Memoria idibgi 2012 by IDIBGI

ANNUAL SCIENTIFIC REPORT 2012

INSTITUT D’INVESTIGACIÓ BIOMÈDICA DE GIRONA DR. JOSEP TRUETA

ANNUAL SCIENTIFIC REPORT 2012 IDIBGI

INDEX

PRESENTATIONS IDIBGI ORGANIZATION

FACTS AND FIGURES JOURNALS

CARDIOVASCULAR AREA CARDIOVASCULAR GENETICS GIRONA HEART REGISTRY (REGICOR)

METABOLISM AREA NUTRITION, EUMETABOLISM AND HEALTH ONTOGENY OF THE METABOLIC SYNDROME

NEUROSCIENCE AREA AGING AND HEALTH CEREBROVASCULAR PATHOLOGY MEDICAL IMAGING NEURODEGENERATION AND NEUROINFLAMMATION

ONCOLOGY AND HEMATOLOGY AREA DESCRIPTIVE EPIDEMIOLOGY, GENETICS AND CANCER PREVENTION HEMATOLOGY HEPATOBILIARY & PANCREATIC SURGERY AND ONCOLOGY MOLECULAR ONCOLOGY

GROUPS ASSOCIATED WITH THE IDIBGI

ICS INTERNAL MEDICINE MICROBIOLOGY AND INFECTIONS IN THE CRITICAL PACIENT NEPHROLOGY

UNIVERSITY OF GIRONA BIOCHEMISTRY OF CANCER BIOPHARMACEUTICAL RESEARCH COMPUTER VISION AND ROBOTICS CONTROL ENGINEERING AND INTELLIGENT SYSTEMS HEALTH AND HEALTHCARE HEALTH PSYCHOLOGY PROTEIN ENGINEERING STATISTICS AND DATA ANALYSIS STATISTICS, ECONOMETRICS AND HEALTH

ANNUAL SCIENTIFIC REPORT 2012 IDIBGI

INTRODUCTION PRESENTATION It is a pleasure for me to present the 2012 Annual Report of the IDIBGI. Here, after giving an overview of the institution as a whole and then taking a look at each of the associated research groups, we once more take up the task of compiling and publishing details of all of the scientific work that has been undertaken during the previous year. The Girona Biomedical Research Institute was established at the Dr. Josep Trueta University Hospital with the aim of being a vehicle for the research of investigators, doctors and nurses of the hospital. The incorporation of the University of Girona and the Generalitat of Catalonia has allowed the IDIBGI to grow as a centre of reference for biomedical research in Girona. The culmination of this phase has been the incorporation of the IDIBGI as a CERCA centre of the Generalitat of Catalonia. This is the story of our centre. It is a story that it is necessary to be familiar with and remember because if we know where we have come from we will be able to work actively to decide where we want to go. This path has taken us to the turning point we are at today where we have many opportunities open to us. Nobody is a stranger to the fact that the present moment is complex and that the economic situation undoubtedly makes it more difficult to do research well. However, we must not become disillusioned. It is necessary to take stock and go forward, working all together to obtain the financing we need to convert the good ideas that are generated in Girona into a reality, and we must remember that crises always go hand in hand with opportunities and new paradigms. We are entering a new more mature phase of consolidation and sustainable growth at the IDIBGI in which there will be good opportunities for us to make our mark internationally. The Strategic Plan that we have been working on sets out the blueprint to be followed over the next five years. We are committing ourselves strongly to the IDIBGI as the umbrella organisation that binds together all of the health investigators in Girona and placing our emphasis on scientific quality, the internationalisation of the institution and our research, and for the valorisation and transfer of the knowledge that we generate. Without doubt it is necessary to promote the social return of all the research that we do so that the society sees the benefits of making a commitment to research and the knowledge society. So, this is the direction that we will be working in: on making our research have a clear impact on the health of our people. Albert Barbera, PhD Director - CEO

ANNUAL SCIENTIFIC REPORT 2012 IDIBGI

INTRODUCTION

ANNUAL SCIENTIFIC REPORT 2012 IDIBGI

IDIBGI ORGANIZATION

BOARD OF TRUSTEES

EXECUTIVE BOARD

CEIC

SCIENTIFIC ADVISORY BOARD

CEEA DIRECTOR

INTERNAL SCIENTIFIC COMMITTEE

RESEARCH GROUPS

SCIENTIFIC PLATFORMS

ADMINISTRATIVE MANAGEMENT

BIOBANK

CLINICAL RESEARCH UNIT

ACCOUNTING AND FINANCE AREA

STATISTICAL & METHODOLOGICAL ASSESSMENT

SCIENTIFIC COORDINATION AREA

INTRODUCTION

ANNUAL SCIENTIFIC REPORT 2012 IDIBGI

INTRODUCTION

ANNUAL SCIENTIFIC REPORT 2012 IDIBGI

Board of Trustees

Executive Board

PRESIDENT Boi Ruíz García Minister for Health – Catalan Government

PRESIDENT Gabriel Capellà Munar Responsible for Health Research and Innovation

1ST VICE-PRESIDENT Andreu Mas-Colell Minister for Economy and Knowledge – Catalan Government

MEMBERS Josep Maria Martorell Rodon Director General of Research, Catalan Government Lluís Rovira i Pato Director of CERCA– Catalan Government Josep Maria Gomez Pallarès Manager of the University of Girona Josep Calbó Angrill Vice-Dean for Research at the University of Girona Vicenç Martínez Ibáñez Catalan Health Institute (ICS) Regional Manager for Girona Joan Profitós Tuset President IAS (Healthcare Institute) Girona Francesc Soler Rotllan ICO Regional Director for Girona

2ND VICE-PRESIDENT Anna Mª Geli de Ciurana Dean of the University of Girona MEMBERS Carles Constante Beitia Director General of Health Planning and Resources Josep Trias i Figueras Regional Delegate Gabriel Capellà Munar Responsible for Health Research and Innovation Antoni Castellà i Clavé Secretary for Universities Iolanda Font de Rubinat Director General of Research Lluís Rovira Pato Director of CERCA– Catalan Government Josep Maria Martorell Rodon Director General of Research, Catalan Government Josep Maria Gomez Pallarès Manager of the University of Girona Josep Calbó Angrill Vice-Dean for Research at the University of Girona Martí Casadesús Fa Vice-Dean for Educational Quality at the University of Girona Joan Profitós Tuset President IAS (Healthcare Institute) Girona Josep Maria Vilà Cortasa ICO Managing Director Antoni Juan Pastor Hospital Director at the Dr. Josep Trueta University Hospital of Girona Vicenç Martínez Ibáñez Catalan Health Institute (ICS) Regional Manager for Girona SECRETARY Albert Barberà Lluís Director of the IDIBGI

SECRETARY Albert Barberà Lluís Director of the IDIBGI

INTRODUCTION

Scientific Advisory Board MEMBERS Silva Arslanian Pediatric Clinical & Translational Research Center, Children’s Hospital of Pittsburgh Angelo Barbato Istituto di Ricerche Farmacologiche Mario Negri, Milan Angel Carracedo Genomic Medicine, University of Santiago de Compostela Josep Figueras European Observatory on Health Systems and Policies, World Health Organization, Brussels Carlos Kase Department of Neurology, Boston Medical Center Blanca Marin University of Navarra, Pamplona Luis Martí-Bonmatí Radiology Department of the Hospital Quirón, Valencia Mike Pringle Royal College of General Practitioners (RCGP), UK Walter A Rocca Epidemiology and Neurology Department, Health Sciences Research Department, Neurology Mayo Clinic, Rochester, Minnesota Marisol Soengas Molecular Pathology Programme, Spanish National Cancer Research Centre, Madrid Antonio Vidal-Puig Cambridge Phenomics Centre, Institute of Metabolic Science, Cambridge

ANNUAL SCIENTIFIC REPORT 2012 IDIBGI

Internal Scientific Committee PRESIDENT Albert Barberà Lluís Director of the IDIBGI MEMBERS IAS Jordi Cid Mental Health Group Leader Josep Garre Aging and Health Group Leader ICS José Manuel Fernández-Real Nutrition, eumetabolism and Health Group Leader Rafel Ramos Girona Heart Registry Group Leader Joaquín Serena Cerebrovascular Pathology Researcher Pilar Sole Coordinator of Research in Nursing of the University Hospital of Girona Montserrat Vendrell Bronchiectasis Group Leader ICO David Gallardo Haematology Group Leader Rafel Marcos-Gragera Descriptive epidemiology, genetics and cancer prevention Group Leader Begoña Martín ICO Clinical Research Unit Coordinator Javier Menéndez Molecular Oncology Group Leader IDI Salvador Pedraza Medical Imaging Group Leader UdG Ramon Brugada Cardiovascular Genetics Group Leader Dolors Juvinyà Health and Health Care Group Leader SECRETARY Guillem Pérez Sánchez Scientific Coordinator

CARDIOVASCULAR AREA

FACTS AND FIGURES

ANNUAL SCIENTIFIC REPORT 2012 IDIBGI

FACTS AND FIGURES

ANNUAL SCIENTIFIC REPORT 2012 IDIBGI

MANAGEMENT REPORT Annual Budget

5.000.000 €

2010

2011

2012

4.486.619,24 €

3.504.806,91 €

4.220.438,92 €

FACTS AND FIGURES

ANNUAL SCIENTIFIC REPORT 2012 IDIBGI

Funds sources and expenses Finantial income

4,12 %

Pharmaceutical companies

28,83 %

European funds (FP7-EU)

9,67 %

Other associations & foundations

0,76 %

La Caixa Foundation

11,85 %

Generalitat de Catalunya

8,98 % MICINN

2,12 %

Donations

2,67 % Other privat funds

3,51 % ISCIII

27,50 %

TOTAL BUDGET

4.220.438,92 € Equipment

11,67 % Collaborations with other institutions

3,62 %

Institutional Running costs

5,63 %

Administration office

10,47 %

Other Services

1,60 %

Publications & academic training

5,08 %

Research support

6,51 %

Collaborations

5,56 %

Lab consumables

16,83 %

Human Resources

33,04 %

TOTAL EXPENSES

3.819.433,73 € 15

FACTS AND FIGURES

ANNUAL SCIENTIFIC REPORT 2012 IDIBGI

SCIENTIFIC REPORT Number of articles

46,75 %

54,19 %

55,63 %

56,44 %

2009

2010

2011

2012

169

179

160

202

FACTS AND FIGURES

ANNUAL SCIENTIFIC REPORT 2012 IDIBGI

Articles by area

ONCOLOGY 2010 2009

2011

54 69 50

CARDIOVASCULAR 2010 2009

2011

2012

METABOLISM 2010 2009

2011

2012

2010

2011

2012

NEUROSCIENCES 2010 2009

2011

2012

OTHERS 2009

FACTS AND FIGURES

ANNUAL SCIENTIFIC REPORT 2012 IDIBGI

Impact Factor per article

2009 > 169

2010 > 179

2011 > 160

2012 > 202

4,60

4,64

4,16

4,51

FACTS AND FIGURES

CLINICAL IMPACT

“Guía de práctica clínica sobre la atención a las personas con esclerosis múltiple”. 2012. Lluís Ramió i Torrentà, Jordi Gich i Ana Quiles. Agència d’Informació, Avaluació i Qualitat en Salut (AIAQS), Generalitat de Catalunya. “Guidelines for the preventive treatment of ischaemic stroke and TIA (I). Update of risk factors and life style”. Neurologia. 2012; 27:560-74. PMID: 21890241. Fuentes B, Gállego J, Gil-Nuñez A, Morales A, Purroy F, Roquer J, Segura T, Tejada J, Lago A, Díez-Tejedor E, Alonso de Leciñana M, Alvarez-Sabin J, Arenillas J, Calleja S, Casado I, Castellanos M, Castillo J, Dávalos A, Díaz-Otero F, Egido JA, López-Fernández JC, Freijo M, García Pastor A, Gilo F, Irimia P, Maestre J, Masjuan J, Martí-Fábregas J, Martínez-Sánchez P, Martínez-Vila E, Molina C, Nombela F, Ribó M, Rodríguez-Yañez M, Rubio F, Serena J, Simal P, Vivancos J; SEN ad hoc Committee of the Cerebrovascular Disease Study Group.

ANNUAL SCIENTIFIC REPORT 2012 IDIBGI

THESES

Title

Doctorate thesis reader

University

Descubrimiento y validación de Fosfo- Eugeni López Bonet AMPKα-Thr172 como marcador de mitosis en el carcinoma de mama: impacto en el grado histológico.

Universitat Autònoma de Barcelona

Regulación del metabolismo lipídico en el tejido adiposo del paciente obeso

Francisco José Ortega Delgado

Universitat de Girona

Implicación de la adiponectina de alto peso Anna Prats Puig molecular en el eje tiroideo y el metabolismo óseo

Universitat de Girona

FACTS AND FIGURES

ANNUAL SCIENTIFIC REPORT 2012 IDIBGI

CLINICAL TRIALS APPROVED AND SIGNED IN 2012 (Annex I)

TOTAL OF STUDIES

2009

2010

2011

2012

2010

2011

2012

CLINICAL TRIALS

2009

CLINICAL TRIALS BY PHASE 2009-2012

PHASE I PHASE II PHASE III PHASE IV

In 2012, a total of 233 clinical studies were carried out at our institution (4 led by IDIBGI researchers)

2009

1 9 19 1 20

2010

0 13 14 2

2011

0 9 17 2

2012

1 11 14 1

JOURNALS

ANNUAL SCIENTIFIC REPORT 2012 IDIBGI

This list reflects all the journals in which investigators of the IDIBGI have published articles during 2012. The journals on Decile 1 are highlighted.

JOURNAL IF Total Articles QUARTILE Published Acta Diabetologica Acta Neurochirurgica Acta Oncologica Aging-Us American Heart Journal American Journal of Alzheimer’s Disease and Other Dementias American Journal of Clinical Nutrition American Journal of Hypertension American Journal of Kidney Diseases American Journal of Neuroradiology Anales de Psicología Annals of Neurology Annals of Nutrition and Metabolism Annals of Surgical Oncology Artificial Intelligence in Medicine Atención Primaria Atherosclerosis Autophagy Biochimica et Biophysica Acta Bioconjugate Chemistry Biology of Blood and Marrow Transplantation Blood Blood Pressure Bmc Cancer Bmc Infectious Diseases Bmc Medicine Bmc Nephrology Bmc Neurology Bmc Public Health Bone Marrow Transplantation Breast British Journal of Cancer British Journal of Haematology Cancer Cancer Epidemiology Cell Cycle Cerebellum Cerebrovascular Diseases Child Indicators Research Cirugía Española Clinical & Translational Oncology Clinical Colorectal Cancer Clinical Neurophysiology Clinical Science Computer Methods and Programs in Biomedicine Cytotherapy Dementia and Geriatric Cognitive Disorders Diabetes Diabetes Care Diabetes Technology & Therapeutics Diabetologia

3.18 1 2 1.52 1 2 3.33 1 2 5.13 3 2 4.65 1 1 1.45 1 3 6.61 1 1 3.67 1 1 5.43 2 1 2.93 1 1 0.55 1 2 11.09 1 1 2.26 1 2 4.17 1 1 1.36 1 1 0.63 3 3 3.97 1 1 7.45 1 1 5.00 1 1 4.93 1 1 3.28 1 2 9.90 2 1 1.43 1 3 3.01 2 2 3.12 1 2 6.04 1 1 1.64 1 3 2.17 1 2 2.08 1 2 3.54 1 2 2.49 1 1 5.08 1 1 4.94 2 1 4.77 1 1 2.01 1 2 5.36 9 1 3.29 1 2 2.72 2 2 0.86 1 2 0.87 1 3 1.33 1 4 1.68 1 3 2.79 1 2 4.32 1 1 1.52 4 1 3.63 1 1 2.14 1 2 8.89 2 1 8.09 1 1 1.93 2 3 6.97 1 1 21

JOURNALS

ANNUAL SCIENTIFIC REPORT 2012 IDIBGI

JOURNAL IF Total Articles QUARTILE Published Digestive Surgery Drugs & Aging European Eating Disorders Review European Journal of Cancer European Journal of Endocrinology European Journal of Epidemiology European Journal of Health Economics European Journal of Human Genetics European Journal of Medical Genetics Forensic Science International Gaceta Sanitaria Geospatial Health Haematologica Heart International Journal for Equity in Health International Journal of Cancer International Journal of Computer Assisted Radiology and Surgery International Journal of Geriatric Psychiatry International Journal of Obesity International Journal of Oncology International Journal of Pediatric Obesity International Journal of Stroke International Psychogeriatrics Investigational New Drugs Journal of Air Transport Management Journal of Antimicrobial Chemotherapy Journal of Business Economics and Management Journal of Chromatography A Journal of Chromatography B-Analytical Technologies in the Biomedical and Life Sciences Journal of Clinical Endocrinology & Metabolism Journal of Clinical Pathology Journal of Diabetes and its Complications Journal of Electrocardiology Journal of Happiness Studies Journal of Health Psychology Journal of Inorganic Biochemistry Journal of Medicinal Chemistry Journal of Neuroimaging Journal of Neurolinguistics Journal of Pediatrics Journal of Proteomics Journal of the American Geriatrics Society Journal of The Royal Statistical Society Series A-Statistics In Society Journal of Transcultural Nursing Journal of Vascular and Interventional Radiology Knowledge-Based Systems Lancet Lancet Neurology Lancet Oncology Leukemia Research 22

1.22 1 3 2.67 1 2 1.38 1 3 5.54 10 1 3.42 1 2 4.71 1 1 2.10 1 1 4.40 1 1 2.18 1 3 2.30 1 2 1.12 1 3 3.00 1 1 6.42 1 1 4.71 1 1 1.84 1 2 4.93 1 1 1.48 2 3 2.03 1 3 5.13 2 1 2.40 1 3 2.99 1 1 2.75 1 2 2.24 2 2 3.01 2 2 0.80 1 4 5.07 1 1 1.88 1 1 4.53 1 1 2.89 1 2 5.97 3 1 2.31 1 2 2.03 1 3 1.14 1 4 1.46 1 1 1.88 1 2 3.35 1 1 5.25 1 1 1.29 1 3 1.97 1 3 4.04 1 1 5.07 1 1 3.74 1 1 1.36 1 2 0.51 1 4 2.08 1 2 4.10 1 1 38.28 1 1 23.46 1 1 22.59 2 1 2.92 2 2

JOURNALS

ANNUAL SCIENTIFIC REPORT 2012 IDIBGI

JOURNAL IF Total Articles QUARTILE Published Medical Image Analysis Medicina Clínica Medicina Intensiva Molecular and Cellular Biology Molecular Nutrition & Food Research Molecular Pharmaceutics Nature Genetics Nefrología Nephrology Dialysis Transplantation Neuroinformatics Neurología Neurological Sciences Neuroradiology New England Journal of Medicine Nutrition, Metabolism & Cardiovascular Diseases Obesity Oncologist Oncology Reports Oncotarget Osteoporosis International Pharmacogenomics Phytomedicine Plos One Rejuvenation Research Respiratory Medicine Revista de Neurología Revista Española de Cardiología Scientific Reports Social Science & Medicine Statistics in Medicine Stroke Vaccine

4.42 1 1 1.39 5 2 1.07 3 4 5.53 1 1 4.71 1 1 4.78 1 1 35.53 1 1 1.00 5 1 3.56 1 1 2.97 1 2 0.79 1 4 1.32 1 3 2.87 1 2 53.30 2 1 3.44 1 1 3.53 1 1 3.91 1 2 1.84 1 3 4.78 2 1 4.86 1 1 3.97 1 1 2.97 1 1 4.09 8 1 3.83 1 1 2.48 1 2 0.65 7 4 2.53 2 2 2.93 1 1 2.70 1 1 1.88 1 1 5.76 5 1 3.49 1 2

CARDIOVASCULAR AREA

CARDIOVASCULAR AREA CARDIOVASCULAR GENETICS GIRONA HEART REGISTRY (REGICOR)

ANNUAL SCIENTIFIC REPORT 2012 IDIBGI

CARDIOVASCULAR AREA

CARDIOVASCULAR GENETICS GROUP MEMBERS Group Leader: Ramon Brugada POST-DOCORATE RESEARCHERS Catarina Allegue Sara Pagans Elisabet Selga Pedro Beltran Guillermo Perez Marcel Verges Oscar Campuzano Fabiana Scornik POST-GRADUATE RESEARCHERS Mireia Alcalde Jesus Matés Olallo Sánchez Cristina Bosch Javier Moncayo Anna Tarradas Monica Coll Helena Riuró TECHNICIANS Irene Mademont Alexandra Pérez Ferran Picó SUPPORT Anna Iglesias STRATEGIC OBJECTIVES Reference centre on a Spanish level for genetic research and analysis of pathologies associated with Sudden Cardiac Death. MAIN LINE OF RESEARCH Genetic and molecular basis of Sudden Cardiac Death.

