Scientific Report 2013/2014

SCIENTIFIC REPORT 2013 ›2014 RESULTS AND PERSPECTIVES

Scientific Report 2013 ›2014 Results and Perspectives

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The yearly Scientific Report represents the occasion to witness how Humanitas addresses the challenges of modern medicine. An evolving process that adapts to research advancement and healthcare needs year by year.

We can describe our activities as a building standing on four basic pillars corresponding to as many answers, and modalities to face the diseases with the highest impact on human health and life expectancy, i.e. cancer, cardiovascular diseases, central nervous system diseases, and musculoskeletal diseases. Nevertheless, it is well known that pillars – however fundamental – are not enough to support a building: several other activities are needed, that at times are very different from foundation, but crucial for building completion and for its stability.

A building, a structure that functions as a combination of basic and complementary elements is an advantage not only for the scientific community but also for society.

The other relevant topic in our scientific report is the close integration between health care, research and training, which enables us to offer our patients the world’s best affordable care. This integration is played on international grounds thanks to the collaboration with the best international institutions at all levels (assistance, research and training).

As far as training is concerned, the best conditions to bring up new talents in medicine are being created at Humanitas, in terms of both knowledge and competence acquisition, and of professional opportunities. The training approach is based on ‘active learning’, which promotes cooperation and team work, as well as critical thinking and by the attractive international vocation, thanks to exchanges with European and American Universities and the opportunity to come into contact with prestigious research environments abroad and – in perspective – to choose to work there successfully if they intend to.

Alberto Mantovani Scientific Director of Humanitas

Contents

8

Humanitas Research Hospital

8

Who we are

in immunology is coming true

interview with alberto mantovani

10 Humanitas at a glance 14 Our history 15

Our philosophy

16 Clinical innovation 19 Our technology 20

Scientific research

27

Education

I mmunity and inflammation

33 After a hundred years, a dream

highlights

35 cecilia garlanda PTX3, a novel therapeutic and diagnostic tool in opportunistic infections

36 domenico mavilio, enrico lugli luca castagna New frontiers in the follow-up and management of bone marrow transplantations 37 sĂŠbastien jaillon

PTX3: a soluble pattern recognition receptor involved in adult and infant innate immunity

38 Gerry Scotti supports 4 young talents to counteract brain drain

30 Translational research

6

Oncology

41 Humanitas’ strategy to

Cardiovascular

53 Clinical practice calls,

Neuroscience

61 Maximal challenges, minimal invasivity

undermine cancer

high tech answers

interview with armando santoro

interview with

gianluigi condorelli

interview with maurizio fornari

highlights

highlights

highlights

42 luca toschi, giovanna finocchiaro 54 roberto papait

Discovering new markers of lung cancer

44 paolo zucali

carmelo carlo-stella

What all researchers dream of

46 vittorio quagliuolo

The epigenetics of heart failure

55 maurizio gasparini

Technology improves the quality of life

56 marie-louise bang

62 lorenzo bello

At the frontier of neurosurgical oncology research

64 michela matteoli Synapses: a complex puzzle with overlapping pieces

Molecular mechanisms leading andrea marrari from mutations in sarcomeric Sarcoma: a rare multifaceted disease proteins to cardiomyopathy with innovative various therapeutic options 58 patrizia presbitero

Twenty years of advances in

skin cancer clinic cardiology

47 lorenza rimassa, luca cozzaglio luca mancini

Multidisciplinary approach to melanoma care, benefits for patients, 67 recent results and future perspectives in the treatment of this disease

Board of Directors 69 Departments and teams

cancer free clinic

49 raffaele cavina, rita mazza

Humanitas Cancer Center’s approach to cured patients: state of the art, open questions, and new challenges

breast unit

69 Clinical Area 74 Scientific Research and Laboratories 76 Papers published 2013

50 marta scorsetti, corrado tinterri

76 Preclinical Research

84 Translational research

rosalba torrisi A comprehensive approach to overcome breast cancer

90 Clinical research

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Humanitas Research Hospital

Who we are

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Humanitas is a highly specialized hospital, research and teaching center of the University of Milan.

Built around centers for prevention and treatment of cancer, cardiovascular, neurological and orthopedic disease – together with an Ophthalmic Center and a Fertility Center – Humanitas also operates a highly specialized Emergency Department.

The first Italian hospital that has been quality-certified

by Joint Commission International, Humanitas is accredited by the National Health-Care System.

Humanitas promotes health, prevention and early

diagnosis by means of innovative and advanced outpatient health care facilities.

Accredited as IRCCS by the Ministry of Health (an accreditation in the Italian system that acknowledges institutions focused on excellence in clinical care and research), Humanitas is a world-famous center of excellence for immune system-related diseases, from cancer to rheumatoid arthritis.

Humanitas Research Hospital is the flagship of a hospital group also present in Bergamo, Turin, Catania and Castellanza (Varese).

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Humanitas at a glance Our people

Clinical activity (yearly)

more than 2,000 in total, of whom,

40,000 inpatients from Italy and abroad 2.4 million outpatients 50,000 Emergency Room (ER) patients

approximately,:

650 physicians and researchers (32%) 1,000 nurses, technicians, biologists

and others (50%)

350 services for patients and staff (18%)

Our facilities 90,000 mq, of which: 75,000 are devoted to clinical activity 5,000 to scientific activity 5,000 to training and teaching other facilities for patients and relatives

747 beds, of which: 75 in the medical, surgical, and oncological day-hospital

28 in the intensive care unit

154 in cardiopulmunary, orthopedic and neuro-motor rehabilitation

28 operating theatres 5 rooms for interventional cardiology and radiology

more than 200 outpatients clinics

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Our key-enabling technologies Magnetic resonance 3 Tesla Open magnetic resonance with ambient light 2 PET-CT Da Vinci Robot EOS imaging system 3D Ultrasound Scan Genetic diagnostics and molecular tests Stereotaxis to treat cardiac arrhythmias Digital tomosynthesis (3D mammography) Excimer laser Femtosecond laser 5 linear accelerators for radiotherapy, of which 2 TrueBeam Gamma Knife and EDGE for brain radiosurgery

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Humanitas at a glance Scientific activities 2,627 = Impact factor in 2013 More than 300 professionals involved into research, of whom: 200 researchers (PIs, Junior PIs/Staff scientists, Postdocs and PhD students, technologists/technicians) more than 100 clinicians involved into research 20 labs 20,000 sqm dedicated to research and education

Research activities Published papers 2009

Raw impact factor* 2009

289

2010

2010

349

2011

125

250

375

2253

2013

421 0

1878

2012

416

2013

1727

2011

363

2012

1587

500

2627 0

500

1000

1500

2000

2500

3000

* The raw IF is the sum of the IF of each journal that publishes the paper with at least one name of an Humanitas physician.

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Papers classified according to their raw IF* 2009

33

2010

31 48

2012

42

55

57 0

230

77

2011 2013

192

65

50 IF>10

100

256 99

275

98

266

150 IF5-10

200

250

300

350

400 450

IF<5

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Our history

1989 The design and construction of Humanitas are assigned to Techint, on the basis of James Gowan’s project.

1996 The hospital construction terminates and – on March 4, 1996 – Humanitas opens its doors and greets its first patient.

1997 Humanitas is subsidized by the National Health System for inpatient services.

1999 Humanitas Foundation is established for psychological and practical support to patients and people who assist them.

2000 Humanitas becomes a teaching center of the University of Milan for the Nursing Degree, followed by Medicine and Biotechnology.

2002 Humanitas becomes a case study for the Master in Business Administration at Harvard University and also receives excellence accreditation by Joint Commission international, becoming the first Italian hospital to be acknowledged by one of the most important bodies for hospital quality certification worldwide.

2003 Humanitas opens the ER and Radiotherapy Unit.

2005 The Ministry of Health accredits Humanitas as IRCCS. Humanitas Foundation for Research is launched.

2007 Inauguration of the Research and Teaching Center.

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2010 Humanitas launches the International Medical School in collaboration with the University of Milan.

2013 The amount of scientific output from Humanitas reaches a total Impact Factor of 2,627. An outstanding result that positions the IRCCS among the first Italian Institutions for quality of research.

2014 Diagnostic services enlargement with new available facilities.

Humanitas University, a new international institution dedicated to the medical sciences, is established.

Our philosophy

Mission Providing people with outstanding and highly specialized diagnostic and therapeutic services: this is our mission at Humanitas. Our daily activity aims at the continual improvement of: • The effectiveness of treatment • The humanization of care • Management efficiency • Innovation in scientific research • The professional development of operators • The education of professionals Scientific research and the education of professionals, both for internal and external staff, are essential for the continuous improvement of provided services and for achieving excellence.

Humanitas and prevention Being proactive is the winning strategy to maintain good health. Even the most serious diseases can be prevented (primary prevention) or improved (secondary prevention) with physical activity and correct lifestyle.

Humanitas is actively involved in life-styles campaigns and focuses on prevention and early diagnosis thanks to daily investments in expertise and technologies.

On the patients’ side Humanitas cooperates with Fondazione Humanitas and Fondazione Ariel to provide support to patients and their families. In particular, Fondazione Humanitas supports patients with chronic diseases and their families by means of dedicated programs and properly trained nursing volunteers, while Fondazione Ariel supports children affected by cerebral palsy and their families through orientation activities, psychological and social support and assistance.

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Clinical innovation Cancer Center

Patient centered care Humanitas is committed to integrating care, research and education in order to offer our patients the world’s best affordable care.

Hundreds of professionals – physicians, researchers, nurses, technicians, and other team staff – stand every day at the frontline to achieve this ambitious aim.

Oncology General, hepatic and pancreatic surgery Thoracic surgery Gynecology Urology Breast unit ENT Nuclear Medicine Radiotherapy Dermatology

Research Hospital Humanitas in Milan is an IRCCS (an accreditation in the Italian system that acknowledges institutions focused to excellence in clinical care and research).

Humanitas is accredited by the Italian National Health Care System. Its diagnostic and therapeutic activities meet patients’ needs at a local, national and international level.

Specialized Centers of Excellence and care pathways Healthcare, supported by the best specialist expertise and integrated by a multidisciplinary approach, is sustained by continual research activities for care improvement and personalization.

Humanitas developed its clinical organization by establishing excellence centers for cancer, cardiovascular, neurological, orthopedic and ophthalmic diseases – besides a Fertility Center – where patients are assisted by multidisciplinary teams and dedicated organizations.

Cardio Center* Heart surgery Cardiology Vascular surgery Electrophysiology Hemodynamics Ecocardiography Cardiac care unit Rehabilitation

Neuro Center Brain and spine neurosurgery Functional neurosurgery Neurology Stroke unit Rehabilitation

Ortho Center Prosthetics

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* Mattia Glauber has been the Director of Humanitas’ Cardio Center since May 2014.

Having performed over 3,000 minimally invasive cardiosurgery procedures, he is considered a key player at an international level in the field of surgical treatments with mini-thoracotomy for heart diseases in adult patients.

Specialised equipes in surgery of: shoulder, knee, hand, foot Traumatology Rehabilitation

Humanitas’ Eye Center A latest generation excimer laser, unique in the world due to the integration of multiple and sophisticated technologies and the dedicated softwares, has been developed with the cooperation of the team of Humanitas’ Eye Center led by Paolo Vinciguerra. It can correct vision defects (myopia, astigmatism, presbiopia, hypermetropia) and represents the cutting edge of this new high specialty Humanitas’ center, set in the heart of the Policlinic: 23 professionals, 797 sqm, an expert team able to assist each day more than 200 patients.

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Clinical innovation

FERTILITY CENTER

Fertility Center Helping couples make their dream of having a child come true, supporting them with humanity and scientific expertise. This is the aim of the team managed by Paolo Emanuele Levi Setti at Humanitas Fertility Center. The team is made up of doctors, nurses, biologists and staff personnel. After 16 years the Center – one of the most important reference points for assistance to infertile couples in Italy and Europe and one of those with the highest cycle number/ number of IVF cycles – reorganized its activity in order to provide couples with an increasingly personalized treatment, supporting them throughout the whole intervention, and not only during medically assisted procreation (MAP) procedures: starting from prevention to thorough diagnostics, from minimally invasive surgery to cryopreservation, for instance for oncologic patients.

Figures of MAP at Humanitas Over 21,000

assisted couples since 1996

>3,000

babies born until 31.12.2013

Artificial insemination techniques at the Center are: • Ovulation monitoring through ultrasonography and hormone levels • IUI (Intrauterine Insemination) • IVF (In Vitro Fertilization) • ICSI (Intracytoplasmic Sperm Injection) • ICSI/TESE (Intracytoplasmic Injection with Testicular Sperm Extraction)

Other techniques

Other methods

Surgical sperm retrieval methods: • MESA (Micro Epididymal Sperm Aspiration) • MESE (Micro Epididymal Sperm Extraction) • PESA (Percutaneous Epididymal Sperm Aspiration) • TESA (Testicular Epididymal Sperm Aspiration) • TESE (bioptic Testicular sperm extraction) • Micro TESE (microbioptic Testicular sperm extraction)

• Cryopreservation of ejaculated sperm • Cryopreservation of sperm from testicular retrieval • Oocyte cryopreservation • Embryo cryopreservation • Ovarian tissue cryopreservation

Humanitas Lab

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Humanitas Lab, our diagnostics center for private patients, offers the possibility to book and perform – in a single session and within few hours – a comprehensive set of medical examination and tests in order to obtain the needed results as promptly as possible.

The center offers to female and male patients personalized clinical pathways addressed to the most common disorders (e.g. irritable bowel disease or gastroesophageal reflux disease) or to prevention of cancer – e.g. melanoma, and gynecological malignancies. Patients are permanently at the core of our assistance in any phase of this pathway, being accompanied and tutored by a dedicated doctor.

Our technology EOS EOS is a newly-designed imaging system that allows to study the spine and lower limbs in standing position (loaded condition).

NMR The 3 Tesla Magnetic Resonance provides higher resolution images in few seconds (that can be acquired during suspended breathing), with the advantage of minimizing the duration of the scan.

Humanitas is considered one of the technologically most-advanced hospitals in Europe. Among the most significant examples, last generation linear accelerators (TrueBeam) for radiotherapy, robotic surgical systems (the new frontier in minimally invasive surgery), next generation laser for ophthalmology, 5 Nuclear Magnetic Resonance, including a 3 Tesla and an open-bore NMR, 2 PET-CT. Humanitas is also equipped with an EOS, a newly-designed imaging system susceptible to 3D reconstruction with a sharply reduced X-ray exposure dose.

TRUEBEAM The linear accelerator TrueBeam adapts to the movement of internal organs due to breathing motion and delivers the highest possible radiation dose to the targeted cancer tissue within millimeter precision, thus sparing healthy surrounding tissue.

