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27 results on '"Roselli, P."'

1. Association of genetic risk and outcomes in patients with atrial fibrillation: interactions with early rhythm control in the EAST-AFNET4 trial.

Author

Kany, Shinwan, Al-Taie, Christoph, Roselli, Carolina, Borof, Katrin, Reinbold, Carla, Suling, Anna, Krause, Linda, Reissmann, Bruno, Schnabel, Renate, Zeller, Tanja, Zapf, Antonia, Wegscheider, Karl, Fabritz, Larissa, Ellinor, Patrick, Kirchhof, Paulus, and Pirruccello, James

Subjects
Atrial fibrillation, Heart failure, Polygenic risk scores, Rhythm control, Stroke, Humans, Female, Aged, Male, Atrial Fibrillation, Brain Ischemia, Stroke, Risk Factors, Heart Failure
Abstract

AIMS: The randomized Early Treatment of Atrial Fibrillation for Stroke Prevention Trial found that early rhythm control reduces cardiovascular events in patients with recently diagnosed atrial fibrillation (AF) compared with usual care. How genetic predisposition to AF and stroke interacts with early rhythm-control therapy is not known. METHODS AND RESULTS: Array genotyping and imputation for common genetic variants were performed. Polygenic risk scores (PRS) were calculated for AF (PRS-AF) and ischaemic stroke risk (PRS-stroke). The effects of PRS-AF and PRS-stroke on the primary outcome (composite of cardiovascular death, stroke, and hospitalization for acute coronary syndrome or worsening heart failure), its components, and recurrent AF were determined.A total of 1567 of the 2789 trial patients were analysed [793 randomized to early rhythm control; 774 to usual care, median age 71 years (65-75), 704 (44%) women]. Baseline characteristics were similar between randomized groups. Early rhythm control reduced the primary outcome compared with usual care [HR 0.67, 95% CI: (0.53, 0.84), P < 0.001]. The randomized intervention, early rhythm control, did not interact with PRS-AF (interaction P = 0.806) or PRS-stroke (interaction P = 0.765). PRS-AF was associated with recurrent AF [HR 1.08 (01.0, 1.16), P = 0.047]. PRS-stroke showed an association with the primary outcome [HR 1.13 (1.0, 1.27), P = 0.048], driven by more heart failure events [HR 1.23 (1.05-1.43), P = 0.010] without differences in stroke [HR 1.0 (0.75, 1.34), P = 0.973] in this well-anticoagulated cohort. In a replication analysis, PRS-stroke was associated with incident AF [HR 1.16 (1.14, 1.67), P < 0.001] and with incident heart failure in the UK Biobank [HR 1.08 (1.06, 1.10), P < 0.001]. The association with heart failure was weakened when excluding AF patients [HR 1.03 (1.01, 1.05), P = 0.001]. CONCLUSIONS: Early rhythm control is effective across the spectrum of genetic AF and stroke risk. The association between genetic stroke risk and heart failure calls for research to understand the interactions between polygenic risk and treatment. REGISTRATION: ISRCTN04708680, NCT01288352, EudraCT2010-021258-20, www.easttrial.org.

Published
2023

2. Genetic insights into resting heart rate and its role in cardiovascular disease.

Author

van de Vegte, Yordi, Eppinga, Ruben, van der Ende, M, Hagemeijer, Yanick, Mahendran, Yuvaraj, Salfati, Elias, Smith, Albert, Tan, Vanessa, Arking, Dan, Ntalla, Ioanna, Appel, Emil, Schurmann, Claudia, Brody, Jennifer, Rueedi, Rico, Polasek, Ozren, Sveinbjornsson, Gardar, Lecoeur, Cecile, Ladenvall, Claes, Zhao, Jing, Isaacs, Aaron, Wang, Lihua, Luan, Jianan, Hwang, Shih-Jen, Mononen, Nina, Auro, Kirsi, Jackson, Anne, Bielak, Lawrence, Zeng, Linyao, Shah, Nabi, Nethander, Maria, Campbell, Archie, Rankinen, Tuomo, Pechlivanis, Sonali, Qi, Lu, Zhao, Wei, Rizzi, Federica, Tanaka, Toshiko, Robino, Antonietta, Cocca, Massimiliano, Lange, Leslie, Müller-Nurasyid, Martina, Roselli, Carolina, Zhang, Weihua, Kleber, Marcus, Guo, Xiuqing, Lin, Henry, Pavani, Francesca, Galesloot, Tessel, Noordam, Raymond, Milaneschi, Yuri, Schraut, Katharina, den Hoed, Marcel, Degenhardt, Frauke, Trompet, Stella, van den Berg, Marten, Pistis, Giorgio, Tham, Yih-Chung, Weiss, Stefan, Sim, Xueling, Li, Hengtong, van der Most, Peter, Nolte, Ilja, Lyytikäinen, Leo-Pekka, Said, M, Witte, Daniel, Iribarren, Carlos, Launer, Lenore, Ring, Susan, de Vries, Paul, Sever, Peter, Linneberg, Allan, Bottinger, Erwin, Padmanabhan, Sandosh, Psaty, Bruce, Sotoodehnia, Nona, Kolcic, Ivana, Arnar, David, Gudbjartsson, Daniel, Holm, Hilma, Balkau, Beverley, Silva, Claudia, Newton-Cheh, Christopher, Nikus, Kjell, Salo, Perttu, Mohlke, Karen, Peyser, Patricia, Schunkert, Heribert, Lorentzon, Mattias, Lahti, Jari, Rao, Dabeeru, Cornelis, Marilyn, Faul, Jessica, Smith, Jennifer, Stolarz-Skrzypek, Katarzyna, Bandinelli, Stefania, Concas, Maria, Sinagra, Gianfranco, Meitinger, Thomas, Waldenberger, Melanie, and Sinner, Moritz

Subjects
Humans, Cardiovascular Diseases, Risk Factors, Heart Rate, Genetic Predisposition to Disease, Atrial Fibrillation, Mendelian Randomization Analysis, Genome-Wide Association Study, Polymorphism, Single Nucleotide
Abstract

Resting heart rate is associated with cardiovascular diseases and mortality in observational and Mendelian randomization studies. The aims of this study are to extend the number of resting heart rate associated genetic variants and to obtain further insights in resting heart rate biology and its clinical consequences. A genome-wide meta-analysis of 100 studies in up to 835,465 individuals reveals 493 independent genetic variants in 352 loci, including 68 genetic variants outside previously identified resting heart rate associated loci. We prioritize 670 genes and in silico annotations point to their enrichment in cardiomyocytes and provide insights in their ECG signature. Two-sample Mendelian randomization analyses indicate that higher genetically predicted resting heart rate increases risk of dilated cardiomyopathy, but decreases risk of developing atrial fibrillation, ischemic stroke, and cardio-embolic stroke. We do not find evidence for a linear or non-linear genetic association between resting heart rate and all-cause mortality in contrast to our previous Mendelian randomization study. Systematic alteration of key differences between the current and previous Mendelian randomization study indicates that the most likely cause of the discrepancy between these studies arises from false positive findings in previous one-sample MR analyses caused by weak-instrument bias at lower P-value thresholds. The results extend our understanding of resting heart rate biology and give additional insights in its role in cardiovascular disease development.

Published
2023

3. Genetics of myocardial interstitial fibrosis in the human heart and association with disease.

Author

Nauffal, Victor, Di Achille, Paolo, Klarqvist, Marcus, Cunningham, Jonathan, Hill, Matthew, Pirruccello, James, Weng, Lu-Chen, Morrill, Valerie, Choi, Seung, Khurshid, Shaan, Friedman, Samuel, Nekoui, Mahan, Roselli, Carolina, Ng, Kenney, Philippakis, Anthony, Batra, Puneet, Ellinor, Patrick, and Lubitz, Steven

Subjects
Humans, Genome-Wide Association Study, Myocardium, Heart, Cardiomyopathies, Fibrosis
Abstract

Myocardial interstitial fibrosis is associated with cardiovascular disease and adverse prognosis. Here, to investigate the biological pathways that underlie fibrosis in the human heart, we developed a machine learning model to measure native myocardial T1 time, a marker of myocardial fibrosis, in 41,505 UK Biobank participants who underwent cardiac magnetic resonance imaging. Greater T1 time was associated with diabetes mellitus, renal disease, aortic stenosis, cardiomyopathy, heart failure, atrial fibrillation, conduction disease and rheumatoid arthritis. Genome-wide association analysis identified 11 independent loci associated with T1 time. The identified loci implicated genes involved in glucose transport (SLC2A12), iron homeostasis (HFE, TMPRSS6), tissue repair (ADAMTSL1, VEGFC), oxidative stress (SOD2), cardiac hypertrophy (MYH7B) and calcium signaling (CAMK2D). Using a transforming growth factor β1-mediated cardiac fibroblast activation assay, we found that 9 of the 11 loci consisted of genes that exhibited temporal changes in expression or open chromatin conformation supporting their biological relevance to myofibroblast cell state acquisition. By harnessing machine learning to perform large-scale quantification of myocardial interstitial fibrosis using cardiac imaging, we validate associations between cardiac fibrosis and disease, and identify new biologically relevant pathways underlying fibrosis.

Published
2023

4. Identification of differential hypothalamic DNA methylation and gene expression associated with sexual partner preferences in rams.

Author

Bhattacharya, Surajit, Amodei, Rebecka, Vilain, Eric, and Roselli, Charles

Subjects
Animals, DNA Methylation, Female, Gene Expression, Humans, Hypothalamus, Male, Sexual Behavior, Animal, Sexual Partners, Sheep, Sheep, Domestic
Abstract

The sheep is a valuable model to test whether hormone mechanisms that sexually differentiate the brain underlie the expression of sexual partner preferences because as many as 8% of rams prefer same-sex partners. Epigenetic factors such as DNA methylation act as mediators in the interaction between steroid hormones and the genome. Variations in the epigenome could be important in determining morphological or behavior differences among individuals of the same species. In this study, we explored DNA methylation differences in the hypothalamus of male oriented rams (MORs) and female oriented rams (FORs). We employed reduced representation bisulfite sequencing (RRBS) to generate a genome-wide map of DNA methylation and RNA-Seq to profile the transcriptome. We found substantial DNA methylation and gene expression differences between FORs and MORs. Although none of the differentially methylated genes yielded significant functional terms directly associated with sex development, three differentially expressed genes were identified that have been associated previously with sexual behaviors. We hypothesize that these differences are involved in the phenotypic variation in ram sexual partner preferences, whereas future studies will have to find the specific mechanisms. Our results add an intriguing new dimension to sheep behavior that should be useful for further understanding epigenetic and transcriptomic involvement.

Published
2022

5. Rare Coding Variants Associated With Electrocardiographic Intervals Identify Monogenic Arrhythmia Susceptibility Genes: A Multi-Ancestry Analysis.