ANNUAL SCIENTIFIC REPORT 2012 IDIBGI

PUBLICATIONS Originals (I.F.: 21.01): 1. Campuzano O, Alcalde M, Iglesias A, Barahona-Dussault C, SarquellaBrugada G, Benito B, Arzamendi D, Flores J, Leung TK, Talajic M, Oliva A, Brugada R. “Arrhythmogenic right ventricular cardiomyopathy: severe structural alterations are associated with inflammation”. Journal of Clinical Pathology. 2012; 65: 1077-83. PMID: 22944624. I.F.: 2.30 2. Bayés de Luna A, Brugada J, Baranchuk A, Borggrefe M, Breithardt G, Goldwasser D, Lambiase P, Riera AP, Garcia-Niebla J, Pastore C, Oreto G, McKenna W, Zareba W, Brugada R, Brugada P. “Current electrocardiographic criteria for diagnosis of Brugada pattern: a consensus report”. Journal of Electrocardiology. 2012; 45:433-42. PMID: 22920782. I.F.: 1.14 3. Grau M, Sala C, Sala J, Masia R, Vila J, Subirana I, Ramos R, Elosua R, Brugada R, Marrugat J. “Sex-related differences in prognosis after myocardial infarction: changes from 1978 to 2007”. European Journal of Epidemiology. 2012; 27:847-55. PMID: 22777715. I.F.: 4.71 4. Hong K, Hu J, Yu J, Brugada R. “Concomitant Brugada-like and short QT electrocardiogram linked to SCN5A mutation”. European Journal of Human Genetics. 2012; 20:1189-92. PMID: 22490985. I.F.: 4.40 5. Brion M, Allegue C, Santori M, Gil R, BlancoVerea A, Haas C, Bartsch C, Poster S, Madea B, Campuzano O, Brugada R, Carracedo A. “Sarcomeric gene mutations in sudden infant death syndrome (SIDS)”. Forensic Science International. 2012; 219:278-81. PMID: 22361390. I.F.: 2.30 6. Marin-Leblanc M, Perreault S, Bahroun I, Lapointe M, Mongrain I, Provost S, Turgeon J, Talajic M, Brugada R, Phillips M, Tardif JC, Dubé MP. “Validation of warfarin pharmacogenetic algorithms in clinical practice”. Pharmacogenomics. 2012; 13:21-9. PMID: 22176621. I.F.: 3.97

7. Campuzano O, Alcalde M, Berne P, Castro V, Guzzo G, Iglesias A, Alonso-Pulpon L, GarciaPavia P, Brugada J, Brugada R. “Genetic Testing of Candidate Genes in Arrhythmogenic Right Ventricular Cardiomyopathy/Dysplasia”. European Journal of Medical Genetics. 2012; 55:225-34. PMID: 22421524. I.F.: 2.18 Reviews (I.F.: 4.71): Zabalza M, Subirana I, Sala J, Lluis-Ganella C, Lucas G, Tomás M, Masiá R, Marrugat J, Brugada R, Elosua R. “Meta-analyses of the association between cytochrome CYP2C19 loss- and gain-of-function polymorphisms and cardiovascular outcomes in patients with coronary artery disease treated with clopidogrel”. Heart. 2012; 98:100-8. PMID: 21693476. I.F.: 4.71 Books: Campuzano O, Allegue C, Sarquella-Brugada G, Brugada R. Genetics of channelopathies associated to sudden cardiac death. Book: Sudden cardiac death: epidemiology, genetics and predictive/prevention strategies. NOVA publishers, 2012 Brugada P, Brugada R, Campuzano O, Sarquella-Brugada G, Brugada P, Brugada V, Brugada J. Chapter 92: Brugada Syndrome 1992-2012: Twenty Years of Scientific Progress. Book: Cardiac Electrophysiology: From Cell to Bedside, 6th Edition. Editors: Zipes/Jalife, 2012 Campuzano O, Allegue C, Brugada R. Suplemento 1: Aspectos genéticos del Síndrome de Brugada. Colección: CARDIOGENETICS and Sudden Death, Ferrer in Code, Elsevier Doyma, 2012 Sarquella-Brugada G, Campuzano O, Brugada J, Brugada P, Berruezo A. Ventricular tachycardias and Sudden Arrhythmic Death. Book: Pediatric Cardiology, Cardiac Surgery and Intensive Care, Springer, 2012 Sarquella-Brugada G, Campuzano O, Brugada R. Capítulo 67: Trastornos del ritmo cardíaco. Libro: Medicina de la adolescencia. Atención integral. Editorial: Sociedad Española de Medicina de la Adolescencia (SEMA), España, 2012

CARDIOVASCULAR AREA

ANNUAL SCIENTIFIC REPORT 2012 IDIBGI

Grants for Research in Progress: Traslación de tecnología genética innovadora al diagnóstico de enfermedades hereditarias relacionadas con la muerte súbita inexplicada Sponsored by: Ministerio de Ciencia e Innovación. Subprograma INNPACTO 2010 Duration: 2010 - 2013 Consorcio Gendiag.exe - Ramon Brugada

Estudio de los mecanismos moleculares que regulan la expresión y función de SCN5A (SAF2011-27627) Sponsored by: Ministerio de Economía y Educación. Investigación fundamental no orientada Duration: 01/01/2012 - 31/12/2014 Sara Pagans

Suport Grups de Recerca Emergent (GRE) (2009-SRG/DGR-0712) Sponsored by: Direcció General de Recerca (DGR) de la Generalitat de Catalunya Duration: 2009 - 2013 Ramon Brugada Sudden cardiac death: Translating basic science into clinical care Sponsored by: CNIC-TRANSLATIONAL 2008 Duration: 2009 - 2014 Ramon Brugada Genotipado de alto rendimiento en el diagnóstico genético del síndrome de Brugada. PI11/01826 Sponsored by: Instituto de Salud Carlos III Duration: 01/01/2012 - 31/12/2014 Ramon Brugada Ayudas predoctorales de formación en investigación en salud. FI10/00453 Sponsored by: Instituto de Salud Carlos III Duration: 01/09/2010 - 31/12/2014 Ramon Brugada Beneficiary: Cristina Bosch Mort sobtada infantil: diagnòstic genètic mitjançant tecnologia d’ultraseqüenciació (next generation sequencing, NGS) Sponsored by: Societat Catalana Cardiologia Duration: 16/07/2012 - 16/07/2014 Ramon Brugada Contrato postdoctoral Sara Borrell (CD10/00275) Sponsored by: Instituto de Salud Carlos III Duration: 01/01/2011 - 31/12/2013 Ramon Brugada Beneficiary: Pedro Beltran

CARDIOVASCULAR AREA

ANNUAL SCIENTIFIC REPORT 2012 IDIBGI

GIRONA HEART REGISTRY (REGICOR) GROUP MEMBERS Group Leader: Joan Sala Group Leader: Rafael Ramos POST-DOCORATE RESEARCHERS Jaime Aboal Daniel Bosch Miquel Quesada Xavier Albert Carlos Cerezo Pascual Solanas Elisabet Balló Pablo de Loma-Osorio MEDICAL RESEARCHERS Maria del Mar Garcia TECHNICIANS Ruth Martí Anna Ponjoan

PUBLICATIONS Originals (I.F.: 64.14):

STRATEGIC OBJECTIVES 1. Analyse the role of emerging risk factors and asymptomatic atherosclerosis as well as the comorbidity of the patient in the prediction of cardiovascular risk. 2. Develop cardiovascular risk functions adapted to specific subpopulation groups (diabetes, patients with a family history of vascular disease, obesity). 3. Evaluate the effectiveness and efficiency of different actions for the prevention and control of atherosclerotic disease in Primary Healthcare using the Information System for the Development of Research in Primary Care (SIDIAP). 4. Analyse the role of CV risk factors and their control in the incidence of dementias. MAIN LINE OF RESEARCH The main line of research of the group is to improve the detection and control of patients with intermediate cardiovascular risk and the detection of CV disease in the asymptomatic phase and analyse the cost effectiveness of the actions taken for the prevention of cardiovascular disease.

1. Grau M, Subirana I, Agis D, Ramos R, Basagaña X, Martí R, de Groot E, Arnold RJ, Marrugat J, Künzli N, Elosua R. “Carotid Intima-media Thickness in the Spanish Population: Reference Ranges and Association with Cardiovascular Risk Factors”. Revista Española de Cardiología. 2012; 65:1086-1093. PMID: 23021836. I.F.: 2.,53 2. Sanchis J, Bardají A, Bosch X, Loma-Osorio P, Marín F, Sánchez PL, Núñez J, Carratalá A, Barrabés JA. “Usefulness of high-sensitivity troponin T for the evaluation of patients with acute chest pain and no or minimal myocardial damage”. American Heart Journal. 2012; 164:194-200.e1. PMID: 22877804. I.F.: 4.65 3. Grau M, Sala C, Sala J, Masia R, Vila J, Subirana I, Ramos R, Elosua R, Brugada R, Marrugat J. “Sex-related differences in prognosis after myocardial infarction: changes from 1978 to 2007”. European Journal of Epidemiology. 2012; 27:847-55. PMID: 22777715. I.F.: 4.713 4. Aymerich M, Carrion C, Gallo P, Garcia M, López-Bermejo A, Quesada M, Ramos R. “Measuring the payback of research activities: a feasible ex-post evaluation methodology in epidemiology and public health”. Social Science & Medicine. 2012; 75:505-10. PMID: 22595067. I.F.: 2.70 5. Lluis-Ganella C, Subirana I, Lucas G, Tomás M, Muñoz D, Sentí M, Salas E, Sala J, Ramos R, Ordovas JM, Marrugat J, Elosua R. “Assessment of the value of a genetic risk score in improving the estimation of coronary risk”. Atherosclerosis. 2012; 222:456-63. PMID: 22521901. I.F.: 3.97 6. Ramos R, Balló E, Marrugat J, Elosua R, Sala J, Grau M, Vila J, Bolíbar B, García-Gil M, Martí R, Fina F, Hermosilla E, Rosell M, Muñoz MA, Prieto-Alhambra D, Quesada M. “Validity for use in research on vascular diseases of the SIDIAP (Information System for the Development of Research in Primary Care): the EMMA study”. Revista Española de Cardiología. 2012; 65:29-37. PMID: 22036238. I.F.: 2.53

CARDIOVASCULAR AREA

7. Bolibar B, Fina Aviles F, Morros R, Del Mar Garcia-Gil M, Hermosilla E, Ramos R, Rosell M, Rodriguez J, Medina M, Calero S, PrietoAlhambra D, SIDIAP G. “SIDIAP database: electronic clinical records in Primary Care as a source of information for epidemiologic research”. Medicina Clínica. 2012; 138:617–621. PMID: 22444996. I.F.: 1.39 8. Myocardial Infarction Genetics Consortium; Wellcome Trust Case Control Consortium, Schwartz SM, Siscovick D, O’Donnell CJ, Melander O, Salomaa V, Purcell S, Altshuler D, Samani NJ, Kathiresan S, Elosua R, Sala J, Ramos R et al. “Hypothesis-based analysis of gene-gene interactions and risk of myocardial infarction”. PLoS One. 2012; 7:e41730. PMID: 22876292. I.F.: 4.09 9. Diabetes Genetics Replication and Metaanalysis Consortium; Myocardial Infarction Genetics Consortium (Ramos R), Kathiresan S, Wijmenga C, Gregersen PK, Alfredsson L, Siminovitch KA, Worthington J, De Bakker PI, Raychaudhuri S, Plenge RM, Stahl EA, Wegmann D, Trynka G, Gutierrez-Achury J, Do R, Voight BF, Kraft P, Chen R, Kallberg HJ, Kurreeman FA; Ramos R, Sala J et al. “Bayesian inference analyses of the polygenic architecture of rheumatoid arthritis”. Nature Genetics. 2012; 44:483-9. PMID: 22446960. I.F.: 35.53 10. Jurado J, Ybarra J, Romeo JH, Garcia M, Zabaleta E. J. “Angiotensin converting enzyme gene polymorphism as a genetic biomarker of diabetic peripheral neuropathy: Longitudinal prospective study”. Journal of Diabetes and its Complications. 2012; 26:77-82. PMID: 22494836. I.F.: 2.03 Review (I.F.: 4.71): Zabalza M, Subirana I, Sala J, Lluis-Ganella C, Lucas G, Tomás M, Masiá R, Marrugat J, Brugada R, Elosua R. “Meta-analyses of the association between cytochrome CYP2C19 loss- and gain-of-function polymorphisms and cardiovascular outcomes in patients with coronary artery disease treated with clopidogrel”. Heart. 2012; 98:100-8. PMID: 21693476. I.F.: 4.71

ANNUAL SCIENTIFIC REPORT 2012 IDIBGI

Grants for Research in Progress: Avances en el manejo del riesgo intermedio. Estudio MARK (improving interMediAte RisK management) (PI10/01088) Sponsored by: Instituto de Salud Carlos III Duration: 2011 - 2013 Rafel Ramos Determinantes genéticos y ambientales de la disfunción vascular en la hipertensión y en la cardiopatía isquémica: Red HERACLES (RD06/0009/1004) Sponsored by: Instituto de Salud Carlos III Duration: 01/01/2008 - 31/12/2013 Joan Sala Efectividad de las estatinas en población de edad avanzada en España. Estudio 4E. (EC11267) Sponsored by: Ministerio de Sanidad y Política Social e Igualdad Duration: 2012 Rafel Ramos El rol de las estatinas en prevención primaria de eventos cardiovasculares en población con Enfermedad Renal Crónica (ERC). Proyecto ECERC. (EC11-349) Sponsored by: Ministerio de Sanidad y Política Social e Igualdad Duration: 2012 Maria del Mar García Medida de la efectividad de las estatinas en la reducción de morbi-mortalidad vascular en la población sin antecedentes de enfermedad vascular atendida en Atención primaria con Riesgo Intermedio e índice tobollizo brazo patólogico. Estudio MARIA. (EC10-083) Sponsored by: Ministerio de Sanidad y Política Social e Igualdad Duration: 2010 - 2012 Rafel Ramos Análisis del coste-efectividad del tratamiento con Estatinas en la Prevención PRimaria de Eventos Vasculares. Proyecto EPREV (EC10084) Sponsored by: Ministerio de Sanidad y Política Social e Igualdad. Duration: 2010 - 2012 Maria del Mar García

METABOLISM AREA

METABOLISM AREA NUTRITION, EUMETABOLISM AND HEALTH ONTOGENY OF THE METABOLIC SYNDROME

ANNUAL SCIENTIFIC REPORT 2012 IDIBGI

METABOLISM AREA

ANNUAL SCIENTIFIC REPORT 2012 IDIBGI

NUTRITION, EUMETABOLISM AND HEALTH

PUBLICATIONS Originals (I.F.: 89.19):

Team involved in:

GROUP MEMBERS Group Leader: José-Manuel Fernández-Real POST-DOCORATE RESEARCHERS José María Moreno (CIBERobn) Francisco José Ortega (CIBERobn) Marta Serrano María Moreno Mar Rodríguez POST-GRADUATE RESEARCHERS Emili Loshuertos Josep Puig Gemma Xifra TECHNICIANS Ester Guerra Gerard Pardo SUPPORT Anna Iglesias NURSING STAFF Oscar Rovira (CIBERobn) SECRETARY Roser Rodríguez

STRATEGIC OBJECTIVES · Microbiome Signature of metabolic diseases: Obesity Type-2 diabetes NASH · Circulating microRNA profile of metabolic diseases · Epigenomic Signature of metabolic diseases · Interaction between System Biology and Microbiome / miRNAs / Innate immune system MAIN LINE OF RESEARCH · Inflammation and insulin resistance. · Proteomics of the adipose tissue. · Metabolism of iron and insulin resistance. · Biomarkers for obesity, insulin resistance and Type-2 diabetes. · Bone as an endocrine organ. · Vascular disease and inflammation.

1. García-Unciti M, Izquierdo M, Idoate F, Gorostiaga E, Grijalba A, Ortega-Delgado F, Martínez-Labari C, Moreno-Navarrete JM, Forga L, Fernández-Real JM, Ibáñez J. “Weight-Loss Diet Alone or Combined with Progressive Resistance Training Induces Changes in Association between the Cardiometabolic Risk Profile and Abdominal Fat Depots”. Annals of Nutrition and Metabolism. 2012; 61:296-304. PMID: 23208159. I.F.: 2.26 2. Queipo-Ortuño MI, Escoté X, CeperueloMallafré V, Garrido-Sanchez L, Miranda M, Clemente-Postigo M, Pérez-Pérez R, Peral B, Cardona F, Fernández-Real JM, Tinahones FJ, Vendrell J. “FABP4 Dynamics in Obesity: Discrepancies in Adipose Tissue and Liver Expression Regarding Circulating Plasma Levels”. PLoS One. 2012; 7:e48605. PMID: 23139800. I.F.: 4.09 3. Torguet-Escuder P, Guasch-Aragay B, Calabia-Martínez J, Martín-Alemany N, García-Méndez I, Maté-Benito G, ClapésSánchez E, Sabater-Masdeu M, FernándezReal JM, Vallès-Prats M. “Fibroblast growth factor 23 (FGF 23) and phosphocalcic metabolism in chronic kidney disease”. Nefrología. 2012; 32:647-54. PMID: 23013951. I.F.: 1.00 4. Fagundo AB, De la Torre R, Jiménez-Murcia S, Agüera Z, Granero R, Tárrega S, Botella C, Baños R, Fernández-Real JM, Rodríguez R, Forcano L, Frühbeck G, Gómez-Ambrosi J, Tinahones FJ, Fernández-García JC, Casanueva FF, Fernández-Aranda F. “Executive functions profile in extreme eating/weight conditions: from anorexia nervosa to obesity”. PLoS One. 2012; 7:e43382. PMID: 22927962. I.F.: 4.09 5. Fernández-Real JM, Bulló M, MorenoNavarrete JM, Ricart W, Ros E, Estruch R, Salas-Salvadó J. “A Mediterranean diet enriched with olive oil is associated with higher serum total osteocalcin levels in elderly men at high cardiovascular risk”. Journal of Clinical Endocrinology & Metabolism. 2012; 97:3792-8. PMID: 22855341. I.F.: 5.97 31

METABOLISM AREA

6. Ortega FJ, Sabater M, Moreno-Navarrete JM, Pueyo N, Botas P, Delgado E, Ricart W, Frühbeck G, Fernández-Real JM. “Serum and urinary concentrations of calprotectin as markers of insulin resistance and type 2 diabetes”. European Journal of Endocrinology. 2012; 167:569-78. PMID: 22822112. I.F.: 3.42 7. Ortega FJ, Moreno-Navarrete JM, Mayas D, García-Santos E, Gómez-Serrano M, Rodriguez-Hermosa JI, Ruiz B, Ricart W, Tinahones FJ, Frühbeck G, Peral B, FernándezReal JM. “Breast cancer 1 (BrCa1) may be behind decreased lipogenesis in adipose tissue from obese subjects”. PLoS One. 2012;

ANNUAL SCIENTIFIC REPORT 2012 IDIBGI

JM. “Circulating lipopolysaccharide-binding protein (LBP) as a marker of obesity-related insulin resistance”. International Journal of Obesity. 2012; 36:1442-9. PMID: 22184060. I.F.: 5.13 13. Moreno-Navarrete JM, Catalán V, Whyte L, Díaz-Arteaga A, Vázquez-Martínez R, Rotellar F, Guzmán R, Gómez-Ambrosi J, Pulido MR, Russell WR, Imbernón M, Ross RA, Malagón MM, Dieguez C, Fernández-Real JM, Frühbeck G, Nogueiras R. “The L-αlysophosphatidylinositol/GPR55 system and its potential role in human obesity”. Diabetes. 2012; 61:281-91. PMID: 22179809. I.F.: 8.89

7:e33233. PMID: 22666314. I.F.: 4.09 8. Moreno-Navarrete JM, Sabater M, Ortega F, Ricart W, Fernández-Real JM. “Circulating zonulin, a marker of intestinal permeability, is increased in association with obesityassociated insulin resistance”. PLoS One. 2012; 7:e37160. PMID: 22629362. I.F.: 4.09 9. Villarejo C, Fernández-Aranda F, JiménezMurcia S, Peñas-Lledó E, Granero R, Penelo E, Tinahones FJ, Sancho C, Vilarrasa N, Montserrat-Gil de Bernabé M, Casanueva FF, Fernández-Real JM, Frühbeck G, De la Torre R, Treasure J, Botella C, Menchón JM. “Lifetime obesity in patients with eating disorders: increasing prevalence, clinical and personality correlates”. European Eating Disorders Review. 2012; 20:250-4. PMID: 22383308. I.F.: 1.38 10. Rodriguez-Cuenca S, Carobbio S, Velagapudi VR, Barbarroja N, MorenoNavarrete JM, Tinahones FJ, Fernandez-Real JM, Orešic M, Vidal-Puig A. “Peroxisome proliferator-activated receptor γ-dependent regulation of lipolytic nodes and metabolic flexibility”. Molecular and Cellular Biology. 2012; 32:1555-65. PMID: 22310664. I.F.: 5.53 11. Pérez-Pérez R, López JA, García-Santos E, Camafeita E, Gómez-Serrano M, OrtegaDelgado FJ, Ricart W, Fernández-Real JM, Peral B. “Uncovering suitable reference proteins for expression studies in human adipose tissue with relevance to obesity”. PLoS One. 2012; 7:e30326. PMID: 22272336. I.F.: 4.09 12. Moreno-Navarrete JM, Ortega F, Serino M, Luche E, Waget A, Pardo G, Salvador J, Ricart W, Frühbeck G, Burcelin R, Fernández-Real 32

14. Bulló M, Moreno-Navarrete JM, Fernández-Real JM, Salas-Salvadó J. “Total and undercarboxylated osteocalcin predict changes in insulin sensitivity and β cell function in elderly men at high cardiovascular risk”. American journal of clinical nutrition. 2012; 95:249-55. PMID: 22170359. I.F.: 6.61 15. Perez-Herrera A, Delgado-Lista J, TorresSanchez LA, Rangel-Zuñiga OA, Camargo A, Moreno-Navarrete JM, Garcia-Olid B, Quintana-Navarro GM, Alcala-Diaz JF, MuñozLopez C, Lopez-Segura F, Fernandez-Real JM, Luque de Castro MD, Lopez-Miranda J, PerezJimenez F. “The postprandial inflammatory response after ingestion of heated oils in obese persons is reduced by the presence of phenol compounds”. Molecular Nutrition & Food Research. 2012; 56:510-4. PMID: 22162245. I.F.: 4.71 16. Fernández-Real JM, Vendrell J, García I, Ricart W, Vallès M. “Structural damage in diabetic nephropathy is associated with TNF-α system activity”. Acta Diabetológica. 2012; 49:301-5. PMID: 22042131. I.F.: 3.18 17. Ibernon M, Moreso F, Sarrias X, Sarrias M, Grinyó JM, Fernandez-Real JM, Ricart W, Serón D. “Reverse dipper pattern of blood pressure at 3 months is associated with inflammation and outcome after renal transplantation”. Nephrology Dialysis Transplantation. 2012; 27:2089-95. PMID: 22015441. I.F.: 3.56 18. Pérez-Pérez R, García-Santos E, OrtegaDelgado FJ, López JA, Camafeita E, Ricart W, Fernández-Real JM, Peral B. “Attenuated metabolism is a hallmark of obesity as

revealed by comparative proteomic analysis of human omental adipose tissue”. Journal of Proteomics. 2012; 75:783-95. PMID: 21989264. I.F.: 5.07 19. Ortega FJ, Jílková ZM, Moreno-Navarrete JM, Pavelka S, Rodriguez-Hermosa JI, Kopeck Ygrave J, Fernández-Real JM. “Type I iodothyronine 5’-deiodinase mRNA and activity is increased in adipose tissue of obese subjects”. International Journal of Obesity. 2012; 36:320-4. PMID: 21610697. I.F.: 5.13 20. Menke A, Muntner P, Fernández-Real JM, Guallar E. “The association of biomarkers of iron status with mortality in US adults”. Nutrition, Metabolism & Cardiovascular Diseases. 2012; 22:734-40. PMID: 21330119. I.F.: 3.44 21. García-Quispes WA, Pastor S, Galofré P, Biarnés J, Castell J, Velázquez A, Marcos R. “Possible Role of the WDR3 Gene on Genome Stability in Thyroid Cancer Patients”. PLoS One. 2012; 7:e44288. PMID: 23049746. I.F.: 4.09 Editorial (I.F.: 13.01): Manco M, Fernandez-Real JM. “Back to past leeches: repeated phlebotomies and cardiovascular risk”. BMC Medicine. 2012; 10:53. PMID: 22647488. I.F.: 6.04 Fernández-Real JM, Pickup JC. “Innate immunity, insulin resistance and type 2 diabetes”. Diabetologia. 2012; 55:273-8. PMID: 22124608. I.F.: 6.97

METABOLISM AREA

Grants for Research in Progress: MicroRNA circulantes y en tejido adiposo como biomarcadores metabólicos (PI11/00214) Sponsored by: Instituto de Salud Carlos III Duration: 2012 - 2015 J.M. Fernández-Real The role of intestinal microflora in nonalcoholic fatty liver disease (FLORINASH) Sponsored by: European Commission. Seventh framework programme Duration: 2010 - 2015 J.M. Fernández-Real (leader WP1) CIBERobn. Centro de Investigación Biomédica en Red-Fisiopatologia de la Obesidad y Nutrición Sponsored by: Instituto de Salud Carlos III J.M. Fernández-Real Signatura microRNA DM-2 Sponsored by: Associació Catalana de Diabetis Duration: 2011 - 2013 J.M. Fernández-Real / Francisco José Ortega Delgado

ANNUAL SCIENTIFIC REPORT 2012 IDIBGI

ONTOGENY OF THE METABOLIC SYNDROME GROUP MEMBERS Group Leader: Abel López Bermejo POST-DOCORATE RESEARCHERS Judit Bassols Anna Prats POST-GRADUATE RESEARCHERS Gemma Carreras Montserrat Gipsert-Saüch Inés Osiniri COLLABORATORS Cristina Casas Pilar Soriano Francis de Zegher Lourdes Ibáñez Joan Carles Vilanova NURSING STAFF Ferran Díaz