DA VINCI The Da Vinci robot is a state-ofthe-art surgical system, with 3D high-definition vision and four robotic arms.

BRAIN RADIOSURGERY Gamma Knife and Edge are dedicated, fully integrated systems for brain radiosurgery, often an alternative to the normal surgery. Gamma Knife and Edge are known for exceptional dose conformity and precision, limiting radiation to the surrounding brain tissue and critical structures.

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Scientific research

Research at Humanitas In 2013, as in the two previous years, Humanitasâ&#x20AC;&#x2122; scientific productivity has been constantly increasing in quality, achieving very high levels, as indicated by bibliometric indexes: over 2,600 Impact Factor points (ranking among the first IRCCS Institutions in scientific output), with particular focus on the immune system. The latter is crucial for contemporary research in medicine, because of its strong impact on different clinical areas, from cancer to cardiovascular, inflammatory and autoimmune diseases.

From labs to patients, rapidly More than 300 researchers work at the University Research and Teaching Center â&#x20AC;&#x201C; which is fully integrated with the hospital â&#x20AC;&#x201C; utilizing key-enabling technology, such as the recently acquired two-photon microscope.

The group operates in close collaboration with the 650 physicians from the hospital, in order to facilitate translation, i.e. the direct application of the most recent advances in healthcare through a systematic and ongoing process of innovation.

Scientists and researchers from 16 countries spanning over four continents carry out innovative research in immunology and are involved in studies on high impact non-communicable diseases, e.g. cancer, myocardial infarction, stroke, and autoimmune diseases.

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Exc % = 25.3%

In Italy among the Top 10%

In Western Europe among the Top 10%

In the World among the Top 10%

Certified excellence

SCImago Research Group publishes a yearly report which evaluates institutions around the world with meaningful scientific output.

SIR World Reports 2013 is the most comprehensive ranking of Worldwide Research Institutions, and includes 4,349 institutions from 114 countries that together have been responsible for more than 80% of worldwide scientific output during the term 2007-11.

The evaluation process is based on several indicators among which it has to be mentioned the Excellence Rate (Exc, in %), which indicates the amount of an institution’s scientific output that is included into the set of the 10% of the most cited papers in their respective scientific fields. It is a measure of high quality output of research institutions. The 25.3% of Humanitas’ scientific output is included in that first decade.

Humanitas, with a NI score of 2.22 is cited 120% above world average. Moreover, Humanitas is one of the 126 health institutions (out of 661 in the world) which obtained in 2013 the Green Label of Research Impact, the highest grade among the levels of NI.

“Progress and growth during the last 3 years has been outstanding. (…)

Exc. (%)

The international recognition

The ranking of Humanitas is also very impressive (…): it is now top 10% in Italy and Western Europe worldwide (SCImago ranking)”.

The recruitment of translational researchers and physician scientists has been particularly successful and should be further expanded. (…)

The overall increase in scientific productivity is particularly impressive. (…)

Progress in education has been outstanding. (…)

The establishment of the International Medical School and the M.D.-Ph.D. program is viewed as a major strength of the HRI, which positions the Institute as a leader in the training of the next generation of physician scientists in Europe. (…)

55 Howard Hughes (USA) Cold Spring Harbor Lab (USA) J. Craig Venter (USA) Sanger Institute Institute for Systems Biology (USA)

45 35

Dana Farber Cancer Institute (USA)

HUMANITAS 25

Sloan Kettering (USA)

Mayo Clinic (USA)

15 5 -5

-5

5

15

25

35

45

55

65

75

85

95 Q1 (%)

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Scientific research

Geographical distribution of foreign researchers at Humanitas (

Europe and

rest of the world)

BOARDING PASS

BOARDING PASS PASSENGER FROM TO FLIGHT

CLASS

DATE

GATE

BOARDING TIME

DEP. TIME

SEAT

Italian researchers who returned after an experience abroad Total 21 ECONOMY

ECONOMY

BOARDING PASS

BOARDING PASS

MARIO ROSSI MILANO/MXP TOKYO/NRT RS 258 Y

MARIO ROSSI TOKYO/NRT MILANO/MXP

PASSENGER FROM TO

29JUL

07L

1155

THROUGH CHECK-IN 043 OFN

FLIGHT

CLASS

RS 258 Y

G05 1125

GATE

DATE

29JUL

BOARDING TIME

07L SEAT

043 OFN RS01245368

22

DEP. TIME

1155

Humanitas firmly believes in assessment. This led Humanitas to be the first polyclinic to be accredited by the Joint Commission International and to be endowed with an Advisory Board for basic research whose chairman is the Nobel Prize awardee Rolf Zinkernagel.

The international Advisory Board includes doctors and researchers from the most important clinical and research Cancer Centers in the world, with which we share clinical and research activities of the Humanitas Cancer Center.

The regularly planned site visit of the Advisory Board, at the end of 2012, ended with overall praise for research activities at Humanitas. This shows that our efforts have been recognized, and stimulates us to improve further.

Fondazione Humanitas per la Ricerca is involved in supporting clinical and basic studies on pathophysiology of immunological defense mechanisms and of risk factors for several diseases, among which chronic inflammatory, cancer, cardiovascular, and neurological diseases.

The research activity of Fondazione Humanitas is monitored by an Advisory Board whose chairman is the Nobel Prize awardee Rolf Zinkernagel.

The Advisory Board of Fondazione Humanitas per la Ricerca: Rolf Zinkernagel, MD/PhD (President) University of Zurich and University Hospital of Zurich Institute of Experimental Immunology Zurich, Switzerland Fabio Cominelli, MD/PhD University Hospital Dept. of Medicine-Gastroenterology Cleveland, Ohio, USA Charles Dinarello, MD Professor of Medicine Division of Infectious Diseases University of Colorado Health Sciences Center Denver, Colorado, USA

Pietro De Camilli, MD Eugene Higgins Professor of Cell Biology and of Neurobiology Director, Yale Program in Cellular Neuroscience and Neurodegeneration and Repair New Haven, Connecticut, USA Napoleone Ferrara, MD/PhD Genentech Inc. South San Francisco, USA Lorenzo Moretta, MD Research Director Giannina Gaslini Pediatric Institute Professor of General Pathology University of Genova - Genova, Italy Gรถran K. Hansson, MD/PhD Karolinska University Hospital Stockholm, Sweden

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austria

czech rep.

UK belgium netherlands NORway denmark sweden germany

usa

germany

GREECE

italy

BeTheCure (IMI)

switzerland

EUROSTARS

ireland spain france

italy

switzerland

france

LeDucq Foundation

italy

germany

usa

netherlands

Scientific research

The network of the EU-sponsored research projects

mRNA translational regulation in heart failure

Marie Curie IIF

Epigenetics and microRNAs in Myocardial Function and Disease

ERC Advanced grant

Signalling compartmentalization and vesicle Trafficking at the Phagocytic Synapses

ERC Advanced grant

Mesenchymal stem cells to reduce liver inflammation

FP7 Collaborative project UK, Ireland, Netherlands, Usa

Structured International Post Doc Programme 2

Marie Curie COFUND program

Global microRNA profiling of normal and Pbx1null hematopoietic stem cells and progenitors for the identification of new regulators of the balance between self-renewal and differentiation Characterization of NK cell distributions and functions in human tissues in HIV-1 pathogenesis Improving adoptive T cell transfer immunotherapy for cancer with T memory stem cells

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Marie Curie CIG

germany

UK

italy

france

italy

WHIM-Thernet (E Rare JTC)

switzerland

brazil

italy

switzerland

TIMER

france

ireland

Ireland

austria

UK belgium netherlands norway denmark sweden germany

usa

ADITEC

The Ethical Committee Since 2005, an Ethical Committee has been active at Humanitas. This is an independent body which protects the rights, security and well being of the parties involved, within the realm of clinical research.

Any experimentation process, be it carried out industrially or within the Institute, depends on the Committeeâ&#x20AC;&#x2122;s decision, which takes into account the correctness and the compliance to ethical standards of new therapeutic methods, or diagnoses, that involve human beings directly.

Key priorities for the Ethical Committee are independence (granted by the fact that its personnel does not work for the same hospital as the one where the Committee operates), and a multifaceted approach, where different professional competencies and skills are indispensable to ensure critical evaluation of different aspects of experimentation.

According to current regulations, the Ethical Committee must be composed by: two clinicians,

a biostatistician, a pharmacologist, a chemist, the Medical Director, the Scientific Director and an expert in law. In addition, the hospital where the Committee is based may appoint other members among GPs and local doctors, nurses and people committed to voluntary work, provided that the independence â&#x20AC;&#x201C; and multifaceted-approach criteria above are met.

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Scientific research

Humanitas’ biobank Advanced research increasingly needs to be supplied with biological samples (small amounts of blood and other biological fluids, or small sections of tissue removed during surgery) to be analyzed. These samples come from donors who suffer from different diseases, and are helpful to understand how patients differ from one another and – in perspective – to develop personalized treatment.

In order to cater for this need, Humanitas has established a biobank. A biobank can be compared to a “current account” where donors “deposit” their own biological material, and obtain “interest” in return, in the form of knowledge of their disease.

By signing an Informed Consent form, and under absolute confidentiality, donors authorize Humanitas to take samples to be used for biomedical research programmes 26 which would otherwise be impossible to carry out.

Education

An international setting, along with innovative educational methods and the close integration with first rate hospital facilities and cutting-edge scientific research are the pillars of the new Humanitas University, a private nonprofit institution dedicated to the medical sciences and strictly interconnected with the identity of the Humanitas Research Hospital and its Foundation for Research. A priority for Humanitas University is developing an educational model that is consistent with the best worldwide experiences, competitive at an international level, and able to attract distinguished minds from all over

At Humanitas University, the degree courses in Medicine and Nursing are based on a more than 10year experience in academic teaching as well as on an active learning approach.

the world. Humanitas University offers young Italian and foreign applicants the opportunity to grow and study alongside greatly experienced professors and professionals with international competence within an international environment, not only in language terms, but also for the educational approaches. The visiting faculty includes Nobel Prize winners and worldwide acknowledged researchers. The teaching activities carried out in English along with the usage of an integrated curriculum, in line with the most advanced educational practices, widen the studentsâ&#x20AC;&#x2122; opportunities for a successful international career.

Initially, Humanitas will offer two degree courses: â&#x20AC;˘ MD, in English â&#x20AC;˘ Nursing BD, in Italian Later, a wider offer

of degree, PhD and specialization courses and masters will be available.

Once fully operating, Humanitas University will accommodate over 700 students.

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International collaborations and recognitions

Collaboration at international level is fundamental for clinical practice. In the last years, collaborations with national and international top-ranking hospitals and the constant effort in implementing the most advanced technologies have led to outstanding results in the treatment of neoplastic, gastrointestinal, cardiovascular, neurological and immunological diseases.

International Advisory Boards Humanitas firmly believes in the evaluation process. For this reason, an Advisory Board for pre-clinic research headed by the Nobel Prize awardee Rolf Zinkernagel has been appointed.

Another International Advisory Board assesses and evaluates Humanitas Cancer Center research and clinical activities on a continuous base.

HARVARD BUSINESS SCHOOL

Harvard University Considered by Harvard University one of the four most innovative hospitals worldwide, Humanitas is a case study for its organization model, which combines quality of care with economic sustainability, development and social responsibility.

Joint Commission Humanitas was the first polyclinic in Italy, and among the very few in Europe, to have been certified by the Joint Commission International. This acknowledgement of excellence has been confirmed and renewed four times since 2002 and has required compliance with over 1,300 standards.

Workers’ safety Humanitas is OHSAS 18001 (Occupational Health and Safety Assessment Specification) certified, an international recognition that highlights the hospital attention to its own workers’ safety and health.

Responsible Payments Humanitas has joined the Codice Italiano Pagamenti Responsabili (The Italian Code of Responsible Payments), an initiative which has been launched by Assolombarda to promote prompt and timely payments to suppliers and aimed at improving national and international reputation of Italian companies, thus strengthening their competitiveness.

Humanitas Lectures

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Humanitas Lectures include a series of top level scientific meetings organised in partnership with the University of Milan.

These lectures represent a focus on the development and the evolution of the biomedical research at the service of human health. Among the speakers, the Nobel Prize awardees Prof.

Rolf Zinkernagel and Prof. Françoise Barré-Sinoussi are worth mentioning.

Humanitas Group in Italy

Castellanza

Bergamo

Humanitas Mater Domini

Humanitas Gavazzeni

www.materdomini.it

www.humanitasgavazzeni.it

1,400 beds 100,000 annual admissions Over 4 million annual outpatients 150,000 sq m 1,000 physicians

Turin Clinica Cellini www.clinicacellini.it

Milan-Rozzano Istituto Clinico Humanitas

www.humanitas.it

Catania Humanitas Centro Catanese di Oncologia www.humanitascatania.it

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Translational research

30

Immunity and inflammation Oncology Cardiovascular Neuroscience

31

Immunity and inflammation

32

After a hundred years, a dream in immunology is coming true

Interview with Alberto Mantovani

Tumour immunotherapy is becoming a reality, rather than a hope. Moreover, immunology provides oncologists with a variety of tools for both diagnosis and treatment of cancer.

In the last issue of 2013, Science highlighted tumour immunotherapy as one of the key advances in the year.

Scientific Director of Humanitas and professor of General Pathology at the University of Milan

The representation of 2013 as a turning point in the fight against cancer is driven by a well deserved enthusiasm.

Nevertheless, it has to be mentioned that this breakthrough has been obtained over the last few years. Its results come from from a great deal of work and research with the contribution of a considerable number of people.

As far as immunology of cancer is concerned, we are living in an extraordinary and exciting moment. We are about to witness a dream come true, in that the founding fathers of modern medicine and immunology had already had already envisaged the possibility of using the weapons of immunity against cancer. The editorial on Science outlines that this journey – which has lasted nearly a hundred years – has certainly been characterised by success, but also by failure and, in the long run, has come to a standpoint.

Now that this long awaited objective has been met, which opportunities lay ahead?

Specific instruments of Humanitas Laboratories Confocal microscopes equipped for FRET analysis, TIRF and fast FRAP CellR for high-quality time-lapse imaging Two-photon microscope ION TORRENT sequencer LSR Fortessa cell Analyzer Bio-Plex multiplex system for the detection and quantification of multiple analytes

At the point we are now, the weapon of immunity can be used for cancer prevention and treatment. Notably, this applies to tumoural conditions normally considered hopeless until a short time ago.

If we start by considering the final stages of this happyending journey, we know that once cancer has settled, it progressively deploys its strategies to escape or to circumvent immunity, that is to suppress the immune responses, or even use them to its advantage, e.g. as a mechanism promoting tumoural progression. What has happened and what the Science editorial certifies, is that for some years now – but well before 2013 – removing the brake to immunity has been proven of relevant clinical advantage.