Author

Choi, Seung Hoan, Jurgens, Sean J, Haggerty, Christopher M, Hall, Amelia W, Halford, Jennifer L, Morrill, Valerie N, Weng, Lu-Chen, Lagerman, Braxton, Mirshahi, Tooraj, Pettinger, Mary, Guo, Xiuqing, Lin, Henry J, Alonso, Alvaro, Soliman, Elsayed Z, Kornej, Jelena, Lin, Honghuang, Moscati, Arden, Nadkarni, Girish N, Brody, Jennifer A, Wiggins, Kerri L, Cade, Brian E, Lee, Jiwon, Austin-Tse, Christina, Blackwell, Tom, Chaffin, Mark D, Lee, Christina J-Y, Rehm, Heidi L, Roselli, Carolina, Regeneron Genetics Center, Redline, Susan, Mitchell, Braxton D, Sotoodehnia, Nona, Psaty, Bruce M, Heckbert, Susan R, Loos, Ruth JF, Vasan, Ramachandran S, Benjamin, Emelia J, Correa, Adolfo, Boerwinkle, Eric, Arking, Dan E, Rotter, Jerome I, Rich, Stephen S, Whitsel, Eric A, Perez, Marco, Kooperberg, Charles, Fornwalt, Brandon K, Lunetta, Kathryn L, Ellinor, Patrick T, Lubitz, Steven A, and NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium

Subjects
Regeneron Genetics Center, NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium, Humans, Long QT Syndrome, Death, Sudden, Cardiac, Genetic Predisposition to Disease, Electrocardiography, Heterozygote, Female, Male, Genetic Variation, Exome Sequencing, death, sudden, cardiac, epidemiology, genetics, genome, population, Clinical Research, Cardiovascular, Genetics, Heart Disease, Human Genome, Biotechnology, Aetiology, 2.1 Biological and endogenous factors, Good Health and Well Being, death, sudden, cardiac
Abstract

BackgroundAlterations in electrocardiographic (ECG) intervals are well-known markers for arrhythmia and sudden cardiac death (SCD) risk. While the genetics of arrhythmia syndromes have been studied, relations between electrocardiographic intervals and rare genetic variation at a population level are poorly understood.MethodsUsing a discovery sample of 29 000 individuals with whole-genome sequencing from Trans-Omics in Precision Medicine and replication in nearly 100 000 with whole-exome sequencing from the UK Biobank and MyCode, we examined associations between low-frequency and rare coding variants with 5 routinely measured electrocardiographic traits (RR, P-wave, PR, and QRS intervals and corrected QT interval).ResultsWe found that rare variants associated with population-based electrocardiographic intervals identify established monogenic SCD genes (KCNQ1, KCNH2, and SCN5A), a controversial monogenic SCD gene (KCNE1), and novel genes (PAM and MFGE8) involved in cardiac conduction. Loss-of-function and pathogenic SCN5A variants, carried by 0.1% of individuals, were associated with a nearly 6-fold increased odds of the first-degree atrioventricular block (P=8.4×10-5). Similar variants in KCNQ1 and KCNH2 (0.2% of individuals) were associated with a 23-fold increased odds of marked corrected QT interval prolongation (P=4×10-25), a marker of SCD risk. Incomplete penetrance of such deleterious variation was common as over 70% of carriers had normal electrocardiographic intervals.ConclusionsOur findings indicate that large-scale high-depth sequence data and electrocardiographic analysis identifies monogenic arrhythmia susceptibility genes and rare variants with large effects. Known pathogenic variation in conventional arrhythmia and SCD genes exhibited incomplete penetrance and accounted for only a small fraction of marked electrocardiographic interval prolongation.

Published
2021

6. Multi-ancestry GWAS of the electrocardiographic PR interval identifies 202 loci underlying cardiac conduction.

Author

Ntalla, Ioanna, Weng, Lu-Chen, Cartwright, James H, Hall, Amelia Weber, Sveinbjornsson, Gardar, Tucker, Nathan R, Choi, Seung Hoan, Chaffin, Mark D, Roselli, Carolina, Barnes, Michael R, Mifsud, Borbala, Warren, Helen R, Hayward, Caroline, Marten, Jonathan, Cranley, James J, Concas, Maria Pina, Gasparini, Paolo, Boutin, Thibaud, Kolcic, Ivana, Polasek, Ozren, Rudan, Igor, Araujo, Nathalia M, Lima-Costa, Maria Fernanda, Ribeiro, Antonio Luiz P, Souza, Renan P, Tarazona-Santos, Eduardo, Giedraitis, Vilmantas, Ingelsson, Erik, Mahajan, Anubha, Morris, Andrew P, Del Greco M, Fabiola, Foco, Luisa, Gögele, Martin, Hicks, Andrew A, Cook, James P, Lind, Lars, Lindgren, Cecilia M, Sundström, Johan, Nelson, Christopher P, Riaz, Muhammad B, Samani, Nilesh J, Sinagra, Gianfranco, Ulivi, Sheila, Kähönen, Mika, Mishra, Pashupati P, Mononen, Nina, Nikus, Kjell, Caulfield, Mark J, Dominiczak, Anna, Padmanabhan, Sandosh, Montasser, May E, O'Connell, Jeff R, Ryan, Kathleen, Shuldiner, Alan R, Aeschbacher, Stefanie, Conen, David, Risch, Lorenz, Thériault, Sébastien, Hutri-Kähönen, Nina, Lehtimäki, Terho, Lyytikäinen, Leo-Pekka, Raitakari, Olli T, Barnes, Catriona LK, Campbell, Harry, Joshi, Peter K, Wilson, James F, Isaacs, Aaron, Kors, Jan A, van Duijn, Cornelia M, Huang, Paul L, Gudnason, Vilmundur, Harris, Tamara B, Launer, Lenore J, Smith, Albert V, Bottinger, Erwin P, Loos, Ruth JF, Nadkarni, Girish N, Preuss, Michael H, Correa, Adolfo, Mei, Hao, Wilson, James, Meitinger, Thomas, Müller-Nurasyid, Martina, Peters, Annette, Waldenberger, Melanie, Mangino, Massimo, Spector, Timothy D, Rienstra, Michiel, van de Vegte, Yordi J, van der Harst, Pim, Verweij, Niek, Kääb, Stefan, Schramm, Katharina, Sinner, Moritz F, Strauch, Konstantin, Cutler, Michael J, Fatkin, Diane, London, Barry, Olesen, Morten, and Roden, Dan M

Subjects
Humans, Cardiovascular Diseases, Genetic Predisposition to Disease, Electrocardiography, Gene Expression, Multifactorial Inheritance, Quantitative Trait Loci, Female, Male, Arrhythmias, Cardiac, Genetic Variation, Genome-Wide Association Study, Genetic Loci, Endophenotypes, Arrhythmias, Cardiac
Abstract

The electrocardiographic PR interval reflects atrioventricular conduction, and is associated with conduction abnormalities, pacemaker implantation, atrial fibrillation (AF), and cardiovascular mortality. Here we report a multi-ancestry (N = 293,051) genome-wide association meta-analysis for the PR interval, discovering 202 loci of which 141 have not previously been reported. Variants at identified loci increase the percentage of heritability explained, from 33.5% to 62.6%. We observe enrichment for cardiac muscle developmental/contractile and cytoskeletal genes, highlighting key regulation processes for atrioventricular conduction. Additionally, 8 loci not previously reported harbor genes underlying inherited arrhythmic syndromes and/or cardiomyopathies suggesting a role for these genes in cardiovascular pathology in the general population. We show that polygenic predisposition to PR interval duration is an endophenotype for cardiovascular disease, including distal conduction disease, AF, and atrioventricular pre-excitation. These findings advance our understanding of the polygenic basis of cardiac conduction, and the genetic relationship between PR interval duration and cardiovascular disease.

Published
2020

7. Genome-wide association and Mendelian randomisation analysis provide insights into the pathogenesis of heart failure.

Author

Shah, Sonia, Henry, Albert, Roselli, Carolina, Lin, Honghuang, Sveinbjörnsson, Garðar, Fatemifar, Ghazaleh, Hedman, Åsa K, Wilk, Jemma B, Morley, Michael P, Chaffin, Mark D, Helgadottir, Anna, Verweij, Niek, Dehghan, Abbas, Almgren, Peter, Andersson, Charlotte, Aragam, Krishna G, Ärnlöv, Johan, Backman, Joshua D, Biggs, Mary L, Bloom, Heather L, Brandimarto, Jeffrey, Brown, Michael R, Buckbinder, Leonard, Carey, David J, Chasman, Daniel I, Chen, Xing, Chen, Xu, Chung, Jonathan, Chutkow, William, Cook, James P, Delgado, Graciela E, Denaxas, Spiros, Doney, Alexander S, Dörr, Marcus, Dudley, Samuel C, Dunn, Michael E, Engström, Gunnar, Esko, Tõnu, Felix, Stephan B, Finan, Chris, Ford, Ian, Ghanbari, Mohsen, Ghasemi, Sahar, Giedraitis, Vilmantas, Giulianini, Franco, Gottdiener, John S, Gross, Stefan, Guðbjartsson, Daníel F, Gutmann, Rebecca, Haggerty, Christopher M, van der Harst, Pim, Hyde, Craig L, Ingelsson, Erik, Jukema, J Wouter, Kavousi, Maryam, Khaw, Kay-Tee, Kleber, Marcus E, Køber, Lars, Koekemoer, Andrea, Langenberg, Claudia, Lind, Lars, Lindgren, Cecilia M, London, Barry, Lotta, Luca A, Lovering, Ruth C, Luan, Jian'an, Magnusson, Patrik, Mahajan, Anubha, Margulies, Kenneth B, März, Winfried, Melander, Olle, Mordi, Ify R, Morgan, Thomas, Morris, Andrew D, Morris, Andrew P, Morrison, Alanna C, Nagle, Michael W, Nelson, Christopher P, Niessner, Alexander, Niiranen, Teemu, O'Donoghue, Michelle L, Owens, Anjali T, Palmer, Colin NA, Parry, Helen M, Perola, Markus, Portilla-Fernandez, Eliana, Psaty, Bruce M, Regeneron Genetics Center, Rice, Kenneth M, Ridker, Paul M, Romaine, Simon PR, Rotter, Jerome I, Salo, Perttu, Salomaa, Veikko, van Setten, Jessica, Shalaby, Alaa A, Smelser, Diane T, Smith, Nicholas L, Stender, Steen, and Stott, David J

Subjects
Regeneron Genetics Center, Humans, Atrial Fibrillation, Cardiomyopathies, Microfilament Proteins, Adaptor Proteins, Signal Transducing, Carrier Proteins, Muscle Proteins, Risk Factors, Case-Control Studies, Ventricular Function, Left, Cyclin-Dependent Kinase Inhibitor p21, Apoptosis Regulatory Proteins, Coronary Artery Disease, Heart Failure, Genome-Wide Association Study, Mendelian Randomization Analysis, Adaptor Proteins, Signal Transducing, Ventricular Function, Left
Abstract

Heart failure (HF) is a leading cause of morbidity and mortality worldwide. A small proportion of HF cases are attributable to monogenic cardiomyopathies and existing genome-wide association studies (GWAS) have yielded only limited insights, leaving the observed heritability of HF largely unexplained. We report results from a GWAS meta-analysis of HF comprising 47,309 cases and 930,014 controls. Twelve independent variants at 11 genomic loci are associated with HF, all of which demonstrate one or more associations with coronary artery disease (CAD), atrial fibrillation, or reduced left ventricular function, suggesting shared genetic aetiology. Functional analysis of non-CAD-associated loci implicate genes involved in cardiac development (MYOZ1, SYNPO2L), protein homoeostasis (BAG3), and cellular senescence (CDKN1A). Mendelian randomisation analysis supports causal roles for several HF risk factors, and demonstrates CAD-independent effects for atrial fibrillation, body mass index, and hypertension. These findings extend our knowledge of the pathways underlying HF and may inform new therapeutic strategies.