STRATEGIC OBJECTIVES · Contracting staff: Stabilisation of Dr. Anna Prats Puig FINANCING · Acadèmia de Ciències Mèdiques (Medical Sciences Academy) · Fondo de Investigaciones Sanitarias (Health Research Fund) · Pfizer grant Ordesa Project · PROLOR Project (International) MAIN LINE OF RESEARCH · Prevention of obesity and cardiovascular risk in infancy · Specific lines of research · Molecular bases of infantile obesity. · Cardiovascular risk markers in infancy

PUBLICATIONS Originals (I.F.: 46.412): 1. Díaz M, Chacón MR, López-Bermejo A, Maymó-Masip E, Salvador C, Vendrell J, De Zegher F, Ibáñez L. “Ethinyl estradiolcyproterone acetate versus low-dose pioglitazone-flutamide-metformin for adolescent girls with androgen excess: divergent effects on CD163, TWEAK receptor, ANGPTL4, and LEPTIN expression in subcutaneous adipose tissue”. Journal of Clinical Endocrinology & Metabolism. 2012; 97:3630-8. PMID: 22791755. I.F.: 5.97 2. Díaz M, Bassols J, López-Bermejo A, GómezRoig MD, De Zegher F, Ibáñez L. “Placental expression of peroxisome proliferatoractivated receptor ү (PPARү): relation to placental and fetal growth”. Journal of Clinical Endocrinology & Metabolism. 2012; 97:E146872. PMID: 22689692. I.F.: 5.97 3. De Zegher F, Sebastiani G, Diaz M, SánchezInfantes D, Lopez-Bermejo A, Ibáñez L. “Body composition and circulating high-molecularweight adiponectin and IGF-I in infants born small for gestational age: breast- versus formula-feeding”. Diabetes. 2012; 61:1969-73. PMID: 22648385. I.F.: 8.89 4. Aymerich M, Carrion C, Gallo P, Garcia M, López-Bermejo A, Quesada M, Ramos R. “Measuring the payback of research activities: a feasible ex-post evaluation methodology in epidemiology and public health”. Social Science & Medicine. 2012; 75:505-10. PMID: 22595067. I.F.: 2.70 5. Sebastiani G, Díaz M, López-Bermejo A, Arranz A, De Zegher F, Ibáñez L. “Circulating follistatin in the human foetus at term birth”. International Journal of Pediatric Obesity. 2012; 7:39-43. PMID: 22434738. I.F.: 2.99 6. De Zegher F, Díaz M, Sebastiani G, MartínAncel A, Sánchez-Infantes D, López-Bermejo A, Ibáñez L. “Abundance of circulating preadipocyte factor 1 in early life”. Diabetes Care. 2012; 35:848-9. PMID: 22338099. I.F.: 8.09 7. Prats-Puig A, Puig T, Sitjar C, Mas-Parareda M, Grau-Cabrera P, Soriano-Rodríguez P, 33

METABOLISM AREA

Montesinos-Costa M, Diaz M, De Zegher F, Ibáñez L, Bassols J, López-Bermejo A. “Soluble fatty acid synthase relates to bone biomarkers in prepubertal children”. Osteoporosis International. 2012; 23:2053-8. PMID: 21877200. I.F.: 4.86 8. Osiniri I, Sitjar C, Soriano-Rodríguez P, Prats-Puig A, Casas-Satre C, Mayol L, De Zegher F, Ibánez L, Bassols J, López-Bermejo A. “Carotid intima-media thickness at 7 years of age: relationship to C-reactive protein rather than adiposity”. Journal of Pediatrics. 2012; 160:276-280.e1. PMID: 21875718. I.F.: 4.04 9. Prats-Puig A, Sitjar C, Ribot R, Calvo M, Clausell-Pomés N, Soler-Roca M, SorianoRodríguez P, Osiniri I, Ros-Miquel M, Bassols J, De Zegher F, Ibáñez L, López-Bermejo A. “Relative hypoadiponectinemia, insulin resistance, and increased visceral fat in euthyroid prepubertal girls with low-normal serum free thyroxine”. Obesity (Silver Spring). 2012; 20:1455-61. PMID: 21738234. I.F.: 3.53

GRANTS FOR RESEARCH IN PROGRESS: Nuevos determinantes moleculares de la resistencia a la insulina en la edad pediátrica. PI10/00553 Sponsored by: Instituto de Salud Carlos III Duration: 2011 - 2013 Abel López Bermejo Efectos endocrino-metabólicos, sobre la adiposidad visceral y parámetros de riesgo cardiovascular de la administración de metformina en niños prepuberales con obesidad y marcadores de riesgo para el síndrome metabólico. EC10/252 Sponsored by: Ministerio de Sanidad y Política Social Duration: 2011 - 2013 Abel López Bermejo Plasticidad del desarrollo de obesidad abdominal y riesgo cardiovascular en la infancia. Sponsored by: Nutribén Duration: 2012 - 2015 Abel López Bermejo

ANNUAL SCIENTIFIC REPORT 2012 IDIBGI

NEUROSCIENCE AREA

NEUROSCIENCE AREA AGING AND HEALTH CEREBROVASCULAR PATHOLOGY MEDICAL IMAGING NEURODEGENERATION AND NEUROINFLAMMATION

ANNUAL SCIENTIFIC REPORT 2012 IDIBGI

NEUROSCIENCE AREA

ANNUAL SCIENTIFIC REPORT 2012 IDIBGI

AGING AND HEALTH

PUBLICATIONS Originals (I.F.: 19.89):

GROUP MEMBERS Group Leader: Secundino López-Pousa

STRATEGIC OBJECTIVES Consolidation as a reference group in the field of normal and pathological aging.

SENIOR RESEARCHERS Gabriel Coll Josep Garre Joan Vilalta

MAIN LINE OF RESEARCH 1. Normal and pathological aging. 2. Dementia and Alzheimer’s disease / neuropsychology / psychopathology of aging and dementias. 3. Adaptation and validation of psychometric instruments in the field of aging, disability and mental health. 4. Epidemiology of aging: fragility, disability and dependence.

POST-DOCORATE RESEARCHERS Laia Calvó POST-GRADUATE RESEARCHERS Oriol Turró MEDICAL RESEARCHERS Saioa Lejarreta Antonio Rodríguez-Poncelas Antoni Turon-Estrada Imma Pericot-Nierga Josefina Turbau COLLABORATORS Mª del Mar Cruz Dagmar Keller Olga Soler TECHNICIANS Sílvia Monserrat-Vila NURSING STAFF Marta Hernández Jordi Llinàs Ivana Trastámara Mª Angeles Lacarra Manoli Lonzano

1. López-Pousa S, Turró-Garriga O, CalvóPerxas L, Carmona O, Gich J, Alsina E, Màrquez F, Viñas M, Turbau J, Vilalta-Franch J, Roig AM, Garre-Olmo J. “Consumption of Pharmaceuticals in Primary Non-Alzheimer’s Degenerative Dementias: A Cross-Sectional Study by the Registry of Dementias of Girona (ReDeGi)”. Drugs Aging. 2012; 29:733-40. PMID: 23018609. I.F.: 2.67 2. Vilalta-Franch J, Garre-Olmo J, LópezPousa S, Llinàs-Reglà J, Calvó-Perxas L, Cubí-Montfort R; SISDDAP. “Feasibility of a telemedicine support system for diagnosing dementia in primary care”. Revista de Neurología. 2012; 55:263-9. PMID: 22930137. I.F.: 0.65 3. Garre-Olmo J, López-Pousa S, TuronEstrada A, Juvinyà D, Ballester D, VilaltaFranch J. “Environmental determinants of quality of life in nursing home residents with severe dementia”. Journal of the American Geriatrics Society. 2012; 60:1230-6. PMID: 22702541. I.F.: 3.74 4. López-Pousa S, Calvó-Perxas L, Lejarreta S, Cullell M, Meléndez R, Hernández E, Bisbe J, Perkal H, Manzano A, Roig AM, Turró-Garriga O, Vilalta-Franch J, Garre-Olmo J; Registry of Dementias of Girona Study Group (ReDeGi Study Group). “Use of antidementia drugs in frontotemporal lobar degeneration”. American Journal of Alzheimer’s Disease and other Dementias. 2012; 27:260-6. PMID: 22605780. I.F.: 1.45 5. Coll-De-Tuero G, Saez M, RodriguezPoncelas A, Barceló-Rado A, Vargas-Vila S, Garre-Olmo J, Sala V, Sieira A, Gelada E, Gelado-Ferrero J. “Why is cardiovascular risk stratification important in hypertensive patients?” Blood Pressure. 2012; 21:182-90. PMID: 22486493. I.F.: 1.43 6. Calvó-Perxas L, López-Pousa S, VilaltaFranch J, Turró-Garriga O, Blankenburg M, Febrer L, Flaqué M, Vallmajó N, Aguirregomozcorta M, Genís D, Casas I, Perkal H, Coromina J, Garre-Olmo J; Registry of Dementias of Girona Study Group. “Central

NEUROSCIENCE AREA

ANNUAL SCIENTIFIC REPORT 2012 IDIBGI

Editorials (I.F.: 1.91): Coll de Tuero G. “Review of the medication in polymedicated elderly patients”. Atención Primaria. 2012; 44:461-2. PMID: 22846344. I.F.: 0.63 Coll-De-Tuero G, Garre-Olmo J, LópezPousa S. “Towards an assessment of the instrumental abilities of the elderly validated in our environment”. Atención Primaria. 2012; 44:317-9. PMID: 22595473. I.F.: 0.63 Fadel N, Velasquez G, Lejarreta-Andres S, Turon-Estrada A, Lopez-Pousa S. “Ischemic stroke and splenic infarction”. Revista de

from the Girona Dementia Registry (ReDeGi)”. Revista de Neurología. 2012; 54:399-406. PMID: 22451126. I.F.: 0.65

Neurología. 2012; 55:702-3. PMID: 23172098. I.F.: 0.65

8. Calvó-Perxas L, De Eugenio RM, MarquezDaniel F, Martínez R, Serena J, Turbau J, Vilalta-Franch J, Viñas M, Turró-Garriga O, Roig AM, López-Pousa S, Garre-Olmo J; In representation of the Girona Dementia Registry Study Group. “Profile and variables related to antipsychotic consumption according to dementia subtypes”. International Psychogeriatrics. 2012; 24:940-7. PMID: 22333005. I.F.: 2.24

Grants for Research in Progress:

9. Turró-Garriga O, López-Pousa S, VilaltaFranch J, Garre-Olmo J. “Evaluation of anosognosia in Alzheimer’s disease”. Revista de Neurología. 2012; 54:193-8. PMID: 22314759. I.F.: 0.65 10. Conde-Sala JL, Garre-Olmo J, VilaltaFranch J, Llinàs-Reglà J, Turró-Garriga O, Lozano-Gallego M, Hernández-Ferrándiz M, Pericot-Nierga I, López-Pousa S. “Predictors of cognitive decline in Alzheimer’s disease and mild cognitive impairment using the CAMCOG: a five-year follow-up”. International Psychogeriatrics. 2012; 24:948-58. PMID: 22278151. I.F.: 2.24

· Projecte AD-retina. Estudi de les troballes fundoscòpiques i tomogràfiques a la retina de pacients amb malaltia d’Alzheimer Sponsored by: Instituto de Salud Carlos III. Fondo de Investigación Sanitaria Duration: 2012 - 2014 Miguel Ángel Zapata Victori · Estils de vida, risc cardiovascular i deteriorament cognitiu: estudi REGICORCog Sponsored by: Instituto de Salud Carlos III. Fondo de Investigación Sanitaria Duration: 2009 - 2012 Josep Garre Olmo · Genetic, lifestyle, and inflammatory factors as predictors of depression in general population Sponsored by: Fundació La Marató de TV3 Duration: 2009 - 2012 Joan Vilalta Franch

11. Vilalta-Franch J, Planas-Pujol X, LópezPousa S, Llinàs-Reglà J, Merino-Aguado J, Garre-Olmo J. “Depression subtypes and 5-years risk of mortality in aged 70 years: a population-based cohort study”. International Journal of Geriatrics Psychiatry. 2012; 27:6775. PMID: 21308792. I.F.: 2.03

NEUROSCIENCE AREA

ANNUAL SCIENTIFIC REPORT 2012 IDIBGI

CEREBROVASCULAR PATHOLOGY Team involved in Red de Enfermedades Vasculares Cerebrales (ICTUS) [Cerebrovascular disease network]

GROUP MEMBERS Group Leader: María del Mar Castellanos POST-DOCORATE RESEARCHERS Gemma Huguet Elisabet Kádár Judith Mallolas POST-GRADUATE RESEARCHERS Susanna Camos Carme Gubern Mikel Terceño Cecile van Eendenburg MEDICAL RESEARCHERS Joaquín Serena Yolanda Silva COLLABORATORS Gerard Blasco Salvador Pedraza Josep Puig TECHNICIANS Rocío Rodríguez NURSING STAFF Martha Kazimierczak

STRATEGIC OBJECTIVES · Evaluate whether alterations in the anisotropy indexes and MRI tractography of the corticospinal tract and arcuate fasciculus predict the neurological progress of patients with acute, subacute and chronic intracerebral hemorrhage. · Study and compare the tractography affectation patterns of patients with cerebral hemorrhage depending on the location of the hematoma (lobar or deep). · Establish tractography patterns for good short and long term functional prognosis in cerebral hemorrhage. · Use brain MRI to study the incidence of contrast extravasation in patients with spontaneous cerebral hemorrhage of < 12 hours of progress, as well as classify these findings according to the location of the contrast extravasation in the hematoma. · Determine whether the presence of contrast extravasation, or any of the patterns defined, is a predictive marker for relevant growth of the hematoma at 72 hours. · Determine whether the presence of contrast extravasation, or any of the patterns defined, is a predictive marker of mortality or early neurological deterioration of patients. · Determine whether the presence of these contrast extravasation patterns in MRI are related to higher serum concentrations of inflammatory markers (IL-6, TNF-a) and/ or markers of blood-brain barrier damage (MMP-9, c-FN, s100 b).

PREVENTION STUDIES · Study the hemodynamic behaviour (flow volume, cerebral hemodynamic reserve and behaviour of the collateral circulation) of the cerebral circulation in conditions prior to surgical operation and during the ischemia induced by carotid clamping in patients with symptomatic carotid stenosis. · Evaluate the indications of shunt placement as a method for the prevention of ischemia 38

due to carotid clamping. · Identify the predictive hemodynamic patterns of patients at risk of presenting a new intra-operatory or immediate postoperatory neurological event. · Correlation between molecular markers analysed in anatomical parts of symptomatic atheroma plaque (endarterectomy) and molecular markers in peripheral blood. · Screening of markers involved in atherogenesis and vulnerable plaque (to be determined): · Adhesion molecules: P-selectin, ICAM-1, VCAM · Endothelin (ET-1) · Asymmetric dimethylarginine (ADMA)

MAIN LINES OF RESEARCH Study of biomarkers predicting progress of ischemic lesions. Prediction of clinical evaluation in patients with cerebral hemorrhage through the study of image markers based on magnetic resonance imaging tractography. Prediction of the growth of cerebral hematoma by assessing the contrast extravasation in the brain MRI. Relationship between the flow rate in the middle cerebral artery and the invasive measurement of the pressure in the internal carotid artery during carotid endarterectomy: identification of patients at risk. Identification of vulnerable plaque through vulnerable blood.

NEUROSCIENCE AREA

PUBLICATIONS Originals (I.F.: 76.26): 1. Puig J, Pedraza S, Daunis-i-Estadella J, Termes H, Blasco G, Guadalupe S, Remollo S, Baños J, Jimenez-Nieto Maria, Serena J, Boada I, Castellanos M. “Quantification of Thrombus Hounsfield Units on Noncontrast CT Predicts Stroke Subtype and Early Recanalization after Intravenous Recombinant Tissue Plasminogen Activator”. American Journal of Neuroradiology. 2012; 33:90-6. PMID: 22158924. I.F.: 2.93 2. Demchuk AM, Dowlatshahi D, RodriguezLuna D, Molina CA, Silva Blas Y, Dzialowski I, Kobayashi A, Boulanger JM, Lum C, Gubitz G, Padma V, Roy J, Kase CS, Kosior J, Bhatia R, Tymchuk S, Subramaniam S, Gladstone DJ, Hill MD, Aviv RI; PREDICT/Sunnybrook ICH CTA Study Group. “Prediction of haematoma growth and outcome in patients with intracerebral haemorrhage using the CT-angiography spot sign (PREDICT): a prospective observational study”. Lancet Neurology. 2012; 11:307-14. PMID: 22405630. I.F.: 23.46 3. Cristobo I, Brea D, Blanco M, Vázquez F, Rodríguez-Yáñez M, Vivancos J, Silva Y, De la Ossa NP, Pumar JM, Forteza J, Castillo J. “Usefulness of material recovered from distal embolic devices after carotid angioplasty for proteomic studies”. Journal of Vascular and Interventional Radiology. 2012; 23:818-24. PMID: 22626270. I.F.: 2.08 4. López-Pousa S, Calvó-Perxas L, Lejarreta S, Cullell M, Meléndez R, Hernández E, Bisbe J, Perkal H, Manzano A, Roig AM, TurróGarriga O, Vilalta-Franch J, Garre-Olmo J; Registry of Dementias of Girona Study Group (ReDeGi Study Group). “Use of antidementia drugs in frontotemporal lobar degeneration”. American Journal of Alzheimer’s Disease and other Dementias. 2012; 27:260-6. PMID: 22605780. I.F.: 1.45 5. Calvó-Perxas L, López-Pousa S, VilaltaFranch J, Turró-Garriga O, Blankenburg M, Febrer L, Flaqué M, Vallmajó N, Aguirregomozcorta M, Genís D, Casas I, Perkal H, Coromina J, Garre-Olmo J; Registry of Dementias of Girona Study Group. “Central

ANNUAL SCIENTIFIC REPORT 2012 IDIBGI

nervous system drug consumption depending on the time between symptom onset and the diagnosis of Alzheimer’s disease: an analysis by the Registry of Dementias of Girona”. Dementia and Geriatric Cognitive Disorders. 2012; 33:104-10. PMID: 22472600. I.F.: 2.14 6. Del Río-Espínola A, Fernández-Cadenas I, Giralt D, Quiroga A, Gutiérrez-Agulló M, Quintana M, Fernández-Álvarez P, Domingues-Montanari S, Mendióroz M, Delgado P, Turck N, Ruíz A, Ribó M, Castellanos M, Obach V, Martínez S, Freijo M.M, Jiménez-Conde J, Cuadrado-Godia E, Roquer J, Chacón P, Martí-Fábregas J, Sánchez J.C, Montaner J, GRECOS investigators. “A predictive clinical-genetic model of t-PA response in acute ischemic stroke”. Annals of Neurology. 2012; 72:716-29. PMID: 23280790. I.F.: 11.09 7. Calvo-Perxas L, Osuna MT, Gich J, EligioHernandez E, Linares M, Vinas M, Casas I, Turro-Garriga O, Lopez-Pousa S, GarreOlmo J; In representation of the Girona Dementia Registry Study Group. “Clinical and demographic characteristics of the cases of dementia diagnosed in the Health District of Girona throughout the period 2007-2010: data from the Girona Dementia Registry (ReDeGi)”. Revista de Neurología. 2012; 54:399-406. PMID: 22451126. I.F.: 0.65 8. Brea D, Roquer J, Serena J, Segura T, Castillo J; on behalf of the ARTICO STUDY. “Oxidative stress markers are associated to vascular recurrence in non-cardioembolic stroke patients non-treated with statins”. BMC Neurology. 2012; 12:65. PMID: 22862793. I.F.: 2.17 9. Fernández-Cadenas I, Del Río-Espínola A, Giralt D, Domingues-Montanari S, Quiroga A, Mendióroz M, Ruíz A, Ribó M, Serena J, Obach V, Freijo MM, Martí-Fábregas J, Delgado P, Montaner J. “IL1B and VWF variants are associated with fibrinolytic early recanalization in patients with ischemic stroke”. Stroke. 2012; 43:2659-65. PMID: 22858724. I.F.: 5.76 10. Alonso M, Castellanos M, Besalú E, Sanchez JM. “A headspace needle-trap method for the analysis of volatile organic compounds in whole blood”. Journal of

Chromatography A. 2012; 1252:23-30. PMID: 22794794. I.F.: 4.53 11. Fernández-Cadenas I, Del Río-Espínola A, Carrera C, Domingues-Montanari S, Mendióroz M, Delgado P, Rosell A, Ribó M, Giralt D, Quintana M, Castellanos M, Obach V, Martínez S, Freijo MM, Jiménez-Conde J, Roquer J, Martí-Fábregas J, Molina CA, Alvarez-Sabín J, Montaner J. “Role of the MMP9 gene in hemorrhagic transformations after tissue-type plasminogen activator treatment in stroke patients”. Stroke. 2012; 43:1398-400. PMID: 22496335. I.F.: 5.76 12. Calvó-Perxas L, De Eugenio RM, MarquezDaniel F, Martínez R, Serena J, Turbau J, Vilalta-Franch J, Viñas M, Turró-Garriga O, Roig AM, López-Pousa S, Garre-Olmo J; Girona Dementia Registry Study Group. “Profile and variables related to antipsychotic consumption according to dementia subtypes”. International Psychogeriatrics. 2012; 24:940-7. PMID: 22333005. I.F.: 2.24 13. Rodrigo-Gil J, Suñer-Soler R, Cruz-Díaz V, Bagot-Prats M, Algans-Coll L, CepedaBautista M, Ribó-Regas M, Serena J. “Care for patients with acute stroke: effectiveness of portable vesical ultrasound imaging in the stroke unit”. Revista de Neurología. 2012; 54:151-8. PMID: 22278891. I.F.: 0.65 14. Suñer-Soler R, Grau A, Gras ME, FontMayolas S, Silva Y, Dávalos A, Cruz V, Rodrigo J, Serena J. “Smoking cessation 1 year poststroke and damage to the insular cortex”. Stroke. 2012; 43:131-6. PMID: 22052507. I.F.: 5.76 15. Leira R, Sobrino T, Blanco M, Campos F, Rodríguez-Yáñez M, Castellanos M, Moldes O, Millán M, Dávalos A, Castillo J. “A higher body temperature is associated with haemorrhagic transformation in patients with acute stroke untreated with recombinant tissue-type plasminogen activator (rtPA)”. Clinical Science. 2012; 122:113-9. PMID: 21861843. I.F.: 4.32 16. Pedraza S, Puig J, Blasco G, Daunis-iEstadella J, Boada I, Bardera A, Castellanos M, Serena J. “Reliability of the ABC/2 method in determining acute infarct volume”. Journal of Neuroimaging. 2012; 22:155-9. PMID: 21447023. I.F.: 1.29 39

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Multicentric (I.F.: 94.30): 1. Dávalos A, Alvarez-Sabín J, Castillo J, DíezTejedor E, Ferro J, Martínez-Vila E, Serena J, Segura T, Cruz VT, Masjuan J, Cobo E, Secades JJ; International Citicoline Trial on acUte Stroke (ICTUS) trial investigators. “Citicoline in the treatment of acute ischaemic stroke: an international, randomised, multicentre, placebo-controlled study (ICTUS trial)”. Lancet. 2012; 380:349-57. PMID: 22691567. I.F.: 38.28

ANNUAL SCIENTIFIC REPORT 2012 IDIBGI

Neurologia. 2012; 27:560-74. PMID: 21890241. I.F.: 0.79 Case Report (I.F.: 1.32): 1. Robles-Cedeño R, Ramió-Torrentà L, Laguillo G, Gich J, Castellanos M. “Long-term clinical and radiological evolution in one case of Susac’s syndrome”. Neurological Sciences. 2012; 33:1407-10. PMID: 22454036. I.F.: 1.32