The first brake removal with positive outcomes has a short name: CTLA-4, which stands for Cytotoxic T-Lymphocyte Antigen 4. It blocks T-cells, preventing them from launching full-out immune attacks, potentially dangerous in healthy individuals, but hopefully effective against the disease in 33 oncologic patients. Removing the brake – i.e. “blocking the

Immunity and inflammation Interview with Alberto Mantovani

blocker” – with an antibody whose name is ipilimumab was a winning strategy to control [advanced/metastatic] melanoma, a kind of cancer against which we had ineffective weapons.

At the moment ipilimumab is approved both in US and Europe. Most steps in this breakthrough have been taken by James Allison, a cancer immunologist.

This is, however, bound to remain a single case… or – rather – could it be considered the first instance in a case-history?

Clearly, these are not everyday events. The case of ipilimumab began in the late 80s and further crucial results about a second brake removal didn’t come for another decade or so, and only recently has its role in the fight against cancer been definitely confirmed. I’m referring to PD-1 – a molecule called Programmed Death 1 by the Japanese biologist who discovered it, (again, this molecule exerts an immunosuppressive effect acting on T-cells), – and to PD-1 antibody or PDL-1. Immunotherapy with PDL-1 is associated to promising results.

However, the most oustanding result is that removing both brakes is significantly better than removing a single brake.

These data are certainly encouraging. Are there any obscure points, however?

Obviously, no medical intervention is risk-free and the balance between risks and benefits has always to be taken into account. Side effects of those treatments are essentially due to the possibility that freeing the immune system completely may trigger a self-harm mechanism. In the case-histories of ipilimumab and PDL-1, benefits clearly outweigh risks. This has been proven by the authorization of ipilimumab by the Medicines Agencies, and the same is expected for PDL-1.

Could you provide an example?

Let’s consider the fundamental role of the immune system against infectious diseases and, in turn, the worrisome relationship between infectious diseases and cancer. In particular, in immunocompromised patients who undergo bone marrow transplantation, a clear-cut increase in infections and related mortality and morbidity is described.

Thus, addressing infectious disease in oncologic patients is a boundary perspective for cancer treatment. At Humanitas, we are walking along a distinctive and innovative way – see the highlights of Cecilia Garlanda and of Sebastien Jaillon – 34 starting from a gene and ending to the bedside.

Which other interesting data are there within this research area?

In 2013, a study from Paola Allavena’s research group has provided evidence of a totally new model in humans for the first time. The protagonist of such a novelty is trabectedin, a natural product of marine origin extracted from a tunicate and endowed with anti-cancer activity. Our group was able to demonstrate that this drug is effective because it targets the immune system rather than the tumour itself. In fact, trabectedin is able to target the tumour microenvironment, more specifically, to kill a subset of immune cells (macrophages) that populate the tumour tissue and are known as tumour-associated macrophages (TAM). These immune cells, instead of defending the body, as they should do, behave as corrupted policemen – the corruptor is the cancer – and help tumoural cells in several different ways.

Trabectedin is now approved for the treatment of soft tissue sarcoma and ovarian cancer. This drug provides another proof of the fact that the flying machine is in fact capable of flying.

There appears to be a wide scope for applications in immunology: is this really so?

This is in fact just the tip of the iceberg, since the contribution of immunology to the fight against cancer is wider. The use of antibodies has deeply changed diagnostics, monoclonal antibodies are broadly used in anti-cancer treatment. They are effective against common tumours, e.g. breast cancer or colorectal cancer, as well as against less frequent and yet aggressive tumours, e.g. melanoma. Moreover, drugs whose mechanism of action is related to immunity – cytokines e.g. interferons or growth factors – are used in oncology. We have already two

vaccines against two specific types of cancer, the hepatitis B vaccine (HBV) developed for the prevention of the viral infection potentially leading to hepatocellular carcinoma and the human papilloma virus (HPV) vaccine which prevents infection with certain viral types associated with cervical cancer, genital warts, and some less common cancers.

This is certainly pioneering. What would you say is among the most innovative developments?

There is still a line of research which is just as challenging and innovative, and that is cellular therapy, specifically T-cells therapy.

As shown in a relevant and recent study by Domenico Mavilio, Enrico Lugli, and Luca Castagna – see the highlight – performed in collaboration with the University of Marseille, T-cells therapy requires the reconstitution of immunological memory.

In this context, Humanitas has the honor and the burden

HIGHLIGHT

PTX3, a novel therapeutic and diagnostic tool in opportunistic infections Preclinical studies conducted by our group in the last years have paved the way for the transfer of PTX3 to the clinic, in particular as potential therapeutic tool in infections, and as diagnostic molecule. PTX3 has been shown to protect from infections, for instance Aspergillus fumigatus, a critical challenge for immunodeficient neutropenic Cecilia Garlanda patients, and Pseudomonas aeruginosa, that is the major cause Principal Investigator of symptomatic lung disease and progressive lung dysfunction in of the Laboratory patients affected by cystic fibrosis. In the last year, important efforts of Experimental have been made to produce clinical grade PTX3, to exclude toxic Immunopathology effects, and to define the clinical context where to test its prophylactic and therapeutic potential. Patients with a history of aspergillosis undergoing haematopoietic stem cell transplantation and cystic fibrosis, and patients infected

by P. aeruginosa will be the first target for phase I/II trials.

In addition, several studies by our group, supported by independent observations by other laboratories, confirmed the potential of PTX3 as novel diagnostic and prognostic biomarker of inflammatory conditions, ranging from severe sepsis to cardiovascular disorders and cancer-associated inflammation. Finally, we contributed to genetic studies on PTX3, which clearly demonstrated that in different infectious disorders, genetic variants of PTX3 are associated to resistance to infections: namely, invasive aspergillosis (published in the New England Journal of Medicine) and urinary tract infections. Thus, these studies provided the evidence that PTX3 is also a genetic marker of resistance to specific infections, that could be transferred to the clinic as prognostic tool to identify patients with a high risk of developing P. aeuruginosa or A. fumigatus active infections.

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Immunity and inflammation Interview with Alberto Mantovani

New frontiers in the follow-up and management of bone marrow transplantations Opportunistic infections, Graft versus Host Diseases (GVHD) and disease relapse are the major causes of morbidity and mortality in blood cancer patients treated with bone marrow and haematopoietic stem cell transplantations (BMT). Since these complications can be largely prevented by immune-mediated mechanisms, preferentially exerted by T and Natural Killer (NK) cells, promotion of immune-reconstitution is pivotal to improve patients’ health and ameliorate their quality of life. We have recently undertaken a project of translational medicine to investigate on the mechanisms regulating the successful immune-reconstitution in individuals affected by haematologic malignancies undergoing haploidentical BMT followed by an early infusion of cyclophosphamide. This non-myeloablative haploidentical BMT recently developed at Johns Hopkins University School of Medicine of Baltimore in the United States is characterized by a lower grade of toxicity compared to other standard myeloablative procedures, thus making it possible to transplant and cure patients in their 6th and even 7th decade of life.

The elucidation of the still unknown mechanisms of immune protection and reconstitution is key for understanding the low rates of transplantation-related mortality, disease relapse and GVHD. Our results demonstrate that, although mature NK and memory T cells are transferred with the donor graft in the recipient, they fail to persist and do not provide an early and efficient barrier of immune protection. Indeed, NK cell recovery requires a newly engaged differentiation process from haematopoietic precursors, while T cells rely on the homeostatic expansion and differentiation of adoptively transferred naïve T cells. In the context of a synergic and collaborative network with the National Institutes of Health (Bethesda, MD, USA), the University of Cardiff (U.K.) and Institut Paoli Calmettes (Marseille, France), we are currently characterizing the phenotypic and functional characteristics of the immune system associated with the prevention of tumor relapse and protection from opportunistic infections as well as from GVHD. The identification of the “missing” components of protective immunity at the single patient level will allow to design preventive patient-specific therapies based on the adoptive transfer of antitumor and/or anti-viral/fungal immune cells before the complications occur. The experimental settings developed at Humanitas Research Hospital will also make it possible to determine NK and T cell immunological profiles associated with patients at high or low risk of infection and/or disease relapse. From a clinical point of view, this strategy will allow to better predict the clinical outcome of BMT by monitoring specific cell subsets used as novel biomarkers and to prevent the onset of life-threatening infections by infusing antigen-specific immune cells.

HIGHLIGHT

Domenico Mavilio MD, PhD Principal Investigator, Laboratory of Clinical and Experimental Immunology

Enrico Lugli, PhD Laboratory of Clinical and Experimental Immunology

Luca Castagna, MD Head of the Unit of Cell Therapy and Bone Marrow Transplantation

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top paper Germano G, Frapolli R, Belgiovine C, Anselmo A, Pesce S, Liguori M, Erba E, Uboldi S, Zucchetti M, Pasqualini F, Nebuloni M, van Rooijen N, Mortarini R, Beltrame L, Marchini S, Fuso Nerini I, Sanfilippo R, Casali PG, Pilotti S, Galmarini CM, Anichini A, Mantovani A, D’Incalci M, Allavena P. to coordinate a large Italian research project funded by the Associazione Italiana per la Ricerca sul Cancro (AIRC) which includes the participation of several distinguished national institutions: the Istituto Gaslini in Genoa, the Sapienza University in Rome, the Ospedale Pediatrico Bambino Gesù in Rome, the Ospedali Riuniti di Bergamo-Papa Giovanni XXIII Hospital in Bergamo, the San Gerardo Hospital in Monza, and the University of Milano-Bicocca.

The priority is to transfer the advances and contributions made by Italian researchers in the use of molecules or cells of the innate immune system against some haematological malignancies (leukaemias or lymphomas) or against bone marrow transplant-associated infections to clinical practices and to bedside. This is an ongoing project, and the preliminary results are quite promising.

Is this another dream coming true?

Yes, and it is bound to integrate happily with reality. In conclusion, it can be said that cancer prevention and tumour immunotherapy are now an established reality, which, anyway, does not replace conventional interventions – i.e. surgery, radiation therapy, chemotherapy, targeted therapy – rather it complements them and more and more it will. That means a great expectation for the fight against cancer in the year to come. ❙❙

Role of macrophage targeting in the antitumor activity of trabectedin.

Cancer Cell. 2013 Feb 11;23(2):249-62.

There is widespread interest in macrophages as a therapeutic target in cancer. Here, we demonstrate that trabectedin, a recently approved chemotherapeutic agent, induces rapid apoptosis exclusively in mononuclear phagocytes. In four mouse tumor models, trabectedin caused selective depletion of monocytes/ macrophages in blood, spleens, and tumors, with an associated reduction of angiogenesis. By using trabectedin-resistant tumor cells and myeloid cell transfer or depletion experiments, we demonstrate that cytotoxicity on mononuclear phagocytes is a key component of its antitumor activity. Monocyte depletion, including tumor-associated macrophages, was observed in treated tumor patients. Trabectedin activates caspase-8-dependent apoptosis; selectivity for monocytes versus neutrophils and lymphocytes is due to differential expression of signaling and decoy TRAIL receptors. This unexpected property may be exploited in different therapeutic strategies.

HIGHLIGHT

PTX3: a soluble pattern recognition receptor involved in adult and infant innate immunity Pentraxins are essential constituents of the humoral arm of innate immunity. Our group identified PTX3, the first member of the long pentraxin subfamily in the early 90s, and showed its involvement in resistance to microbes.

In newborns and infants, functional immaturity of the immune system is responsible of high susceptibility to infections. Breastfeeding compensates, providing optimal immune protection, and Sébastien Jaillon, is considered the most effective protective mean to limit mortality of under-5 children. We recently PhD addressed the issue of whether PTX3 contributes to the immune protective functions of breastfeeding Laboratory of and we observed that defective production of PTX3 in neonates was compensated by breast milk, Experimental which contains high levels of PTX3 that rapidly distributes in neonatal tissues. Oral administration of Immunopathology PTX3 improved neonatal resistance against P. aeruginosa infection, a microbe causing severe acute and chronic infections. Therefore, PTX3 might represent a therapeutic tool for treating neonatal infections and contributes to the beneficial effects of breastfeeding on neonates’ health.

In addition, we found that PTX3 is an essential component of innate resistance against urinary tract infections, a disease that remains a major public health problem, despite improved hygiene and the widespread use of antibiotics. We observed that PTX3 is expressed by uroepithelial cells, and plays an important role in the protection against uropathogenic E.coli. In patients, genetic variants of PTX3 are correlated with susceptibility to acute pyelonephritis. Our study shows for the first time that the cellular and humoral arms of innate immunity exert complementary functions in mediating resistance against urinary tract infections.

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Gerry Scotti supports 4 young talents to counteract brain drain It’s the third time that the famous TV presenter has funded research projects for four talented researchers.Thanks to these one-year- grants Marco Carbone, Barbara Cassani, Giuseppe Celesti, and Kelly Hudspeth will be able to carry out their studies in Italy, either returning from abroad or staying in our country.

Studying liver to understand immunity Marco Carbone, 33 years old, graduated in Medicine and specialized Gastroenterology and Hepatology. Since 2011 he’s worked at the Division of Gastroenterology and Hepatology of the University Hospital in Cambridge where he is involved in both clinical practice and research. He’s a highly competent statistician and epidemiologist. Thanks to Gerry Scotti’s research grant, Marco Carbone has returned to Italy, at the Laboratory of Hepatobiliary Immunopathology in Humanitas led by Pietro Invernizzi, where he will work specifically on autoimmunity and liver inflammation.

«The liver is a crucial organ when studying immunologic responses and inflammation, especially in relation to the onset of both cancer and autoimmune diseases, which affect mostly women. Notably, primary biliary cirrhosis, an autoimmune liver disease characterized by chronic inflammation of intrahepatic bile ducts is an excellent model to understand why women are more susceptible to these autoimmune 38 disorders.»

Returning to Italy to fight against genetic immunodeficiency disorders Barbara Cassani, 36 years old, holds a degree in Pharmacy, and is coming back from the United States thanks to the grant.

There, she has worked for several years at the Massachusetts General Hospital and at the Harvard Medical School where she has performed relevant experiments on the immune system and, specifically, on immunodeficiency disorders, i.e. those cases when the immune system is inefficient. At CNR (National Research Council) laboratories directed by Paolo Vezzoni and Anna Villa, Barbara Cassani is investigating the mechanisms of autoimmune diseases in patients with primary immunodeficiency disorders, and, in particular, the pathogenetic role of intestinal microbiota.

«Studying these conditions is essential to find new therapies for these rare diseases on one hand, and on the other it is helpful to reach deeper understanding of the functions of the immune system in order to treat more common diseases.»