Published
2020

8. Whole Genome Sequencing to Characterize Monogenic and Polygenic Contributions in Patients Hospitalized with Early-Onset Myocardial Infarction

Author

Khera, Amit V, Chaffin, Mark, Zekavat, Seyedeh M, Collins, Ryan L, Roselli, Carolina, Natarajan, Pradeep, Lichtman, Judith H, D'Onofrio, Gail, Mattera, Jennifer, Dreyer, Rachel, Spertus, John A, Taylor, Kent D, Psaty, Bruce M, Rich, Stephen S, Post, Wendy, Gupta, Namrata, Gabriel, Stacey, Lander, Eric, Ida Chen, Yii-Der, Talkowski, Michael E, Rotter, Jerome I, Krumholz, Harlan M, and Kathiresan, Sekar

Subjects
Biomedical and Clinical Sciences, Cardiovascular Medicine and Haematology, Health Sciences, Clinical Sciences, Sports Science and Exercise, Genetics, Clinical Research, Atherosclerosis, Human Genome, Prevention, Digestive Diseases, Heart Disease, Heart Disease - Coronary Heart Disease, Cardiovascular, 2.1 Biological and endogenous factors, Aetiology, Aged, Cholesterol, LDL, Female, Genetic Predisposition to Disease, Genome, Human, Humans, Hyperlipoproteinemia Type II, Male, Middle Aged, Multifactorial Inheritance, Myocardial Infarction, Whole Genome Sequencing, genetics, humans, hypercholesterolemia, myocardial infarction, risk, Cardiorespiratory Medicine and Haematology, Public Health and Health Services, Cardiovascular System & Hematology, Cardiovascular medicine and haematology, Clinical sciences, Sports science and exercise
Abstract

BackgroundThe relative prevalence and clinical importance of monogenic mutations related to familial hypercholesterolemia and of high polygenic score (cumulative impact of many common variants) pathways for early-onset myocardial infarction remain uncertain. Whole-genome sequencing enables simultaneous ascertainment of both monogenic mutations and polygenic score for each individual.MethodsWe performed deep-coverage whole-genome sequencing of 2081 patients from 4 racial subgroups hospitalized in the United States with early-onset myocardial infarction (age ≤55 years) recruited with a 2:1 female-to-male enrollment design. We compared these genomes with those of 3761 population-based control subjects. We first identified individuals with a rare, monogenic mutation related to familial hypercholesterolemia. Second, we calculated a recently developed polygenic score of 6.6 million common DNA variants to quantify the cumulative susceptibility conferred by common variants. We defined high polygenic score as the top 5% of the control distribution because this cutoff has previously been shown to confer similar risk to that of familial hypercholesterolemia mutations.ResultsThe mean age of the 2081 patients presenting with early-onset myocardial infarction was 48 years, and 66% were female. A familial hypercholesterolemia mutation was present in 36 of these patients (1.7%) and was associated with a 3.8-fold (95% CI, 2.1-6.8; P3-fold increased odds of early-onset myocardial infarction. However, high polygenic score has a 10-fold higher prevalence among patients presents with early-onset myocardial infarction.Clinical trial registrationURL: https://www.clinicaltrials.gov . Unique identifier: NCT00597922.

Published
2019

9. Multi-ethnic genome-wide association study for atrial fibrillation

Author

Roselli, Carolina, Chaffin, Mark D, Weng, Lu-Chen, Aeschbacher, Stefanie, Ahlberg, Gustav, Albert, Christine M, Almgren, Peter, Alonso, Alvaro, Anderson, Christopher D, Aragam, Krishna G, Arking, Dan E, Barnard, John, Bartz, Traci M, Benjamin, Emelia J, Bihlmeyer, Nathan A, Bis, Joshua C, Bloom, Heather L, Boerwinkle, Eric, Bottinger, Erwin B, Brody, Jennifer A, Calkins, Hugh, Campbell, Archie, Cappola, Thomas P, Carlquist, John, Chasman, Daniel I, Chen, Lin Y, Chen, Yii-Der Ida, Choi, Eue-Keun, Choi, Seung Hoan, Christophersen, Ingrid E, Chung, Mina K, Cole, John W, Conen, David, Cook, James, Crijns, Harry J, Cutler, Michael J, Damrauer, Scott M, Daniels, Brian R, Darbar, Dawood, Delgado, Graciela, Denny, Joshua C, Dichgans, Martin, Dörr, Marcus, Dudink, Elton A, Dudley, Samuel C, Esa, Nada, Esko, Tonu, Eskola, Markku, Fatkin, Diane, Felix, Stephan B, Ford, Ian, Franco, Oscar H, Geelhoed, Bastiaan, Grewal, Raji P, Gudnason, Vilmundur, Guo, Xiuqing, Gupta, Namrata, Gustafsson, Stefan, Gutmann, Rebecca, Hamsten, Anders, Harris, Tamara B, Hayward, Caroline, Heckbert, Susan R, Hernesniemi, Jussi, Hocking, Lynne J, Hofman, Albert, Horimoto, Andrea RVR, Huang, Jie, Huang, Paul L, Huffman, Jennifer, Ingelsson, Erik, Ipek, Esra Gucuk, Ito, Kaoru, Jimenez-Conde, Jordi, Johnson, Renee, Jukema, J Wouter, Kääb, Stefan, Kähönen, Mika, Kamatani, Yoichiro, Kane, John P, Kastrati, Adnan, Kathiresan, Sekar, Katschnig-Winter, Petra, Kavousi, Maryam, Kessler, Thorsten, Kietselaer, Bas L, Kirchhof, Paulus, Kleber, Marcus E, Knight, Stacey, Krieger, Jose E, Kubo, Michiaki, Launer, Lenore J, Laurikka, Jari, Lehtimäki, Terho, Leineweber, Kirsten, Lemaitre, Rozenn N, Li, Man, Lim, Hong Euy, Lin, Henry J, and Lin, Honghuang

Subjects
Biological Sciences, Genetics, Heart Disease, Cardiovascular, Human Genome, Biotechnology, 2.1 Biological and endogenous factors, Aetiology, Atrial Fibrillation, Case-Control Studies, Ethnicity, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Quantitative Trait Loci, Transcriptome, Medical and Health Sciences, Developmental Biology, Agricultural biotechnology, Bioinformatics and computational biology
Abstract

Atrial fibrillation (AF) affects more than 33 million individuals worldwide1 and has a complex heritability2. We conducted the largest meta-analysis of genome-wide association studies (GWAS) for AF to date, consisting of more than half a million individuals, including 65,446 with AF. In total, we identified 97 loci significantly associated with AF, including 67 that were novel in a combined-ancestry analysis, and 3 that were novel in a European-specific analysis. We sought to identify AF-associated genes at the GWAS loci by performing RNA-sequencing and expression quantitative trait locus analyses in 101 left atrial samples, the most relevant tissue for AF. We also performed transcriptome-wide analyses that identified 57 AF-associated genes, 42 of which overlap with GWAS loci. The identified loci implicate genes enriched within cardiac developmental, electrophysiological, contractile and structural pathways. These results extend our understanding of the biological pathways underlying AF and may facilitate the development of therapeutics for AF.

Published
2018

10. Discovery of novel heart rate-associated loci using the Exome Chip

Author

van den Berg, Marten E, Warren, Helen R, Cabrera, Claudia P, Verweij, Niek, Mifsud, Borbala, Haessler, Jeffrey, Bihlmeyer, Nathan A, Fu, Yi-Ping, Weiss, Stefan, Lin, Henry J, Grarup, Niels, Li-Gao, Ruifang, Pistis, Giorgio, Shah, Nabi, Brody, Jennifer A, Müller-Nurasyid, Martina, Lin, Honghuang, Mei, Hao, Smith, Albert V, Lyytikäinen, Leo-Pekka, Hall, Leanne M, van Setten, Jessica, Trompet, Stella, Prins, Bram P, Isaacs, Aaron, Radmanesh, Farid, Marten, Jonathan, Entwistle, Aiman, Kors, Jan A, Silva, Claudia T, Alonso, Alvaro, Bis, Joshua C, de Boer, Rudolf, de Haan, Hugoline G, de Mutsert, Renée, Dedoussis, George, Dominiczak, Anna F, Doney, Alex SF, Ellinor, Patrick T, Eppinga, Ruben N, Felix, Stephan B, Guo, Xiuqing, Hagemeijer, Yanick, Hansen, Torben, Harris, Tamara B, Heckbert, Susan R, Huang, Paul L, Hwang, Shih-Jen, Kähönen, Mika, Kanters, Jørgen K, Kolcic, Ivana, Launer, Lenore J, Li, Man, Yao, Jie, Linneberg, Allan, Liu, Simin, Macfarlane, Peter W, Mangino, Massimo, Morris, Andrew D, Mulas, Antonella, Murray, Alison D, Nelson, Christopher P, Orrú, Marco, Padmanabhan, Sandosh, Peters, Annette, Porteous, David J, Poulter, Neil, Psaty, Bruce M, Qi, Lihong, Raitakari, Olli T, Rivadeneira, Fernando, Roselli, Carolina, Rudan, Igor, Sattar, Naveed, Sever, Peter, Sinner, Moritz F, Soliman, Elsayed Z, Spector, Timothy D, Stanton, Alice V, Stirrups, Kathleen E, Taylor, Kent D, Tobin, Martin D, Uitterlinden, André, Vaartjes, Ilonca, Hoes, Arno W, van der Meer, Peter, Völker, Uwe, Waldenberger, Melanie, Xie, Zhijun, Zoledziewska, Magdalena, Tinker, Andrew, Polasek, Ozren, Rosand, Jonathan, Jamshidi, Yalda, van Duijn, Cornelia M, Zeggini, Eleftheria, Jukema, J Wouter, Asselbergs, Folkert W, Samani, Nilesh J, and Lehtimäki, Terho

Subjects
Biological Sciences, Genetics, Human Genome, Biotechnology, Heart Disease, Prevention, Cardiovascular, Stem Cell Research, Clinical Research, Aetiology, 2.1 Biological and endogenous factors, Adult, Alleles, Exome, Female, Gene Frequency, Genetic Loci, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotype, Heart Rate, Humans, Male, Middle Aged, Oligonucleotide Array Sequence Analysis, Polymorphism, Single Nucleotide, Risk Factors, White People, Medical and Health Sciences, Genetics & Heredity
Abstract

Resting heart rate is a heritable trait, and an increase in heart rate is associated with increased mortality risk. Genome-wide association study analyses have found loci associated with resting heart rate, at the time of our study these loci explained 0.9% of the variation. This study aims to discover new genetic loci associated with heart rate from Exome Chip meta-analyses.Heart rate was measured from either elecrtrocardiograms or pulse recordings. We meta-analysed heart rate association results from 104 452 European-ancestry individuals from 30 cohorts, genotyped using the Exome Chip. Twenty-four variants were selected for follow-up in an independent dataset (UK Biobank, N = 134 251). Conditional and gene-based testing was undertaken, and variants were investigated with bioinformatics methods.We discovered five novel heart rate loci, and one new independent low-frequency non-synonymous variant in an established heart rate locus (KIAA1755). Lead variants in four of the novel loci are non-synonymous variants in the genes C10orf71, DALDR3, TESK2 and SEC31B. The variant at SEC31B is significantly associated with SEC31B expression in heart and tibial nerve tissue. Further candidate genes were detected from long-range regulatory chromatin interactions in heart tissue (SCD, SLF2 and MAPK8). We observed significant enrichment in DNase I hypersensitive sites in fetal heart and lung. Moreover, enrichment was seen for the first time in human neuronal progenitor cells (derived from embryonic stem cells) and fetal muscle samples by including our novel variants.Our findings advance the knowledge of the genetic architecture of heart rate, and indicate new candidate genes for follow-up functional studies.