Grants for Research in Progress: 2. Benavente OR, Hart RG, McClure LA, Szychowski JM, Coffey CS, Pearce LA, SPS3 Investigators. Autor cooperativo. “Effects of clopidogrel added to aspirin in patients with recent lacunar stroke”. New England Journal of Medicine. 2012; 367:817-25. PMID: 22931315. I.F.: 53.30 3. Purroy F, Jiménez Caballero PE, Gorospe A, Torres MJ, Alvarez-Sabin J, Santamarina E, Martínez-Sánchez P, Cánovas D, Freijo MM, Egido JA, Girón JM, Ramírez-Moreno JM, Alonso A, Rodríguez-Campello A, Casado I, Delgado-Medeiros R, Martí-Fàbregas J, Fuentes B, Silva Y, Quesada H, Cardona P, Morales A, De la Ossa N, García-Pastor A, Arenillas JF, Segura T, Jiménez C, Masjuán J; Stroke Project of the Spanish Cerebrovascular Diseases Study Group. “Prediction of early stroke recurrence in transient ischaemic attack patients from the PROMAPA study: a comparison in prognostic risk scores”. Cerebrovascular Diseases. 2012; 33:182-9. PMID: 22237056. I.F.: 2.72 Review (I.F.: 0.79): 1. Fuentes B, Gállego J, Gil-Nuñez A, Morales A, Purroy F, Roquer J, Segura T, Tejada J, Lago A, Díez-Tejedor E, Alonso de Leciñana M, Alvarez-Sabin J, Arenillas J, Calleja S, Casado I, Castellanos M, Castillo J, Dávalos A, Díaz-Otero F, Egido JA, López-Fernández JC, Freijo M, García Pastor A, Gilo F, Irimia P, Maestre J, Masjuan J, Martí-Fábregas J, Martínez-Sánchez P, Martínez-Vila E, Molina C, Nombela F, Ribó M, Rodríguez-Yañez M, Rubio F, Serena J, Simal P, Vivancos J; SEN ad hoc Committee of the Cerebrovascular Disease Study Group. “Guidelines for the preventive treatment of ischaemic stroke and TIA (I). Update of risk factors and life style”. 40

Estudio de alteración de la permeabilidad de la barrera hematoencefálica y relación con los mecanismos moleculares predictivos de transformación hemorrágica en isquemia cerebral tratada con rt-PA. (PI10/01309) Sponsored by: Instituto de Salud Carlos III Duration: 2011 - 2013 Mar Castellanos Red Neurovascular: RENEVAS (RD07/0026/2002) Sponsored by: Instituto de Salud Carlos III Duration: 01/01/2009 - 31/12/2012 Joaquín Serena

NEUROSCIENCE AREA

ANNUAL SCIENTIFIC REPORT 2012 IDIBGI

MEDICAL IMAGING

GROUP MEMBERS Group Leader: Salvador Pedraza

PUBLICATIONS Originals (I.F.: 23.45):

STRATEGIC OBJECTIVES Validation of Imaging Biomarkers

1. Warach S, Al-Rawi Y, Furlan AJ, Fiebach JB, Wintermark M, Lindstén A, Smyej J, Bharucha DB, Pedraza S, Rowley HA. “Refinement of the magnetic resonance diffusion-perfusion mismatch concept for thrombolytic patient selection: insights from the desmoteplase in acute stroke trials”. Stroke. 2012; 43:2313-8. PMID: 22738918. I.F.: 5.76

PREVENTION STUDIES POST-DOCORATE RESEARCHERS Elda Balliu Jorge Guibernau Josep Puig Gerard Blasco Elsa Pérez Laia Valls COLLABORATORS Brigitte Beltran Gemma Laguillo Sebastian Remollo Imma Boada Alberto Prats Guadalupe Soria Ana Carrera Teresa Puig Enric Verdú Eva Gómez Ana Quiles David Hernández Josep Daunis Francisco Reina TECHNICIANS Joan Banyos NURSING STAFF Javier Molina

Validation of the usefulness of Diffusion Tensor in the management and prognosis of stroke patients. Validation of the usefulness of Diffusion Tensor in the assessment of the evolution time of stroke. Validation of the usefulness of the Diffusion/ FLAIR mismatch in the treatment of patients with wake-up stroke. Validation of perfusion CT in the diagnosis of stroke. Usefulness of the study of arterial wall elasticity in the prediction of cardiovascular risk. Usefulness of intravascular contrast in defining the real extension of aggressive brain tumors. Usefulness of the Diffusion Tensor in the assessment of lumbar disc degeneration. Validation of echographic biomarkers (mean intima-media index degree d; hepatic steatosis) on estimating the metabolic syndrome in obese patients. Usefulness of Diffusion Tensor in the management of patients with hydrocephaly.

2. Fiebach JB, Al-Rawi Y, Wintermark M, Furlan AJ, Rowley HA, Lindstén A, Smyej J, Eng P, Warach S, Pedraza S. “Vascular occlusion enables selecting acute ischemic stroke patients for treatment with desmoteplase”. Stroke. 2012; 43:1561-6. PMID: 22474060. I.F.: 5.76 3. Prados F, Boada I, Feixas M, Prats-Galino A, Blasco G, Puig J, Pedraza S. “Informationtheoretic approach for automated white matter fiber tracts reconstruction”. Neuroinformatics. 2012; 10:305-18. PMID: 22467471. I.F.: 2.97 4. Pedraza S, Puig J, Blasco G, Daunis-iEstadella J, Boada I, Bardera A, Castellanos M, Serena J. “Reliability of the ABC/2 method in determining acute infarct volume”. Journal of Neuroimaging. 2012; 22:155-9. PMID: 21447023. I.F.: 1.29 5. Prats-Galino A, Soria G, De Notaris M, Puig J, Pedraza S. “Functional anatomy of subcortical circuits issuing from or integrating at the human brainstem”. Clinical Neurophysiology. 2012; 123:4-12. PMID: 22055838. I.F.: 2.79 6. Diéguez Vide F., Gich Fullà J., PuigAlcantara J, Sánchez-Benavides G., PeñaCasanova J. “Chinese-Spanish-Catalan trilingual aphasia: A case study”. Journal of Neurolinguistics. 2012; 25:630-641. I.F.: 1.97 7. Puig J, Pedraza S, Demchuck A, Daunis J, Termes H, Blasco G, Soria G, Boada I, Remollo S, Baños J, Serena J, Castellanos M. “Quantification of Thrombus Hounsfield Units on Noncontrast CT Predicts Stroke Subtype and Early Recanalization after Intravenous Recombinant Tissue Plasminogen”. American 41

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Journal of Neuroradiology. 2012; 33:90-6. PMID: 22158924. I.F.: 2.93 Multicentrics (I.F.: 2,75): 1. Von Kummer R, Albers GW, Mori E; DIAS Steering Committees. Collaborators (Pedraza). “The Desmoteplase in Acute Ischemic Stroke (DIAS) clinical trial program”. International Journal of Stroke. 2012; 7:58996. PMID: 22989394. I.F.: 2.75

GRANTS FOR RESEARCH IN PROGRESS: · WAKEUP. Efficacy and safety of MRIbased thrombolysis in wake-up stroke: a randomised, double-blind, placebocontrolled trial Sponsored by: European Union. 7th Framework Programme Duration: 2011 - 2016 Chistian Gerlof – Salvador Pedraza · Validación de nuevos parámetros de Difusión tensor como biomarcadores de imagen en el infarto cerebral. Estudio anatómico de Tracto Corticoespinal (PI09/0596) Sponsored by: Instituto de Salud Carlos III Duration: 2010 - 2013 Salvador Pedraza · Developing computer radiological game as a tool for problem based-learning (PBL) of radiology for undergraduate medical education (MEDGAME) Sponsored by: Radiological Society of North America Duration: 2012 Salvador Pedraza

ANNUAL SCIENTIFIC REPORT 2012 IDIBGI

NEUROSCIENCE AREA

ANNUAL SCIENTIFIC REPORT 2012 IDIBGI

NEURODEGENERATION AND NEUROINFLAMMATION GROUP MEMBERS Group Leader: David Genís Batlle SENIOR RESEARCHERS Lluís Ramió POST-DOCORATE RESEARCHERS Ester Quintana POST-GRADUATE RESEARCHERS Jordi Gich Rebeca Menéndez René Robles Fabian Márquez Ana Quiles COLLABORATORS Laura Fábregas Hector Perkal Pepi López Miguel Ángel Robles TECHNICIANS Neus Pueyo NURSING STAFF Judit Guerrero Miguel Merchan

STRATEGIC OBJECTIVES

MAIN LINES OF RESEARCH

· Be the reference group in the province of Girona for research and education in multiple sclerosis and other neurodegenerative diseases. · Have a national and international presence in the field of research into multiple sclerosis. · Consolidate clinical research in multiple sclerosis. · Initiate and consolidate basic research into multiple sclerosis. · Promote and lead research into new treatments for multiple sclerosis. · Initiate clinical research into other neurodegenerative diseases (Parkinson’s disease). · Consolidate clinical research into hereditary ataxia. · Establish research collaboration with other national and international groups working on multiple sclerosis. · Promote research into multiple sclerosis in nursing and neuropsychology. · Promote training and education in multiple sclerosis for healthcare professionals, specialists and aff ected patients and their family.

Priority clinical-healthcare lines: 1. Study of neuropsychological disorders and cognitive rehabilitation in multiple sclerosis. 2. Study of the emotional impact, ability to cope, and adaptation to the diagnosis of multiple sclerosis. 3. Study of fatigue in multiple sclerosis. 4. Improve compliance with immunomodulatory treatment in multiple sclerosis. 5. Application of new brain MRI techniques as prognosis markers in multiple sclerosis. 6. Computer-based organisation of lesions detected by brain MRI in patients with multiple sclerosis. Priority lines in basic research: 1. Study of the gene expression in demyelinating diseases including multiple sclerosis. 2. Study of the molecular expression in multiple sclerosis as a model of chronic infl ammatory disease. 3. Determination of biological prognosis factors in cerebrospinal fluid and serum for the evolution of multiple sclerosis (genetic factors, biochemical factors, environmental factors such as vitamin D, virus and others). 4. Determination of biological response factors (genetic and biochemical) to immunomodulatory treatments in multiple sclerosis. 5. Bank of DNA, CSF and serum samples of neuroimmunological diseases.

NEUROSCIENCE AREA

PUBLICATIONS Originals (I.F.: 11.12): 1. López-Pousa S, Turró-Garriga O, CalvóPerxas L, Carmona O, Gich J, Alsina E, Màrquez F, Viñas M, Turbau J, Vilalta-Franch J, Roig AM, Garre-Olmo J. “Consumption of Pharmaceuticals in Primary Non-Alzheimer’s Degenerative Dementias: A Cross-Sectional Study by the Registry of Dementias of Girona (ReDeGi)”. Drugs & Aging. 2012; 29:733-40. PMID: 23018609. I.F.: 2.67 2. López-Pousa S, Calvó-Perxas L, Lejarreta S, Cullell M, Meléndez R, Hernández E, Bisbe J, Perkal H, Manzano A, Roig AM, TurróGarriga O, Vilalta-Franch J, Garre-Olmo J; Registry of Dementias of Girona Study Group (ReDeGi Study Group). “Use of antidementia drugs in frontotemporal lobar degeneration”. American Journal of Alzheimer’s Disease and other Dementias. 2012; 27:260-6. PMID: 22605780. I.F.: 1.45 3. Calvó-Perxas L, López-Pousa S, VilaltaFranch J, Turró-Garriga O, Blankenburg M, Febrer L, Flaqué M, Vallmajó N, Aguirregomozcorta M, Genís D, Casas I, Perkal H, Coromina J, Garre-Olmo J; Registry of Dementias of Girona Study Group. “Central nervous system drug consumption depending on the time between symptom onset and the diagnosis of Alzheimer’s disease: an analysis by the Registry of Dementias of Girona”. Dementia and Geriatric Cognitive Disorders. 2012; 33:104-10. PMID: 22472600. I.F.: 2.14 4. Calvo-Perxas L, Osuna MT, Gich J, EligioHernandez E, Linares M, Vinas M, Casas I, Turro-Garriga O, Lopez-Pousa S, GarreOlmo J; In representation of the Girona Dementia Registry Study Group. “Clinical and demographic characteristics of the cases of dementia diagnosed in the Health District of Girona throughout the period 2007-2010: data from the Girona Dementia Registry (ReDeGi)”. Revista de Neurología. 2012; 54:399-406. PMID: 22451126. I.F.: 0.65 5. Calvó-Perxas L, De Eugenio RM, MarquezDaniel F, Martínez R, Serena J, Turbau J, Vilalta-Franch J, Viñas M, Turró-Garriga O, Roig AM, López-Pousa S, Garre-Olmo J; Girona Dementia Registry Study Group. 44

ANNUAL SCIENTIFIC REPORT 2012 IDIBGI

“Profile and variables related to antipsychotic consumption according to dementia subtypes”. International Psychogeriatrics. 2012; 24:940-7. PMID: 22333005. I.F.: 2.24 6. Diéguez Vide F., Gich Fullà J., PuigAlcantara J, Sánchez-Benavides G., PeñaCasanova J. “Chinese-Spanish-Catalan trilingual aphasia: A case study”. Journal of Neurolinguistics. 2012; 25:630-641. I.F.: 1.97 Multicentric (I.F.: 53.30): 1. Comi G, Jeffery D, Kappos L, Montalban X, Boyko A, Rocca MA, Filippi M; ALLEGRO Study Group. “Placebo-controlled trial of oral laquinimod for multiple sclerosis”. New England Journal of Medicine. 2012; 366:10009. PMID: 22417253. I.F.: 53.30 Reviews (I.F.: 7.46): 1. Fernandez O, Alvarez-Cermeno JC, ArroyoGonzalez R, Brieva L, Calles-Hernandez MC, Casanova-Estruch B, Comabella M, De las Heras V, Garcia-Merino JA, Hernandez-Perez MA, Izquierdo G, Meca-Lallana JE, MunozGarcia D, Olascoaga J, Oreja-Guevara C, Prieto JM, Ramio-Torrenta L, Rodriguez-Antiguedad A, Romero-Pinel L, Sanchez F, Tellez N, Tintore M, Montalban X; Post-ECTRIMS group. “Review of the novelties presented at the 27th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) (II)”. Revista de Neurología. 2012; 54:734-49. PMID: 22673950. I.F.: 0.65 2. Fernández Ó, Álvarez-Cermeño JC, ArroyoGonzález R, Brieva L, Calles-Hernández MC, Casanova-Estruch B, Comabella M, De las Heras V, García-Merino JA, Hernández-Pérez MA, Izquierdo G, Meca-Lallana JE, MuñozGarcía D, Olascoaga J, Oreja-Guevara C, Prieto JM, Ramió-Torrentà L, Rodríguez-Antigüedad A, Romero-Pinel L, Sanchez F, Téllez N, Tintoré M, Montalban X; Post-ECTRIMS group. “Review of the novelties presented at the 27th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) (I)”. Revista de Neurología. 2012; 54:677-91. PMID: 22627749. I.F.: 0.65 3. Lladó X, Ganiler O, Oliver A, Martí R, Freixenet J, Valls L, Vilanova JC, RamióTorrentà L, Rovira A. “Automated detection

of multiple sclerosis lesions in serial brain MRI”. Neuroradiology. 2012; 54:787-807. PMID: 22179659. I.F.: 2.87 4. Saute JA, Donis KC, Serrano-Munuera C, Genis D, Ramirez LT, Mazzetti P, Pérez LV, Latorre P, Sequeiros J, Matilla-Dueñas A, Jardim LB; Iberoamerican Multidisciplinary Network for the Study of Movement Disorders (RIBERMOV) Study Group. “Ataxia rating scales--psychometric profiles, natural history and their application in clinical trials”. Cerebellum. 2012; 11:488-504. PMID: 21964941. I.F.: 3.29 Case Report (I.F.: 1.32): 1. Robles-Cedeño R, Ramió-Torrentà L, Laguillo G, Gich J, Castellanos M. “Long-term clinical and radiological evolution in one case of Susac’s syndrome”. Neurological Sciences. 2012; 33:1407-10. PMID: 22454036. I.F.: 1.32

Grants for Research in Progress: · Estudi clínic i de lligament genètic en una estirp gitana afecta per esclerosi múltiple. PI10/02649 Sponsored by: Instituto de Salud Carlos III Duration: 2011 - 2013 Lluís Ramió i Torrentà · Esclerosi múltiple i vitamina D: relació entre els nivells circulants de 25-hidroxivitamina D i evolució clínica i radiològica dels pacients amb esclerosi múltiple Sponsored by: Agrupació de Ciències Mèdiques de Girona Duration: 2012 - 2013 René Robles Cedeño · Marcadors genètics i bioquímics en sèrum i LCR i evolució clínica i radiològica dels pacients amb esclerosi múltiple a la província de Girona (estudi BioEM) Sponsored by: Agrupació de Ciències Mèdiques de Girona Duration: 2011 - 2012 René Robles Cedeño

NEUROSCIENCE AREA

· SALEM: Segmentació automàtica de lesions d’esclerosi múltiple en imatges de ressonància magnètica. PI09/91018 Sponsored by: Instituto de Salud Carlos III Duration: 2010 - 2012 Xavier Lladó

· Red Española de Esclerosis Múltiple: REEM (RD07/0060/0022) Sponsored by: Instituto de Salud Carlos III Duration: 2008 - 2012 Lluís Ramió i Torrentà

ANNUAL SCIENTIFIC REPORT 2012 IDIBGI

ONCOLOGY AND HEMATOLOGY AREA

ANNUAL SCIENTIFIC REPORT 2012 IDIBGI

ONCOLOGY AND HEMATOLOGY AREA DESCRIPTIVE EPIDEMIOLOGY, GENETICS AND CANCER PREVENTION HEMATOLOGY HEPATOBILIARY & PANCREATIC SURGERY AND ONCOLOGY MOLECULAR ONCOLOGY

ONCOLOGY AND HEMATOLOGY AREA

ANNUAL SCIENTIFIC REPORT 2012 IDIBGI

DESCRIPTIVE EPIDEMIOLOGY, GENETICS AND CANCER PREVENTION GROUP MEMBERS Group Leader: Rafael Marcos-Gragera POST-DOCORATE RESEARCHERS Rafael Fuentes Bernat Serdà Neus Vilar POST-GRADUATE RESEARCHERS Maria Buxó Judit Moreno Jordi Rubió Carme Carmon Gemma Osca Loreto Vilardell Angel Izquierdo Monserrat Puig SECRETARY Joana Fuentes

STRATEGIC OBJECTIVES 1. Descriptive and analytical epidemiology of cancer. · Population-based cancer register of the province of Girona (national and international collaborations). a) Population-based incidence and prevalence of cancer, projections of the incidence of cancer. b) Population-based cancer survival (international collaborations: EUROCARE and CONCORD programs). · Study of genetic and molecular prognostic factors in breast cancer and hematological tumors. · Study of environmental and genetic risk factors in breast cancer and chronic lymphocytic leukemia.

PUBLICATIONS Originals (I.F.: 36.22): 1. Osca-Gelis G, Puig-Vives M, Saez M, Gallardo D, Solé F, Marcos-Gragera R. “Incidence and survival of chronic myelomonocytic leukemia in Girona (Spain): a population-based study, 1993-2007”. Leukemia Research. 2012; 36:1262-6. PMID: 22784713. I.F.: 2.92

2. Prevention of cancer. • Assessment of the organized breast cancer screening program. · Benefits and side effects of breast cancer screening: method to improve the measurement of the results of early detection. · Assessment of the rate of interval cancer and its determining factors in the program for early detection of breast cancer in the Girona Healthcare Region. • Assessment of the opportunistic screening program for cervical cancer. · Determination of the sensitivity and specificity of cervical cytology (Pap test). · Assessment of the effectiveness of vaccination against human papillomavirus. 3. Genetics (genetic epidemiology of cancer). Assessment of the risk of developing cancer. Study of the genetic risk factors for cancer. Genetic susceptibility to cancer. MAIN LINE OF RESEARCH: Descriptive and analytical epidemiology of cancer.