Investivating micro-environment to defeat colorectal cancer

An American in Milan to disclose the secrets of mucosal killer γδ T lymphocytes

Giuseppe Celesti, 31 years old, with a degree in in Biotechnology, and a PhD in Molecular Medicine. At the Laboratory of Molecular Gastroenterology led by Luigi Laghi, he has focused his investigation on the micro-environment surrounding tumours and favouring their growth and progression. This young scientist has made an important contribution to the identification of the molecular mechanisms of epithelial-to-mesenchymal transition.

«The current model of metastasis comprises a sequence of steps which enable cancer to progress towards metastasis and implies the transition of the epithelial cancer cells to a mesenchymal-like state, referred to as epithelial to mesenchymal transition (EMT). After having documented the EMT occurrence during the invasion step of human colorectal cancer, at the moment we are investigating the relevance of circulating cancer cells with mesenchymal features in the blood of patients with colorectal and pancreatic cancer. Our data unveil that messenger RNAs coding for EMT genes are detectable since the early tumor stages, and that their levels are highly sensitive and specific for cancer diagnosis. In parallel, we are also setting-up an innovative model of “blood-bornetumor-grafts” to study and possibly predict the occurrence of metastasis.»

Kelly Hudspeth, 35 years old, comes from the United States. She graduated in Biological Sciences, and has a PhD in Experimental Pathology and Neuropathology. The grant allows her to work at the Laboratory of Clinical and Experimental Immunology directed by Domenico Mavilio. Her research is focused on γδ T lymphocytes, cells of the immune system, which play a major part in the fight against tumors and viral infections. She has investigated in depth both intestinal mucosal immunity as well as the role of γδ T lymphocytes in the immune response against colorectal cancer and of inflammatory bowel diseases.

«Understanding the causative mechanisms of these conditions, whose incidence is progressively increasing, is crucial for the development of therapies for diseases such as these that currently have no effective cure.»

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Oncology

40

Humanitas’ strategy to undermine cancer

Interview with Armando Santoro

All the possible strategies are being deployed against the disease: from innovative organizational solutions to the newest therapeutic options. Always with the patient at the center.

Who is going to win this decades-long battle against cancer?

Director of Humanitas Cancer Center

After so many years, optimism is making its way, as the first signs of decrease in the disease are starting to show.

In the US, the Annual Report on the Status of Cancer, covering the period 1975-2010, and published at the end of 2013 on Cancer showed decreased death rates for four big killers like lung, colorectal, breast, and prostate cancer.

Additionally the report confirmed a trend toward a global reduction in death rates for all cancer types that began about 20 years ago. Even if we must take a distinction from the American context, these results are encouraging and show the effectiveness of the different strategies used, including early diagnosis, better treatment options and a more appropriate follow-up. Humanitas is at the forefront of this strategic plan.

What is the most significant new advance carried out at Humanitas within this effort against cancer?

Specific instruments of Humanitas Laboratories Confocal microscopes equipped for FRET analysis, TIRF and fast FRAP CellR for high-quality time-lapse imaging Two-photon microscope

We are developing an ambitious and challenging project, where the key words are multidisciplinarity, collaboration, and integration. It consists of the so-called “clinics”, which are modules devoted to the assistential activity of a certain condition/disease, based on the close cooperation and shared objectives of several professionals that have different specialized competences. They demand organization, locations and resources, and offer an unquestionable advantage in terms of standards of care and best practice.

The first three clinics we implemented at the moment are the Breast Unit, the Cancer-free Clinic and the Skin Cancer Clinic.

ION TORRENT sequencer BD FacsAria Olympus VS120 Virtual Microscopy Slide Scanning System Robosep Cell Isolation

Could you provide an example from the patient’s point of view?

For each patient, clinics offer tailored pathways, which start from the admission and follow up until the discharge;

41

Oncology Interview with Armando Santoro

without neglecting the patients when dwelling home. Let’s consider a woman with a breast cancer or a patient with a suspicious skin nodule. They enter their way, being visited by the physician, the surgeon, the plastic surgeon, the oncologist which share a plan and participate according to their competences.

Diagnostic-therapeutic pathways are not imposed from the top-down, they are rather co-built making use of Humanitas’ structures and resources.

This strategy is fundamental, since cancer patients have more and more complex needs and conditions in terms of diagnosis, staging, combined interventions, innovation, management of comorbidities and long-term survival. Clinics grant excellent standard levels in terms of quality of treatments, due to a combination of clinical assistance highly specialized in oncology and an integrated multidisciplinarity.

Moreover, there are potential advantages in this strategy, particularly when considering the introduction of specialist structures that allow to implement the four main tools

against cancer: prevention, assistance, research and innovation.

Let us now consider these four tools and start from prevention.

Preventive diagnostics and screening deserve more and more attention and investment. Going back to the above mentioned Annual Report, the recent larger drop – significantly faster than in previous years in lung cancer deaths, which account for more than one in four cancer deaths – is the result of decreased cigarette smoking prevalence over many years. The Stop Smoking Center has been operational at Humanitas since 2008 and has followed over 500 patients their effort to give up smoking.

It combines motivational and pharmacological approaches according to the recommendations of international guidelines.

For the advances in lung cancer diagnosis, see the highlight of Luca Toschi and Giovanna Finocchiaro.

Discovering new markers of lung cancer

42

Lung cancer is the leading cause of cancer deaths worldwide and survival rates are poor. In the last few years, a number of approaches have been investigated with the purpose of reducing lung cancer mortality or prolonging overall survival, with encouraging results. First, lung cancer screening with low dose CT scan in high risk populations has been shown to produce a 20% reduction in lung cancer mortality.

Such unprecedented results – albeit at the cost of useless diagnostic procedures Luca Toschi Giovanna triggered by false positive findings – have led several scientific societies to Finocchiaro Division of Medical implement lung cancer screening recommendations in smokers. Second, a Oncology and Division of Medical number of oncogenes that can be therapeutically targeted have been recently Haematology, Oncology and identified, particularly for patients with advanced lung adenocarcinoma, leading Humanitas Cancer Haematology, to the development of novel agents that produced significant improvements in Humanitas Cancer patient outcomes with acceptable toxicities. Third, after years of failures in the clinical setting, recent data indicate that immunotherapy approaches could finally play a key role in lung cancer treatment; thus, the preliminary results from ongoing clinical trials are eagerly awaited.

Despite these promising steps towards better lung cancer treatment there is still much more to be achieved. A major issue is represented by the high relapse rate even in early-stage lung cancer patients after curative surgery, reflecting the subtle behaviour of this disease. In this setting, in collaboration with the University of Colorado Cancer Center, we were able to identify SOX2 gene copy number as a key prognostic factor, suggesting that selected molecular markers can serve as useful tools to predict patient outcomes. Additionally, we are currently investigating the use of novel tools to monitor the activity of targeted anti-cancer agents. More specifically, we are testing whether circulating microRNAs, that can be isolated from blood samples, could predict drug sensitivity in selected patients.

What other prevention-oriented services are available at Humanitas?

Genetic counselling for breast and ovary cancer or colorectal cancer is offered to high risks patients. These outpatient services are lead by Monica Zuradelli and Luigi Laghi, respectively.

We have already dealt with assistance reorganisation in clinics. What is worth mentioning in terms of research and innovation?

Humanitas remains a key player in clinical research, supporting development and testing of new drugs. At the moment, the most substantial innovation comes from the area of biological drugs (also called molecular or targeted drugs) which may be the future for oncologic treatments, as demonstrated by the fact that each year new drugs are being added to the list. Relevant improvements in outcomes have been observed for lung

HIGHLIGHT

cancer, breast cancer and colorectal cancer, mesothelioma, soft tissue sarcoma, hepato-bilio-pancreatic cancer and haematological tumors like lymphoma, myeloma and leukemias. Humanitas’ researchers give their contribution to all phases of clinical trials.

What can be considered the most significant changes in the therapeutic approach against cancer in the last 2 yeras?

The management of melanoma, a cancer that had a poor prognosis until not so long ago, has seen promising advances in terms of improvement in survival, thanks to two innovative treatments, both endowed with a targetaction mechanism, i.e. ipilimumab, a monoclonal antibody which enables the activation of the immune system against cancer, and anti-BRAF drugs, targeted against a BRAF mutation found in 40% of melanomas.

Sarcoma is another cancer whose management is challenging due the variety of its subtypes, but the recent steps towards a better control of the disease are quite promising, see the highlight of Vittorio Quagliolo and Andrea Marrari.

A revolution has begun also in the field of haematooncology, an area of excellence at Humanitas.

A series of promising drugs – e.g. monoclonal antibodies – for chronic lymphocytic leukemia, non-Hodgkin lymphomas, as well as for myelodysplastic syndromes and myeloproliferative neoplasms, is at the moment in an advanced experimental phase.

How can these drugs be revolutionary in haematological tumorsy?

Hopefully, they can modify the criteria and the indication of a treatment. In fact, these new molecules offer the advantage of a frequent induction of remission and the consequent possibility to address a high number of patients for transplantation. In addition, there is a chance that the indication to transplantations may be overcome by the positive outcome of the treatment.

We are taking part in international clinical trials – see the highlight of Carmelo Carlo-Stella and Paolo Zucali – from phase 1 (evaluation of safety and dose-finding of new drugs) to phases 2 and 3 (evaluation of drug-effectiveness and/or comparison to other therapeutic options available in a large group of patients).

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Oncology Interview with Armando Santoro

Paolo Zucali

Carmelo Carlo-Stella

Medical Oncology and Haematology, Unit of Clinical Pharmacology, Humanitas Cancer Center

Medical Oncology and Haematology, Unit of Haematology and Cancer Therapeutics, Humanitas Cancer Center

What all reseachers dream of The dream of researchers who are committed to the development of cancer drugs is living – once in their life – an imatinib-like story, that is tracking step-by-step the unprecedented therapeutic success that imatinib has represented for chronic myelogenous leukemia, starting their experience with the identification of a cancer-driving genetic lesion and leading on to the generation of a genetargeting drug. In actual fact however, at the end of the day cancer drug development is a game of chess against cancer, a brilliant enemy with the innate ability to bypass almost any obstacle. Moreover, year after year, the scenario is getting more and more exciting. And, as we become increasingly able to read the genome, we find new molecules and new delivery systems allowing to stop cancer cells from growing.

Last year, idelalisib, an oral inhibitor of phosphoinositide 3-kinase (PI3K) delta, and ibrutinib, an oral inhibitor of Bruton’s tyrosine kinase, emerged among several other 44

drugs as the ones which would be able to change our approach for “curing” a variety of diseases, ranging from chronic lymphocytic leukemia to indolent lymphomas. Notably, “curing” implies the capacity to block the effects of genetic redundancy by attacking multiple battlefronts in distinct phases, i.e. the capacity of developing several targeted drugs to be used sequentially or in combination in order to co-target mutiple cancer-driving lesions efficiently, thereby overcoming redundant signaling of tumor cells and eventually preventing the development of adaptative resistance.

Targeted cancer therapies provide doctors with a better tailored cancer treatment, especially when a target is present in some but not all solid tumors of a particular type. Crizotinib, an anti-cancer drug acting as an ALK (anaplastic lymphoma kinase) and ROS1 (c-ros oncogene 1) inhibitor, was recently approved for the treatment of patients with non-small cell lung carcinoma carrying the ALK fusion gene. In 90% of cases,

HIGHLIGHT

this molecule induces tumor shrinkage or stabilization.

Vemurafenib, a small-molecule drug able to block the activity of a permanently activated mutant form of the serine/threonine kinase BRAF (known as BRAF V600E) was also recently approved to treat patients with inoperable or metastatic melanoma carrying this particular gene mutation.

Humanitas Cancer Center is at the forefront of translational research and represents a valuable and worthwhile setting with laboratories of molecular and cellular biology, clinical pharmacology and cancer therapeutics, an extensive program of biobanking, as well as clinical units devoted to drug development in Oncology and Haematology. In particular, our current priorities are: • understanding epigenetic mechanisms of refractory lymphomas

• identifying biomarkers predictive of response to several drugs • understanding molecular mechanisms underlying the onset of multiple tumor types in the same patient • developing new targeted drugs in pre-clinical and early phase clinical setting.

Developing strong translational research programs, combining an appropriate mechanistic understanding of diseases with early pre-clinical drug development and early phase clinical development is the strategy to be pursued for reconciling the huge amount of scientific information with the growing armamentarium of targeted therapeutics, and the validation of truly relevant, non-cosmetic antitumor therapies.

• searching for genetic-based stratifications in thymoma 45

Oncology Interview with Armando Santoro

A laboratory of Clinical Pharmacology is supporting our activity in basic and translational research.

Can this be considered revolutionary for patients as well, and for their destiny?

Thanks to advances in treatment, but also in diagnosis, the prevalence of patients with a long survival is at present considerably high and, hopefully, increasing. We are trying to meet patients’ needs once they have gone through the initial (and worst) phase of the oncologic disease.

Actually they are demanding needs, related not only to cancer disease and treatment, but also to the long-term follow-up of their psychological status. To support longsurviving patients in starting a new phase of their life, we are developing special pathways which include prevention as a priority. In fact, evidence is emerging that prevention and lifestyle are crucial to extend survival and improve the quality of life.

Can the trend towards a steady increase in the number of transplant patients be confirmed?

Yes, transplantations will be available to a greater number of patients for different reasons: excellent support therapies, the availability of alternative sources of stem cells, the increasing number of candidate patients for allogeneic transplantation.

We are working on innovative models of haploidentical bone marrow transplants for haematological malignancies in collaboration with the preclinical and translational research group at Humanitas.

Preliminary data are promising, since the incidence of infections and transplant rejections is low. These procedures are likely to represent a realistic alternative to traditional allogenic bone marrow transplant in the near future, thus solving the problem of donor’s compatibility.

This is another outstanding aspect of the revolution that is in progress. ❙❙

HIGHLIGHT

Sarcoma: a rare multifaceted disease with innovative various therapeutic options

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Sarcomas are rare cancers of mesenchymal origin, including more than 50 entities and over 150 molecular subtypes, with different clinical presentations and peculiar sensitivity to medical therapies.

This heterogeneity makes the treatment of patients with sarcoma truly challenging: besides, tailoring tumor treatment requires a multidisciplinary Vittorio Andrea Marrari team made of surgeons, medical and radiation oncologists, pathologists and Quagliuolo Division of Medical radiologists,.

Oncology and Director of the Surgery is the mainstay treatment for patients with local disease, while radiation Haematology, Division of General therapy may be added to improve local control. With a few exceptions, namely Humanitas Cancer and Oncologic Ewing’s sarcoma, osteosarcoma, and rhabdomyosarcoma, chemotherapy does Center Surgery not represent the standard and is offered on an individual basis to patients with unfavorable characteristics of the disease. However, despite adequate treatment, up to 50% of the patients with localized sarcoma experience a recurrence, mainly localized to their lungs.