Published
2017

11. Genetic Risk Prediction of Atrial Fibrillation

Author

Lubitz, Steven A, Yin, Xiaoyan, Lin, Henry J, Kolek, Matthew, Smith, J Gustav, Trompet, Stella, Rienstra, Michiel, Rost, Natalia S, Teixeira, Pedro L, Almgren, Peter, Anderson, Christopher D, Chen, Lin Y, Engström, Gunnar, Ford, Ian, Furie, Karen L, Guo, Xiuqing, Larson, Martin G, Lunetta, Kathryn L, Macfarlane, Peter W, Psaty, Bruce M, Soliman, Elsayed Z, Sotoodehnia, Nona, Stott, David J, Taylor, Kent D, Weng, Lu-Chen, Yao, Jie, Geelhoed, Bastiaan, Verweij, Niek, Siland, Joylene E, Kathiresan, Sekar, Roselli, Carolina, Roden, Dan M, van der Harst, Pim, Darbar, Dawood, Jukema, J Wouter, Melander, Olle, Rosand, Jonathan, Rotter, Jerome I, Heckbert, Susan R, Ellinor, Patrick T, Alonso, Alvaro, and Benjamin, Emelia J

Subjects
Epidemiology, Health Sciences, Stroke, Cardiovascular, Prevention, Brain Disorders, Heart Disease, Genetics, Clinical Research, Aged, Atrial Fibrillation, Female, Humans, Incidence, Male, Middle Aged, Risk Factors, atrial fibrillation, atrial flutter, forecasting, genetic association studies, stroke, AFGen Consortium, Cardiorespiratory Medicine and Haematology, Clinical Sciences, Public Health and Health Services, Cardiovascular System & Hematology, Cardiovascular medicine and haematology, Clinical sciences, Sports science and exercise
Abstract

BackgroundAtrial fibrillation (AF) has a substantial genetic basis. Identification of individuals at greatest AF risk could minimize the incidence of cardioembolic stroke.MethodsTo determine whether genetic data can stratify risk for development of AF, we examined associations between AF genetic risk scores and incident AF in 5 prospective studies comprising 18 919 individuals of European ancestry. We examined associations between AF genetic risk scores and ischemic stroke in a separate study of 509 ischemic stroke cases (202 cardioembolic [40%]) and 3028 referents. Scores were based on 11 to 719 common variants (≥5%) associated with AF at P values ranging from

Published
2017

12. Canine Trypanosoma cruzi infection in the Bolivian Chaco

Author

Simona Gabrielli, Michele Spinicci, Fabio Macchioni, David Rojo, Valentina Totino, Patricia Rojas, Mimmo Roselli, Herlan Gamboa, Gabriella Cancrini, and Alessandro Bartoloni

Subjects
Trypanosoma cruzi, Chagas disease, Dogs, Humans, Bolivia, Infectious and parasitic diseases, RC109-216
Abstract

Abstract A cross-sectional study on Trypanosoma cruzi was carried out in 2013 to evaluate the role of dogs as possible source of infection for humans in two rural communities of the highly endemic Bolivian Chaco (Bartolo, Chuquisaca Department, n = 57 dogs; and Ivamirapinta, Santa Cruz Department, n = 48 dogs). Giemsa-stained thick and thin smears, rapid immunochromatographic test (ICT) (Chagas Quick test, Cypress Diagnostic, Belgium) and polymerase chain reaction for T. cruzi on dried blood spots were performed. All smears proved negative by microscopic examination, whereas 23/103 (22%) were positive by ICT and 5/105 (5%) blood samples contained T. cruzi DNA, evidencing the potential role of dogs in the domestic transmission of the parasite.

Published
2018
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14. Human Babesiosis, Bolivia, 2013

Author

Simona Gabrielli, Valentina Totino, Fabio Macchioni, Freddy Zuñiga, Patricia Rojas, Yuni Lara, Mimmo Roselli, Alessandro Bartoloni, and Gabriella Cancrini

Subjects
Babesia microti, humans, Bolivia, ticks, vector-borne infections, parasites, Medicine, Infectious and parasitic diseases, RC109-216
Abstract

To investigate human babesiosis in the Bolivian Chaco, in 2013 we tested blood samples from 271 healthy persons living in 2 rural communities in this region. Microscopy and PCR indicated that 3.3% of persons were positive for Babesia microti parasites (US lineage); seroprevalence was 45.7%. Appropriate screening should mitigate the risk for transfusion-associated babesiosis.

Published
2016
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15. 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

16. 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

17. Enteral versus intravenous approach for the sedation of critically ill patients: A randomized and controlled trial 11 Medical and Health Sciences 1103 Clinical Sciences

Author

Mistraletti, G., Umbrello, M., Salini, Sara, Cadringher, P., Formenti, P., Chiumello, D., Villa, C., Russo, R., Francesconi, S., Valdambrini, F., Bellani, G., Palo, A., Riccardi, F., Ferretti, E., Festa, M., Gado, A. M., Taverna, M., Pinna, C., Barbiero, A., Ferrari, P. A., Iapichino, G., Morabito, A., Langer, M., Valenza, F., Malacrida, R., Rambaldi, M., Spanu, P., Anania, S., Andrighi, E., Di Carlo, A., Martinetti, F., Barello, Serena, Noto, A., Capello, G., Sabatelli, B., Brenna, G., Astori, M., Placido, P., Gattinoni, L., Protti, A., Pagan, F., Berto, V., Roselli, P., Ronzoni, G., Beck, E., Gaiotto, M., Radrizzani, D., Ferla, L., Giudici, R., Merlini, L., Pesenti, A., La Bruna, A., Rezoagli, E., Lucchini, A., Braschi, A., Niebel, T., Selvini, M., Cortesi, S., Quaini, A., Iotti, G., Contri, E., Sacchi, A., Livigni, S., Naretto, G., Deprado, A., Venturi Degli Esposti, V., Caironi, P., Radeschi, G., Odetto, L., Ferrero, D., Cognolato, S., Penso, R., Vacchelli, R., Cardellino, S., Bosco, E., Bresciani, A., Pozzo, I., Alessio, A., Clarindo Rodrigues, V., Biase, E., Vivaldi, N., Nava, A., Ponzetta, F., Bavutti, L., Martina, P., Palacios, B., and Bergonzini, G.

Subjects
Male, Simplified Acute Physiology Score, Patient care planning, Critical Illness, Central Nervous System Depressants, Hypnotics and sedatives, Antipruritics, Middle Aged, Hydroxyzine, Melatonin, Nursing education research, Aged, Anesthesia, Deep Sedation, Enteral Nutrition, Female, Humans, Hypnotics and Sedatives, Intensive Care Units, Poisson Distribution, Single-Blind Method, Settore MED/41 - ANESTESIOLOGIA
Published
2019

18. Clinical patterns of hepatocellular carcinoma in nonalcoholic fatty liver disease: A multicenter prospective study

Author

Piscaglia, Fabio, Svegliati Baroni, Gianluca, Barchetti, Andrea, Pecorelli, Anna, Marinelli, Sara, Tiribelli, Claudio, Bellentani, Stefano, Bernardi M, Biselli M, Bernardi M, Biselli M, Caraceni P, Domenicali M, Garuti F, Gramenzi A, Lenzi B, Magalotti D, Cescon M, Ravaioli M, Del Poggio P, Olmi S, Rapaccini GL, Balsamo C, Di Nolfo MA, Vavassori E, Alberti A, Benvegnù L, Gatta A, Giacomin A, Vanin V, Pozzan C, Maddalo G, Giampalma E, Cappelli A, Golfieri R, Mosconi C, Renzulli M, Roselli P, Dell'Isola S, Ialungo AM, Risso D, Marenco S, Sammito G, Bruzzone L, Bosco G, Grieco A, Pompili M, Rinninella E, Siciliano M, Chiaramonte M, Guarino M, Cammà C, Maida M, Costantino A, Barcellona MR, Schiadà L, Gemini S, Lanzi A, Stefanini GF, Dall'Aglio AC, Cappa FM, Suzzi A, Mussetto A, Treossi O, Missale G, Porro E, Mismas V, Vivaldi C, Bolondi L, Zoli M, Granito A, Malagotti D, Tovoli F, Trevisani F, Venerandi L, Brandi G, Cucchetti A, Bugianesi E, Vanni E, Mezzabotta L, Cabibbo G, Petta S, Fracanzani A, Fargion S, Marra F, Fani B, Biasini E, Sacco R, CAPORASO, NICOLA, Colombo M, D'Ambrosio R, Crocè LS, Patti R, Giannini EG, Loria P, Lonardo A, Baldelli E, Miele L, Farinati F, Borzio M, Dionigi E, Soardo G, Caturelli E, Ciccarese F, Virdone R, Affronti A, Foschi FG, Borzio F., MORISCO, FILOMENA, Piscaglia, Fabio, Svegliati Baroni, Gianluca, Barchetti, Andrea, Pecorelli, Anna, Marinelli, Sara, Tiribelli, Claudio, Bellentani, Stefano, Bernardi M, Biselli M, Bernardi, M, Biselli, M, Caraceni, P, Domenicali, M, Garuti, F, Gramenzi, A, Lenzi, B, Magalotti, D, Cescon, M, Ravaioli, M, Del Poggio, P, Olmi, S, Rapaccini, Gl, Balsamo, C, Di Nolfo, Ma, Vavassori, E, Alberti, A, Benvegnù, L, Gatta, A, Giacomin, A, Vanin, V, Pozzan, C, Maddalo, G, Giampalma, E, Cappelli, A, Golfieri, R, Mosconi, C, Renzulli, M, Roselli, P, Dell'Isola, S, Ialungo, Am, Risso, D, Marenco, S, Sammito, G, Bruzzone, L, Bosco, G, Grieco, A, Pompili, M, Rinninella, E, Siciliano, M, Chiaramonte, M, Guarino, M, Cammà, C, Maida, M, Costantino, A, Barcellona, Mr, Schiadà, L, Gemini, S, Lanzi, A, Stefanini, Gf, Dall'Aglio, Ac, Cappa, Fm, Suzzi, A, Mussetto, A, Treossi, O, Missale, G, Porro, E, Mismas, V, Vivaldi, C, Bolondi, L, Zoli, M, Granito, A, Malagotti, D, Tovoli, F, Trevisani, F, Venerandi, L, Brandi, G, Cucchetti, A, Bugianesi, E, Vanni, E, Mezzabotta, L, Cabibbo, G, Petta, S, Fracanzani, A, Fargion, S, Marra, F, Fani, B, Biasini, E, Sacco, R, Morisco, Filomena, Caporaso, Nicola, Colombo, M, D'Ambrosio, R, Crocè, L, Patti, R, Giannini, Eg, Loria, P, Lonardo, A, Baldelli, E, Miele, L, Farinati, F, Borzio, M, Dionigi, E, Soardo, G, Caturelli, E, Ciccarese, F, Virdone, R, Affronti, A, Foschi, Fg, Borzio, F., Fabio Piscagliaxxx, Gianluca Svegliati-Baroni, Andrea Barchetti, Anna Pecorellixxx, Sara Marinellixxx, Claudio Tiribelli, and, Stefano Bellentani, on behalf of the HCC-NAFLD Italian Study Group [, Mauro Bernardi, Maurizio Biselli, Paolo Caraceni, Marco Domenicali, Francesca Garuti, Annagiulia Gramenzi, Barbara Lenzi, Donatella Magalotti, Matteo Cescon, Matteo Ravaioli, Emanuela Giampalma, Rita Golfieri, Cristina Mosconi, Luigi Bolondi, Marco Zoli, Alessandro Granito, Francesco Tovoli, Franco Trevisani, Laura Venerandi, Giovanni Brandi, Alessandro Cucchetti, ], DIPARTIMENTO DI MEDICINA SPECIALISTICA, DIAGNOSTICA E SPERIMENTALE, DIPARTIMENTO DI SCIENZE MEDICHE E CHIRURGICHE, Facolta' di MEDICINA e CHIRURGIA, AREA MIN. 06 - Scienze mediche, Da definire, Croce', Saveria, and HCC NAFLD Italian Study, Group