2. Marcos-Gragera R, Salmerón D, Izarzugaza I, Ardanaz E, Serdà BC, Larrañaga N, San Román E, Navarro C, Chirlaque MD. “Trends in prostate cancer survival in Spain: results from population-based cancer registries”. Clinical & Translational Oncology. 2012; 14:458-64. PMID: 22634535. I.F.: 1.33 3. Fernández-Rodríguez J, Quiles F, Blanco I, Teulé A, Feliubadaló L, Valle JD, Salinas M, Izquierdo A, Darder E, Schindler D, Capellá G, Brunet J, Lázaro C, Pujana MA. “Analysis of SLX4/FANCP in non-BRCA1/2-mutated breast cancer families”. BMC Cancer. 2012; 12:84. PMID: 22401137. I.F.: 3.01 4. Clèries R, Ribes J, Buxo M, Ameijide A, Marcos-Gragera R, Galceran J, Miguel Martínez J, Yasui Y. “Bayesian approach to predicting cancer incidence for an area without cancer registration by using cancer incidence data from nearby areas”. Statistics in Medicine. 2012; 31:978-87. PMID: 22237653. I.F.: 1.88 5. Visser O, Trama A, Maynadié M, Stiller C, Marcos-Gragera R, De Angelis R, Mallone S, Tereanu C, Allemani C, Ricardi U, Schouten HC; RARECARE Working Group. “Incidence, survival and prevalence of myeloid malignancies in Europe”. European Journal of Cancer. 2012; 48:3257-66. PMID: 22770878. I.F.: 5.54 6. Salmerón D; Chirlaque MD; M Isabel Izarzugaza; Sánchez MJ; Marcos-Gragera R; Ardanaz E; Galceran J; Mateos A; Navarro C. “Lung cancer prognosis in Spain: The role of histology, age and sex”. Respiratory Medicine. 2012; 106:1301-8. PMID: 22749756. I.F.: 2.48 7. Mallone S; De Vries E; Guzzo M; Midena E; Verne J; Coebergh JW; Marcos-Gragera 47

ONCOLOGY AND HEMATOLOGY AREA

R; Ardanaz E; Martinez R; Chirlaque MD; Navarro C; Virgili G; RARECARE Working Group. “Descriptive epidemiology of malignant mucosal and uveal melanomas and adnexal skin carcinomas in Europe”. European Journal of Cancer. 2012; 48:1167-1175. PMID: 22119735. I.F.: 5.54 8. Buxó-Pujolràs M, Martínez JM, Yasui Y, Borrell C, Martín JC, Vergara M, Cervantes M, Benach J. “Monitoring the cluster of high-risk mortality areas in the southwest of Spain”. Geospatial Health. 2012; 7:73-81. PMID: 23242682. I.F.: 3.00 9. Ibáñez R, Moreno-Crespi J, Sardà M, Autonell J, Fibla M, Gutiérrez C, Lloveras B, Alejo M, Català I, Alameda F, Casas M, Bosch FX, De Sanjosé S. “Prediction of cervical intraepithelial neoplasia grade 2+ (CIN2+) using HPV DNA testing after a diagnosis of atypical squamous cell of undetermined significance (ASC-US) in Catalonia, Spain”. BMC Infectious Diseases. 2012; 12:25. PMID: 22280073. I.F.: 3.12 10. Puig M, Pollán M, Rué M,Osca G, Saez M, Izquierdo A, Marcos-Gragera R. “Rapid increase in incidence of breast ductal carcinoma in situ in Girona, Spain 1983-2007”. Breast. 2012; 21:646-51. PMID: 22340960. I.F.: 2.49 11. Sant M, Minicozzi P, Lagorio S, Børge Johannesen T, Marcos-Gragera R, Francisci S; EUROCARE Working Group. “Survival of European patients with central nervous system tumors”. International Journal of Cancer. 2012; 131:173-85. PMID: 21805473. I.F.: 4.93 Multicentric (I.F.: 72.22): 1. Gavin AT, Francisci S, Foschi R, Donnelly DW, Lemmens V, Brenner H, Anderson LA; EUROCARE-4 Working Group (MarcosGragera R, Vilardell ML, Izquierdo A). “Oesophageal cancer survival in Europe: a EUROCARE-4 study”. Cancer Epidemiology. 2012; 36:505-12. PMID: 22910036. I.F.: 2.01 2. Van der Zwan JM, Mallone S, Van Dijk B, Bielska-Lasota M, Otter R, Foschi R, Baudin E, Links TP; RARECARE WG (Marcos-Gragera R). “Carcinoma of endocrine organs: results 48

ANNUAL SCIENTIFIC REPORT 2012 IDIBGI

of the RARECARE project”. European Journal of Cancer. 2012; 48:1923-31. PMID: 22361014. I.F.: 5.54

and survival of rare urogenital cancers in Europe”. European Journal of Cancer. 2012; 48:456-64. PMID: 22119351. I.F.: 5.54

3. Oberaigner W, Minicozzi P, Bielska-Lasota M, Allemani C, De Angelis R, Mangone L, Sant M; Eurocare Working Group (Marcos-Gragera R, Vilardell ML, Izquierdo A). “Survival for ovarian cancer in Europe: the across-country variation did not shrink in the past decade”. Acta Oncologica. 2012; 51:441-53. PMID: 22313338. I.F.: 3.33

10. Trama A, Mallone S, Nicolai N, Necchi A, Schaapveld M, Gietema J, Znaor A, Ardanaz E, Berrino F; RARECARE Working Group (Marcos-Gragera R). “Burden of testicular, paratesticular and extragonadal germ cell tumours in Europe”. European Journal of Cancer. 2012; 48:159-69. PMID: 22142457. I.F.: 5.54

4. Siesling S, Van der Zwan JM, Izarzugaza I, Jaal J, Treasure T, Foschi R, Ricardi U, Groen

11. Collaborative Group on Hormonal Factors in Breast Cancer (Pau Viladiu, Angel

H, Tavilla A, Ardanaz E; RARECARE Working Group (Marcos-Gragera R). “Rare thoracic cancers, including peritoneum mesothelioma”. European Journal of Cancer. 2012; 48:949-60. PMID: 22406029. I.F.: 5.54

Izquierdo). “Menarche, menopause, and breast cancer risk: individual participant metaanalysis, including 118,964 women with breast cancer from 117 epidemiological studies”. Lancet Oncology. 2012; 13:1141-51. PMID: 23084519. I.F.: 22.59

5. Van Dijk BA, Gatta G, Capocaccia R, Pierannunzio D, Strojan P, Licitra L; RARECARE Working Group (Marcos-Gragera R). “Rare cancers of the head and neck area in Europe”. European Journal of Cancer. 2012; 48:783-96. PMID: 22051735. I.F.: 5.54 6. Faivre J, Trama A, De Angelis R, Elferink M, Siesling S, Audisio R, Bosset JF, Cervantes A, Lepage C; RARECARE Working Group (Marcos-Gragera R). “Incidence, prevalence and survival of patients with rare epithelial digestive cancers diagnosed in Europe in 1995-2002”. European Journal of Cancer. 2012; 48:1417-24. PMID: 22169462. I.F.: 5.54 7. Crocetti E, Trama A, Stiller C, Caldarella A, Soffietti R, Jaal J, Weber DC, Ricardi U, Slowinski J, Brandes A; RARECARE Working Group (Marcos-Gragera R). “Epidemiology of glial and non-glial brain tumours in Europe”. European Journal of Cancer. 2012; 48:1532-42. PMID: 22227039. I.F.: 5.54 8. Gatta G, Ferrari A, Stiller CA, Pastore G, Bisogno G, Trama A, Capocaccia R; RARECARE Working Group (Marcos-Gragera R). “Embryonal cancers in Europe”. European Journal of Cancer. 2012; 48: 1425-33. PMID: 22357215. I.F.: 5.54 9. Visser O, Adolfsson J, Rossi S, Verne J, Gatta G, Maffezzini M, Franks KN; RARECARE Working Group (Marcos-Gragera R). “Incidence

Reviews (I.F.: 1.52): 1. Pérez-Bovet J, Garcia-Armengol R, BuxóPujolràs M, Lorite-Díaz N, Narváez-Martínez Y, Caro-Cardera JL, Rimbau-Muñoz J, JolyTorta MC, Castellví-Joan M, Martín-Ferrer S. “Decompressive craniectomy for encephalitis with brain herniation: case report and review of the literature”. Acta Neurochirurgica. 2012; 154:1717-24. PMID: 22543444. I.F.: 1.52

GRANTS FOR RESEARCH IN PROGRESS: · Estudio multicaso-control de base poblacional (cáncer de mama y leucemia linfática crónica) (PI11/02213) Sponsored by: Instituto de Salud Carlos III. Fondo de Investigación Sanitaria (FIS) Duration: 01/01/2012 - 31/12/2014 Loreto Vilardell Gil · Evaluación del efecto del programa de detección precoz del cáncer de mama de la Región Sanitaria Girona mediante el cruce con Registro poblacional de cáncer de Girona (PI09/90127) Sponsored by: Instituto de Salud Carlos III Duration: 01/01/2010 - 31/12/2012 Rafael Marcos Gragera

ONCOLOGY AND HEMATOLOGY AREA

· Evaluación del efecto del programa de detección precoz del cáncer de mama de la “Regió Sanitaria de Girona” mediante el cruce con Registro poblacional de cáncer de Girona Sponsored by: Ministerio de Educación. Programa de Formación del Profesorado Universitario (FPU) Duration: 2010 - 2014 Rafael Marcos-Gragera / Marc Saez · Epidemiologia de les neoplàsies hematològiques Sponsored by: Agaur. Programa de Formació d’investigadors (FI) Duration: 2010 - 2014 Rafael Marcos-Gragera / Marc Saez · Densidad mamográfica, susceptibilidad genética y cáncer de mama en mujeres de familias de alto riesgo (PROYECTO DMBRCA) (PS09/01024) Sponsored by: Instituto de Salud Carlos III Principal Investigator: Teresa Ramón y Cajal Asensio Collaborating Investigator: Angel Izquierdo · Incidencia, supervivencia y tendencias del cáncer en adolescentes en España: Un estudio cooperativo de 11 registros de càncer (PI10/01617) Sponsored by: Ministerio de Economía y Competitividad Duration: 2011 - 2013 Principal Investigator: Rafael Peris Bonet Collaborating Investigator: Rafael MarcosGragera

ANNUAL SCIENTIFIC REPORT 2012 IDIBGI

ONCOLOGY AND HEMATOLOGY AREA

ANNUAL SCIENTIFIC REPORT 2012 IDIBGI

HEMATOLOGY

PUBLICATIONS Originals (I.F.: 18.31): 1. Osca-Gelis G, Puig-Vives M, Saez M, Gallardo D, Solé F, Marcos-Gragera R. “Incidence and survival of chronic myelomonocytic leukemia in Girona (Spain): a population-based study, 1993-2007”. Leukemia Research. 2012; 36:1262-6. PMID: 22784713. I.F.: 2.92

Team involved in Red Temática de Investigación Cooperativa en Cáncer (RTICC) [Spanish Cancer Research Networks]

GROUP MEMBERS Group Leader: David Gallardo Giralt POST-GRADUATE RESEARCHERS Gemma Osca Nazly Santos MEDICAL RESEARCHERS Rosa Coll Yolanda González Josep Mª Roncero Cristalina Fernández Ramon Guardia Esperanza Tuset Santiago Gardella Natàlia Lloveras

STRATEGIC OBJECTIVES - Consolidate the DNA library of allogeneic HPT of GETH as part of the IDIBGI biobank. - Establish relations with research groups in the rest of Catalonia and Spain for specific subjects related to our lines of research. MAIN LINES OF RESEARCH: · Study of minor histocompatibility antigens and gene polymorphisms involved in the immune response as predictors of survival and implant disease against the host after allogenic transplant of hematopoietic progenitors. · Study of the expression of hematopoiesis regulating genes in myelodysplastic syndromes. · Analysis of genetic polymorphisms as predictors of the progression of multiple myeloma. · Study of the genetic polymorphisms involved in the response to treatment for chronic lymphocytic leukemia.

2. Sancho JM, Morgades M, Grifols JR, Juncà J, Guardia R, Vives S, Ferrà C, Batlle M, Ester A, Gallardo D, Millà F, Feliu E, Ribera JM. “Predictive factors for poor peripheral blood stem cell mobilization and peak CD34(+) cell count to guide pre-emptive or immediate rescue mobilization”. Cytotherapy. 2012; 14:823-9. PMID: 22540329. I.F.: 3.63 3. Bosch-Vizcaya A, Pérez-García A, Brunet S, Solano C, Buño I, Guillem V, MartínezLaperche C, Sanz G, Barrenetxea C, Martínez C, Tuset E, Lloveras N, Coll R, Guardia R, González Y, Roncero JM, Bustins A, Gardella S, Fernández C, Buch J, Gallardo D; GvHD/ Immunotherapy committee of the Spanish Group for Hematopoietic Transplant (GETH). “Donor CTLA-4 genotype influences clinical outcome after T cell-depleted allogeneic hematopoietic stem cell transplantation from HLA-identical sibling donors”. Biology of Blood and Marrow Transplantation. 2012; 18:100-5. PMID: 21703972. I.F.: 3.28 4. Ribera JM, Morgades M, González-Barca E, Miralles P, López-Guillermo A, Gardella S, López A, Abella E, García M, Navarro JT, Feliu E. “Long-term follow-up of patients with HIV-related diffuse large B-cell lymphomas treated in a phase II study with rituximab and CHOP”. British Journal of Haematology. 2012 Jun; 157(5):637-9. PMID: 22313456. I.F.: 4.94 5. Bastos Oreiro M, Castilla-Llorente C, De la Guía AL, De Paz R, Van Domselaar M, Nieto J, Rodriguez A, Gallardo D, Canales M. “Fecal calprotectin in allogeneic stem cell transplantation for the diagnosis of acute intestinal graft versus host disease”. Bone Marrow Transplantation. 2012; 47:1241-2. PMID: 22307017. I.F.: 3.54

ONCOLOGY AND HEMATOLOGY AREA

Multicentric (I.F.: 38.86): 1. Delgado J, Espinet B, Oliveira AC, Abrisqueta P, De la Serna J, Collado R, Loscertales J, Lopez M, Hernandez-Rivas JA, Ferra C, Ramirez A, Roncero JM, Lopez C, Aventin A, Puiggros A, Abella E, Carbonell F, Costa D, Carrio A, Gonzalez M. “Chronic lymphocytic leukaemia with 17p deletion: a retrospective analysis of prognostic factors and therapy results”. British Journal of Haematology. 2012; 157(1):67-74. PMID: 22224845. I.F.: 4.94 2. Valcárcel D, Montesinos P, Sánchez-Ortega I, Brunet S, Esteve J, Martínez-Cuadrón D, Ribera JM, Tormo M, Bueno J, Duarte R, Llorente A, Torres JP, Guardia R, Sanz MA, Sierra AJ. “A scoring system to predict the risk of death during induction with anthracycline plus cytarabine-based chemotherapy in patients with de novo acute myeloid leukemia”. Cancer. 2012; 118:410-7. PMID: 21717435. I.F.: 4.77 3. Rosiñol L, García-Sanz R, Lahuerta JJ, Hernández-García M, Granell M, De la Rubia J, Oriol A, Hernández-Ruiz B, Rayón C, Navarro I, García-Ruiz JC, Besalduch J, Gardella S, López Jiménez J, Díaz-Mediavilla J, Alegre A, San Miguel J, Bladé J. “Benefit from autologous stem cell transplantation in primary refractory myeloma? Different outcomes in progressive versus stable disease”. Haematologica. 2012; 97:616-21. PMID: 22058223. I.F.: 6.42 4. Rosiñol L, Oriol A, Teruel AI, Hernández D, López-Jiménez J, De la Rubia J, Granell M, Besalduch J, Palomera L, González Y, Etxebeste MA, Díaz-Mediavilla J, Hernández MT, De Arriba F, Gutiérrez NC, Martín-Ramos ML, Cibeira MT, Mateos MV, Martínez J, Alegre A, Lahuerta JJ, San Miguel J, Bladé J. ”Superiority of bortezomib, thalidomide, and dexamethasone (VTD) as induction pretransplantation therapy in multiple myeloma: a randomized phase 3 PETHEMA/ GEM study.” Blood. 2012; 120:1589-96. PMID: 22791289. I.F.: 9.90 5. Nomdedéu J, Hoyos M, Carricondo M, Esteve J, Bussaglia E, Estivill C, Ribera JM, Duarte R, Salamero O, Gallardo D, Pedro C, Aventin A, Brunet S, Sierra J. “Adverse impact of IDH1 and IDH2 mutations in primary AML: experience

ANNUAL SCIENTIFIC REPORT 2012 IDIBGI

of the Spanish CETLAM group”. Leukemia Research. 2012; 36:990-7. PMID: 22520341. I.F.: 2.92 6. Mateos MV, Oriol A, Martínez-López J, Gutiérrez N, Teruel AI, López de la Guía A, López J, Bengoechea E, Pérez M, Polo M, Palomera L, De Arriba F, González Y, Hernández JM, Granell M, Bello JL, Bargay J, Peñalver FJ, Ribera JM, Martín-Mateos ML, García-Sanz R, Lahuerta JJ, Bladé J, San-Miguel JF. “Maintenance therapy with bortezomib plus thalidomide or bortezomib plus prednisone in elderly multiple myeloma patients included in the GEM2005MAS65 trial”.

· Polimorfismos genéticos implicados en la enfermedad del injerto contra el huésped y en la supervivencia tras trasplante alogénico de progenitores hematopoyéticos. Banco nacional de ADN. (PI080413) Sponsored by: Instituto de Salud Carlos III Duration: 2009 - 2013 David Gallardo

Blood. 2012; 120:2581-8. PMID: 22889759. I.F.: 9.90

Grants for Research in Progress:

· Papel de los polimorfismos genéticos de CD38 y CD31 en la leucemia linfática crónica Sponsored by: Fundación Mutua Madrileña Duration: 2011 - 2013 Josep Maria Roncero · Biobanco de aloTPH del GETH. Polimorfismos en antígenos menores de histocompatibilidad y genes moduladores de respuesta inmune como predictores de alorreactividad. (PI11/01690) Sponsored by: Instituto de Salud Carlos III Duration: 2012 - 2014 David Gallardo · Minor histocompatibility antigens as mediators of immune alloreactivity in human transplantation Sponsored by: Fundació Marató TV3. Duration: 2013 - 2015 David Gallardo · Implicación de los antígenos menores de histocompatibilidad en el éxito del trasplante alogénico de progenitores hematopoyéticos Sponsored by: Fundación Mutua Madrileña Duration: 2009 - 2013 David Gallardo 51

ONCOLOGY AND HEMATOLOGY AREA

HEPATOBILIARY & PANCREATIC SURGERY AND ONCOLOGY GROUP MEMBERS Group Leader: Joan Figueras Felip MEDICAL RESEARCHERS Ernest Castro Xavi Hernández Pere Planellas Antoni Codina Santiago López-Ben Bernat Queralt Esther Diaz Albert Maroto Silvia Torres Laia Falgueras Rosa Ortiz Raquel Guardeño Berta Pardina COLLABORATORS Eugeni Casals Hector Daniel González Pilar Solé Mª José Ferri Carina Jardí Jordi Soriano Charo Garcia Rosa Peracaula

ANNUAL SCIENTIFIC REPORT 2012 IDIBGI

PUBLICATIONS Originals (I.F.: 9.10): 1. Adam R, De Gramont A, Figueras J, Guthrie A, Kokudo N, Kunstlinger F, Loyer E, Poston G, Rougier P, Rubbia-Brandt L, Sobrero A, Tabernero J, Teh C, Van Cutsem E; JeanNicolas Vauthey of the EGOSLIM (Expert Group on OncoSurgery Management of Liver Metastases) group. “The oncosurgery approach to managing liver metastases from colorectal cancer: a multidisciplinary international consensus”. Oncologist. 2012; 17:1225-39. PMID: 22962059. I.F.: 3.91 2. Oliveras-Ferraros C, Massaguer VallLlovera A, Vazquez-Martin A, Salip DC, Queralt B, Cufí S, Martin-Castillo B, BoschBarrera J, Brunet J, De Llorens R, Menendez JA. “Transcriptional upregulation of HER2 expression in the absence of HER2 gene amplification results in cetuximab resistance that is reversed by trastuzumab treatment”. Oncology Reports. 2012; 27:1887-92. PMID: 22427198. I.F.: 1.84 3. Oliveras-Ferraros C, Massaguer VallLlovera A, Salip DC, Vazquez-Martin A, Cufí S, Queralt B, Martin-Castillo B, Brunet J, De Llorens R, Menendez JA. “Evolution of the predictive markers amphiregulin and epiregulin mRNAs during long-term cetuximab treatment of KRAS wild-type tumor cells”. Investigational New Drugs. 2012; 30:846-52. PMID: 21161326. I.F.: 3.36 Multicentric (I.F.: 5.84): 1. Viganò L, Capussotti L, Barroso E, Nuzzo G, Laurent C, Ijzermans JN, Gigot JF, Figueras J, Gruenberger T, Mirza DF, Elias D, Poston G, Letoublon C, Isoniemi H, Herrera J, Sousa FC, Pardo F, Lucidi V, Popescu I, Adam R. “Progression while receiving preoperative chemotherapy should not be an absolute contraindication to liver resection for colorectal metastases”. Annals of Surgical Oncology. 2012; 19:2786-96. PMID: 22622469. I.F.: 4.17 2. Benavides M, Pericay C, ValladaresAyerbes M, Gil-Calle S, Massutí B, Aparicio J, Dueñas R, González-Flores E, Carrato A, Marcuello E, Gómez A, Cabrera E, Queralt B,

Gómez MJ, Guasch I, Etxeberría A, Alfaro J, Campos JM, Reina JJ, Aranda E. “Oxaliplatin in combination with infusional 5-fluorouracil as first-line chemotherapy for elderly patients with metastatic colorectal cancer: a phase II study of the Spanish Cooperative Group for the Treatment of Digestive Tumors”. Clinical Colorectal Cancer. 2012; 11:200-6. PMID: 22421001. I.F.: 1.68 Reviews (I.F.: 2.10): 1. Ramia JM, Figueras J, De la Plaza R, GarcíaParreño J. “Resection of liver metastases in patients with extrahepatic disease”. Cirugía Española. 2012; 90:483-9. PMID: 22682358. I.F.: 0.87 2. Scalzone R, Lopez-Ben S, Figueras J. “How to transect the liver? A history lasting more than a century”. Digestive Surgery. 2012; 29:30-4. PMID: 22441617. I.F.: 1.22

Grants for Research in Progress:

· Ventajas hemodinámicas y metabólicas del pinzamiento hiliar selectivo en las resecciones hepáticas segmentarias frente al pinzamiento hiliar completo (PI11/01269) Sponsored by: Instituto de Salud Carlos III Duration: 2012 - 2014 Joan Figueras Felip

ONCOLOGY AND HEMATOLOGY AREA

ANNUAL SCIENTIFIC REPORT 2012 IDIBGI

MOLECULAR ONCOLOGY

GROUP MEMBERS Group Leader: Javier Menéndez Post-Docorate Researchers Alejandro Vázquez Post-graduate Researchers Bruna Corominas Sílvia Cufí Cristina Oliveras COLLABORATORS Joaquim Bosch Eugeni López Begoña Martin

PUBLICATIONS Originals (I.F.: 87.62): 1. Vazquez-Martin A, Sauri-Nadal T, Menendez OJ, Oliveras-Ferraros C, Cufí S, CorominasFaja B, López-Bonet E, Menendez JA. “Ser2481autophosphorylated mTOR colocalizes with chromosomal passenger proteins during mammalian cell cytokinesis”. Cell Cycle. 2012; 11:4211-21. PMID: 23095638. I.F.: 5.36

MAIN LINES OF RESEARCH · Metabolism and cancer. · Bioenergetic metabolism of tumour stem cells. · Molecular and pre-clinical basis for the metabolic treatment of cancer. · Autophagy and cancer. · Autophagy in tumor stem cells. · Autophagy and resistance to cancer treatments. · Bioenergetic metabolism, autophagy and aging. · Biocompounds: anti-tumor and antiaging activity. · Repositioning of anti-metabolic drugs for the metabolic treatment of cancer.

2. Corominas-Faja B, Quirantes-Piné R, Oliveras-Ferraros C, Vazquez-Martin A, Cufí S, Martin-Castillo B, Micol V, Joven J, SeguraCarretero A, Menendez JA. “Metabolomic fingerprint reveals that metformin impairs one-carbon metabolism in a manner similar to the antifolate class of chemotherapy drugs”. Aging. 2012; 4:480-98. PMID: 22837425. I.F.: 5.13 3. Menendez JA, Oliveras-Ferraros C, Cufí S, Corominas-Faja B, Joven J, Martin-Castillo B, Vazquez-Martin A. “Metformin is synthetically lethal with glucose withdrawal in cancer cells”. Cell Cycle. 2012; 11:2782-92. PMID: 22809961. I.F.: 5.36

STRATEGIC OBJECTIVES 1. Definition of a new intrinsic characteristic (“hallmark”) of cancer: “METABO-STEMNESS” (the bioenergetic metabolism as a causal mechanism of the properties of selfrenovation, immortality and pluripotency of tumor stem cells). 2. Treatment of cancer through strategies to reprogram the tumor metabolism: Repositioning of anti-metabolic drugs from other diseases to increase and diversify the arsenal of anti-tumor drugs.

