50. Years of life that could be saved from prevention of hepatocellular carcinoma

Author

Andrea Costantino, Marcello Maida, Fabio Farinati, Laura Schiadà, Stefano Tamberi, Alessandro Moscatelli, Elena Rastrelli, Maria Chiaramonte, Paolo Poggio, Gianluca Svegliati Baroni, Matteo Renzulli, Fabio Piscaglia, Filomena Morisco, Paola Roselli, Roberto Virdone, Anna Maria Lalungo, Matteo Ravaioli, E.G. Giannini, Anna Chiara Dall’Aglio, Antonio Daniele Pinna, Elena Vavassori, Fabiana Marchetti, Eugenio Caturelli, Marco Domenicali, Calogero Cammà, Giulia Bosco, Carla Serra, Claudia Balsamo, Donatella Magalotti, Gian Ludovico Rapaccini, Valeria Mismas, S. Gemini, Stefano Olmi, Alberto Masotto, V. Feletti, Francesca Murer, Gaia Pellegatta, Maria Rosa Barcellona, A. Gazzola, Andrea Mega, Luigi Bolondi, Paolo Caraceni, Laura Bucci, Rita Golfieri, Annagiulia Gramenzi, Francesca Ciccarese, Rodolfo Sacco, Cristina Mosconi, Franco Borzio, Emanuele Rinninella, M. Di Marco, Alberta Cappelli, Marco Zoli, V. Vanin, Luisa Benvegnù, Mauro Bernardi, Emanuela Porro, Matteo Valerio, A. Pecorelli, Antonino Picciotto, Federica Mirici Cappa, Martina Felder, Elisabetta Biasini, Antonio Gasbarrini, Maurizio Biselli, Alessandro Cucchetti, Gabriele Missale, L. Venerandi, Serena Dell'Isola, Franco Trevisani, Elga Neri, Vincenzo Savarino, Maria Guarino, C. Pozzan, Giuseppe Cabibbo, F.G. Foschi, Giuseppe Francesco Stefanini, Arianna Lanzi, Andrea Affronti, Cucchetti, A, Trevisani, F, Bucci, L, Ravaioli, M, Farinati, F, Giannini, E. G, Ciccarese, F, Piscaglia, F, Rapaccini, G. L, Di Marco, M, Caturelli, E, Zoli, M, Borzio, F, Sacco, R, Maida, M, Felder, M, Morisco, Filomena, Gasbarrini, A, Gemini, S, Foschi, F. G, Missale, G, Masotto, A, Affronti, A, Bernardi, M, Pinna, A. D., Giannini, Eg, Rapaccini, Gl, Morisco, F, Foschi, Fg, Pinna, AD, Italian Liver Cancer (ITA.LI.CA.) Group, Bolondi, L, Biselli, M, Caraceni, P, Domenicali, M, Gramenzi, A., Cucchetti, A., Trevisani, F., Bucci, L., Ravaioli, M., Farinati, F., Giannini, E. G., Ciccarese, F., Piscaglia, F., Rapaccini, G. L., Di Marco, M., Caturelli, E., Zoli, M., Borzio, F., Sacco, R., Maida, M., Felder, M., Morisco, F., Gasbarrini, A., Gemini, S., Foschi, F. G., Missale, G., Masotto, A., Affronti, A., Bernardi, M., Bolondi, L., Biselli, M., Caraceni, P., Domenicali, M., Magalotti, D., Pecorelli, A., Serra, C., Venerandi, L., Gazzola, A., Murer, F., Pozzan, C., Vanin, V., Del Poggio, P., Olmi, S., Balsamo, C., Vavassori, E., Benvegnu, L., Cappelli, A., Golfieri, R., Mosconi, C., Renzulli, M., Bosco, G., Roselli, P., Dell'Isola, S., Lalungo, A. M., Rastrelli, E., Moscatelli, A., Pellegatta, G., Picciotto, A., Savarino, V., Barcellona, M. R., Camma, C., Cabibbo, G., Costantino, A., Virdone, R., Mega, A., Rinninella, E., Mismas, V., Dall'Aglio, A. C., Feletti, V., Lanzi, A., Cappa, F. M., Neri, E., Stefanini, G. F., Tamberi, S., Biasini, E., Porro, E., Guarino, M., Baroni, G. S., Schiada, L., Chiaramonte, M., Marchetti, F., and Valerio, M.

Subjects
Registrie, Male, Pediatrics, Databases, Factual, Hepatocellular carcinoma, 0302 clinical medicine, prevention, 80 and over, Secondary Prevention, Pharmacology (medical), Prospective Studies, Registries, Young adult, Prospective cohort study, Secondary prevention, Aged, 80 and over, education.field_of_study, Liver Neoplasms, Gastroenterology, Disease Management, Middle Aged, Primary Prevention, diagnosi, Italy, Liver Neoplasm, 030220 oncology & carcinogenesis, 030211 gastroenterology & hepatology, Female, Human, Adult, medicine.medical_specialty, Carcinoma, Hepatocellular, Adolescent, Population, life expentancy, Milan criteria, 03 medical and health sciences, Databases, Young Adult, Life Expectancy, medicine, Humans, Aged, education, Factual, Hepatology, business.industry, Carcinoma, Settore MED/09 - MEDICINA INTERNA, Hepatocellular, medicine.disease, Surgery, Prospective Studie, Years of potential life lost, Life expectancy, business
Abstract

Summary Background Hepatocellular carcinoma (HCC) causes premature death and loss of life expectancy worldwide. Its primary and secondary prevention can result in a significant number of years of life saved. Aim To assess how many years of life are lost after HCC diagnosis. Methods Data from 5346 patients with first HCC diagnosis were used to estimate lifespan and number of years of life lost after tumour onset, using a semi-parametric extrapolation having as reference an age-, sex- and year-of-onset-matched population derived from national life tables. Results Between 1986 and 2014, HCC lead to an average of 11.5 years-of-life lost for each patient. The youngest age-quartile group (18–61 years) had the highest number of years-of-life lost, representing approximately 41% of the overall benefit obtainable from prevention. Advancements in HCC management have progressively reduced the number of years-of-life lost from 12.6 years in 1986–1999, to 10.7 in 2000–2006 and 7.4 years in 2007–2014. Currently, an HCC diagnosis when a single tumour

Published
2016

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