Subjects
Male, Cirrhosis, Survival, Chronic liver disease, Gastroenterology, 0302 clinical medicine, Non-alcoholic Fatty Liver Disease, Nonalcoholic fatty liver disease, 80 and over, Prospective Studies, Chronic, Prospective cohort study, Aged, 80 and over, Medicine (all), Liver Neoplasms, hepatocellular carcinoma, Middle Aged, Hepatitis C, Liver Neoplasm, 030220 oncology & carcinogenesis, Hepatocellular carcinoma, Competing risk analysi, 030211 gastroenterology & hepatology, Female, Non Alcoholic SteatoHepatitis=NASH, Human, medicine.medical_specialty, Aged, Carcinoma, Hepatocellular, Hepatitis C, Chronic, Humans, Hepatology, Competing risk analysis, Milan criteria, 03 medical and health sciences, Internal medicine, medicine, Survival rate, business.industry, Settore MED/09 - MEDICINA INTERNA, Carcinoma, nutritional and metabolic diseases, Hepatocellular, medicine.disease, digestive system diseases, Nonalcoholic fatty liver disease, hepatocellular carcinoma, clinical patterns, business, clinical patterns
Abstract

none 31 no Nonalcoholic fatty liver disease (NAFLD) represents the hepatic manifestation of metabolic syndrome and may evolve into hepatocellular carcinoma (HCC). Only scanty clinical information is available on HCC in NAFLD. The aim of this multicenter observational prospective study was to assess the clinical features of patients with NAFLD-related HCC (NAFLD-HCC) and to compare them to those of hepatitis C virus (HCV)-related HCC. A total of 756 patients with either NAFLD (145) or HCV-related chronic liver disease (611) were enrolled in secondary care Italian centers. Survival was modeled according to clinical parameters, lead-time bias, and propensity analysis. Compared to HCV, HCC in NAFLD patients had a larger volume, showed more often an infiltrative pattern, and was detected outside specific surveillance. Cirrhosis was present in only about 50% of NAFLD-HCC patients, in contrast to the near totality of HCV-HCC. Regardless of tumor stage, survival was significantly shorter (P = 0.017) in patients with NAFLD-HCC, 25.5 months (95% confidence interval 21.9-29.1), than in those with HCV-HCC, 33.7 months (95% confidence interval 31.9-35.4). To eliminate possible confounders, a propensity score analysis was performed, which showed no more significant difference between the two groups. Additionally, analysis of patients within Milan criteria submitted to curative treatments did not show any difference in survival between NAFLD-HCC and HCV-HCC (respectively, 38.6 versus 41.0 months, P = nonsignificant) CONCLUSIONS: NAFLD-HCC is more often detected at a later tumor stage and could arise also in the absence of cirrhosis, but after patient matching, it has a similar survival rate compared to HCV infection; a future challenge will be to identify patients with NAFLD who require more stringent surveillance in order to offer the most timely and effective treatment. Fabio Piscagliaxxx; Gianluca Svegliati-Baroni; Andrea Barchetti; Anna Pecorellixxx; Sara Marinellixxx; Claudio Tiribelli; and; Stefano Bellentani; on behalf of the HCC-NAFLD Italian Study Group [;Mauro Bernardi; Maurizio Biselli; Paolo Caraceni; Marco Domenicali; Francesca Garuti; Annagiulia Gramenzi; Barbara Lenzi; Donatella Magalotti; Matteo Cescon; Matteo Ravaioli; Emanuela Giampalma; Rita Golfieri; Cristina Mosconi; Luigi Bolondi; Marco Zoli; Alessandro Granito; Francesco Tovoli; Franco Trevisani; Laura Venerandi; Giovanni Brandi; Alessandro Cucchetti;] Fabio Piscagliaxxx; Gianluca Svegliati-Baroni; Andrea Barchetti; Anna Pecorellixxx; Sara Marinellixxx; Claudio Tiribelli; and; Stefano Bellentani; on behalf of the HCC-NAFLD Italian Study Group [;Mauro Bernardi; Maurizio Biselli; Paolo Caraceni; Marco Domenicali; Francesca Garuti; Annagiulia Gramenzi; Barbara Lenzi; Donatella Magalotti; Matteo Cescon; Matteo Ravaioli; Emanuela Giampalma; Rita Golfieri; Cristina Mosconi; Luigi Bolondi; Marco Zoli; Alessandro Granito; Francesco Tovoli; Franco Trevisani; Laura Venerandi; Giovanni Brandi; Alessandro Cucchetti;]

Published
2016

19. Estimation of lead-time bias and its impact on the outcome of surveillance for the early diagnosis of hepatocellular carcinoma

Author

Cucchetti A., Trevisani F., Pecorelli A., Erroi V., Farinati F., Ciccarese F., Rapaccini G. L., Di Marco M., Caturelli E., Giannini E. G., Zoli M., Borzio F., Cabibbo G., Felder M., Gasbarrini A., Sacco R., Foschi F. G., Missale G., Morisco F., Baroni G. S., Virdone R., Bernardi M., Pinna A. D., Bolondi L., Biselli M., Caraceni P., Garuti F., Gramenzi A., Lenzi B., Magalotti D., Piscaglia F., Serra C., Ravaioli M., Venerandi L., Del Poggio P., Olmi S., Balsamo C., Di Nolfo M. A., Vavassori E., Alberti A., Benvegnu L., Gatta A., Giacomin A., Vanin V., Pozzan C., Maddalo G., Giampalma E., Cappelli A., Golfieri R., Mosconi C., Renzulli M., Dell'Isola S., Ialungo A. M., Roselli P., Risso D., Marenco S., Sammito G., Bruzzone L., Bosco G., Grieco A., Pompili M., Rinninella E., Siciliano M., Chiaramonte M., Guarino M., Camma C., Maida M., Di Martino A., Barcellona M. R., Schiada L., Gemini S., Biasini E., Porro E., del Ricambio M., Mismas V., Vivaldi C., Cucchetti, A, Trevisani, F, Pecorelli, A, Erroi, V, Farinati, F, Ciccarese, F, Rapaccini, Gl, Di Marco, M, Caturelli, E, Giannini, Eg, Zoli, M, Borzio, F, Cabibbo, G, Felder, M, Gasbarrini, A, Sacco, R, Foschi, Fg, Missale, G, Morisco, Filomena, Baroni, G, Virdone, R, Bernardi, M, Pinna, Ad, Italian Liver Cancer, Group, Alessandro, Cucchetti, Franco, Trevisani, Anna, Pecorelli, Virginia, Erroi, Fabio, Farinati, Francesca, Ciccarese, Gian, Lodovico Rapaccini, Mariella Di, Marco, Eugenio, Caturelli, Edoardo, G. Giannini, Marco, Zoli, Franco, Borzio, Giuseppe, Cabibbo, Martina, Felder, Antonio, Gasbarrini, Rodolfo, Sacco, Francesco, Giuseppe Foschi, Gabriele, Missale, Filomena, Morisco, Gianluca, Svegliati Baroni, Roberto, Virdone, Mauro, Bernardi, Antonio D., Pinna, for the Italian Liver Cancer Group [.., Bolondi, Luigi, Maurizio, Biselli, Piscaglia, Fabio, ]., Cucchetti, A., Trevisani, F., Pecorelli, A., Erroi, V., Farinati, F., Ciccarese, F., Rapaccini, G. L., Di Marco, M., Caturelli, E., Giannini, E. G., Zoli, M., Borzio, F., Cabibbo, G., Felder, M., Gasbarrini, A., Sacco, R., Foschi, F. G., Missale, G., Morisco, F., Baroni, G. S., Virdone, R., Bernardi, M., Pinna, A. D., Bolondi, L., Biselli, M., Caraceni, P., Garuti, F., Gramenzi, A., Lenzi, B., Magalotti, D., Piscaglia, F., Serra, C., Ravaioli, M., Venerandi, L., Del Poggio, P., Olmi, S., Balsamo, C., Di Nolfo, M. A., Vavassori, E., Alberti, A., Benvegnu, L., Gatta, A., Giacomin, A., Vanin, V., Pozzan, C., Maddalo, G., Giampalma, E., Cappelli, A., Golfieri, R., Mosconi, C., Renzulli, M., Dell'Isola, S., Ialungo, A. M., Roselli, P., Risso, D., Marenco, S., Sammito, G., Bruzzone, L., Bosco, G., Grieco, A., Pompili, M., Rinninella, E., Siciliano, M., Chiaramonte, M., Guarino, M., Camma, C., Maida, M., Di Martino, A., Barcellona, M. R., Schiada, L., Gemini, S., Biasini, E., Porro, E., del Ricambio, M., Mismas, V., and Vivaldi, C.

Subjects
Male, medicine.medical_specialty, Pediatrics, Carcinoma, Hepatocellular, Time Factors, Hepatocellular carcinoma, Settore MED/12 - GASTROENTEROLOGIA, Disease, Gastroenterology, Bias, Internal medicine, Overall survival, medicine, Humans, Early Detection of Cancer, Aged, Estimation, Surveillance, Hepatology, business.industry, Liver Neoplasms, medicine.disease, digestive system diseases, Lead time bias, Cirrhosis, Female, business, Lead-time bias, Follow-Up Studies
Abstract

Lead-time is the time by which diagnosis is anticipated by screening/surveillance with respect to the symptomatic detection of a disease. Any screening program, including surveillance for hepatocellular carcinoma (HCC), is subject to lead-time bias. Data regarding lead-time for HCC are lacking. Aims of the present study were to calculate lead-time and to assess its impact on the benefit obtainable from the surveillance of cirrhotic patients. Background & Aims: Lead-time is the time by which diagnosis is anticipated by screening/surveillance with respect to the symptomatic detection of a disease. Any screening program, including surveillance for hepatocellular carcinoma (HCC), is subject to lead-time bias. Data regarding lead-time for HCC are lacking. Aims of the present study were to calculate lead-time and to assess its impact on the benefit obtainable from the surveillance of cirrhotic patients. Methods: One-thousand three-hundred and eighty Child–Pugh class A/B patients from the ITA.LI.CA database, in whom HCC was detected during semiannual surveillance (n = 850), annual surveillance (n = 234) or when patients came when symptomatic (n = 296), were selected. Lead-time was estimated by means of appropriate formulas and Monte Carlo simulation, including 1000 patients for each arm. Results: The 5-year overall survival after HCC diagnosis was 32.7% in semiannually surveilled patients, 25.2% in annually surveilled patients, and 12.2% in symptomatic patients (p

Published
2014

20. Alpha-fetoprotein has no prognostic role in small hepatocellular carcinoma identified during surveillance in compensated cirrhosis

Author

Giannini, EG, Marenco, S, Borgonovo, G, Savarino, V, Farinati, F, Del Poggio, P, Rapaccini, GL, Di Nolfo, MA, Benvegnu, L, ZOLI, MARCO, Borzio, F, Caturelli, E, Chiaramonte, M, TREVISANI, FRANCO, Italian Liver Canc ITA LI CA Grp [. . ., BERNARDI, MAURO, BISELLI, MAURIZIO, CASSINI, ROMINA, CARACENI, PAOLO, DOMENICALI, MARCO, Erroi V, FRIGERIO, MARTA, GRAMENZI, ANNAGIULIA, Lenzi B, Magalotti D, Balsamo C, Di Marco M, Vavassori E, Gilardoni L, Mattiello M, Alberti A, Gatta A, Gios M, Giacomin A, Vanin V, Pozzan C, Maddalo G, RAVAIOLI, MATTEO, CUCCHETTI, ALESSANDRO, Giampalma E, Golfieri R, MOSCONI, CRISTINA, RENZULLI, MATTEO, Ghittoni G, Roselli P, Bosco G, Giannini, EG, Marenco, S, Borgonovo, G, Savarino, V, Farinati, F, Del Poggio, P, Rapaccini, GL, Di Nolfo, MA, Benvegnu, L, Zoli, M, Borzio, F, Caturelli, E, Chiaramonte, M, Trevisani, F, Italian Liver Canc ITA LI CA Grp [.., Bernardi M, Biselli M, Cassini R, Caraceni P, Domenicali M, Erroi V, Frigerio M, Gramenzi A, Lenzi B, Magalotti D, Balsamo C, Di Marco M, Vavassori E, Gilardoni L, Mattiello M, Alberti A, Gatta A, Gios M, Giacomin A, Vanin V, Pozzan C, Maddalo G, Ravaioli M, Cucchetti A, Giampalma E, Golfieri R, Mosconi C, Renzulli M, Ghittoni G, Roselli P, Bosco G, and ].