4. Vazquez-Martin A, Cufi S, Corominas-Faja B, Oliveras-Ferraros C, Vellon L, Menendez JA. “Mitochondrial fusion by pharmacological manipulation impedes somatic cell reprogramming to pluripotency: new insight into the role of mitophagy in cell stemness”. Aging. 2012; 4:393-401. PMID: 22713507. I.F.: 5.13 5. Carrión-Salip D, Panosa C, Menendez JA, Puig T, Oliveras G, Pandiella A, De Llorens R, Massaguer A. “Androgen-independent prostate cancer cells circumvent EGFR inhibition by overexpression of alternative HER receptors and ligands”. International Journal of Oncology. 2012; 41:1128-38. PMID: 22684500. I.F.: 2.40 6. Vazquez-Martin A, Cufí S, Oliveras-Ferraros C, Menendez JA. “Polo-like kinase 1 directs the AMPK-mediated activation of myosin regulatory light chain at the cytokinetic cleavage furrow independently of energy balance”. Cell Cycle. 2012; 11:2422-6. PMID: 22672936. I.F.: 5.36 53

ONCOLOGY AND HEMATOLOGY AREA

7. García-Villalba R, Carrasco-Pancorbo A, Oliveras-Ferraros C, Menéndez JA, SeguraCarretero A, Fernández-Gutiérrez A. “Uptake and metabolism of olive oil polyphenols in human breast cancer cells using nano-liquid chromatography coupled to electrospray ionization-time of flight-mass spectrometry”. Journal of Chromatography B-Analytical Technologies in the Biomedical and Life Sciences. 2012; 898:69-77. PMID: 22608806. I.F.: 2.89 8. Cufi S, Corominas-Faja B, Vazquez-Martin A, Oliveras-Ferraros C, Dorca J, Bosch-Barrera J, Martin-Castillo B, Menendez JA. “Metformininduced preferential killing of breast cancer initiating CD44+CD24-/low cells is sufficient to overcome primary resistance to trastuzumab in HER2+ human breast cancer xenografts”. Oncotarget. 2012; 3:395-8. PMID: 22565037. I.F.: 4.78 9. Joven J, Espinel E, Rull A, Aragonès G, Rodríguez-Gallego E, Camps J, Micol V, Herranz-López M, Menéndez JA, Borrás I, Segura-Carretero A, Alonso-Villaverde C, Beltrán-Debón R. “Plant-derived polyphenols regulate expression of miRNA paralogs miR103/107 and miR-122 and prevent diet-induced fatty liver disease in hyperlipidemic mice”. Biochimica et Biophysica Acta. 2012; 1820:8949. PMID: 22503922. I.F.: 5.00 10. Oliveras-Ferraros C, Massaguer VallLlovera A, Vazquez-Martin A, Salip DC, Queralt B, Cufí S, Martin-Castillo B, BoschBarrera J, Brunet J, De Llorens R, Menendez JA. “Transcriptional upregulation of HER2 expression in the absence of HER2 gene amplification results in cetuximab resistance that is reversed by trastuzumab treatment”. Oncology Reports. 2012; 27:1887-92. PMID: 22427198. I.F.: 1.84 11. Cufí S, Vazquez-Martin A, Oliveras-Ferraros C, Quirantes R, Segura-Carretero A, Micol V, Joven J, Bosch-Barrera J, Del Barco S, MartinCastillo B, Vellon L, Menendez JA. “Metformin lowers the threshold for stress-induced senescence: a role for the microRNA-200 family and miR-205”. Cell Cycle. 2012; 11:1235-46. PMID: 22356767. I.F.: 5.36 12. Oliveras-Ferraros C, Cufí S, VazquezMartin A, Menendez OJ, Bosch-Barrera 54

ANNUAL SCIENTIFIC REPORT 2012 IDIBGI

J, Martin-Castillo B, Joven J, Menendez JA. “Metformin rescues cell surface major histocompatibility complex class I (MHC-I) deficiency caused by oncogenic transformation”. Cell Cycle. 2012; 11:865-70. PMID: 22333588. I.F.: 5.36 13. Vazquez-Martin A, Vellon L, Quirós PM, Cufí S, Ruiz de Galarreta E, Oliveras-Ferraros C, Martin AG, Martin-Castillo B, López-Otín C, Menendez JA. “Activation of AMP-activated protein kinase (AMPK) provides a metabolic barrier to reprogramming somatic cells into stem cells”. Cell Cycle. 2012; 11:974-89. PMID: 22333578. I.F.: 5.36 14. Vazquez-Martin A, Fernández-Arroyo S, Cufí S, Oliveras-Ferraros C, Lozano-Sánchez J, Vellón L, Micol V, Joven J, Segura-Carretero A, Menendez JA. “Phenolic secoiridoids in extra virgin olive oil impede fibrogenic and oncogenic epithelial-to-mesenchymal transition: extra virgin olive oil as a source of novel antiaging phytochemicals”. Rejuvenation Research. 2012; 15:3-21. PMID: 22229524. I.F.: 3.83 15. Oliveras-Ferraros C, Massaguer VallLlovera A, Salip DC, Vazquez-Martin A, Cufí S, Queralt B, Martin-Castillo B, Brunet J, De Llorens R, Menendez JA. “Evolution of the predictive markers amphiregulin and epiregulin mRNAs during long-term cetuximab treatment of KRAS wild-type tumor cells”. Investigational New Drugs. 2012; 30:846-52. PMID: 21161326. I.F.: 3.36 16. Herranz-López M, Fernández-Arroyo S, Pérez-Sanchez A, Barrajón-Catalán E, Beltrán-Debón R, Menéndez JA, AlonsoVillaverde C, Segura-Carretero A, Joven J, Micol V. “Synergism of plant-derived polyphenols in adipogenesis: perspectives and implications”. Phytomedicine. 2012; 19:253261. PMID: 22280831. I.F.: 2.97 17. Oliveras-Ferraros C, Cufí S, Queralt B, Vazquez-Martin A, Martin-Castillo B, de Llorens R, Bosch-Barrera J, Brunet J, Menendez JA. “Cross-suppression of the EGFR ligands amphiregulin and epiregulin and acquisition of FGFR3 signaling decrease responsiveness of KRAS wild-type tumour cells to cetuximab”. British Journal of Cancer. 2012; 106: 1406-1414. PMID: 22491422. I.F.: 5.08

18. Cufí S, Vazquez-Martin A, OliverasFerraros C, Corominas-Faja B, Urruticoechea A, Martin-Castillo B, Menendez JA. “Autophagy-related gene 12 (ATG12) is a novel determinant of primary resistance to trastuzumab (Herceptin)”. Oncotarget. 2012; 3: 1600-14. PMID: 23307622. I.F.: 4.78 19. Vazquez-Martin A, Cufi S, Lopez-Bonet E, Corominas-Faja B, Oliveras-Ferraros C, Martin-Castillo B, Menendez JA. “Metformin limits the tumourigenicity of iPS cells without affecting their pluripotency”. Scientific Reports. 2012; 2:964. PMID: 23236586. I.F.: 2.93 20. Oliveras-Ferraros C, Corominas-Faja B, Cufí S, Vazquez-Martin A, Martin-Castillo B, Iglesias JM, López-Bonet E, Martin AG, Menendez JA. “Epithelial-to-mesenchymal transition (EMT) confers primary resistance to trastuzumab (Herceptin)”. Cell Cycle. 2012; 11:4020-32. PMID: 22992620. I.F.: 5.36 Editorial (I.F.: 17.23): 1. Menendez JA, Vazquez-Martin A. “Rejuvenating regeneration: Metformin activates endogenous adult stem cells”. Cell Cycle. 2012; 11:3521-2. PMID: 22935702. I.F.: 5.36 2. Joven J, Menendez JA. “Human immunodeficiency virus infection as a model of premature aging: perspectives and implications”. Medicina Clínica. 2012; 139:24951. PMID: 22425150. I.F.: 1.39 3. Menendez JA, Vazquez-Martin A. “AMPK: a bona fide resident of the mitotic spindle midzone”. Cell Cycle. 2012; 11:841-2. PMID: 22336917. I.F.: 5.36 4. Menendez JA, Joven J. “One-carbon metabolism: An aging-cancer crossroad for the gerosuppressant metformin”. Aging. 2012; 4:894-898. PMID: 23525940. I.F.: 5.13 Reviews (I.F.: 7.45): 1. Klionsky DJ et al. “Guidelines for the use and interpretation of assays for monitoring autophagy”. Autophagy. 2012; 8:445-544. PMID: 22966490. I.F.: 7.45

ONCOLOGY AND HEMATOLOGY AREA

GRANTS FOR RESEARCH IN PROGRESS:

· Pemetrexed y cisplatino en combinación con ácido zoledrónico en cáncer de pulmón no microcítico: estudio preclínico en busca de sinergia antitumoral Sponsored by: Fundació Roses Contra el Càncer. Convocatòria d’ajut a un projecte d’investigació sobre el càncer Duration: 2010 - 2012 Joaquim Bosch Barrera / Javier A. Menendez · Energy metabolism, autophagy and breast cancer genetic instability: molecular dynamics and therapeutic opportunities. (SAF2009-11579) Sponsored by: Ministerio de Ciencia e Innovación. Plan Nacional de I+D+I (2008 - 2011). Duration: 2009 - 2012 Javier A. Menendez · Contratos Postdoctorales de Perfeccionamiento en Investigación en Salud “Sara Borrell” (CD08/00283) Sponsored by: Instituto de Salud Carlos III Duration: 2009 - 2012 Javier A. Menendez · Ensayo en fase II, aleatorizado, abierto, multicéntrico de tratamiento neoadyuvante con quimioterapia y trastuzumab con o sin la adición de metformina en mujeres diagnosticadas de cáncer de mama primario HER2/ ErbB2 positivo. (EC10-125) Sponsored by: Ministerio de Sanidad Duration: 2010 - 2013 Begoña Martin Castillo (Javier A. Menendez, Collaborating Investigator -Project Scientific Coordinator)

ANNUAL SCIENTIFIC REPORT 2012 IDIBGI

GROUPS ASSOCIATED WITH THE IDIBGI

ANNUAL SCIENTIFIC REPORT 2012 IDIBGI

GROUPS ASSOCIATED WITH THE IDIBGI INTERNAL MEDICINE MICROBIOLOGY AND INFECTIONS IN THE CRITICAL PACIENT NEPHROLOGY BIOCHEMISTRY OF CANCER BIOPHARMACEUTICAL RESEARCH COMPUTER VISION AND ROBOTICS CONTROL ENGINEERING AND INTELLIGENT SYSTEMS HEALTH AND HEALTHCARE HEALTH PSYCHOLOGY PROTEIN ENGINEERING STATISTICS AND DATA ANALYSIS STATISTICS, ECONOMETRICS AND HEALTH

GROUPS ASSOCIATED WITH THE IDIBGI

ANNUAL SCIENTIFIC REPORT 2012 IDIBGI

ICS INTERNAL MEDICINE

MICROBIOLOGY AND INFECTIONS IN THE CRITICAL PACIENT

GROUP MEMBERS

Group Leader: Ferran García-Bragado

Group Leader: Josep Maria Sirvent

STRATEGIC OBJECTIVES: PUBLICATIONS Case Report (I.F.: 1.39): 1. Rexach Fumanya M, Castro Guardiola A, García-Bragado Dalmau F. “Ollier’s disease”. Medicina Clínica. 2012; 139:e5. PMID: 22197370. I.F.: 1.39 Review (I.F.: 1.39): 1. García-Bragado Dalmau F. “The new medicine and the new anticoagulants”. Medicina Clínica. 2012; 138:438-40. PMID: 22285494. I.F.: 1.39

More than 10 years ago a research group was created in the IdIBGi called “Microbiology and inflammation”. This group included all projects on infections of the University Hospital of Girona Doctor Josep Trueta (HUGDJT) as well as a group from the University of Girona working in conjunction with them. The leaders of this group were Dr. Josep Maria Sirvent (HUGDJT) and Prof. Jesús García-Gil (UdG). Over the last three years collaborative research has not been very frequent and, in fact, there is only scientific production in one group and always in reference to infectious diseases in the critically ill patient. It should also be mentioned that Dr. Josep Maria Sirvent forms part of a CIBER respiratory Group, Group 14Dr. Antoni Torres of Hospital Clínic. http://www.ciberes.org/index.php?option=com_personal&view=personal&grupo_id=14 &Itemid=77 In order to update the group and suitably redefine the projects and research staff actively involved, we will create an internal specific, dynamic group for the study of infectious diseases in the critically ill patient: Group for Studies of Microbiology and Infections in Critically ill Patients (GMIC-ICU).

MAIN LINE OF RESEARCH: - Studies of Microbiology and Infections in the critically ill patient. - Study of sepsis. - Study of community-acquired pneumonia.

PUBLICATIONS Originals (I.F.: 3.00): 1. Rodríguez A, Alvarez-Rocha L, Sirvent JM, Zaragoza R, Nieto M, Arenzana A, Luque P, Socías L, Martín M, Navarro D, Camarena J, Lorente L, Trefler S, Vidaur L, Solé-Violán J, Barcenilla F, Pobo A, Vallés J, Ferri C, MartínLoeches I, Díaz E, López D, López-Pueyo MJ, Gordo F, Del Nogal F, Marqués A, Tormo S, Fuset MP, Pérez F, Bonastre J, Suberviola B, Navas E, León C; GETGAG; Infectious Diseases Work Group (GTEI) of Spanish Society of Intensive and Critical Care Medicine and Coronary Units (SEMICYUC); Infections in Critically Ill Patients Study Group (GEIPC) of Spanish Society of Infectious Diseases and Clinical Microbiology. “Recomendaciones del Grupo de Trabajo Enfermedades Infecciosas (GTEI) de la Sociedad Española de Medicina Intensiva, Crítica y Unidades Coronarias (SEMICYUC) y el Grupo de Estudio de Infecciones en el Paciente Crítico (GEIPC) de la Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica (SEIMC) para el diagnóstico y tratamiento de la gripe A/H1N1 en pacientes adultos graves hospitalizados en las Unidades de Cuidados Intensivos”. Medicina Intensiva. 2012; 36:103137. PMID: 22245450. I.F.: 1.07 2. Lorencio C, Leal Y, Bonet A, Bondia J, Palerm CC, Tache A, Sirvent JM, Vehi J. “Realtime continuous glucose monitoring in an intensive care unit: better accuracy in patients with septic shock”. Diabetes Technology & Therapeutics. 2012; 14:568-75. PMID: 22512288. I.F.: 1.93 Editorial (I.F.: 1.07): 1. Lorencio C, Sirvent JM. “Noninvasive ventilation: when, how and where?” Medicina Intensiva. 2012; 36:601-3. PMID: 23040612. I.F.: 1.07 Reviews (I.F.: 1.00): 1. Baró-Serra A, Guasch-Aragay B, MartínAlemany N, Sirvent JM, Vallès-Prats M. “The importance of early haemodiafiltration in the treatment of lactic acidosis associated with the administration of metformin”. Nefrología. 2012; 32:664-9. PMID: 23013954. I.F.: 1.00 57

GROUPS ASSOCIATED WITH THE IDIBGI

Case Report (I.F.: 1.07): Murcia-Gubianas C, Valls-Masot L, RognoniAmrein G. “Brain magnetic resonance imaging in heat stroke”. Medicina Intensiva. 2012; 36:526. PMID: 21676501. I.F.: 1.07

ANNUAL SCIENTIFIC REPORT 2012 IDIBGI

NEPHROLOGY

GROUP MEMBERS Group Leader: Martí Vallès Prats

Post-graduate Researchers Jordi Calabia Isabel García Nàdia Martin

Collaborators Yaima Barreiro Gerard Maté Cristina Noboa Christian Cordoba Carolina Molina Cristina Martinez Pere Torguet

Nursing Staff Jennifer Moreno Montse Jubany

Strategic Objectives Consolidate the method for studying cardiovascular risk and the atheroma burden in patients with chronic kidney disease, high blood pressure and Diabetes Mellitus with diabetic nephropathy.

Main Lines of Research Study of the macro and microvascular affectation of inflammatory markers and bone-mineral metabolism markers in chronic kidney disease and their most frequent pathologies: high blood pressure and diabetic nephropathy.

PUBLICATIONS Originals (I.F.: 11.61): 1. Torguet-Escuder P, Guasch-Aragay B, Calabia-Martínez J, Martín-Alemany N, García-Méndez I, Maté-Benito G, ClapésSánchez E, Sabater-Masdeu M, FernándezReal JM, Vallès-Prats M. “Fibroblast growth factor 23 (FGF 23) and phosphocalcic metabolism in chronic kidney disease”. Nefrología. 2012; 32:647-54. PMID: 23013951. I.F.: 1.00 2. Faur D, Martín N, Archuleta JM, Torguet P. “Quiz page August 2012: a man with nephrotic syndrome and a mediastinal mass”. American Journal of Kidney Disease. 2012; 60:A25-7. PMID: 22805523. I.F.: 5.43 3. Fernández-Real JM, Vendrell J, García I, Ricart W, Vallès M. “Structural damage in diabetic nephropathy is associated with TNF-α system activity”. Acta Diabetologia. 2012; 49:301-5. PMID: 22042131. I.F.: 3.18 4. Faur D, García-Méndez I, Martín-Alemany N, Vallès-Prats M. “Mono-bacterial peritonitis caused by Bacteroides thetaiotaomicron in a patient on peritoneal dialysis”. Nefrología. 2012; 32:694-0. PMID: 23013969. I.F.: 1.00 5. Núñez-Torras M, Martín-Alemany N, VallèsPrats M, Albert-Bertran X. “Amyloidosis AL with severe renal and cardiac involvement: a very rare association of terrible prognosis, two case reports”. Nefrología. 2012; 32:848-850. PMID: 23169377. I.F.: 1.00 Reviews (I.F.: 1.00): 1. Baró-Serra A, Guasch-Aragay B, MartínAlemany N, Sirvent JM, Vallès-Prats M. “The importance of early haemodiafiltration in the treatment of lactic acidosis associated with the administration of metformin”. Nefrología. 2012; 32:664-9. PMID: 23013954. I.F.: 1.00 Case Reports (I.F.: 6.43): 1. Faur D, Martín N, Archuleta JM, Torguet P. “A man with nephrotic syndrome and a mediastinal mass”. American Journal of Kidney Diseases. 2012; 60: A25-A27. PMID: 22805523. I.F.: 5.43

GROUPS ASSOCIATED WITH THE IDIBGI

ANNUAL SCIENTIFIC REPORT 2012 IDIBGI

University of Girona 2. García-Méndez I, Remollo S, Hernández D, Martín-Alemany N, Calabia-Martínez J, Torguet-Escuder P, Maté-Benito G, VallèsPrats M. “Catheterography: a simple technique for the diagnosis of poor peritoneal dialysis catheter functioning”. Nefrología. 2012; 32:677-8. PMID: 23013957. I.F.: 1.00

BIOCHEMISTRY OF CANCER

GROUP MEMBERS Group Leader: Rafael de Llorens and Rosa Peracaula

Hospital Dr. J. Trueta of Girona, and with the group led by Drs. R. Dwek and P. Rudd at Oxford University. B. PCI (potato carboxypeptidase inhibitor) as an antitumoral agent (cytostatic). Antitumoral effects of recombinant protease inhibitors. Development of new derivatives with increased EGFR affinity and more cytotoxic agents. Studies combined with other therapeutic agents. In collaboration with the group headed by Drs. F.X. Avilés and E. Querol of the IBB of the UAB, and Dr. R. Colomer of Hospital Dr. J. Trueta of Girona.

SENIOR Researchers Rosa Núria Aleixandre Josep Comet Manuel Ramírez

Post-DOCTORATE Researchers Sílvia Barrabés Esther Llop María Angeles Martínez Anna Massaguer

Post-graduate Researchers Montserrat Ferrer Meritxell Balmaña

C. Influence of sialyltransferases on the invasive and metastatic properties of pancreatic cancer: Studies of the expression of the sialyltransferases responsible for the biosynthesis of sialyl-Lewis x and sialyl-Lewis a glycosidic antigens involved in the processes adhesion and metastasis of tumor cells. Study of the factors that regulate the expression of sialyltransferases, as well as inhibitors of the biosynthesis of sialyl-Lewis antigens. In collaboration with the group headed by Dr. C. de Bolós of the IMIM in Barcelona and Dr. P. Clapés of the CSIC, Barcelona.

Main Lines of Research The research is focused on the field of therapy and diagnosis of cancer. It is based on the development of antitumor molecules that target specific parts of cancer cells, find molecular markers that enable the early diagnosis of cancer where current therapies are most effective, and which can also be used to improve the prognosis and follow-up of the tumor, as well as the study of the enzymes involved in processes of adhesion and metastasis, and so counteract their effects. A. Tumor markers: Aberrant glycosylation of various serum proteins as possible tumor markers for carcinomas. Currently focused on pancreatic and prostatic carcinomas, specifically the aberrant glycosylation of human pancreatic ribonuclease and PSA (prostate specific antigen). Also applicable to other glycoproteins (Proteomics and Glycomics). In collaboration with groups working on Digestive, Urology and Clinical Analysis of 59

GROUPS ASSOCIATED WITH THE IDIBGI

PUBLICATIONS Originals (I.F.: 20.96): 1. Aliende C, Pérez-Manrique M, Jalón FA, Manzano BR, Rodríguez AM, Cuevas JV, Espino G, Martínez MÁ, Massaguer A, González-Bártulos M, De Llorens R, Moreno V. “Preparation of new half sandwich ruthenium arene complexes with aminophosphines as potential chemotherapeutics”. Journal of Inorganic Biochemistry. 2012; 117:171-88. PMID: 23085598. I.F.: 3.35 2. Barragán F, Carrion-Salip D, Gómez-Pinto I, González-Cantó A, Sadler PJ, De Llorens R, Moreno V, González C, Massaguer A, Marchán V. “Somatostatin subtype-2 receptortargeted metal-based anticancer complexes”. Bioconjugate Chemistry. 2012; 23:1838-55. PMID: 22871231. I.F.: 4.93 3. Carrión-Salip D, Panosa C, Menendez JA, Puig T, Oliveras G, Pandiella A, De Llorens R, Massaguer A. “Androgen-independent prostate cancer cells circumvent EGFR inhibition by overexpression of alternative HER receptors and ligands”. International Journal of Oncology. 2012; 41:1128-38. PMID: 22684500. I.F.: 2.40 4. Oliveras-Ferraros C, Massaguer VallLlovera A, Vazquez-Martin A, Salip DC, Queralt B, Cufí S, Martin-Castillo B, BoschBarrera J, Brunet J, De Llorens R, Menendez JA. “Transcriptional upregulation of HER2 expression in the absence of HER2 gene amplification results in cetuximab resistance that is reversed by trastuzumab treatment”. Oncology Reports. 2012; 27:1887-92. PMID: 22427198. I.F.: 1.84 5. Oliveras-Ferraros C, Massaguer VallLlovera A, Carrion Salip D, Vazquez-Martin A, Cufí S, Queralt B, Martin-Castillo B, Brunet J, de Llorens R, Menendez JA. “Crosssuppression of the EGFR ligands amphiregulin and epiregulin and acquisition of FGFR3 signaling decrease responsiveness of KRAS wild-type tumour cells to cetuximab”. British Journal of Cancer. 2012; 106: 1406-1414. PMID: 22491422. I.F.: 5.08

ANNUAL SCIENTIFIC REPORT 2012 IDIBGI

6. Oliveras-Ferraros C, Massaguer VallLlovera A, Carrion Salip D, Vazquez-Martin A, Cufí S, Queralt B, Martin-Castillo B, Brunet J, De Llorens R, Menendez JA. “Evolution of the predictive markers amphiregulin and epiregulin mRNAs during long-term cetuximab treatment of KRAS wild-type tumor cells”. Investigational New Drugs. 2012; 30:846-52. PMID: 21161326. I.F.: 3.36

GROUPS ASSOCIATED WITH THE IDIBGI

ANNUAL SCIENTIFIC REPORT 2012 IDIBGI

BIOPHARMACEUTICAL RESEARCH

PUBLICATIONS

GROUP MEMBERS

2. Carrión-Salip D, Panosa C, Menendez JA, Puig T, Oliveras G, Pandiella A, De Llorens R, Massaguer A. “Androgen-independent prostate cancer cells circumvent EGFR inhibition by overexpression of alternative HER receptors and ligands”. International Journal of Oncology. 2012; 41:1128-38. PMID: 22684500. I.F.: 2.40

Group Leader: Maria Teresa Puig

Post-Doctorate Researchers Rut Porta

Post-graduate Researchers Adriana Blancafort Glòria Oliveras Serrat Cristina Rosés

Originals (I.F.: 13.91): 1. Relat J, Blancafort A, Oliveras G, Cufí S, Haro D, Marrero PF, Puig T. “Different fatty acid metabolism effects of (-)-epigallocatechin-3-gallate and C75 in adenocarcinoma lung cancer”. BMC Cancer. 2012; 12:280. PMID: 22769244. I.F.: 3.01