The aim of the Sarcoma Group at Humanitas Cancer Center is to improve the clinical care of patients with local and metastatic disease. Given the rarity and heterogeneity of the neoplasm, the collaboration between referral centers is mandatory. Humanitas participates in national and international collaborative working groups and is involved in multicentric clinical trials on specific histotypes and/or disease presentation.

In the last decades, the progress in surgical techniques, the evolution of radiation therapy, as well as the introduction of multiagents chemotherapy and drugs designed to target specific molecular alteration, has revolutionized the treatment of some sarcoma subtypes. However, further improvements will definitely stem from a better understanding of the biology of sarcoma: hence, the close collaboration of the Sarcoma Group with many research labs at our institution.

skin cancer clinic

Multidisciplinary approach to melanoma care, benefits for patients, recent results and future perspectives in the treatment of this disease

Lorenza Rimassa Vice director of Medical Oncology Unit, Humanitas Cancer Center

Luca Cozzaglio Division of General and Oncologic Surgery

Luca Mancini Division of Dermatology

Melanoma represents the fifth most common type of cancer. Its incidence is rising worldwide, but thin melanomas (<1.0-mm Breslow depth) have overtaken thick melanomas as the most common type and account for most of the increased incidence of melanoma in recent years.

Thin melanomas now comprise approximately 50-70% of newly diagnosed melanomas as compared with approximately 20% in the early 1980s. This positive result is the consequence of skin cancer education and prevention campaigns. Patients go to the doctor for skin control more frequently and thus receive surgical excision earlier when the melanoma is thinner and associated with a better prognosis.

Treatment of more advanced disease includes surgery, chemotherapy, biologic therapy, radiotherapy, and new targeted agents. Very recently, the use of targeted agents such as vemurafenib, a BRAF inhibitor (almost 50% of melanomas harbor BRAF mutations), and ipilimumab has significantly improved the survival of patients with metastatic melanoma.

However, there is still need to optimize patient care and to promote translational and clinical research, and new agents are being developed or combined to overcome the limitations of the current therapies.

As mentioned above, melanoma care is a field that requires input from several medical and surgical specialists but individual physicians may give different recommendations for work-up, treatment, and follow-up with inconsistent results in patient management. A multidisciplinary melanoma team allows to coordinate care among different specialties as dermatology, dermatopathology, surgical and medical oncology, plastic surgery, but also radiation oncology, otorhinolaryngology, nuclear medicine, ophthalmology, gynecology, genetics, nursing, social work, and data management. A coordinate group approach, that follows consensus and evidence-based clinical practice guidelines, can allow for a maximum utilization of physiciansâ&#x20AC;&#x2122; time and resources, improve quality of care, reduce practice variation, define and measure outcomes, and promote education and research.

At Humanitas Cancer Center, patients with melanoma are discussed and managed by a multidisciplinary team including all the specialists involved in the diagnosis, treatment and follow-up of this disease. Every day, dermatologists examine patients with suspected skin lesions using a dermatoscope and a video imaging system to early detect melanoma.

Patients with advanced disease have the possibility to receive standard treatment as well as new biologic targeted agents in international clinical trials. The integration of translational and clinical research will allow to improve clinical outcomes, identify potential markers of response, transform care to more personalized management based on the individual patientâ&#x20AC;&#x2122;s cancer biology.

This will allow patients who are likely to benefit to receive optimal care, while sparing those unlikely to benefit from unnecessary toxicity and cost.

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Oncology Interview with Armando Santoro

Köln, Germany

Andreas Engert Köln University Clinic Dublin, Ireland

John Crown St. Vincent University Hospital Boston, Usa

Eric Van Cutsen

Harvard Medical School and Dana-Farber Cancer Institute

University Hospital Gasthuisberg

New York, Usa

New York University School of Medicine

Humanitas Cancer Center Advisory 48 Board Members

Ruprecht Karl University and Salem-Hospital

Leuven, Belgium

Kenneth C. Anderson

Silvia Formenti Antonella Surbone

Heidelberg, Germany

Markus Büchler

milano, Italy

Alberto Costa European School of Oncology

Tokyo, Japan

Masatoshi Makuuchi Tokyo University

Cancer Free Clinic

Humanitas Cancer Center’s approach to cured patients: state of the art, open questions, and new challenges

Raffaele Cavina Division of Medical Oncology and Haematology, Humanitas Cancer Center

Rita Mazza Division of Medical Oncology and Haematology, Humanitas Cancer Center

In the last decades the advances in diagnosis and therapy have transformed the prognosis of cancer from a largely fatal disease to a condition in which the majority of diagnosed patients receive treatments that result in a long-term disease-free survival.

This results in an increasing number of survivors with special needs.

Almost 2 million people in Italy is experiencing or has experienced cancer treatment. Among these, over a half have lived longer than 5 years from the diagnosis and are referred to as survivors or long survivors. They are classified in two main groups: disease free patients, without evidence of recurrence, and patients with chronic cancer who are receiving continuous therapy.

Long-term risks and concerns associated to neoplasm and its treatment, and the following cancer-induced change in patient’s self-image, personal relationships, family dynamics, and social roles, tend to perpetuate the perception to be different from “healthier” people. All these long-lasting changes in the physical, emotional, and practical domains of life require a constant attention and care, that goes beyond the conventional instrumental follow up merely aimed at diagnosing cancer recurrence.

The optimization of long-term survivors management is a major issue for the most influential oncologic organizations such as the National Comprehensive Cancer Network (NCCN), the European Society for Medical Oncology (ESMO), and the American Society of clinical Oncology (ASCO) .

Our response to the problem is the establishment of dedicated ambulatory activity for long survivors. The main purposes of the cancer free clinic are the following: • evaluation/prevention of late and long-term anticancer treatment effects • surveillance for subsequent neoplasms (due to mutagenic effects of chemo/ radiotherapy, genetic susceptibilities, and/or shared causative exposure) and surveillance for recurrence • improvement in patients’ compliance to cancer screening programs • health promotion awareness: implementing behavioral change with counselling on diet and physical activity program and smoke cessation program • extended familiar screening, when appropriate • assessment of sexual and reproductive impairment • assessment of the psychological impact (personal, social, relational) that follows a cancer diagnosis and its treatment Long term survivors should be regularly followed up according to a personalized plan tailored to their cancer type, the treatment/s received, characteristics and severity of long term negative effects that potentially occurred. An optimal management requires the intervention of different specialists such as an oncologist, a geneticist, a cardiologist, a gynecologist, and so on, to guarantee disease surveillance, side effects treatment, preventive care, and adherence to recommendations about healthy behavior.

Providing survivors with appropriate care is a work in progress; the great challenge is to adapt flexibly to each patient’s personal history, needs and characteristics with the aim of preserving physical and psychosocial functions.

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Oncology Interview with Armando Santoro

breast unit

A comprehensive approach to overcome breast cancer

Marta Scorsetti Director of the Division of Radiotherapy and Radiosurgery

Corrado Tinterri Director of the Breast Unit, Humanitas Cancer Center

Rosalba Torrisi Division of Medical Oncology and Haematology, Humanitas Cancer Center

50

Breast cancer is the most common malignancy in women. Effective loco-regional (surgery and radiation therapy) as well as systemic treatment options have made breast cancer a curable disease for the vast majority of early-stage patients. Conservative management has become the routine first choice option. Recently, increased knowledge of breast cancer biology, improvements in systemic therapy options, and the advances made in radiation therapy techniques have allowed physicians to further tailor therapy to individual disease presentations. In 2013, systemic therapy has accomplished substantial achievements in tailoring therapy thanks to three new targeted drugs: pertuzumab, trastuzumab-emtansine (T-DM1), and everolimus, which are being registered for specific subsets of breast tumors. Among these, T-DM1 seems to fulfill the requirements for optimal targeted therapy, that is maximizing efficacy while minimizing toxicity. Altered fractionation in radiotherapy (hypofractionated WBI and Accelerated Partial Breast Irradiation) can reduce the overall treatment time for many women with low-risk, early-stage breast cancer, and this is particularly relevant for older women who may encounter practical and clinical problems with a 6-week course of daily radiotherapy. Particular attention is paid to radio-guided surgery, oncoplastic and reconstructive surgery, as outlined by the criteria established by EUSOMA for the Breast Unit, which have been certified for years now. Making treatment recommendations for patients taking into account age-related, in addition to tumor-related issues can be challenging; thus the discussion in multidisciplinary breast oncology teams should lead to the best results for patients in terms of cancer specific outcomes and quality of life. Care for patients through a personalized approach remains a central issue, and clinicians are currently more likely to provide selective interventions to minimize acute and late toxicity without compromising efficacy.

top paper Santoro A, Rimassa L, Borbath I, Daniele B, Salvagni S, Van Laethem JL, Van Vlierberghe H, Trojan J, Kolligs FT, Weiss A, Miles S, Gasbarrini A, Lencioni M, Cicalese L, Sherman M, Gridelli C, Buggisch P, Gerken G, Schmid RM, Boni C, Personeni N, Hassoun Z, Abbadessa G, Schwartz B, Von Roemeling R, Lamar ME, Chen Y, Porta C.

Tivantinib for second-line treatment of advanced hepatocellular carcinoma: a d, placebo-controlled phase 2 study.

Lancet Oncol. 2013 Jan;14(1):55-63. Epub 2012 Nov 20.

Background: Tivantinib (ARQ 197), a selective oral inhibitor of MET, has shown promising antitumour activity in hepatocellular carcinoma as monotherapy and in combination with sorafenib. We aimed to assess efficacy and safety of tivantinib for second-line treatment of advanced hepatocellular carcinoma.

Methods: In this completed, multicentre, randomised, placebo-controlled, double-blind, phase 2 study, we enrolled patients with advanced hepatocellular carcinoma and Child-Pugh A cirrhosis who had progressed on or were unable to tolerate first-line systemic therapy. We randomly allocated patients 2:1 to receive tivantinib (360 mg twice-daily) or placebo until disease progression. The tivantinib dose was amended to 240 mg twice-daily because of high incidence of treatment-emergent grade 3 or worse neutropenia. Randomisation was done centrally by an interactive voice-response system, stratified by Eastern Cooperative Oncology Group performance status and vascular invasion. The primary endpoint was time to progression, according to independent radiological review in the intention-to-treat population. We assessed tumour samples for MET expression with immunohistochemistry (high expression was regarded as ≥2+ in ≥50% of tumour cells). This study is registered with ClinicalTrials.gov, number NCT00988741.

Findings: 71 patients were randomly assigned to receive tivantinib (38 at 360 mg twice-daily and 33 at 240 mg twice-daily); 36 patients were randomly assigned to receive placebo. At the time of analysis, 46 (65%) patients in the tivantinib group and 26 (72%) of those in the placebo group had progressive disease. Time to progression was longer for patients treated with tivantinib (1·6 months [95% CI 1·4-2·8]) than placebo (1·4 months [1·4-1·5]; hazard ratio [HR] 0·64, 90% CI 0·43-0·94; p=0·04). For patients with MET-high tumours, median time to progression was longer with tivantinib than for those on placebo (2·7 months [95% CI 1·48·5] for 22 MET-high patients on tivantinib vs 1·4 months [1·4-1·6] for 15 MET-high patients on placebo; HR 0·43, 95% CI 0·19-0·97; p=0·03). The most common grade 3 or worse adverse events in the tivantinib group were neutropenia (ten patients [14%] vs none in the placebo group) and anaemia (eight [11%] vs none in the placebo group). Eight patients (21%) in the tivantinib 360 mg group had grade 3 or worse neutropenia compared with two (6%) patients in the 240 mg group. Four deaths related to tivantinib occurred from severe neutropenia. 24 (34%) patients in the tivantinib group and 14 (39%) patients in the placebo group had serious adverse events.

Interpretation: Tivantinib could provide an option for second-line treatment of patients with advanced hepatocellular carcinoma and well-compensated liver cirrhosis, particularly for patients with MET-high tumours. Confirmation in a phase 3 trial is needed, with a starting dose of tivantinib 240 mg twice-daily.

Funding: ArQule, Daiichi Sankyo (Daiichi Sankyo Group).

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Cardiovascular

52

Clinical practice calls, high tech answers

Interview with Gianluigi Condorelli

Director of Cardiovascular Research and professor of cardiology, University of Milan

Our research group, which is among the top in Europe, carries out comprehensive programmes ranging from basic research to diagnosis and therapy. Our key word is collaboration.

After a start-up phase, in 2013, the Cardiovascular Research Laboratory was expected to develop a broad range of competitive, high-quality projects. Could you describe the goals that have been accomplished so far?

We have fulfilled our commitments. In fact, after the initial phase of the basic research activity, the progression to scientific production has been quite satisfactory in terms of quantity and, more importantly, quality. Our projects are conducted in parallel by research teams that maintain a mutual and profitable cross-talk, and are intimately integrated with projects carried out by some of the best international institutions.

What is the international atmosphere in the international research field at the moment?

Specific instruments High frequency, high resolution VeVo 2100 digital imaging platform with linear array technology and Color Doppler Mode Mikro-Tip Pressure Volume System (MPVS)-Ultra Foundation System

It’s a great time for translational research because the European Commission is strongly promoting what is commonly referred to as the “bench-to-bedside” approach, which encompasses aspects going all the way from laboratory studies to clinical applications. The main reason for this strategic choice is that translational research meets the goals of the European Union: to improve the health of European citizens and boost the competitiveness of health-related industries and businesses, while addressing global health issues. The interesting fact is that translational research impacts on the general population.

Besides, as it regards human beings, it is strictly regulated and controlled. This increases complexity and requires collaborative work, which in turn is encouraged by the European Commission.

Telemetry for blood pressure and ECG assessment Scanning Ion Conductance Microscopy Optical Mapping for electrical Impulse Propagation IonOptix for Ca2+ transient and contractile assessment Patch-Clamp instruments for studies on action potential Tecan for liquid handling automatization

Could we refer to this scenario as ‘European Research’?

As far as human resources are concerned, there is no doubt we are witnessing an appreciable flow of young scientists, both coming in and going out. For example, we are currently funded by two Marie Curie fellowships, which are part of the European research grants included in the Horizon 2020 Framework Programme for Research

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Cardiovascular Interview with Gianluigi Condorelli

HIGHLIGHT

The epigenetics of heart failure

Roberto Papait Laboratory of Inflammation and Immunology in Cardiovascular Institute of Genetics and Biomedical Research, National Research Council of Italy (CNR)

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«Heart failure (HF) is a leading cause of mortality worldwide and a major financial burden on the healthcare system. Identification of new therapeutic targets could considerably advance the treatment of this syndrome. At the molecular level, HF is associated with the expression of certain genes that are normally expressed in foetal hearts. This reexpression of “foetal” genes in the adult heart contributes to the development of the pathology. Although epigenetics is important in regulating transcription, our understanding of its role in cardiac hypertrophy remains scant.