Subjects
Liver Cirrhosis, Male, Cirrhosis, IMPACT, medicine.medical_treatment, MULTICENTER, Kaplan-Meier Estimate, Liver transplantation, Gastroenterology, RECOMMENDATIONS, Cohort Studies, Aged, 80 and over, Biopsy, Needle, Liver Neoplasms, ASSOCIATION, Middle Aged, Prognosis, LIVER-TRANSPLANTATION, Immunohistochemistry, Hepatocellular carcinoma, SURVIVAL, Female, alpha-Fetoproteins, Liver cancer, medicine.medical_specialty, Carcinoma, Hepatocellular, RESECTION, Risk Assessment, Sensitivity and Specificity, Statistics, Nonparametric, Internal medicine, Biomarkers, Tumor, medicine, Hepatectomy, Humans, Neoplasm Invasiveness, Aged, Neoplasm Staging, Retrospective Studies, Tumor marker, Hepatology, Performance status, business.industry, CLINICAL-FEATURES, medicine.disease, Survival Analysis, digestive system diseases, ADVANCED HEPATITIS-C, ROC Curve, PERCUTANEOUS ETHANOL INJECTION, Percutaneous ethanol injection, business
Abstract

Alpha-fetoprotein is a tumor marker that has been used for surveillance and diagnosis of hepatocellular carcinoma (HCC) in patients with cirrhosis. The prognostic capability of this marker in patients with HCC has not been clearly defined. In this study our aim was to evaluate the prognostic usefulness of serum alpha-fetoprotein in patients with well-compensated cirrhosis, optimal performance status, and small HCC identified during periodic surveillance ultrasound who were treated with curative intent. Among the 3,027 patients included in the Italian Liver Cancer study group database, we selected 205 Child-Pugh class A and Eastern Cooperative Group Performance Status 0 patients with cirrhosis with a single HCC ≤3 cm of diameter diagnosed during surveillance who were treated with curative intent (hepatic resection, liver transplantation, percutaneous ethanol injection, radiofrequency thermal ablation). Patients were subdivided according to alpha-fetoprotein serum levels (i.e., normal ≤20 ng/mL; mildly elevated 21-200 ng/mL; markedly elevated >200 ng/mL). Patient survival, as assessed by the Kaplan-Meier method, was not significantly different among the three alpha-fetoprotein classes (P = 0.493). The same result was obtained in the subgroup of patients with a single HCC ≤2 cm (P = 0.714). An alpha-fetoprotein serum level of 100 ng/mL identified by receiver operating characteristic curve had inadequate accuracy (area under the curve = 0.536, 95% confidence interval = 0.465-0.606) to discriminate between survivors and deceased patients. Conclusion: Alpha-fetoprotein serum levels have no prognostic meaning in well-compensated cirrhosis patients with single, small HCC treated with curative intent. (HEPATOLOGY 2012)

Published
2012

21. Cost-effectiveness of semi-annual surveillance for hepatocellular carcinoma in cirrhotic patients of the Italian Liver Cancer population

Author

CUCCHETTI, ALESSANDRO, TREVISANI, FRANCO, CESCON, MATTEO, ERCOLANI, GIORGIO, ZOLI, MARCO, PINNA, ANTONIO DANIELE, GRAMENZI, ANNAGIULIA, Farinati F., Poggio P. D., Rapaccini G., Nolfo M. A., Benvegnù L., Borzio F., Giannini E. G., Caturelli E., Chiaramonte M., BERNARDI, MAURO, Buccione D., CARACENI, PAOLO, Domenicali M., Erroi V., Fatti G., Frigerio M., Santi V., Magalotti D., Balsamo C., DI MARCO, MARIACRISTINA, Vavassori E., Gilardoni L., Mattiello M., Alberti A., Gatta A., Gios M., Cazzagon N., Giacomin A., Pozzan C., Sergio A., Vanin V., Giampalma E., Golfieri R., Mosconi C., Renzulli M., Ghittoni G., Roselli P., Bodini G., Corbo M., Savarino V., DOMENICALI, MARCO, Cucchetti A., Trevisani F., Cescon M., Ercolani G., Farinati F., Poggio P.D., Rapaccini G., Nolfo M.A., Benvegnù L., Zoli M., Borzio F., Giannini E.G., Caturelli E., Chiaramonte M., Pinna A.D., Bernardi M., Buccione D., Caraceni P., Domenicali M., Erroi V., Fatti G., Frigerio M., Gramenzi A., Santi V., Magalotti D., Balsamo C., Di Marco M., Vavassori E., Gilardoni L., Mattiello M., Alberti A., Gatta A., Gios M., Cazzagon N., Giacomin A., Pozzan C., Sergio A., Vanin V., Giampalma E., Golfieri R., Mosconi C., Renzulli M., Ghittoni G., Roselli P., Bodini G., Corbo M., and Savarino V.

Subjects
Adult, Liver Cirrhosis, Male, medicine.medical_specialty, Carcinoma, Hepatocellular, Cost effectiveness, Cost-Benefit Analysis, medicine.medical_treatment, Population, COST-EFFECTIVENESS ANALYSIS, Liver transplantation, Risk Factors, Internal medicine, SURVEILLANCE, medicine, Humans, HEPATOCELLULAR CARCINOMA, Intensive care medicine, education, Survival rate, CIRRHOSIS, Aged, Aged, 80 and over, education.field_of_study, Hepatology, Relative survival, business.industry, Incidence, Liver Neoplasms, Odds ratio, Middle Aged, Prognosis, medicine.disease, Markov Chains, Survival Rate, Italy, Population Surveillance, Female, business, Liver cancer, Incremental cost-effectiveness ratio
Abstract

BACKGROUND AND AIMS: It was recently shown that semi-annual surveillance for hepatocellular carcinoma (HCC) in cirrhotic patients provides a prognostic advantage over the annual program; however, its cost-effectiveness (CE) in the general cirrhotic population still needs to be defined. METHODS: A Markov model was built to compare CE of these two strategies, considering literature results and treatment modalities of 918 cirrhotic patients from the Italian Liver Cancer (ITA.LI.CA) database. RESULTS: Results from the Markov model suggest that, compared to annual surveillance, semi-annual surveillance leads to a gain in quality-adjusted life expectancy, in an unselected cirrhotic population, of 1.35 quality-adjusted life-months (QALMs) over 10 years since surveillance start in compensated patients, and of 0.73 QALMs in decompensated patients. Semi-annual surveillance was more cost-effective in compensated than in decompensated cirrhosis, with an incremental CE ratio (ICER) of 1997 and 3814€/QALM, respectively. In compensated cirrhosis, semi-annual surveillance was more cost-effective than the annual program when the annual HCC incidence was ≥3.2% and the relative survival gain after cancer diagnosis was ≥20% with respect to the annual program. In decompensated cirrhosis, semi-annual surveillance was cost-effective in patients amenable to liver transplantation. In both groups, CE of semi-annual surveillance improved with the increase of annual incidence and the survival benefit obtainable with HCC treatment. CONCLUSIONS: Both surveillance strategies for HCC in cirrhotic patients can be recommended, according to the individual risk profile for HCC occurrence and the expected survival gain obtainable after tumor diagnosis and therapy.

Published
2012

22. Liver transplantation for hepatocellular carcinoma in clinical practice: the lesson from a 20-year multicentre experience in Italy

Author

Farinati Fabio, Giacomin Anna, Vanin Veronica, Sergio Adriana, Burra Patrizia, Cillo Umberto, Di Nolfo Annamaria, Del Poggio Paolo, Benvegnu Luisa, Zoli Marco, Borzio Franco, Giannini Edoardo, Caturelli Eugenio, Cazzagon Nora, Rapaccini Gian Ludovico, Trevisani Franco, for the Italian Liver Cancer (ITA. LI. CA) group, Andreone P, Bernardi M, Biselli M, Caraceni P, di Micoli A, Domenicali M, Magalotti D, Cappa FM, Santi V, Zambruni A, Balsamo C, Di Marco M, Vavassori E, Gilardoni L, Mattiello M, Alberti A, Gatta A, Gios M, Molaro M, Sala M, Savarino V, Risso D, Ghittoni G, Roselli P, Grazi GL, Nardo B, Ravaioli M, Pinna AD, Giampalma E, Golfieri R, Farinati Fabio, Giacomin Anna, Vanin Veronica, Sergio Adriana, Burra Patrizia, Cillo Umberto, Di Nolfo Annamaria, Del Poggio Paolo, Benvegnu Luisa, Zoli Marco, Borzio Franco, Giannini Edoardo, Caturelli Eugenio, Cazzagon Nora, Rapaccini Gian Ludovico, Trevisani Franco, for the Italian Liver Cancer (ITA.LI.CA) group [.., Andreone P, Bernardi M, Biselli M, Caraceni P, di Micoli A, Domenicali M, Magalotti D, Cappa FM, Santi V, Zambruni A, Balsamo C, Di Marco M, Vavassori E, Gilardoni L, Mattiello M, Alberti A, Gatta A, Gios M, Molaro M, Sala M, Savarino V, Risso D, Ghittoni G, Roselli P, Grazi GL, Nardo B, Ravaioli M, Pinna AD, Giampalma E, Golfieri R, and ]

Subjects
Male, medicine.medical_specialty, Carcinoma, Hepatocellular, medicine.medical_treatment, Liver transplantation, Guideline, Gastroenterology, Internal medicine, Carcinoma, Medicine, Humans, guidelines, neoplasms, Selection (genetic algorithm), Aged, Hepatology, business.industry, General surgery, HEPATOCELLULAR CARCINOMA, LIVER TRANSPLANTATION, Guidelines, Evidence-based approach, Patient Selection, Liver Neoplasms, hepatocellular carcinoma, evidence-based approach, liver transplantation, Middle Aged, medicine.disease, Prognosis, digestive system diseases, Liver Transplantation, Neoplasm Proteins, Clinical Practice, Transplantation, Treatment Outcome, Italy, Hepatocellular carcinoma, Practice Guidelines as Topic, Female, Guideline Adherence, alpha-Fetoproteins, business, Epidemiologic Methods
Abstract

INTRODUCTION: Hepatocellular carcinoma (HCC) is an established indication for liver transplantation (LT), but the selection criteria and priority are still debated. AIMS: To ascertain the number and features of patients with HCC who undergo transplantation in a Western country, the number of patients eligible for LT according to the American Association for the Study of Liver Diseases (AASLD) guidelines, the number of patients who actually undergo transplantation and whether adherence affects survival. METHODS: This is a retrospective analysis from a multicentre Italian database of 2042 cases of HCC, recruited prospectively and consecutively. Kaplan-Meier (log rank) and Cox multivariate analysis estimated survival. RESULTS: Patients who had undergone transplantation (50, 2.5%, with no change over time) had a median survival of 133 months, significantly influenced by the number of lesions and alpha-fetoprotein levels, which were found to be independent predictors of survival on multivariate analysis. Milan criteria were fulfilled in 68%, impacting on survival, whereas 48% fulfilled AASLD guidelines, without such an impact. Two hundred and twenty-eight (11%) patients were eligible for LT according to AASLD; in this group, alpha-fetoprotein levels and Child-Pugh class were independent predictors of survival. CONCLUSION: Among patients with HCC, those undergoing LT represent a small minority; even fewer (1%) are those who undergo transplantation according to AASLD guidelines, adherence to which only marginally affects survival. Overall, LT impact on HCC patients' treatment is very limited

Published
2011

23. Hepatocellular carcinoma in patients with cryptogenic cirrhosis

Author

Edoardo Giovanni Giannini, Elisa Marabotto, Vincenzo Savarino, Maria Anna di Nolfo, Paolo Del Poggio∥, Luisa Benvegnù, Fabio Farinati, Franco Borzio, Eugenio Caturelli, Maria Chiaramonte, Italian Liver Cancer Group [. . ., Cursaro C., Di Micoli A., Frigerio M., Cappa F. M., Santi V., Zambruni A., GRAZI, GIAN LUCA, Ravaioli M., Giampalma E., Di Marco M., Vavassori E., Gilardoni L., Mattiello M., Alberti A., Gatta A., Gios M., De Giorgio M., Gianni S., Rinaldi M., Roselli P., Ghittoni G., TREVISANI, FRANCO, ZOLI, MARCO, ANDREONE, PIETRO, BERNARDI, MAURO, CARACENI, PAOLO, DOMENICALI, MARCO, GRAMENZI, ANNAGIULIA, NARDO, BRUNO, GOLFIERI, RITA, Edoardo Giovanni Giannini, Elisa Marabotto, Vincenzo Savarino, Franco Trevisani, Maria Anna di Nolfo, Paolo Del Poggio∥, Luisa Benvegnù, Fabio Farinati, Marco Zoli, Franco Borzio, Eugenio Caturelli, Maria Chiaramonte, Italian Liver Cancer (ITALICA) Group [.., Andreone P., Bernardi M., Caraceni P., Cursaro C., Di Micoli A., Domenicali M., Gramenzi A., Frigerio M., Cappa F.M., Santi V., Zambruni A., Grazi G.L., Nardo B., Ravaioli M., Giampalma E., Golfieri R., Di Marco M., Vavassori E., Gilardoni L., Mattiello M., Alberti A., Gatta A., Gios M., De Giorgio M., Gianni S., Rinaldi M., Roselli P., Ghittoni G., and ]