3. Turrado C, Puig T, García-Cárceles J, Artola M, Benhamú B, Ortega-Gutiérrez S, Relat J, Oliveras G, Blancafort A, Haro D, Marrero PF, Colomer R, López-Rodríguez ML. “New synthetic inhibitors of fatty acid synthase with anticancer activity”. Journal of Medicinal Chemistry. 2012; 55:5013-23. PMID: 22559865. I.F.: 5.25

Abreu D, Lopez-Vivanco G, Gebbia V, FerreraDelgado L, Bombaron P, Bernabe R, Bearz A, Artal A, Cortesi E, Rolfo C, Sanchez-Ronco M, Drozdowskyj A, Queralt C, De Aguirre I, Ramirez JL, Sanchez JJ, Molina MA, Taron M, Paz-Ares L; Spanish Lung Cancer Group in collaboration with Groupe Français de Pneumo-Cancérologie and Associazione Italiana Oncologia Toracica. “Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): a multicentre, open-label, randomised phase 3 trial”. Lancet Oncology. 2012; 13:239-46. PMID: 22285168. I.F.: 22,59

Grants for Research in Progress: · Caracterización preclínica de la inhibición de la sintasa de ácidos grasos (FASN) en modelos resistentes a fármacos anti-HER2 Sponsored by: UdG Duration: 2012 - 2013 Teresa Puig

4. Castro J, Ribó M, Puig T, Colomer R, Vilanova M, Benito A. “A cytotoxic ribonuclease reduces the expression level of P-glycoprotein in multidrug-resistant cell lines”. Investigational New Drugs. 2012; 30:880-8. PMID: 21286781. I.F.: 3.36 Review (I.F.: 1.39): 1. Viñas G, Puig T, Porta R. “Oxidative stress in patients with cancer: two sides of the same coin”. Medicina Clínica . 2012; 139:171-5. PMID: 22266084. I.F.: 1.39 Multicentric (I.F.: 22.59): 1. Rosell R, Carcereny E, Gervais R, Vergnenegre A, Massuti B, Felip E, Palmero R, Garcia-Gomez R, Pallares C, Sanchez JM, Porta R, Cobo M, Garrido P, Longo F, Moran T, Insa A, De Marinis F, Corre R, Bover I, Illiano A, Dansin E, De Castro J, Milella M, Reguart N, Altavilla G, Jimenez U, Provencio M, Moreno MA, Terrasa J, Muñoz-Langa J, Valdivia J, Isla D, Domine M, Molinier O, Mazieres J, Baize N, Garcia-Campelo R, Robinet G, Rodriguez61

GROUPS ASSOCIATED WITH THE IDIBGI

COMPUTER VISION AND ROBOTICS

Recognised as a consolidated research group (2009 SGR 380)

GROUP MEMBERS Group Leader: Joan Martí

ANNUAL SCIENTIFIC REPORT 2012 IDIBGI

PUBLICATIONS

Grants for Research in Progress:

Originals (I.F.: 13.00):

· ASSURE: Personalised Breast Cancer Screening Sponsored by: European Comission – 7th Framework Program – HEALTH 2012 Duration: 2012-2015 Robert Martí

1. Oliver A, Torrent A, Lladó X, Tortajada M, Tortajada L, Sentís M, Freixenet J, Zwiggelaar R. “Automatic microcalcification and cluster detection in digital and digitised mammograms (KBS 2012)”. Knowledge-Based Systems. 2012; 28:68-75. I.F.: 4.10 2. Ghose S, Oliver A, Martí R, Lladó X, Vilanova JC, Freixenet J, Mitra J, Sidibé D, Meriaudeau F. “A survey of prostate segmentation methodologies in ultrasound, magnetic resonance and computed tomography images”. Computer Methods and Programs in Biomedicine. 2012; 108:262-87. PMID: 22739209. I.F.: 1.52

Post-Doctorate Researchers Yago Díez Jordi Freixenet Rafael García Xavier Lladó Robert Martí Arnau Oliver

3. Mitra J, Kato Z, Martí R, Oliver A, Lladó X, Sidibé D, Ghose S, Vilanova JC, Comet J, Meriaudeau F. “A spline-based non-linear diffeomorphism for multimodal prostate registration”. Medical Image Analysis. 2012; 16:1259-79. PMID: 22705289. I.F.: 4.42

Post-graduate Researchers

4. Mitra J, Martí R, Oliver A, Lladó X, Ghose S, Vilanova JC, Meriaudeau F. “Prostate multimodality image registration based on B-splines and quadrature local energy”. International Journal of Computer Assisted Radiology and Surgery. 2012;.7:445-54. PMID: 21706302. I.F.: 1.48

Mariano Cabezas Onur Ganiler Soumya Ghose Albert Gubern Konstantin Korotkov Guillaume Lemaître Joan Massich Jhimli Mitra Gerard Pons Josep Quintana Mojdeh Rastgodastjerdi Meritxell Tortajada

5. Ghose S, Oliver A, Martí R, Lladó X, Freixenet J, Mitra J, Vilanova JC, Comet-Batlle J, Meriaudeau F. “Statistical shape and texture model of quadrature phase information for prostate segmentation”. International Journal of Computer Assisted Radiology and Surgery. 2012;.7:43-55. PMID: 21629983. I.F.: 1.48

Main Lines of Research: · Combination and recording of multimodal images (RX, MRI, US ...). · Detection, segmentation and characterisation of lesions and regions of interest. · Computer aided diagnosis systems (CAD). · 3D reconstruction.

Review (I.F.: 2.87): 1. Lladó X, Ganiler O, Oliver A, Martí R, Freixenet J, Valls L, Vilanova JC, RamióTorrentà L, Rovira A. “Automated detection of multiple sclerosis lesions in serial brain MRI”. Neuroradiology. 2012;.54:787-807. PMID: 22179659. I.F.: 2.87 2. Korotkov, K.; Garcia, R. “Computerized analysis of pigmented skin lesions: A review”. Artificial Intelligence in Medicine. 2012;56:6990. PMID: 23063256. I.F.: 1,36

· M3CAD: Multi-modality and muli-view mammographic computer aided diagnosos system Sponsored by: MINECO Duration: 2012 Robert Martí · SALEM: Segmentación automática de lesiones de esclerosis múltiple en imágenes de resonancia magnética Sponsored by: Instituto de Salud Carlos III Duration: 2010-2012 Xavier Lladó

GROUPS ASSOCIATED WITH THE IDIBGI

ANNUAL SCIENTIFIC REPORT 2012 IDIBGI

CONTROL ENGINEERING AND INTELLIGENT SYSTEMS GROUP MEMBERS Group Leader: Josep Vehí

Post-Doctorate Researchers Joaquim Armengol Ningsu Luo Ren Remei Calm Francisco Llaneras

Post-graduate Researchers Ines Ferrer Yeimy Morales Fabián León Maira García Yenny Teresa Leal Guangqi Xu

PUBLICATIONS Originals (I.F.: 6.89): 1. León-Vargas F, Calm R, Bondia J, Vehí J. “Improving the computational effort of setinversion-based prandial insulin delivery for its integration in insulin pumps”. Journal of Diabetes Science and Technology. 2012; 6:1420-8. PMID: 23294789.

Main Lines of Research Artificial pancreas: modeling and control of glucose metabolism This project aims at the development of Advanced Strategies for Closed-loop Glucose Control in Type 1 Diabetes Mellitus and Critically-ill Patients. Modeling, identification and control of complex systems Modeling, identification and robust control of complex systems that present uncertainties, nonlinearities, and different types of dynamic behaviour, etc. and their application to networked control systems, mobile robotics, automotive and aeronautic systems, civil engineering structures, wind turbines, and industrial processes. Model-based fault detection and diagnosis in dynamic systems A system is considered as faulty when there is a malfunction. This abnormal behaviour may have consequences ranging from economic losses (lower quality, lower production, higher costs) to damages to people or the environment. Many different techniques have been developed in the recent years to detect (determine the presence of a fault) and diagnose (locate, quantify, characterize) faults. Methods and tools based on interval analysis The imprecision and the uncertainty of complex systems can often be represented by interval models. One of our research projects is to develop methods and tools based on interval analysis to deal with this kind of system. Interval analysis has been applied in several fields such as modeling, simulation, fault detection, set inversion, optimization problems, robust control analysis and design, computer graphics, etc.

2. Herrero P, Calm R, Vehí J, Armengol J, Georgiou P, Oliver N, Tomazou C. “Robust fault detection system for insulin pump therapy using continuous glucose monitoring”. Journal of Diabetes Science and Technology. 2012; 6:1131-41. PMID: 23063040. 3. Rossetti P, Ampudia-Blasco FJ, Laguna A, Revert A, Vehì J, Ascaso JF, Bondia J. “Evaluation of a novel continuous glucose monitoring-based method for mealtime insulin dosing--the iBolus--in subjects with type 1 diabetes using continuous subcutaneous insulin infusion therapy: a randomized controlled trial”. Diabetes Technology and Therapeutics. 2012; 14:1043-52. PMID: 23003329. I.F.: 1.93 4. Lorencio C, Leal Y, Bonet A, Bondia J, Palerm CC, Tache A, Sirvent JM, Vehi J. “Realtime continuous glucose monitoring in an intensive care unit: better accuracy in patients with septic shock”. Diabetes Technology and Therapeutics. 2012; 14:568-75. PMID: 22512288. I.F.: 1.93 5. Herrero P, Bondia J, Palerm CC, Vehí J, Georgiou P, Oliver N, Toumazou C. “A simple robust method for estimating the glucose rate of appearance from mixed meals”. Journal of Diabetes Science and Technology. 2012; 6:15362. PMID: 22401334. 6. García-Jaramillo M, Calm R, Bondia J, Vehí J. “Prediction of postprandial blood glucose under uncertainty and intra-patient variability in type 1 diabetes: a comparative study of three interval models”. Computer Methods and Programs in Biomedicine. 2012; 8:224-233. PMID: 22677264. I.F.: 1.52

GROUPS ASSOCIATED WITH THE IDIBGI

7. García-Jaramillo M, Calm R, Bondia J, Tarín C, Vehí J. “Insulin dosage optimization based on prediction of postprandial glucose excursions under uncertain parameters and food intake”. Computer Methods and Programs in Biomedicine. 105:61-69. PMID: 22677264. I.F.: 1.52 8. Rossetti P, Vehí J, Revert A, Calm R, Bondia J. Commentary on “Performance of a glucose meter with a built-in automated bolus calculator versus manual bolus calculation in insulin-using subjects”. Journal of Diabetes Science and Technology. 2012; 6:345-7. PMID: 22538145.

GRANTS FOR RESEARCH IN PROGRESS: · Monitoring & Managing your Health and Well-being Sponsored by: Ministerio de Economía y Competitividad Duration: 2011 - 2014 Josep Vehí · New strategies for post-prandial glycaemic control using insulin pump therapy in type 1 diabetes (CLOSEDLOOP4MEAL) Sponsored by: Ministerio de Ciencia e Innovación Duration: 2011 - 2013 Josep Vehí · Advanced Structural Control Strategies for Mitigating the Dynamic Load Eff ects on Floating Off shore Wind Turbines (WINFLOAT) Sponsored by: Ministerio de Ciencia e Innovación Duration: 2012 - 2014 Ningsu Luo Ren

ANNUAL SCIENTIFIC REPORT 2012 IDIBGI

GROUPS ASSOCIATED WITH THE IDIBGI

ANNUAL SCIENTIFIC REPORT 2012 IDIBGI

HEALTH AND HEALTHCARE

GROUP MEMBERS Group Leader: Dolors Juvinyà

POST-DOCTORATE RESEARCHERS Carme Bertran Concepció Fuentes

POST-GRADUATE RESEARCHERS David Ballester Neus Brugada Josep Olivet

POST-GRADUATE RESEARCHERS Alme Domingo

PUBLICATIONS Originals (I.F.: 4.37): 1. Garre-Olmo J; López-Pousa S; TuronEstrada A; Juvinyà D; Ballester D; VilaltaFranch J. “Environmental determinants of quality of life in nursing home residents with severe dementia”. Journal of the American Geriatrics Society. 2012; 60:1230-1236. PMID: 22702541. I.F.: 3.74

MAIN LINES OF RESEARCH: Promotion of health Research into the promotion of health covers a wide range of actions in different areas: Healthcare institutions (Health Promoting Hospitals): assessment of quality from an organisational, healthcare and reference aspect, as well as assessment of the competence of the healthcare professionals employed. Educational institutions: schools and universities. Community: healthcare service user groups. Health literacy. Salutogenesis. Workplace Health. Mental health. The aged and carers This line develops research within the framework of care of the elderly, dependence and the fragile population. Mention should be made of research aimed at improving the quality of life of untrained carers and the development of tools for the general assessment of dependence. Women, gender and health The research developed in this area is focused on providing the necessary scientific knowledge to design actions that distinguish discriminatory components in the field of health and which affect the healthcare professions, health professionals and users. Health emergencies The work carried out in this area is related to the assessment of competence in the area of basic and advanced reanimation and the creation of new tools for the assessment of professional competence. This activity takes place in the laboratory the group has in the Science and Technological Park where they impart training and qualification courses.

2. Jurado-Campos J; Zabaleta-Del-Olmo E; Farré-Grau C; Barceló-Prats J; JuvinyàCanal D. “Recursos y modelos de atención al pie diabético en Cataluña (España): estudio descriptivo sobre espacios de mejora”. Atencion Primaria. 2012; 44:394-401. PMID: 22037162. I.F.: 0.63 Grants for Research in Progress: · ETFERSASO - Centre Transfronterer: Formació i Investigació Sanitària i Social (EFA56/08) Sponsored by: Programa operativo de cooperación territorial España · Francia · Andorra Duration: 2009 - 2012 Dolors Juvinyà · Estudi de la percepció de la població en relació a la instal·lació de DEA fixos als municipis. Elaboració d’una enquesta, recollida, processament i interpretació de la informació. (077/11 20/12/11) Sponsored by: Diputació de Girona (DIPSALUT) Duration: 23/11/2011 - 28/01/2012 Dolors Juvinyà · Formació per a la recertificació de l’ús del DEA adreçada a 547 participants de la demarcació de Girona, per a l’any 2012 Sponsored by: Diputació de Girona (DIPSALUT) Duration: 2012 Dolors Juvinyà

GROUPS ASSOCIATED WITH THE IDIBGI

HEALTH PSYCHOLOGY

Recognised as a consolidated research group by the Generalitat of Catalonia: 2009 SGR 618

GROUP MEMBERS Group Leader: Mª Eugènia Gras Montserrat Planes

Post-Doctorate Researchers Maria Aymerich Sílvia Font-Mayolas Rosa Suñer Natàlia Cebrián Armand Grau Maria Carme Timoneda Mònica Cunill Josefina Patiño

Post-graduate Researchers Anna Belén Gómez Francesc Prat

Main Lines of Research Sexual behaviour of risk and prevention of AIDS, other STD and unwanted pregnancies. Behaviour of risk and prevention for users of motor vehicles and pedestrians. Substance dependence. Stress, pain and quality of life. Quality of life during aging. Processes of loss and mourning.

ANNUAL SCIENTIFIC REPORT 2012 IDIBGI

PUBLICATIONS Originals (I.F.: 8.15): 1. Planes M, Gras ME, Cunill M, Chagane HC, Sullman M, Gómez AB. “Perceived acceptance of condom use by partners, close friends and parents in Spanish and Mozambican heterosexual adolescents”. Journal of Transcultural Nursing. 2012; 23:22-28. PMID: 22052093. I.F.: 0.51 2. Planes, M, Prat, FX, Gómez, AB, Gras, ME, Font-Mayolas, S. “Ventajas e inconvenientes del uso del preservativo con una pareja afectiva heterosexual”. Anales de Psicología; 2012; 28: 161-70. I.F. 0,55 3. Prat F, Planes M, Gras ME, Sullman MJ. “Stages of change and decisional balance for condom use with a romantic partner”. Journal of Health Psychology. 2012; 17:1193-202. PMID: 22311882. I.F.: 1.88 4. Suñer-Soler R, Grau A, Gras ME, FontMayolas S, Silva Y, Dávalos A, Cruz V, Rodrigo J, Serena J. “Smoking cessation 1 year poststroke and damage to the insular cortex”. Stroke. 2012; 43:131-6. PMID: 22052507. I.F.: 5.76

GROUPS ASSOCIATED WITH THE IDIBGI

ANNUAL SCIENTIFIC REPORT 2012 IDIBGI

PROTEIN ENGINEERING

Recognised as a consolidated research group (SGR2009-657)

GROUP MEMBERS Group Leader: Maria Vilanova

SENIOR Researchers Antoni Benito Marc Ribó

Post-Doctorate Researchers Jessica Castro

Post-graduate Researchers Mariona Callís Glòria García Veronica Gordo Santiago Ruiz David Soler Anna Vert

Main Lines of Research: 1.- To study protein folding and oligomerization using ribonucleases as a model. Essentially, we construct by site-directed mutagenesis new protein variants to reveal the molecular determinants of the folding and oligomerization processes. We are interested in the role of the hydrophobic core on foldingunfolding kinetics induced by pressure and temperature. We construct new variants of RNase A in which hydrophobic / polar side chains are changed and we compare their stability and folding kinetics to map how the folding transition state of the protein is attained. One of the main mechanisms of protein oligomerization is the domain-swapping process that has been implicated in the formation of different pathological aggregates. We investigate the role of different residues located at different interacting interfaces between monomers by changing their side chains and investigating their effect on domain-swapping and dimerization. 2.- To study the molecular basis of the cytotoxic mechanism of pancreatic ribonucleases and to design, produce and characterize new cytotoxic human pancreatic ribonuclease (HP-RNase). To this end, we use protein engineering approaches to produce new recombinant proteins. These new variants are constructed by inserting tumor-specific nuclear targeting signals, by fusing them to tumor cell-selective peptides or by changing their final fate once they are internalized into the cells. We characterize these protein using techniques from biophysical to cell biology fields. For the most interesting variants, presenting significant antitumor abilities in vitro we evaluate their in vivo antitumor capacity.

Our technology is directed at destroying RNA as a therapeutic approach for the treatment of cancer and viral or bacterial infections. Our products constitute a novel anticancer strategy because they are not classical pharmacological approaches of “small molecules” or radiotherapy to treat the multifactorial cancer disease. They are non-genotoxic products since they degrade cellular RNA leaving DNA undamaged and it is difficult that they may generate resistance. In addition, its human origin warrants poor or null immunogenicity when used in clinical. 3.- To study the mechanism of protein transsplicing and to apply this methodology to direct the cytotoxicity of ribonucleases. It is anticipated that the information gleaned from the elemental studies will help in the design of strategies that make possible to control in vitro and in vivo the cytotoxicity of ribonucleases. Protein splicing is a post-translational event in which an intervening sequence, termed an intein, is excised from a precursor polypeptide, concomitantly creating a new peptide bond between its two flanking regions, the exteins. Therefore, inteins can be used to develop novel systems that allow splicing to occur only in the presence of a chemical or physical inducer. In principle, these conditional splicing techniques provide a way to splice together inactive protein domains. More generally, this strategy should endow with a means to trigger the post-translational synthesis of a target protein from two fragments and thus, temporarily control the ‘on-switch’ of protein’s structure and function.

GROUPS ASSOCIATED WITH THE IDIBGI

PUBLICATIONS Originals (I.F.: 8.14): 1. Vert A, Castro J, Ruiz-Martínez S, Tubert P, Escribano D, Ribó M, Vilanova M, Benito A. “Generation of new cytotoxic human ribonuclease variants directed to the nucleus”. Molecular Pharmaceutics. 2012; 9:2894-902. PMID: 22957849. I.F.: 4.78 2. Castro J, Ribó M, Puig T, Colomer R, Vilanova M, Benito A. “A cytotoxic ribonuclease reduces the expression level of P-glycoprotein in multidrug-resistant cell lines”. Investigational New Drugs. 2012; 30:880-8. PMID: 21286781. I.F.: 3.36

Grants for Research in Progress: · Bases moleculares del plegamiento y citotoxicidad de las ribonucleasas pancreáticas. Evaluación de la actividad citotóxica y diseño de estrategias para su control mediante splicing proteico. (BFU2009-06935) Sponsored by: Ministerio de Ciencia e Innovación Duration: 2010 - 2012 Maria Vilanova Brugués · Grup d’investigació consolidat (SGR2009-657) Sponsored by: DGU Generalitat de Cataluña Duration: 2009 - 2013 Maria Vilanova · Microscopio Láser Espectral Confocal (UNGI10-4E-471) Sponsored by: Ministerio de Ciencia y Innovación. Convocatoria de Infraestructura Científico Tecnológica Duration: 2012 - 2016 Marc Ribó Panosa · Estudis estructurals i funcionals de inteínas i ribonucleases per a l’obtenció de molècules amb aplicacions biotecnològiques i biomèdiques. (SING12/04) Sponsored by: Universitat de Girona Duration: 2012 - 2013 Antoni Benito Mundet 68

ANNUAL SCIENTIFIC REPORT 2012 IDIBGI

STATISTICS AND DATA ANALYSIS

PUBLICATIONS

GROUP MEMBERS

2. Puig J, Pedraza S, Demchuk A, Daunisi-Estadella J, Termes H, Blasco G, Soria G, Boada I, Prados F, Remollo S, Banys, Soria G, Serena J, Castellanos M. “Quantification of Thrombus Hounsfield Units on Noncontrast CT Predicts Stroke Subtype and Early Recanalization after Intravenous recombinant Tissue Plasminogen Activato”. American Journal of Neuroradiology. 2012; 33:90-6. PMID: 22158924. I.F.: 2.93

Group Leader: Vera Pawlowsky

Post-Doctorate Researchers Carles Barceló Jose Antonio Martín Santiago Thio Fernandez Josep Daunis M. Gloria Mateu

Post-graduate Researchers Marc Comas Marina Vives

Originals (I.F.: 4.22): 1. Pedraza S, Puig J, Blasco G, Daunis-iEstadella J, Boada I, Bardera A, Castellanos M, Serena J. “Reliability of the ABC/2 method in determining acute infarct volume”. Journal of Neuroimaging. 2012; 22:155-9. PMID: 21447023. I.F.: 1.29

GROUPS ASSOCIATED WITH THE IDIBGI

STATISTICS, ECONOMETRICS AND HEALTH (GRECS)

GROUP MEMBERS Group Leader: Marc Saez

Post-Doctorate Researchers Maria Antònia Barceló Lluís Coromina Carme Saurina Germà Coenders Gemma Renart

Post-graduate Researchers Carme Cañizares Berta Ferrer Laia Maynou Gemma Osca Montserrat Puig Amjad Abu Rmileh Laura Serra

ANNUAL SCIENTIFIC REPORT 2012 IDIBGI

PUBLICATIONS Originals (I.F.: 26.04): 1. Osca-Gelis G, Puig-Vives M, Saez M, Gallardo D, Solé F, Marcos-Gragera R. “Incidence and survival of chronic myelomonocytic leukemia in Girona (Spain): a population-based study, 1993-2007”. Leukemia Research. 2012; 36:1262-6. PMID: 22784713. I.F.: 2.92 2. Coll-De-Tuero G, Saez M, RodríguezPoncelas A, Barceló MA, Vargas-Vila S, Garré-Olmo J, Sala V, Siera A, Gelada E, Gelado-Ferrero J. “Why is cardiovascular risk stratification important in hypertensive patients?” Blood Pressure. 2012; 21:182-90. PMID: 22486493. I.F.: 1.43 3. Saez M, González-Vázquez S, GonzálezPenedo M, Barceló MA, Pena-Seijo M, Coll-DeTuero G, Pose-Reino A. “Development of an automated system to classify retinal vessels into arteries and veins”. Computer Methods and Programs in Biomedicine. 2012; 108:36776. PMID: 22424729. I.F.: 1.52 4. Puig M, Pollán M, Rué M, Osca G, Saez M, Izquierdo A, Marcos-Gragera R. “Rapid increase in incidence of breast ductal carcinoma in situ in Girona, Spain 1983-2007”. Breast. 2012; 21:646-51. PMID: 22340960. I.F.: 2.49 5. Saurina C, Vall·llosera L, Saez M. “Factors determining access to and use of primary health care services in the Girona Health Region”. European Journal of Health Economics. 2012; 13:419-27. PMID: 21499790. I.F.: 2.10 6. Bodlaj M, Coenders G, Žabkar V. “Responsive and proactive market orientation and innovation success under market and technological turbulence”. Journal of Business Economics and Management.2012;13:666-687. I.F.: 1,88 7. Casas F, Coenders G, González M, Malo S, Bertran I, Figuer C. Testing the Relationship Between Parents’ and Their Children’s Subjective Well-Being. Journal of Happiness Studies 2012; 13(6):1031-1051. I.F.: 1,46