A goal of our laboratory is to study the role of epigenetics in regulating gene expression changes occurring in cardiac hypertrophy. Through the combination of high-throughput approaches used for studying the epigenome and traditional methodologies employed for studying cardiovascular disease, we found that a large part of the genes modulated in cardiac hypertrophy is characterized by a specific histone-modification signature, defined by histone acetylation and methylation, that distinguishes specific functional classes of genes. In addition, we identified for the first time a population of regulatory DNA sequences (enhancers) whose activity is altered in cardiac hypertrophy.

The association of cardiac hypertrophy with a specific epigenetic profile provides a new basis for understanding the molecular mechanisms underlying HF, and opens up the possibility of developing new therapies based on the control of the epigenetic profile of cardiomyocytes.»

and Innovation available to researchers regardless of their nationality or field of work. These grants give researchers the opportunity to gain experience abroad and in the private sector, and to complete training with skills or disciplines that are useful for their careers.

In addition, we are in close contact with prestigious research environments (among which, the University of California San Diego, Leicester University and Maastrich University) and participate in distinguished networks of international scientists. This is a great opportunity that implies an exchange of information of optimal structures and organization, including state-of-the-art laboratories, large databases, an efficient biobank and close integration of research and clinical activities. All this is written in Humanitas’ DNA.

Which research project are you currently focussing on?

A cutting-edge project is addressing the epigenetics of cardiovascular diseases, an area that is poorly studied and understood. It can reveal how factors other than genetics, typically external environmental components, can affect genes independently of the individual’s DNA sequence.

Epigenetic changes can modify chromatin, that is to say the combination of regulatory proteins called histones and the strands of DNA, and in this way switch genes on or off to determine which proteins are transcribed, and, ultimately, influence predisposition to a disease.

Studying the epigenetics of the heart and vascular system is not only challenging, but also of great public interest considering the high prevalence of cardiovascular disease and its socioeconomic burden.

How does it work, and what do these studies entail?

It is a massive effort which implies the analysis of billions of DNA base pairs, each being a potential target of external noxae. Our approach consists in high-throughput DNA sequencing followed by bioinformatics analysis, because

HIGHLIGHT Technology improves the quality of life Our research projects are aimed at improving patients’ quality of life, even by way of a reduction in hospital lenght of stay. A Maurizio Gasparini randomized clinical trial published in Director of Division of 2013 on the Journal of the American Electrophysiology and Medical Association has shown that setting a long detection window Electrostimulation associated to antitachycardia pacing in cardioverter-defibrillator results in a lower incidence of negative outcomes, e.g. inappropriate shocks. Other two studies, at the moment in press on the Journal of the American Medical Association and Circulation respectively describe the net benefits on costs for the Italian National Health System of this delayed arrhythmia window in any kind of cardioverter-defibrillators as well as in patients with or without a history of previous myocardial infarction.

As far as our clinical activity is concerned, we are harvesting the fruits of what we have achieved through our work at Humanitas.

We have addressed/ faced the control of any type of arrhythmia with breaktrough technologies, in particular those implying the use of Stereotaxis – the robotic navigation designed for the treatment of cardiac arrhythmias – or the most advanced implantable cardioverter-defibrillators either endocavitary or subcutaneous.

Finally, we have started using a new subcutaneously implantable loop recorder, which has been available for just a few weeks. This device is really tiny, has a battery life of nearly 3-years and enables the recording, with the minimal impact on patient’s life, of pre- and post-interventional arrhythmias.

55

Cardiovascular Interview with Gianluigi Condorelli

this methodology enables us to identify clearly the thousands of areas/sequences changed in the genome.

Thus, the integration of biomedical and informatics skills is indispensable, and will be even more so in the future with the setting up of an ad hoc database, again partially supported by European funding.

And what are your expectations?

The big question to be answered is: do epigenetic changes represent a sort of DNA pre-imprinting that can be used as a hallmark for a certain disease? We are studying somatic cells exposed to environmental factors, including cardiomyocytes (very specialized and homogeneously oriented to a contractile function).

Blood cells have been the most studied up to now, specifically as models of epigenetic changes triggering the

HIGHLIGHT

Molecular mechanisms leading from mutations in sarcomeric proteins to cardiomyopathy

Marie-Louise Bang Principal Investigator of the Laboratory of Sarcomers in cardiac pathology Institute of Genetic and Biomedical Research, National Research Council of Italy (CNR)

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The proper function of the heart is dependent on the assembly and maintenance of a complex network of structural and regulatory proteins, which form the highly organized sarcomere, the basic contractile unit of striated muscle, and are responsible for efficient contraction and synchronized transmission of force. The Z-line, a multiprotein complex at the boundary between sarcomeres, connects the contractile apparatus with the cytoskeleton and extracellular matrix, and plays an essential role for efficient force generation and maintenance of striated muscle structure and function and is a focal point for mechanosensing and signal transduction. Its important role is illustrated by the identification of a growing number of mutations in Z-line proteins associated with various forms of cardiomyopathies, including dilated (DCM) and hypertrophic (HCM) cardiomyopathy. DCM is defined by the presence of ventricular dilation and systolic dysfunction and has a prevalence of 1/2,500, while HCM is characterized by ventricular hypertrophy and diastolic dysfunction and affects 1/500. About 60% of HCM and 30-50% of DCM cases are familial with autosomal dominant inheritance and are often caused by mutations in genes encoding sarcomeric proteins, and in particular Z-line proteins. Our goal is to provide new insights into the molecular mechanisms leading from mutations in Z-line proteins to cardiac diseases, which is the requisite for the development of novel therapeutic approaches for their treatment and cure. Through cellular, molecular, biochemical, and physiological analyses, we have demonstrated an association between the Z-line proteins myopalladin, palladin, and myospryn and dilated cardiomyopathy with associated systolic dysfunction and our ongoing studies are focused on dissecting the underlying pathways. Furthermore, in collaboration with Elisa di Pasquale, who is part of the cardiovascular research group at Humanitas Research Hospital, we are planning to study the effect of DCM-causing mutations in cardiomyocytes from patient-derived induced pluripotent stem cells. With this integrated approach we hope to provide new insights into the molecular pathways underlying DCM and HCM, which may ultimately lead to the development of novel therapies.

development of cancer or as tumoral cell lines showing a change in biological behaviour. Currently, we are collaborating with Carmelo Carlo-Stella’s group on the epigenetic-dependent drug responsiveness of lymphomas.

What about cardiomyocytes then?

Thanks to high-throughput sequencing technologies, we have generated large amounts of data on several heart failure models. We are now replicating this effort for vascular disease. Remarkable data is also emerging from a cooperation with Marinos Kallikourdis’ group. For example, we now have detailed information on the role of immunity – both innate and adaptive – in the onset of heart failure.

A similar approach is being adopted for the diagnosis of familial primary cardiomyopathies, which are caused by mutations in genes that affect the function of heart muscle.

Our aim is to detect the mutations by means of DNA sequencing. Today, it is possible for even single research groups to generate sequence data very rapidly and at a relatively low cost, a feat unimaginable until a few years ago. The road ahead may seem straightforward, but we’ll still encounter problems along the way. For example, it is well known that the genome of each individual carries a number of “stop codons” – genetic mutations causing the premature termination of a protein’s biosynthesis – not necessarily linked to a disease. Thus, when a mutation is found running in various individuals of a family, it has to be verified whether it is the real culprit.

How can we go about this?

An initial clue is usually provided by bioinformatics and by sharing of data with other centres having similar interests.

To get definite proof of a cause–effect link, we need to work on the candidate gene and modify it. But a short-cut is possible thanks to induced pluripotent cells (iPSCs), a very promising model that can be applied to genetic disorders. iPSCs can be derived from easily obtainable cells (skin, hair follicles, blood) of patients. The harvested cells are programmed into an undifferentiated stage, that is into iPSCs, which can, in turn, be reprogrammed to generate cardiomyocytes harbouring the original mutated gene or genes. Functional properties can then be evaluated in adequate experimental conditions: it took us two years to complete the electrophysiology setup needed for these studies and to establish that the cardiomyocytes obtained in this way mimic characteristics of the diseased cells, such as

their predisposition for accelerated death, arrhythmogenesis and hypertrophic growth.

A potentially important facet of this type of research is the possibility of “correcting” the cell in vitro. Thus, besides producing data with diagnostic value, iPSC-based models of disease may engender therapeutic options in a near future, which are especially needed for rare cardiovascular diseases.

Which other current studies are being carried out in the diagnostic field?

The development of biomarkers predicting predisposition to a disease and of pharmacogenomic biomarkers.

As far as the former are concerned, we are studying circulating microRNAs – small non-coding RNAs sequences

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Cardiovascular Interview with Gianluigi Condorelli

HIGHLIGHT

Twenty years of advances in cardiology The last two decades have brought about continuous innovation in cardiology.

Nowadays we can use advanced and minimally invasive techniques to treat coronary artery Patrizia Presbitero disease, valvular heart disease – the aortic valve replacement can be performed through Director of Divison the femoral artery through a small cut, thus of Haemodynamics, avoiding thoracotomy – and arrhythmias.

Invasive Cardiology and Coronary Care Talking about prevention, outstanding results – in particular a reduction in the incidence of heart diseases – have been obtained, thanks to public health campaigns about cardiovascular risk factors, and to the availability of highly effective drugs such as statins and anti-platelet agents.

Much more remains to be done, however, and not only in terms of technological advances. Steps forward are needed towards a better understanding of the pathophysiological mechanisms involved in blood vessel ageing, atheromatous plaques’ initiation and progression, impairment in heart contractility resulting from various noxae, e.g. arterial hypertension and viral infections. All these open questions can find an appropriate answer only with translational research that implies close integration between bench and bedside.

Considering gender medicine, in particular gender cardiology, in the last ten years relevant progress has been made in the knowledge of the causes of mortality following a myocardial infarction in female patients and gender-related heart failure that must be treated accordingly.

Research is developing increasingly small instruments – stents, balloons, and valves, which facilitate endovascular procedures, especially in women whose vessels are smaller and are more prone to dissection.

Tako-Tsubo cardiomyopathy is a really interesting example of feminine heart disease: also called “broken heart syndrome”, it is actually a stress-linked non-ischaemic cardiomyopathy mimicking a myocardial infarction in which a sudden temporary weakening of the myocardium occurs.

58

that regulate gene expression – correlated to the degree of ventricular hypertrophy and fibrosis. We have recently published a study on cardiomyopathy in which we show that the level of miR-29a in peripheral plasma is correlated with hypertrophy and fibrosis, two components of myocardial remodelling leading to heart failure.

What can you say about pharmacogenetic biomarkers?

The role of pharmacogenetics in predicting an individual’s response to a drug is a very intriguing topic. As a paradigm, I can mention a study on clopidogrel that we conducted in collaboration with the Clinica Mediterranea in Naples. This antiplatelet agent is broadly used to prevent blood clotting in coronary artery disease and other vascular pathologies.

Its effectiveness depends on a drug-metabolizing enzyme whose activity is highly variable on account of genetic polymorphism. Approximately 15% of patients are “low metabolizers”, which means they do not respond to clopidogrel and have, as a consequence, a higher risk of adverse cardiac events. If their metabolizer status goes undiagnosed, coronary revascularization becomes an increasingly more hazardous procedure. We have shown in over 1,400 patients scheduled for stent implantation that genetic genotyping is, on average, superior to the more conventional platelet function testing, the latter having the same predictive value as genotyping only in subsets of high-risk patients.

Can this be considered an important step forward in pharmacogenetics?

Yes, because pharmacogenetics has moved forward from the research laboratory to reach hospital laboratories and wards. In fact, this approach is sustainable nowadays in terms of affordability and feasibility. In addition, a further advantage, both clinical and economic, may arise from a more selective use in clopidogrel-resistant patients of alternative drugs, which are already available but expensive, that is to say the platelet aggregation inhibitors acting via a direct mechanism. An increasing trend towards tailored therapy is apparent, and soon regulatory agencies will ask for prescriptions supported by a genetic profile.

Thus, genotyping will no longer be considered merely a “speculative experiment”, but rather a standard diagnostic test for clinical practice, a test that is industrially developed and validated for use even in small, primary care hospitals. ❙❙

top paper Papait R, Cattaneo P, Kunderfranco P, Greco C, Carullo P, Guffanti A, Viganò V, Stirparo GG, Latronico MV, Hasenfuss G, Chen J, Condorelli G.

Genome-wide analysis of histone marks identifying an epigenetic signature of promoters and enhancers underlying cardiac hypertrophy.

Proc Natl Acad Sci USA. 2013 Dec 10;110(50):20164-9.

Epub 2013 Nov 27.

Abstract: Cardiac hypertrophy, initially an adaptive response of the myocardium to stress, can progress to heart failure. The epigenetic signature underlying this phenomenon is poorly understood. Here, we report on the genome-wide distribution of seven histone modifications in adult mouse cardiomyocytes subjected to a prohypertrophy stimulus in vivo. We found a set of promoters with an epigenetic pattern that distinguishes specific functional classes of genes regulated in hypertrophy and identified 9,207 candidate active enhancers whose activity was modulated. We also analyzed the transcriptional network within which these genetic elements act to orchestrate hypertrophy gene expression, finding a role for myocyte enhancer factor (MEF)2C and MEF2A in regulating enhancers. We propose that the epigenetic landscape is a key determinant of gene expression reprogramming in cardiac hypertrophy and provide a basis for understanding the role of chromatin in regulating this phenomenon.

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Neuroscience

60

Maximal challenges, minimal invasivity

Interview with Maurizio Fornari

Neurosurgical research is engaged in many different activities, in order to tackle changes in disease epidemiology and its increasing complexity.

Where is research in the neurosurgery field heading?

At the moment, research in neurosurgery is focused on three main areas.

Director of the Neurosurgery Division

The first is cancer-related neurological conditions, where the crucial point is developing and assessing innovative treatments for brain malignant tumors. The advancements of radiotherapy and chemotherapy made over the last quarter of a century have been largely unsatisfactory.

However, new promising therapeutic options are emerging.

The second is the continuous effort towards reducing surgical invasivity, especially when the intervention is performed on central nervous system vessels (i.e. to treat brain aneurysmatic or angiomatous lesions). To this aim, tried and tested interventional radiology techniques in coronary surgery are being increasingly replicated in neurosurgical research since they allow to reach brain vessels and treat vascular lesions through peripheral arterial access.

Specific instruments

BoneScalpel Ultrasonic Osteotome

Last but not least, degenerative spine is currently a considerable challenge for neurosurgical research. Notably, this condition was simply not described 30 years ago, at least with the severity and the frequency it is being referred to as now, simply because the average age in the population was lower. Nowadays more than 20% of the Italian population is over 65 years old; in terms of population ageing, Italy is second only to Germany, and this figure is similar across the Western countries.