Subjects
Adult, Liver Cirrhosis, Male, medicine.medical_specialty, Carcinoma, Hepatocellular, HEPATOCELLULAR CARCINOMA, CRYPTOGENIC CIRRHOSIS, Hepatitis C virus, medicine.disease_cause, Gastroenterology, Internal medicine, medicine, Carcinoma, Humans, Transaminases, Aged, Hepatitis, Chronic, Hepatitis B virus, Hepatitis, Aged, 80 and over, Hepatology, business.industry, Platelet Count, Middle Aged, medicine.disease, digestive system diseases, Cryptogenic cirrhosis, Hepatocellular carcinoma, Female, Liver function, business, Liver cancer
Abstract

BACKGROUND & AIMS: Patients with cryptogenic cirrhosis (CC) can develop hepatocellular carcinoma (HCC), although the clinical characteristics of HCC in these patients have not been completely defined. We aimed to characterize the clinical features of patients diagnosed with HCC after CC during a 15-year period (1992-2006). METHODS: The clinical characteristics of 45 consecutive CC patients with HCC were analyzed, along with modality of diagnosis, tumor stage, treatment, survival, and causes of death. Data were compared with those of 426 consecutive patients with HCC and only hepatitis C virus (HCV) infection, diagnosed during the same period at the Italian Liver Cancer group centers. RESULTS: HCC patients with CC had similar impairments in liver function as patients with HCV infection (Child-Pugh class A: 53% vs 65%; P = .141). However, the HCC patients with CC had lower aminotransferase levels (P < .001) and higher platelet counts (P < .001). HCC was significantly less likely to be diagnosed during surveillance in CC patients (29% vs 64%; P < .0001). Patients with CC had a significantly greater prevalence of advanced HCC stage, according to Milano criteria (69% vs 41%; P < .0005), larger HCC size (4.9 vs 3.0 cm; P = .0001), lower amenability to any treatment (27% vs 42%; P = .036), and shorter survival times (P = .009, log-rank test) compared with HCV patients. Causes of death were similar in the 2 groups. CONCLUSIONS: Compared with HCV patients, HCC in CC patients often is diagnosed at an advanced stage, probably owing to lack of surveillance; this leads to limited treatment options and shorter survival times.

Published
2009

24. Neurological assessment with validated tools in general ICU: multicenter, randomized, before and after, pragmatic study to evaluate the effectiveness of an e-learning platform for continuous medical education

Author

Mistraletti, G, Umbrello, M, Anania, S, Andrighi, E, Di Carlo, A, Martinetti, F, Barello, S, Sabbatini, G, Formenti, P, Maraffi, T, Marrazzo, F, Palo, A, Bellani, G, Russo, R, Francesconi, S, Valdambrini, F, Cigada, M, Riccardi, F, Moja, E, Iapichino, G, Spanu, P, Cappello, G, Baglio, L, Sabatelli, B, Brenna, G, Astori, M, Villa, C, Placido, P, Gattinoni, L, Protti, A, Pagan, F, Berto, V, Sparacino, C, Roselli, P, Noé, E, Mauri, I, Poti, F, Ronzoni, G, Beck, E, Gaiotto, M, Radrizzani, D, Ferla, L, Giudici, R, Merlini, L, Pesenti, A, Rezoagli, E, La Bruna, A, Lucchini, A, Braschi, A, Niebel, T, Selvini, M, Cortesi, S, Quaini, A, Iotti, G, Contri, E, Sacchi, A, Scartezzini, A, Malagò, G, Furletti, F, Morandini, M, Mistraletti, G, Umbrello, M, Anania, S, Andrighi, E, Di Carlo, A, Martinetti, F, Barello, S, Sabbatini, G, Formenti, P, Maraffi, T, Marrazzo, F, Palo, A, Bellani, G, Russo, R, Francesconi, S, Valdambrini, F, Cigada, M, Riccardi, F, Moja, E, Iapichino, G, Spanu, P, Cappello, G, Baglio, L, Sabatelli, B, Brenna, G, Astori, M, Villa, C, Placido, P, Gattinoni, L, Protti, A, Pagan, F, Berto, V, Sparacino, C, Roselli, P, Noé, E, Mauri, I, Poti, F, Ronzoni, G, Beck, E, Gaiotto, M, Radrizzani, D, Ferla, L, Giudici, R, Merlini, L, Pesenti, A, Rezoagli, E, La Bruna, A, Lucchini, A, Braschi, A, Niebel, T, Selvini, M, Cortesi, S, Quaini, A, Iotti, G, Contri, E, Sacchi, A, Scartezzini, A, Malagò, G, Furletti, F, and Morandini, M

Subjects
Adult, Male, medicine.medical_specialty, Critical Care, Sedation, MEDLINE, Settore M-PSI/06 - PSICOLOGIA DEL LAVORO E DELLE ORGANIZZAZIONI, medical, law.invention, Education, Education, Distance, 03 medical and health sciences, Neurological assessment, 0302 clinical medicine, Randomized controlled trial, law, medicine, Humans, distance-Education, continuing-Neurophysiological monitoring-Pain-Delirium, Pain Measurement, Neurologic Examination, Medical education, 030505 public health, Distance, Critically ill, business.industry, Delirium, 030208 emergency & critical care medicine, Pain scale, Continuing, Middle Aged, Education, distance-Education, medical, continuing-Neurophysiological monitoring-Pain-Delirium, Intensive Care Units, Anesthesiology and Pain Medicine, Controlled Before-After Studies, Assessment methods, Physical therapy, Education, Medical, Continuing, Female, Clinical Competence, medicine.symptom, 0305 other medical science, business, Computer-Assisted Instruction
Abstract

BACKGROUND: International guidelines recommend systematic assessment of pain, agitation/sedation and delirium with validated scales for all ICU patients. However, these evaluations are often not done. We have created an e-learning training platform for the continuous medical education, and assessed its efficacy in increasing the use of validated tools by all medical and nursing staff of the participating ICUs during their daily practice. METHODS: Multicenter, randomized, before and after study. The eight participating centers were randomized in two groups, and received training at different times. The use of validated tools (Verbal Numeric Rating or Behavioral Pain Scale for pain; Richmond Agitation-Sedation Scale for agitation; Confusion Assessment Method for the ICU for delirium) was evaluated from clinical data recorded in medical charts during a week, with follow-up up to six months after the training. All the operators were invited to complete a questionnaire, at baseline and after the training. RESULTS : Among the 374 nurses and physicians involved, 140 (37.4%) completed at least one of the three courses. The assessment of pain (38.1 vs. 92.9%, P

25. A meta-analysis of single HCV-untreated arm of studies evaluating outcomes after curative treatments of HCV-related hepatocellular carcinoma

Author

Cabibbo, Giuseppe, Petta, Salvatore, Barbã ra, Marco, Missale, Gabriele, Virdone, Roberto, Caturelli, Eugenio, Piscaglia, Fabio, Morisco, Filomena, Colecchia, Antonio, Farinati, Fabio, Giannini, Edoardo, Trevisani, Franco, Craxã¬, Antonio, Colombo, Massimo, Cammã , Calogero, Bucci, Laura, Zoli, Marco, Garuti, Francesca, Lenzi, Barbara, Biselli, Maurizio, Caraceni, Paolo, Cucchetti, Alessandro, Gramenzi, Annagiulia, Granito, Alessandro, Magalotti, Donatella, Serra, Carla, Negrini, Giulia, Napoli, Lucia, Salvatore, Veronica, Benevento, Francesca, Benvegnã¹, Luisa, Gazzola, Alessia, Murer, Francesca, Pozzan, Caterina, Vanin, Veronica, Moscatelli, Alessandro, Pellegatta, Gaia, Picciotto, Antonino, Savarino, Vincenzo, Ciccarese, Francesca, Del Poggio, Paolo, Olmi, Stefano, de Matthaeis, Nicoletta, Balsamo, Mariella Di Marco Claudia, Vavassori, Elena, Roselli, Paola, Dell’Isola, Serena, Ialungo, Anna Maria, Rastrelli, Elena, Attardo, Simona, Rossi, Margherita, Costantino, Andrea, Affronti, Andrea, Affronti, Marco, Mascari, Marta, Felder, Martina, Mega, Andrea, Gasbarrini, Antonio, Pompili, Maurizio, Rinninella, Emanuele, Sacco, Rodolfo, Mismas, Valeria, Foschi, Francesco Giuseppe, Dall’Aglio, Anna Chiara, Feletti, Valentina, Lanzi, Arianna, Cappa, Federica Mirici, Neri, Elga, Stefanini, Giuseppe Francesco, Tamberi, Stefano, Olivani, Andrea, Biasini, Elisabetta, Nardone, Gerardo, Guarino, Maria, Svegliati-Baroni, Gialuca, Ortolani, Alessio, Masotto, Alberto, Marchetti, Fabiana, Valerio, Matteo, Marra, Fabio, Aburas, Sami, Inghilesi, Andrea L, Cappelli, Alberta, Golfieri, Rita, Mosconi, MARIA CRISTINA, Renzulli, Matteo, Coccoli, Piero, Zamparelli, Marco Sanduzzi, Benvegnu', Luisa, Cabibbo, Giuseppe, Petta, Salvatore, Barbàra, Marco, Missale, Gabriele, Virdone, Roberto, Caturelli, Eugenio, Piscaglia, Fabio, Morisco, Filomena, Colecchia, Antonio, Farinati, Fabio, Giannini, Edoardo, Trevisani, Franco, Craxì, Antonio, Colombo, Massimo, Cammà, Calogero, Nardone, GERARDO ANTONIO PIO, Cabibbo, G., Petta, S., Barbara, M., Missale, G., Virdone, R., Caturelli, E., Piscaglia, F., Morisco, F., Colecchia, A., Farinati, F., Giannini, E., Trevisani, F., Craxi, A., Colombo, M., Camma, C., Bucci, L., Zoli, M., Garuti, F., Lenzi, B., Biselli, M., Caraceni, P., Cucchetti, A., Gramenzi, A., Granito, A., Magalotti, D., Serra, C., Negrini, G., Napoli, L., Salvatore, V., Benevento, F., Benvegnu, L., Gazzola, A., Murer, F., Pozzan, C., Vanin, V., Moscatelli, A., Pellegatta, G., Picciotto, A., Savarino, V., Ciccarese, F., Del Poggio, P., Olmi, S., de Matthaeis, N., Balsamo, M. D. M. C., Vavassori, E., Roselli, P., Dell'Isola, S., Ialungo, A. M., Rastrelli, E., Attardo, S., Rossi, M., Costantino, A., Affronti, A., Affronti, M., Mascari, M., Felder, M., Mega, A., Gasbarrini, A., Pompili, M., Rinninella, E., Sacco, R., Mismas, V., Foschi, F. G., Dall'Aglio, A. C., Feletti, V., Lanzi, A., Cappa, F. M., Neri, E., Stefanini, G. F., Tamberi, S., Olivani, A., Biasini, E., Nardone, G., Guarino, M., Svegliati-Baroni, G., Ortolani, A., Masotto, A., Marchetti, F., Valerio, M., Marra, F., Aburas, S., Inghilesi, A. L., Cappelli, A., Golfieri, R., Mosconi, C., Renzulli, M., Coccoli, P., Zamparelli, M. S., Barbã ra, Marco, Craxã¬, Antonio, Cammã , Calogero, Bucci, Laura, Zoli, Marco, Garuti, Francesca, Lenzi, Barbara, Biselli, Maurizio, Caraceni, Paolo, Cucchetti, Alessandro, Gramenzi, Annagiulia, Granito, Alessandro, Magalotti, Donatella, Serra, Carla, Negrini, Giulia, Napoli, Lucia, Salvatore, Veronica, Benevento, Francesca, Benvegnã¹, Luisa, Gazzola, Alessia, Murer, Francesca, Pozzan, Caterina, Vanin, Veronica, Moscatelli, Alessandro, Pellegatta, Gaia, Picciotto, Antonino, Savarino, Vincenzo, Ciccarese, Francesca, Del Poggio, Paolo, Olmi, Stefano, de Matthaeis, Nicoletta, Balsamo, Mariella Di Marco Claudia, Vavassori, Elena, Roselli, Paola, Dellâ isola, Serena, Ialungo, Anna Maria, Rastrelli, Elena, Attardo, Simona, Rossi, Margherita, Costantino, Andrea, Affronti, Andrea, Affronti, Marco, Mascari, Marta, Felder, Martina, Mega, Andrea, Gasbarrini, Antonio, Pompili, Maurizio, Rinninella, Emanuele, Sacco, Rodolfo, Mismas, Valeria, Foschi, Francesco Giuseppe, Dallâ aglio, Anna Chiara, Feletti, Valentina, Lanzi, Arianna, Federica Mirici, Cappa, Neri, Elga, Stefanini, Giuseppe Francesco, Tamberi, Stefano, Olivani, Andrea, Biasini, Elisabetta, Nardone, Gerardo, Guarino, Maria, Svegliati-Baroni, Gialuca, Ortolani, Alessio, Masotto, Alberto, Marchetti, Fabiana, Valerio, Matteo, Marra, Fabio, Aburas, Sami, Inghilesi, Andrea L, Cappelli, Alberta, Golfieri, Rita, Mosconi, Cristina, Renzulli, Matteo, Coccoli, Piero, Zamparelli, Marco Sanduzzi, Camma', C., Benvegnã¹, L., Balsamo, M., Dell’Isola, S., Ialungo, A., Foschi, F., Dall’Aglio, A., Cappa, F., Stefanini, G., Inghilesi, A., and Zamparelli, M.