8. Coll-De-Tuero G, Saez M, Roca-Saumell C, Rodríguez-Poncelas A, Franco P, Dalfó-Baqué A, Calvó-Perxas L, Pose-Reino A, Bayó-Libre J. Evolution of target organ damage by different values of self blood pressure measurement in untreated hypertensive patients. American Journal of Hypertension 2012; 25(12):12561263. PMID: 22914254. I.F.: 3,67 9. Martínez-Garcia E, Ferrer-Rosell B, Coenders G. “Profile of business and leisure travelers on low cost carriers in Europe”. Journal of Air Transport Management. 2012; 20:12-14. I.F.: 0,80 10. Casas F, Castellà-Sarriera J, Abs da Cruz D, Coenders G, Alfaro J, Saforcada E, Tonon G. “Subjective indicators of personal well-being among adolescents. Performance and results for different scales in Latin-language speaking countries: A contribution to the international debate”. Child Indicators Research 2012; 5:128. I.F.: 0,86 11. Coll De Tuero G, Mata-Cases M, RodríguezPoncelas A, Pepió JA, Roura P, Belén B, Franch-Nadal J, Saez M. “Chronic kidney disease in the type 2 diabetic patients: prevalence and associated variables in a random sample of 2642 patients of a Mediterranean area”. BMC Nephrology. 2012; 13:87. PMID: 22905926. I.F.: 1.64 12. Salcedo N, Saez M, Bragulat B, Saurina C. “Does the effect of gender modify the relationship between deprivation and mortality?”. BMC Public Health. 2012; 12:574. PMID: 22846597. I.F.: 2.08 13. Saurina C, Vall•Llosera L, Saez M. “Factors determining family planning in Catalonia”. Sources of inequity. International Journal for Equity in Health. 2012; 11:35. PMID: 22818829. I.F.: 1.84 14. Saez M, Barceló MA, Martos C, Saurina C, Marcos-Gragera R, Renart G, Ocaña-Riola R, Feja C, Alcalá T. “Spatial variability in relative survival from female breast cancer”. Journal of the Royal Statistical Society. 2012; 175:107134. I.F.: 1.36

GROUPS ASSOCIATED WITH THE IDIBGI

Review (I.F.: 1.96): 1. Juan P, Mateu J, Saez M. “Pinpointing spatiotemporal interactions in wildfire patterns”. Stochastic Environmental Research and Risk Assessment (SERRA) 2012; 26:1131-1150. I.F.:1,96 Multicentric (I.F.: 13.77): 1. González-Candelas F, Astray J, Alonso J, Castro A, Cantón R, Galán JC, Garin O, Saez M, Soldevila N, Baricot M, Castilla J, Godoy P, Delgado-Rodríguez M, Martín V, Mayoral JM, Pumarola T. “Sociodemographic factors and clinical conditions associated to hospitalization in influenza a (H1N1) 2009 virus infected patients in Spain, 2009-2010”. PloS ONE. 2012; 7:e33139. PMID: 22412995. I.F.: 4.09 2. Delgado-Rodríguez M, Castilla J, Godoy P, Martín V, Soldevila N, Alonso J, Astray J, Baricot M, Cantón R, Castro A, GonzálezCandelas F, Mayoral JM, Quintana JM, Pumarola T, Tamames S, Saez M, Domínguez A; on behalf of CIBERESP Cases and Controls in Pandemic Influenza Working Group. “Prognosis of hospitalized patients with 2009 H1N1 influenza in Spain: influence of neuraminidase inhibitors”. The Journal of Antimicrobial Chemotherapy. 2012; 67: 17391745. PMID: 22467633. I.F.: 5.07 3. Sala M, Salas D, Zubizarreta R, Ascunce N, Rué M, Castells X; en nombre de los grupos de investigación RAFP e INCA (Castells X, Macià F, Román M, Sala M, Almazán R, Belén Fernández A, Queiro MT, Zubizarreta R, Ascunce N, Ederra M, Erdozain N, Delfrade I, Cuevas D, Ibáñez J, Miranda J, Salas D, de la Vega MO, de la Lastra ID, Galceran J, Natal C, Baroja A, Baré M, González-Román I, Belvis F, Ferrer J, Laso MS, Sánchez M, Vega A, Blanch J, Comas M, Domingo L, Macià F, Martínez J, Román M, Romero A, Alberich C, Lluch A, Torrella A, de Galicia X, Conde M, Corujo M, Barata T, Reyes JM, Vasco P, Otegi A, Sarriugarte G, Torà N, Renart G, MarcosGragera R, Puig M, Martínez-Alonso M, Roso A, Rué M, Vilaprinyó E, Carles M, Gregori A, José Pérez M, Pla R). “Situación de la investigación en el cribado de cáncer de mama en España: implicaciones para la prevención”. Gaceta Sanitaria. 2012; 26:574-581. PMID: 22424970. I.F.:1.12 70

ANNUAL SCIENTIFIC REPORT 2012 IDIBGI

4. Domínguez A, Castilla J, Godoy P, DelgadoRodríguez M, Martín V, Saez M, Soldevila N, Quintana JM, Mayoral JM, Astray J, GonzálezCandelas F, Cantón R, Tamames S, Castro A, Baricot M, Alonso J, Pumarola T and the CIBERESP Cases and Controls in Pandemic Influenza Working Group. “Effectiveness of pandemic and seasonal influenza vaccines in preventing pandemic influenza-associated hospitalization”. Vaccine. 2012; 30:5644-5650. PMID: 22796136. I.F.:3.49

Grants for Research in Progress: · “Socioeconomic inequalities in mortality: evidence and policies in cities of Europe (INEQ-CITIES)”. DG-SANCO A/101156 Sponsored by: European Commission. Seventh framework programme Duration: 2009 - 2012 Marc Saez (partner) · Subvención para la movilidad de profesores visitantes de los programas de doctorado con Mención hacia la Excelencia. Programa oficial de doctorado en ciencias experimentales y sostenibilidad. (MHE201100258) Sponsored by: Ministerio de Educación, Cultura y Deporte Duration: 2012 Marc Saez

ANNEXES

ANNUAL SCIENTIFIC REPORT 2012 IDIBGI

Annex 1. Clinical Trials List ANESTHESIA SCD-ANA-2010-01. Josep Vilaplana Birba. “Estudio observacional prospectivo longitudinal de la utilización de tratamientos analgésicos en las unidades del dolor en Cataluña” GRU-DOL-2012-02. Antoni Arxer Tarres i Joaquim Pujol Aguila. “Estudio epidemiológico para determinar las diferencias en el impacto sobre la calidad de vida en pacientes con dolor crónico de moderado a intenso de tipo nociceptivo, neuropático y mixto” GENERAL SURGERY ILEUS-GASTRO. Antoni Codina Cazador. “Estudio clínico prospectivo aleatorizado doble ciego sobre la utilidad terapéutica del gastrografin en ileo paralítico en el postoperatorio de cirugía colorrectal” ORTHOPEDIC SURGERY AND TRAUMATOLOGY B3D-MC-GHDN. Josep María Muñoz Vives. “Efecto de la teriparatida en la consolidación de la fractura de cuello femoral” B3D-EW-GHDX. Josep María Muñoz Vives. “Efecto de Teriparatida comparado con Risedronato en la densidad mineral ósea lumbar en hombres y mujeres postmenopausicas con baja masa ósea y reciente fractura pertrocanterea de cadera” DIGESTIVE ABB-BIO-2011-01 (IMPLICA). Xavier Aldeguer Mante. “Estudio para evaluar las preferencias declaradas por los pacientes respecto al tratamiento de la enfermedad de crohn” QTM/ABB009. Xavier Aldeguer Mante. “Estudio clínico para evaluar el efecto de un complemento alimenticio en el alivio de síntomas de antibioterapia en pacientes tratados para la infección por Helicobacter pylori” ABB-TCU-2012-01 (EPICURE). David Busquets Casals. “Prevalencia, perfil clínico y manejo terapéutico del paciente con colitis ulcerosa (CU) en servicios hospitalarios de gastroenterología de España” M/000LIN/01 (IBIS-C). Esther Fort Martorell. “Estudio observacional y prospectivo en Europa para evaluar la carga económica directa e indirecta del síndrome del colon irritable con estreñimiento moderado o grave”

JAN-HEP-2011-01 (DISHCOVERY). Manuela Hombrados Verde. “Estudio observacional no intervencionista para analizar el perfil clínico de los pacientes con hepatitis C crónica, su manejo y seguimiento en los hospitales de España” ENDOCRINOLOGY ESTEVE-SIGM-204. Eduardo Esteve Lafuente. “Ensayo clinico exploratorio de fase II, aleatorizado, doble ciego, controlado, de grupos paralelos, para evaluar la eficacia y seguridad de E-52862 (400mg) por via oral, en pacientes con neuropatía diabética dolorosa” INTERNAL MEDICINE NOV-ANT-2011-01 (DAPTOKIDNEY). Mercè Blázquez Llistosella. “Prevalencia y manejo clínico de pacientes hospitalizados infectados por gram-positivos con disfuncion renal en España” FEE-VEL-2011-01 (SEGAVELA). Ferran GarcíaBragado Dalmau. “Desarrollo y validación de marcadores relacionados con la respuesta inmune en la enfermedad de Gaucher tipo1 y su utilidad en la seguridad y eficacia en términos de respuesta a tratamiento enzimático sustitutivo con velaglucerasa” SHI-TSE-2011-01. Ferran García-Bragado Dalmau. “Estudio epidemiológico sobre el estado actual de los pacientes con enfermedad de Gaucher tipo I en España, evaluados mediante la Therapeutic Goals MAP (Monitor, Action and Progress) Tool©” ROC-BIO-2011-01 (BIO-MONO). Ferran García-Bragado Dalmau. “Estudio sobre el perfil y el manejo clínico de los pacientes con artritis reumatoide tratados con terapias biológicas en monoterapia” BAY-RIV-2012-01 (XALIA). Ferran García-Bragado Dalmau. “Xarelto para la anticoagulación a largo plazo e inicial en el tromboembolismo venoso (TEV)” BAY-FIB-2012-01. Antoni Juan Pastor. “Implementación de las guías de fibrilación auricular y profilaxis de ictus de los servicios de urgencias estudio emerg-af (emergency department stroke prophylaxis and guidelines implementation in atrial fibrillation)”

ANNEXES

INTENSIVE CARE MEDICINEA INTENSIVA CIGMA 982. Josep Maria Sirvent. “Estudio de fase II, aleatorizado, doble ciego, controlado con placebo multicéntrico, de grupos paralelos, adaptativo, con secuencia de grupos, para determinar la eficacia y seguridad de BT086 como tratamiento complementario en casos de neumonía grave adquirida en la comunidad (SCAP)” MK-7655-004. Josep Maria Sirvent. “Ensayo clinico de fase II aleatorizado y contralado con comparador activo para estudiar la seguridad, la tolerabilidad y la eficacia de MK-7655 + Imipenen/Cilastatina frente a Imipenen/ Cilastatina solos en pacientes con infección intraabdominal complicada (IIAC)” NEPHROLOGY 402-C-0903 (BEACON). Martí Vallès i Prats “Estudio de bardoxolona metilo en pacientes con enfermedad renal cronica y diabetes tipo 2: aparicion de episodios renales” NEUROLOGY P261-401 (ARTEMIS-1). Albert Molins Albanell. “Estudio aleatorizado, doble ciego, controlado por placebo de la seguridad y eficacia de midazolam intranasal (USL261) en el tratamiento ambulatorio de sujetos con crisis en racimo artemis-1: terapia aguda de rescate para la epilepsia con nebulizador intranasal de midazolam-1” BIE-EPI-2011-01 (IMDYVA). Albert Molins Albanell. “Estudio epidemiológico de la depresión en pacientes con epilepsia focal y su impacto en la calidad de vida” LACO-EXP. Albert Molins Albanell. “Estudio observacional retrospectivo de efectividad y tolerabilidad en pacientes en tratamiento con lacosamida” AB07002. Lluís Ramió i Torrentà. “Estudio prospectivo fase III, multicéntrico, randomizado, doble ciego, de dos grupos paralelos, controlado con placebo y de 96 semanas de duración, para comparar la eficac y seguridad de masitinib a la dosis de 6mg/kg/ dia con placebo en el tratamiento de pacientes con esclerosis múltiple primaria”

ANNUAL SCIENTIFIC REPORT 2012 IDIBGI

11-AVR-130 (AVANIR). Lluís Ramió i Torrentà. “Estudio fase II, doble ciego, aleatorizado, controlado con placebo, 4 grupos multicéntrico, de búsqueda de dosis para evaluar la seguridad y la eficacia de tres niveles de dosis de AVP-923 (dextrometorfano/quinidina) en el tratamiento del dolor neuropático central en pacientes con esclerosis múltiple” WA21093 (OPERA II). Lluís Ramió i Torrentà. “Estudio aleatorizado, a doble ciego, con doble simulación y de grupos paralelos para evaluar la eficacia y la seguridad de ocrelizumab en comparación con Interferon beta-1 (REBIF) en pacientes con esclerosis múltiple recidivante” CP-NU 100-01.00. Lluís Ramió i Torrentà. “Estudio fase III, multicéntrico, doble ciego, aleatorizado controlado con placebo y con grupos paralelos que evalúa la seguridad y eficacia de NU100 en pacientes con formas recidivantes de esclerosis múltiple” ACA-FIN-2011-01 (GILENYA). Lluís Ramió i Torrentà. “Registro español de pacientes tratados con gilenya (Fingolimod)” OMS112831. Lluís Ramió i Torrentà. “Estudio aleatorizado, doble-ciego, controlado con placebo, de grupos paralelos, para investigar la eficacia mediante RM y la seguridad y la administración de ofatumumab durante un período de 6 meses en sujetos con esclerosis múltiple remitente-recurrente” STR01. Joaquim Serena Leal. “Validación de un panel de biomarcadores para: el diagnóstico precoz del ictus y su diferenciación de patologías análogas” F02695 LP 2 05 (LIFE). Joaquim Serena Leal. “Efecto del tratamiento con F2695 (75 mg una vez al día) durante 3meses en la mejoría de la recuperación funcional de pacientes con accidente cerebrovascular isquémico. Estudio multicéntrico, aleatorizado, doble ciego, en grupos paralelos y controlado con placebo” PEDIATRICS SCI-SPAI-2012-02. Àngels Puigdevall Dalmau. “Estudio epidemiológico de incidencia de infección aguda de las vías respiratorias (IRA) por virus respiratorio sincitial (VRS) que requiere ingreso hospitalario en poblaciones pediátricas con enfermedad cardiaca diferente a la cardiopatía congénita hemodinámicamente significativa (CCHS)”

SCI-SPAI-2012-01. Alberto Trujillo Fagundo. “Estudio epidemiológico de incidencia de infección aguda de las vías respiratorias (IRA) por virus respiratorio sincitial (VRS) que requiere ingreso hospitalario en poblaciones pediátricas con enfermedad cardiaca diferente a la cardiopatía congénita hemodinámicamente significativa (CCHS)” PNEUMOLOGY GS-US-219-0104 (AIR-BX2). Montserrat Vendrell. “Estudio fase III, doble ciego, multicéntrico, aleatorizado, controlado con placebo, con el fin de evaluar tandas repetidas de Aztreonam en 1solución para inhalación (75mg d aztreonam en polvo y disolvente para solución nobulizadora) en pacientes con bronquiectasias no asociadas a fibrosis quística e infecciones endobronquiales gramnegativa” ORTHOPEDIC SURGERY AND TRAUMATOLOGY / ANESTHESIA SMILE. Josep Vilaplana Birba, Lluis Marull Serra y Juan José Muñoz Gómez. “Estudio epidemiológico, observacional, prospectivo para evaluar la presencia de las distintas etiologías del dolor lumbar en el ámbito sanitario español” ICO – ONCOLOGY ONC-RT-01-11 (ADRESCAP). Lluis Anglada Tort. “Estudio sobre el manejo del paciente con cancer de prostata tras cirugía radical en los servicios de oncologia radioterápica” EC-FV-06. Pilar Barretina Ginesta. “Estudio de fase III, aleatorizado y doble ciego para comparar EC145 y doxorubicina liposómica pegilada (DLP/DOXIL®/CAELYX®) en combinación frente a DLP en pacientes con cáncer de ovario resistente al platino” AGO-OVAR OP.4. Miquel Beltran Fabregat. “Ensayo clínico fase III, multicéntrico aleatorizado para comparar la eficacia de la adición de la cirugía de citoreducción a la quimioterapia frente a la quimioterapia exclusiva en cáncer de ovario recidivado sensible a platino” I2I-MC-JMMG. Joaquim Bosch Barrera. “Estudio de fase I /fase II aleatorizada para evaluar la combinación de LY2603618 con pemetrexed y cisplatino en pacientes con cancer de pulmon no microcitico en estadio IV”

ANNEXES

AFI-QUI-2011-01 (NEURISK). Joan Brunet Vidal “Modelos predictivos de valoración del riesgo de neutropenia febril y neutropenia grado 3/4 en pacientes con cáncer no-hematológico en tratamiento con quimioterapia convencional” GEICAM/2011-03 S1007. Joan Dorca Ribugent. “Ensayo aleatorizado, de fase III, de terapia endocrina adyuvante estándar +/- quimioterapia en pacientes con cáncer de mama positivo para receptores hormonales y neativo para HER2 con afectación de 1 a 3 score (RS) de 25 o inferior” CINC424A2401 (JUMP). Cristalina Fernández. “Estudio abierto, multicéntrico, de acceso expandido de INC424 en pacientes con mielofibrosis primaria (PMF) o mielofibrosis posterior a trombocitemia esencial (PET-MF)” CICL670A2301. David Gallardo Giralt. “Estudio observacional de vigilancia en pacientes con hemosiderosis transfusional tratados con exjade en la practica clinica habitual” MO28107 (MAB-EASE). Santiago Gardella Company. “Estudio fase IIIb, comparativo, aleatorizado, de grupos paralelos, multicéntrico, para investigar la eficacia de rituximab subcutáneo (SC) versus rituximab intravenoso, ambos en combinación con CHOP (R-CHOP), en pacientes con linfoma difuso de células B grandes (LDCBG) CD20 positivo, no tratados previamente” CEL-MIE-2012-01 (MIR50). Yolanda González Montes. “Estudio observacional post-autorización para evaluar la respuesta de la funcion renal al tratamiento de pacientes con mieloma múltiple en recaida y con aclaramiento de creatinina <50ml/ min/1,73m2 (CRCL<50ml/min/1,73m2)” TTD-12-01 (VISNU1). Xavier Hernández Yagüe. “Ensayo clínico fase III aleatorizado, para evaluar la eficacia de FOLFOX + bevacizumab versus FOLFOXIRI + bevacizumab como tratamiento de primera línea de pacientes con cáncer colorrectal metastásico no tratado previamente con tres o más células tumorales circulantes”

ANNUAL SCIENTIFIC REPORT 2012 IDIBGI

TTD-12-02 (VISNU2). Xavier Hernández Yagüe. “Ensayo clínico fase II aleatorizado para explorar la influencia del estado de BRAF y PI3K, en la eficacia de FOLFIRI + Bevacizumab ó Cetuximab, como tratamiento de primera línea de pacientes con cáncer colorrectal metastásico con KRAS nativo y menos de tres células tumorales circulantes” ROC-ERL-2011-01 (WILT). Rut Porta Balanyà. “Estudio multicéntrico, prospectivo, observacional para identificar diferentes factores pronóstico relacionados con la supervivencia en pacientes con CPCNP avanzado tratado previamente, portadores del gen nativo del receptor del factor de crecimiento epidermico (EGFR)” ETOP2-11 (BELIEF). Rut Porta Balanyà. “Ensayo clínico fase II, abierto, de erlotinib y bevacizumab en pacientes con cáncer de pulmón no microcítico avanzado y con mutación de EGFR” GS-US-295-0203. Bernardo Queralt Merino. “Estudio de fase 2, aleatorizado, doble ciego, controlado con placebo para evaluar la eficacia y seguridad del GS-6624 combinado con FOLFIRI como tratamiento de segunda línea para el adenocarcinoma colorrectal metastásico con mutaciones en KRAS que ha experimentado progresión después de un tratamiento de primera línea con oxaliplatino y fluoropirimidina” 1200.43 (LUX). Jordi Rubio Casadevall. “Estudio aleatorizado, abierto, de fase III para evaluar la eficacia y seguridad de afatinib oral (BIBW 2992) frente a metotrexato intravenoso en pacientes con carcinoma de celulas escamosas de cabeza y cuello recurrente y/o metastásico que hayan mostrado progresión tras terapia con platino” JEVTCC-SOGUG-2011-04. Nuria Sala González. “Estudio fase II de cabazitaxel en pacientes con cáncer avanzado o metastásico de células transicionales de urotelio que han progresado un intervalo inferior a 12 meses después de una quimoterapia basada en platino” SOG-SUN-2011-01. Nuria Sala González. “Valoración en la utilidad de las guías de manejo de fármaco antidiana en cancer renal en la práctica clínica” PFI-TEM-2010-01. Nuria Sala González. “Estudio retrospectivo de casos clínicos de pacientes con carcinoma de Células Renales o con Linfoma de Células del Manto tratados con Temsirolimus”

BAY-SOR-2012-01 (NEXTEP). Nuria Sala González. “Uso secuencial de sorafenib y sunitinib en pacientes con cancer renal metastasico. Experiencia multicéntrica española” MO28047 (PERUSE). Gemma Viñas Villaro. “Estudio multicéntrico abierto, con un solo grupo de tratamiento de pertuzumab en combinación con trastuzumab y un taxano como tratamiento de primera línea de pacientes con cáncer de mama avanzado (metastásico o localmente recurrente) HER2 positivo” CNIO-BR-01-2010/GEICAM/2010-10. Gemma Viñas Villaro. “Ensayo clínico de fase I/II, aleatorizado, de paclitaxel neoadyuvante frente a imprimación con BIBF 1120 seguida por BIBF 1120 más paclitaxel en cáncer de mama HER-2 negativo con estudios correlativos proteómicos y de imagen dinàmica” IDI – MAGNETIC RESONANCE IMAGING BAY-GAD-2011-01 (GARDIAN). Salvador Pedraza Gutierrez. “Estudio para evaluar la seguridad y tolerabilidad de GADOVIST® en pacientes que precisen una resonancia magnética realizada con este medio de contraste”

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Institut d’Investigació Biomèdica de Girona Dr. Josep Trueta Edifici Hospital Universitari de Girona Dr. Josep Trueta Avda. de França s/n. 17007 Girona Tel: +34 972 940 282 fundacio@idibgi.org www.idibgi.org