Neuromonitoring and neuronavigation combined with intra-operative 3D ultrasound to treat deep brain lesions/ for [stereotactic] excision of deep brain lesions

Does this entail that this condition is bound to increase in frequency? As he gets older, the Homo erectus tends to

2 operating theatres equipped with O-Arm (threedimensional imaging device) coupled to a neuronavigation system Cavitron Ultrasonic Surgical Aspirator (CUSA) for parenchymal tumor tissues or bone tissues

3D endoscopic tools/endoscopy tools for skull-base surgery 5 NMR (among which 1 3-Tesla, 1 open with ambient light) NMR equipment for functional MR imaging studies Acquisition and processing workstation for diffusion MRI tractography 4 TC (among which 1 64-slice)

develop â&#x20AC;&#x201C; over time â&#x20AC;&#x201C; a degenerative disorder consisting in a gradual loss of normal structure and function of intervertebral discs and vertebral bodies. This results in a progressive spine imbalance that ultimately prevents him from standing upright and walking. Standing upright is a primary function for human beings, crucial to using arms and, indirectly, to exerting cerebral functions related to handling. Thus, preserving the ability to stand upright is the starting point towards tackling human ageing.

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Neuroscience Interview with Maurizio Fornari

Lorenzo Bello Director of Oncologic Neurosurgery Division

At the frontier of neurosurgical oncology research Research in neurosurgical oncology has advanced further in the last year, focusing on several fields, and moving from the clinic to the laboratory.

Several projects are running in the context of the integrative approach of combining neurosurgery, neuroimaging, intraoperative neurophysiology, and neuropsychology for tumor removal. A large ongoing program is studying new and specific neurophysiological stimulation paradigms for the characterization of the various components of the corticospinal tract; we are currently investigating the physiological properties of the primary motor cortex, the supplementary motor area, and the premotor cortices; specific efforts have been performed for the definition of the functional properties of the ventral premotor cortex and related frontal areas, at both cortical and subcortical level, for their involvement in motor and language control. At the same time, many studies are in progress to identify â&#x20AC;&#x201C; through the integration of neuropsychology and intraoperative neurophysiology â&#x20AC;&#x201C; the brain sites involved in the control of short-term memory and emotions, and to understand the network(s) serving these unique and peculiar functions. For language, new stimulation neurophysiological paradigms have been developed, particularly suitable for patients with a long history of seizures and poor seizures control, usually not amenable to functional resection with the standard 62

HIGHLIGHT

Moreover, given that the number of elderly people is generally increasing, several conditions deserve increasing recognition and care, in particular neurodegenerative diseases – i.e. Parkinson’s disease, multiple sclerosis, and dementia – peripheral neuropathies, and ischemic cerebrovascular disorders.

Let us now dwell a bit more on spinal surgery…

methodology. Neuropsychological and neurophysiological findings obtained with surgery have been also correlated with imaging data, designing functional maps of various areas of the brain. The aim of these studies is to develop new surgical tools that are able to extend surgical indications, increase the extent of resection, impacting on the natural history of the tumor and at the same time maintaining the patient’s functional integrity, reaching important oncological and functional endpoints. Simultaneously, they allow a better understanding of the functional organization of the brain, particularly at the level of its connectivity.

Many other projects are ongoing, which study the aim of imaging and molecular biology, the structural heterogeneity of tumors, and develop MR sequences and PET imaging. In this way, it is possible to provide a better correlation with the molecular profile and biological behaviour of tumors, and allow to obtain a better tumor characterization at first diagnosis.

In collaboration with INSERM, we are also performing a large translational program aimed – thanks to advanced molecular biology techniques – at the identification of molecular determinants of glioma angiogenesis and progression, and associated to tumor response to therapies, particularly to anti-angio-angiogenic drugs and chemotherapy. Further studies are investigating molecular mechanisms of glioma-associated angiogenesis and angiogenesis inhibition, translating findings obtained at cellular and in vivo and ex vivo tumor models, into the clinical practice. This large group of studies aims at obtaining a better patient stratification, identifying molecular factors associated with prognosis and response to therapy, and to elaborate new strategies for therapeutical and monitoring purposes.

The key aspects are complexity and technology.

Spinal surgery and related research are a field of excellence, as many pathologies (for example lumbar spinal stenosis and spondylolisthesis) have been tackled brilliantly, and different options are available to cure them.

At the moment, the challenge is represented by severe spinal deformities such as degenerative scoliosis, which used to be quite rare, but is now getting increasingly common. Researchers are working both on technologies and surgical techniques, as well as on innovative therapeutic options that are able to prevent the occurrence of the disease or control its progression.

Spinal neurosurgery is being geared towards accomplishing the specific and demanding needs of cancer patients.

The close collaboration with Humanitas Cancer Center requires us to face a great deal of complexity. Even in this intricate scenario however, we have obtained positive outcomes: a significant number of demanding and complex cases have undergone successful interventions thanks to the merging of multiple surgical competences from the teams of Thoracic Surgery (led by Marco Alloisio) specialized in head and neck surgery, of Abdominal Oncologic Surgery, and of Vascular Surgery (led by Pier Luigi Giorgetti). For example, radical vertebrectomies have been performed successfully, with a relatively mild impact in terms of adverse effects and complications.

What is the role of technologies within this scenario?

Specific applications of all emerging diagnostic technologies – such as computed tomography (CT), or nuclear magnetic resonance (NMR) – have been developed for the brain and the neuraxis.

The same is true for high-tech instruments and equipments currently used in the operating theatre, such as ultrasonic surgical aspirators, ultrasonic osteotome (BoneScalpel), neuronavigation systems, computer-assisted surgery equipments, electrocoagulation devices, and intraoperative 63

Neuroscience Interview with Maurizio Fornari

neurophysiological monitoring (see also the highlight of Lorenzo Bello).

In some respects, we are so immersed in technology and live in such a close and routinary connection with it, that we are almost unaware of its presence. But it has certainly been technological progress that has allowed the most relevant advances in neurosurgery, inside and outside the operating theatre; conversely, no other specialty fields have stimulated biotechnological research more than neurology, with ever-lasting benefits.

Yes. Let us consider how the main trend in sugery in the past 30 years has been minimal invasivity. Does this apply to neurosurgery as well?

Pursuing minimal invasivity does apply in particular to ablative surgery, where we must go even further, i.e. towards non invasive surgery. I think that ablative surgery with the removal of “ill” tissues or organs from the body is going to be progressively abandoned in the future. For

Synapses: a complex puzzle with overlapping pieces

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HIGHLIGHT

Investigations of synapses hold the key to understanding brain processing and function. Synaptic proteins (release machinery, receptors, transporters, scaffolding proteins) are organized in molecular networks at both the pre- and postsynaptic level, and their dysfunction can be the origin of synaptic defects called “synaptopathies”. They cause major psychiatric, neurological and childhood developmental disorders, including autism, schizophrenia, ADHD (Attention-Deficit/Hyperactivity Disorder), depression, intellectual disabilities. In the last years, there has been extraordinary progress on the genetics of these disorders, which has generated Michela Matteoli Principal investigator new hypotheses about their etiology and provided data on the genetic architectures of these conditions.

One unexpected finding emerged from these studies is that specific mutations for a psychiatric disease (e.g. of the Laboratory of schizophrenia) have a large effect on the liability to other diseases (e.g. autism or bipolar disorder). These data Pharmacology and imply the existence of shared biological pathways between different neurodevelopmental conditions, and Brain Pathology suggest that brain diseases with similar phenotypes and symptom spectra may arise from disruption of partially overlapping complexes and interacting proteins within the synapse proteome. Interestingly, in most cases, these protein complexes are located at the level of the dendritic spines, small membranous protrusions from a neuron’s dendrite that typically receive input from presynaptic terminals and serve as sites for controlling synaptic strength and memory storage.

During 2013, our laboratory has identified two proteins involved in the control of dendritic spine morphology, and showed that a reduction in their levels of expression results in spine abnormalities and in learning defects. Among these proteins, Eps8 (Menna et al, EMBO J 2013), an actin capping protein, when expressed at lower levels, makes the spine immature, and unables the morphological changes that are typical of learning, Notably, we have found that Eps8 is reduced in the brain of autistic patients. Another protein, called SNAP-25, is involved in schizophrenia and in ADHD. According to our data, its absence or reduction, as occurs in schizophrenic brains, results in defects in short-term presynaptic plasticity (Antonucci et al, EMBO Rep 2013), and in alterations in spine morphology (Tomasoni et al, Nature Comm 2013) and plasticity (Fossati et al, submitted). These studies have provided evidence about the molecular mechanisms by which proteins involved in psychiatric disorders negatively affect the structure and function of synapses.

However, we are still far from getting a grasp of the whole picture. It is indeed becoming more and more evident that understanding a given synaptopathy at the level of its genetic, molecular, and synaptic dysfunction is typically insufficient to explain the disease symptoms and to design therapeutic strategies. Dysfunctions of specific neuronal networks underlying the peculiar presentation of each clinical condition may in fact depend on additional genetics, epigenetics, and environmental factors which remain to be outlined. It is reasonable to hypothesize that putative environmental factors that have an impact on these networks during development, may modify their correct organization, possibly leading to a psychiatric phenotype. This is the next challenge, and this is the direction where we are moving now.

instance, Gamma Knife is a type of radiation therapy used to treat tumors and other abnormalities in the brain where the traditional surgical knife is replaced by radiation energy. In relation to this, I would like to mention that Gamma Knife as a good example of how technology has provided instruments and equipment to be used not only in the operating room, but also in radiosurgery.

On the other hand, reparative surgery – be it on coronary and artery vessels or on the musculoskeletal system, – has

remained highly invasive for a really long time.

Recently, vascular procedures – including those performed on brain vessels – have become mini-invasive thanks to an endovascular approach. Reparative surgery of the musculoskeletal system is following the path of minimal invasivity as well. More and more often, mini-open surgery is mentioned: even if it is too early for a totally endoscopic approach, open surgery with a minimum level of low invasivity is already feasible. ❙❙

top paper Menna E, Zambetti S, Morini R, Donzelli A, Disanza A, Calvigioni D, Braida D, Nicolini C, Orlando M, Fossati G, Cristina Regondi M, Pattini L, Frassoni C, Francolini M, Scita G, Sala M, Fahnestock M, Matteoli M.

Eps8 controls dendritic spine density and synaptic plasticity through its actin-capping activity.

EMBO J. 2013 Jun 12;32(12):1730-44. Epub 2013 May 17.

Michela Matteoli has been awarded the “Nature Mentoring Award” – a yearly award given by the Nature magazine since 2005 for “outstanding scientific mentorship”.

2013 year’s edition was dedicated to Italy. Michela Matteoli – professor of Pharmacology at University of Milan, BIOMETRA Department, in charge of the Pharmacology and Brain Pathology laboratory, and Director of Humanitas Neuroscience programme – was the winner of the “mid-career award”.

On Monday, November 25th, during a ceremony at the Quirinale Palace, the award has been given out by President of the Italian Republic Giorgio Napolitano together with Philip Campbell, the editor-in-chief of the Nature magazine.

«I am really glad to have received this important award especially because my nomination came from former and present students in the lab. Since the laboratory came into being in 1992, I have followed dozens of students who have come a long way, and I am really proud of this – Michela Matteoli explains – . My research laboratory studies synapses and, in particular, the functional role of some synaptic proteins involved in some neurodevelopmental and psychiatric disorders».

Abstract: Actin-based remodelling underlies spine structural changes occurring during synaptic plasticity, the process that constantly reshapes the circuitry of the adult brain in response to external stimuli, leading to learning and memory formation. A positive correlation exists between spine shape and synaptic strength and, consistently, abnormalities in spine number and morphology have been described in a number of neurological disorders. In the present study, we demonstrate that the actin-regulating protein, Eps8, is recruited to the spine head during chemically induced long-term potentiation in culture and that inhibition of its actin-capping activity impairs spine enlargement and plasticity. Accordingly, mice lacking Eps8 display immature spines, which are unable to undergo potentiation, and are impaired in cognitive functions.

Additionally, we found that reduction in the levels of Eps8 occurs in brains of patients affected by autism compared to controls. Our data reveal the key role of Eps8 actincapping activity in spine morphogenesis and plasticity and indicate that reductions in actin-capping proteins may characterize forms of intellectual disabilities associated with spine defects.

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Clinical & Research Departments

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Clinical Research Director Humanitas Cancer Center Director

Luciano Ravera

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Norberto Silvestri

Education

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Piero Melodia

Rolf Zinkernagel (President) Charles Dinarello Fabio Cominelli Lorenzo Moretta

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Departments and teams Clinical Area

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Updated as of 31st March 2014 BREAST UNIT division director: Corrado Tinterri Claudio Andreoli Marco Eboli Carlos Garcia Etienne (**) Wolfgang Gatzemeier (•) Carlo Marco Rossetti Arianna Rubino Andrea Sagona MEDICAL ONCOLOGY AND Haematology division director: Armando Santoro

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Diagnostic Laboratory Services Department LABORATORY TESTS division director: Alessandro Montanelli Valentina Achille Roberto Assandri Barbara Barbieri Gianluca Basso Daniela Bettio Paolo Bianchi Simona Brambilla Elena Bredi Maria Calabrò Erminia Anna Casari Elisabetta Corsi Concetta De Luca Antonella Ferrario Rossana Mineri Marta Noemi Monari Francesca Morabito Carla Barbara Ripamonti (°) Cristina Scuderi

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GASTROENTEROLOGY AND DIGESTIVE ENDOSCOPY

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PATHOLOGY division director: Massimo Roncalli Silvia Armenia Serena Battista Raimondo Boeri Paola Bossi Tatiana Brambilla Piergiuseppe Colombo (•) Annarita Destro Luca Di Tommaso Bethania Fernandes Andrea Ferretti Barbara Fiamengo Chiara Lo Russo Sofia Manara Daoud Rahal (•) Paola Spaggiari

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division director: Alessandro Repici Andrea Anderloni Alessandra Carlino Silvia Carrara Camilla Ciscato Elisa Chiara Ferrara Giuseppe Strangio GENERAL MEDICINE AND HEPATOLOGY division director: Pietro Invernizzi Ilaria Bianchi Roberto Ceriani (•) Ana Lleo De Nalda (**)

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director: Marco Montorsi

director: Paolo E. Levi Setti

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Fabio Baticci (°) Stefano Bona (•) Michele Maria Carvello Martina Ceolin Hayato Kurihara (•) Mattia Molteni Davide Poldi (°) Antonino Spinelli (•) Pancreatic Surgery division director: Alessandro Zerbi Giovanni Capretti Francesca Gavazzi Cristina Ridolfi GENERAL AND ONCOLOGIC SURGERY division director: Vittorio Quagliuolo Antonella Ardito Pietro Francesco Bagnoli Andrea Brocchi Ferdinando Carlo Cananzi (°) Luca Cozzaglio (•) Chiara Erminia Mussi Ombretta Nucca Gastroesophageal Surgery division director: Uberto Fumagalli Romario (Riccardo Rosati until 31st December 2014) Pietro Dante Muselli Matteo Porta LIVER SURGERY division director: Guido Torzilli Daniele Del Fabbro Matteo Donadon Angela Palmisano