Subjects
Oncology, medicine.medical_specialty, Carcinoma, Hepatocellular, recurrence, Hepatitis C virus, medicine.medical_treatment, medicine.disease_cause, survival, law.invention, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, law, Internal medicine, medicine, Adjuvant therapy, hepatocellular carcinoma, prognosis, recurrences, Humans, Survival analysis, Hepatology, business.industry, Liver Neoplasms, medicine.disease, Hepatitis C, 030220 oncology & carcinogenesis, Meta-analysis, Hepatocellular carcinoma, 030211 gastroenterology & hepatology, Neoplasm Recurrence, Local, business, Adjuvant, prognosi
Abstract

Background & Aims: Determining risk for recurrence or survival after curative resection or ablation in patients with hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC) is important for stratifying patients according to expected outcomes in future studies of adjuvant therapy in the era of direct-acting antivirals (DAAs). The aims of this meta-analysis were to estimate the recurrence and survival probabilities of HCV-related early HCC following complete response after potentially curative treatment and to identify predictors of recurrence and survival. Methods: Studies reporting time-dependent outcomes (HCC recurrence or death) after potentially curative treatment of HCV-related early HCC were identified in MEDLINE through May 2016. Data on patient populations and outcomes were extracted from each study by three independent observers and combined using a distribution-free summary survival curve. Primary outcomes were actuarial probabilities of recurrence and survival. Results: Eleven studies met the inclusion criteria. Pooled estimates of actuarial recurrence rates were 7.4% at 6months and 47.0% at 2years. Pooled estimates of actuarial survival rates were 79.8% at 3years and 58.6% at 5years. Heterogeneity among studies was highly significant for all outcomes. By univariate meta-regression analyses, lower serum albumin, randomized controlled trial study design and follow-up were independently associated with higher recurrence risk, whereas tumour size and alpha-foetoprotein levels were associated with higher mortality. Conclusions: This meta-analysis showed that recurrence risk and survival are extremely variable in patients with successfully treated HCV-related HCC, providing a useful benchmark for indirect comparisons of the benefits of DAAs and for a correct design of randomized controlled trials in the adjuvant setting.

Published
2017

26. 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, Gian Ludovico, Di Marco, M., Caturelli, E., Zoli, M., Borzio, F., Sacco, R., Virdone, R., Marra, F., Felder, M., Morisco, F., Benvegnù, L., Gasbarrini, Antonio, 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, Delpoggio, Paolo, Olmi, Stefano, De Matthaeis, Nicoletta, Balsamo, Claudia, Vavassori, Elena, Roselli, Paola, Dell’Isola, Serena, Ialungo, Anna Maria, Rastrelli, Elena, Rini, Francesca, Costantino, Andrea, Affronti, Andrea, Affronti, Marco, Mascari, Marta, Mega, Andrea, Pompili, Maurizio, Rinninella, Emanuele, Mismas, Valeria, Dall’Aglio, 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, Zamparelli, Marco Sanduzzi, Petta, Salvatore, Cabibbo, Giuseppe, Barbara, Marco, Attardo, Simona, Bucci, Laura, Farinati, Fabio, Giannini, Edoardo G., Tovoli, Francesco, Ciccarese, Francesca, Rapaccini, Gian Lodovico, Dimarco, Maria, Caturelli, Eugenio, Zoli, Marco, Borzio, Franco, Sacco, Rodolfo, Virdone, Roberto, Marra, Fabio, Felder, Martina, Morisco, Filomena, Benvegnù, Luisa, Svegliati-Baroni, Gianluca, Foschi, Francesco Giuseppe, Olivani, Andrea, Masotto, Alberto, Nardone, Gerardo, Colecchia, Antonio, Persico, Marcello, Boccaccio, Vincenzo, Craxì, Antonio, Bruno, Savino, Trevisani, Franco, Cammà, Calogero, 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, Filomena, Benvegnù, L, Gasbarrini, A, Svegliati Baroni, G, Foschi, F. G, Olivani, A, Masotto, A, Nardone, GERARDO ANTONIO PIO, Colecchia, A, Persico, M, Boccaccio, V, Craxì, A, Bruno, S, Trevisani, F, Cammà, C., DIPARTIMENTO DI MEDICINA SPECIALISTICA, DIAGNOSTICA E SPERIMENTALE, DIPARTIMENTO DI SCIENZE MEDICHE E CHIRURGICHE, Facolta' di MEDICINA e CHIRURGIA, Da definire, AREA MIN. 06 - Scienze mediche, Petta, S., Cabibbo, G., Barbara, M., Attardo, S., Bucci, L., Farinati, F., Giannini, E., Tovoli, F., Ciccarese, F., Rapaccini, G., Di Marco, M., Caturelli, E., Zoli, M., Borzio, F., Sacco, R., Virdone, R., Marra, F., Felder, M., Morisco, F., Benvegnã¹, L., Gasbarrini, A., Svegliati-Baroni, G., Foschi, F., Olivani, A., Masotto, A., Nardone, G., Colecchia, A., Persico, M., Boccaccio, V., Craxi, A., Bruno, S., Trevisani, F., Camma', C., Biselli, M., Caraceni, P., Cucchetti, A., Domenicali, M., Piscaglia, F., Gramenzi, A., Granito, A., Magalotti, D., Serra, C., Negrini, G., Napoli, L., Salvatore, V., Benevento, F., Gazzola, A., Murer, F., Pozzan, C., Vanin, V., Moscatelli, A., Pellegatta, G., Picciotto, A., Savarino, V., Delpoggio, P., Olmi, S., Dematthaeis, N., Balsamo, C., Vavassori, E., Roselli, P., Dell’Isola, S., Ialungo, A., Rastrelli, E., Rini, F., Costantino, A., Affronti, A., Affronti, M., Mascari, M., Mega, A., Pompili, M., Rinninella, E., Mismas, V., Dall’Aglio, A., Feletti, V., Lanzi, A., Cappa, F., Neri, E., Stefanini, G., Tamberi, S., Biasini, E., Missale, G., Guarino, M., Ortolani, A., Chiaramonte, M., Marchetti, F., Valerio, M., Aburas, S., Inghilesi, A., Cappelli, A., Golfieri, R., Mosconi, C., Renzulli, M., Coccoli, P., Zamparelli, M., Giannini, E.G., Rapaccini, G.L., Benvegnù, L., Foschi, F.G., Craxì, A., Cammà, C, the Italian Liver Cancer (ITALICA) Group [, Maurizio Biselli, Paolo Caraceni, Alessandro Cucchetti, Marco Domenicali, Fabio Piscaglia, Annagiulia Gramenzi, Alessandro Granito, Donatella Magalotti, Carla Serra, Giulia Negrini, Lucia Napoli, Veronica Salvatore, Francesca Benevento, ], Giannini, E. G., Rapaccini, G. L., Benvegnu, L., Foschi, F. G., Camma, C., Dell'Isola, S., Ialungo, A. M., Dall'Aglio, A. C., Cappa, F. M., Stefanini, G. F., Inghilesi, A. L., and Zamparelli, M. S.

Subjects
Liver Cirrhosis, Male, Cirrhosis, Databases, Factual, Gastroenterology, HCV-infected cirrhotic patients, hepatocellular carcinoma, HCC, sustained viral eradication, SVR, interferon, 0302 clinical medicine, Retrospective Studie, Pharmacology (medical), Prospective Studies, Prospective cohort study, Aged, 80 and over, Liver Neoplasms, virus diseases, Hepatitis C, Middle Aged, Liver Neoplasm, 030220 oncology & carcinogenesis, Hepatocellular carcinoma, Catheter Ablation, Interferon, 030211 gastroenterology & hepatology, Female, Liver cancer, Human, Adult, medicine.medical_specialty, Carcinoma, Hepatocellular, Liver Cirrhosi, Antiviral Agents, Follow-Up Studie, 03 medical and health sciences, Internal medicine, medicine, Carcinoma, Early Hepatocellular Carcinoma, Humans, Aged, Retrospective Studies, Antiviral Agent, Hepatology, business.industry, Settore MED/09 - MEDICINA INTERNA, Retrospective cohort study, medicine.disease, digestive system diseases, Surgery, Prospective Studie, Interferons, Neoplasm Recurrence, Local, business, Follow-Up Studies
Abstract

none 48 no Background: In HCV-infected cirrhotic patients with successfully treated early hepatocellular carcinoma (HCC), the time to HCC recurrence and the effects of sustained viral eradication (SVR) by interferon (IFN)-based or IFN-free regimens on HCC recurrence remain unclear. Aim: To perform an indirect comparison of time to recurrence (TTR) in patients with successfully treated early HCC and active HCV infection with those of patients with SVR by IFN-based and by IFN-free regimens. Methods: We evaluated 443 patients with HCV-related cirrhosis and Barcelona Clinic Liver Cancer Stage A/0 HCC who had a complete radiological response after curative resection or ablation. Active HCV infection was present in 328, selected from the Italian Liver Cancer group cohort; 58 patients had SVR achieved by IFN-free regimens after HCC cure, and 57 patients had SVR achieved by IFN-based regimens after HCC cure. Individual data of patients in the last two groups were extracted from available publications. Results: TTR by Kaplan–Meier curve was significantly lower in patients with active HCV infection compared with those with SVR both by IFN-free (P = 0.02) and by IFN-based (P < 0.001) treatments. TTR was similar in patients with SVR by IFN-free or by IFN-based (P = 0.49) strategies. Conclusion: In HCV-infected, successfully treated patients with early HCC, SVR obtained by IFN-based or IFN-free regimens significantly reduce tumour recurrence without differences related to the anti-viral strategy used. 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; the Italian Liver Cancer (ITALICA) Group [ ; Maurizio Biselli; Paolo Caraceni; Alessandro Cucchetti; Marco Domenicali; Fabio Piscaglia; Annagiulia Gramenzi; Alessandro Granito; Donatella Magalotti; Carla Serra; Giulia Negrini; Lucia Napoli; Veronica Salvatore; Francesca Benevento;] 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; the Italian Liver Cancer (ITALICA) Group [ ; Maurizio Biselli; Paolo Caraceni; Alessandro Cucchetti; Marco Domenicali; Fabio Piscaglia; Annagiulia Gramenzi; Alessandro Granito; Donatella Magalotti; Carla Serra; Giulia Negrini; Lucia Napoli; Veronica Salvatore; Francesca Benevento;]

Published
2017

27. 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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