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Internal Medicine Department director: Mauro Podda vice director: Salvatore Badalamenti ACCIDENT & EMERGENCY UNIT division directors: Salvatore Badalamenti, Antonio Voza Alessandro Barraco Giuseppe Biancofiore Alessandro Bottani Gianluigi Citterio Giuseppe Civitavecchia Luca Contu Carlo Fedeli Giovanni Giorgino Elisabetta Lavezzi Alfonso Maiorino Alessandra Melis Jasmina Micari Silvia Oldani Stefano Ottolini Maria Gioia Lea Pich Marta Ripoll Pons DERMATOLOGY division director: Marcello Monti Luca Livio Mancini Francesco Sacrini Federica Sanna Francesca Savalli Luca Speroni ENDOCRINOLOGY AND DIABETOLOGY division director: Andrea Lania Paolo Colombo GENERAL MEDICINE AND pneumology division director: Michele Ciccarelli Maria Francesca Barmina Massimo Crippa Alessandra Ibba Alessia Marseglia (°) Francesca Puggioni Lucia Testoni

INTERNAL MEDICINE division director: Raffaello Furlan Maria Italia Sara Achenza Franca Barbic (°) Enrico Brunetta (*) Franca Dipaola Alberto Grassi NEPHROLOGY AND DIALYSIS division director: Salvatore Badalamenti Claudio Angelini (•) Paola Arosio Cesare Berra (•) Albania Calvetta Giuseppe Favacchio Silvia Finazzi Giorgio Graziani (°) Marco Mirani Rosa Pedale Bruno Pessano (°) Silvia Santostasi Rossella Valentino Simona Verdesca RHEUMATOLOGY and clinical immunology division director: Carlo Francesco Selmi Angela Ceribelli (**) Maria De Santis Gianluigi Fabbriciani Bianca Marasini (°) Marco Sergio Massarotti Francesca Meda THROMBOSIS Centre division director: Corrado Lodigiani Monica Bacci Anna Colombo Monica Demarco Paola Ferrazzi Luca Librè Grazia Loredana Mendolicchio Ilaria Quaglia OUTPATIENT AREA Giovanni Covini (•) Barbara Bianchini (°) Vanessa Ronzoni

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Neuro Center

Ortho Center

EMERGENCY NEUROLOGY AND STROKE UNIT division director: Simona Marcheselli

Arthroscopic SURGERY of the knee division director: Enrico Arnaldi

Beatrice Albano Elisa Coloberti Manuel Corato Lara Fratticci Mariacarmela Spinelli Laura Straffi NEUROLOGY II division director: Eduardo Nobile Orazio Mariangela Bianco Mohamed Ziad Fayoumi (°) Francesca Gallia Claudia Giannotta (**) Fabrizia Terenghi NEUROSURGERY division director: Maurizio Fornari Luca Attuati Simonetta Beluffi (°) Massimo Borroni (°) Marco Brayda Bruno (°) Andrea Cardia (•) Paola Carmagnini (°) Francesco Costa Giuseppe D’Aviri (°) Giovanni Battista Lasio (•) Guido Menasce (°) Davide Milani Alessandro Ortolina Armando Pellanda (°) Piero Picozzi Alberto Pollini (°) Stefania Radice Riccardo Rodriguez Y Baena (°) Giorgio Savoia (°) Massimo Tomei (°) ONCOLOGIC NEUROSURGERY

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division director: Lorenzo Bello Alessandra Casarotti Alessandro Comi Enrica Maria Fava Federico Pessina

Stefano Bertora (°) Andrea Bruno Andrea Bruno Massimo De Donato Paolo Dupplicato Alexander Kirienko (°) Antonio Orgiani Paolo Pesenti (°) HAND SURGERY division director: Alberto Lazzerini Alessandra Martano Luciana Marzella Ilaria Papini Zorli Pier Luigi Raimondi (°) Angela Trabucco Fabiana Zura Puntaroni HIP AND KNEE PROsTHEtIC SURGERY division director: Guido Grappiolo Franco Astore Andrea Baldini (°) Giovanna Borello (°) Emanuele Caldarella Federico D’Aria (°) Federico Della Rocca Alessandro Eusebio Matteo Carlo Ferrari Antonino Gurgone Federica Martorelli Giuseppe Mazziotta Damiano Ricci Riccardo Ruggeri Giuseppe Santoro Marco Scardino Francesco Traverso knee ORTHOPAEDICS and sport traumatology division director: Piero Volpi Corrado Bait Matteo G.M. Denti (°) Emanuele Prospero

PaEDIATRIC AND NEURO-ORTHOPAEDICS SURGERY division director: Nicola Portinaro Maurizio Mori (°) Artemisia Panou SHOULDER AND ELBOW SURGERY division director: Alessandro Castagna Mario Borroni Silvana De Giorgi (°) Giacomo Delle Rose Paolo Renato Rolla FOOT SURGERY division director: Leonardo Maradei Antonio Giardella Nikolaos Markopoulos Luigi Milano (°) TRAUMATOLOGY division director: Marco Berlusconi Matteo Cavanna Lorenzo Di Mento Davide Marchettini Mattia Mocchi Josè Antonio Puchol Incertis Ivano Scarabello

Rehabilitation Department director: Stefano Respizzi Cardiac & Respiratory Rehabilitation division director: Stefano Aglieri Anna Beretta Franco Rusconi (°) Neurologic Rehabilitation division director: Bruno Bernardini Giovanna Cerina Viviana Colantonio Carla Corsini Sara Ghirmai Marco Augusto Pagani Orthopaedic Rehabilitation division director: Stefano Respizzi Barbara Baroni Maria Cristina D’Agostino Gianluca Galimberti (•) Giuseppe Patavino Elisabetta Tibalt SPORTS AND EXERCISE MEDICINE Daniela Lucini (•)

Specialised Divisions of Surgery EYE CENTER division director: Paolo Vinciguerra Elena Albè Laura Balia Fabrizio Ivo Camesasca Carlo Castellani Marco Criscito (°) Alessandra Di Maria Alessia Dipietro Riccardo Gizzi Marco Gramigna Emanuela Legrottaglie Raffaele Piscopo Grazia Maria Quaranta (°) Alessandro Randazzo Mario Romano Pietro Rosetta Riccardo Scotti Adriana Sergio Maria Ingrid Torres Munoz Laura Tranchina Rosario Urso Josè Luis Vallejo Garcia Pietro Paolo Vico OTORHINOLARYNGOLOGY division director: Arturo Poletti Fabio Bertone Giovanni Colombo Gioavanni Cugini Susanna Di Pietro Luca Malvezzi Stefano Miceli Vanessa Rossi

SURGICAL DAY HOSPITAL division director: Roberta Monzani Marco Aldo Babbini Benedetta Basta Francesco Carrera Aljosa Ciarloni Barbara Crescimbini Laura Crozzoli Michele De Ruvo Chiara Ferrari Stefania Gherardi Fabio Intelligente Annarita Larocca Marco Maiola Oreste Davide Montino Maria Del Carmen Rodriguez Beatrice Rossi Claudio Sacchi Alessandro Scafella UROLOGY division director: Pierpaolo Graziotti Alessio Benetti Luigi Castaldo Guido Giusti (•) Rodolfo Hurle Luisa Pasini Roberta Peschechera Alessandro Pizzocaro Silvia Proietti Roberta Ribali Mauro Seveso Gianluigi Taverna (•) Silvia Zandegiacomo De Zorzi

PLASTIC SURGERY II division director: Marco Klinger

(*) Phisycian dealing with activity in the Research laboratories too (**) Research Staff

Valeria Bandi Barbara Banzatti Claudio Cordani Silvia Giannasi Alessandra Veronesi

(***) Research Nurse (•) Head of unit (°) Consultant ■ Divisions that join in the Humanitas Cancer Center

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Departments and teams Scientific Research and Laboratories Updated as of 31 March 2014 st

Scientific Superintendence director: Nicola Dioguardi Sonia Di Biccari Barbara Franceschini

Scientific Direction and Research Laboratories director: Alberto Mantovani Annunciata Vecchi

Clinical trials office director: Michele Tedeschi Alessandra Giampà Francesco Minuti Emanuela Morenghi Silvia Spagnoli

Innovation Office Alessandra Orlandi

Grant office Monica Di Meglio Danilo Petroni

(•) Group leader (1) MD-PhD. In addition to research s/he works as a clinician in Endocrinology (2) MD-PhD. In addition to research s/he works as a clinician in Reumathology (3) MD-PhD. In addition to research s/he works as a clinician in Inflammatory Bowel Disease (4) M D-PhD. In addition to research s/he works as a clinician in Epathology

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(5) MD-PhD. In addition to research s/he works as a clinician in Medical Oncology and Haematology

Adaptive Immunity principal investigator: Antonella Viola junior principal investigator: Marinos Kallikourdis Roberta Angioni Stefano Garetto Paola Larghi Eliana Laurenzano Elisa Martini Cristina Mazzon Michela Muscolini Cristina Ploia Giuliana Roselli Cristiana Soldani Chiu-Hui Wang Lucia Zanotti CELLULAR AND MOLECULAR ENDOCRINOLOGY principal investigator: Andrea Lania (1) Valeria Cambiaghi Eleonora Vitali CELLULAR IMMUNOLOGY principal investigator: Paola Allavena Cristina Belgiovine Francesca Bergomas Giovanni Castino Marco Erreni Manuela Liguori Federica Marchesi Samantha Angela Pesce Imran Siddiqui CLINICAL AND EXPERIMENTAL IMMUNOLOGY principal investigator: Domenico Mavilio Francesca Calcaterra Silvia Della Bella (•) Kelly Lorraine Hudspeth Enrico Lugli Irene Mattiola Joanna Mikulak Elena Pontarini Alessandra Roberto Paolo Francesco Tentorio Veronica Zanon

CLINICAL IMMUNOLOGY AND AUTOIMMUNITY AND METABOLISM principal investigator: Carlo Francesco Selmi (2) Francesca Cavaciocchi Angela Ceribelli (2) Maria De Santis (2) Francesca Meda (2) EXPERIMENTAL IMMUNOPATHOLOGY principal investigator: Cecilia Garlanda Marialuisa Barbagallo Eduardo Bonavita Francesca Feruglio Maria Rosaria Galdiero Stefania Gentile Sebastien Jaillon Martina Molgora Fabio Pasqualini Nadia Polentarutti Marcello Rubino Vanessa Zambelli GASTROINTESTINAL IMMUNOPATHOLOGY principal investigator: Silvio Danese (3) Carmen Correale Silvia D’Alessio Francesca De Santis Philippe Fonteyne Alessandro Gandelli Marco Genua Luciana Petti Carlotta Tacconi Stefania Vetrano HEPATOBILIARY IMMUNOPATHOLOGY principal investigator: Pietro Invernizzi (4) Francesca Bernuzzi Ilaria Bianchi (4) Margherita Correnti Ana Lleo De Nalda (4) Chiara Raggi Ilaria Sogno IMMUNOPHARMACOLOGY principal investigator: Barbara Bottazzi Antonio Inforzato Ilaria Laface Roberto Leone Francesca Petroni Marina Sironi Sonia Valentino

LEUKOCYTE BIOLOGY principal investigator: Massimo Locati Ornella Bonavita Raffaella Bonecchi (•) Cinzia Cancellieri Nicoletta Caronni Graziella Curtale Florian Pesant Stefania Recalcati Tiziana Renzi Benedetta Savino Naths Grazia Sukubo Federica Tomay Alessandro Vacchini LEUKOCYTE MIGRATION principal investigator: Silvano Sozzani Annalisa Del Prete MOLECULAR IMMUNOLOGY principal investigator: Antonio Sica Francesca Maria Consonni Alessandro Ippolito Sara Morlacchi Chiara Porta Elena Riboldi Maria Antonietta Sabatino Laura Strauss Cristina Travelli Francesco Zitelli ONCOLOGY EXPERIMENTAL THERAPIES principal investigator: Carmelo Carlo-Stella (5) Giulia Bottai Alessandra Inguscio Silvia Laura Locatelli Laura Paladini Elena Saba Libero Santarpia Nadia Sessarego PHARMACOLOGY AND BRAIN PATHOLOGY principal investigator: Michela Matteoli Flavia Antonucci Chiara Adriana Elia Fabia Filipello Giuliana Fossati Maria Malosio Sonia Mazzitelli

Elisabetta Menna Raffaella Morini Davide Pozzi Marco Rasile Matteo Tamborini Romana Tomasoni Claudia Verderio PHYSIOLOGY principal investigator: Elisabetta Cerri Valentina Ferpozzi Luca Fornia

BIOBANK Giorgia Ceva Grimaldi Nina Patricia Machado Torres Valentina Paleari Alice Pezzoni Daniela Pistillo COMMON RESEARCH SERVICES Achille Anselmo Javier Cibella Andrea Doni Fabio Grizzi Gianpaolo Milite Diego Morone Monica Rimoldi Paolo Somma Silvia Tartari

NATIONAL RESEARCH COUNCIL (CNR) HUMAN GENOME AND medical biotechnologies human genome principal investigator: Anna Villa Barbara Cassani Maria Luisa Focarelli Virginia Maina Stefano Mantero Veronica Marrella Eleonora Palagano Federica Rapposelli Rosita Rigoni Cristina Sobacchi Dario Strina

MEDICAL BIOTECHNOLOGIES principal investigator: Paolo Vezzoni Maria Elena Caldana Alessandra Castelli Isabel Chapa Laura Crisafulli Lorenzo Diomede Francesca Faggioli Francesca Ficara Michela Lizier Sharon Muggeo Tui Anna Neri Giovanni Pacchiana Marianna Paulis Lucia Susani INFLAMMATION AND IMMUNOLOGY IN CARDIOVASCULAR principal investigator: Gianluigi Condorelli Pierluigi Carullo Anna Castaldo Laura Catarozzo Montserrat Climent Salarich Elisa Di Pasquale Leonardo Elia Barbara Gargano Carolina Greco Paolo Kunderfranco Michele Latronico Michele Miragoli Hiroko Nakahama Miriam Pagin Laura Papa Roberto Papait (•) Manuela Quintavalle Alessandra Rodanò Francesca Rusconi Nicolò Salvarani Giuliano Stirparo Chiara Viviani Anselmi sarcomers in CARDIAC PATHOLOGY ) principal investigator: Marie Louise Bang Maria Carmela Filomeno Giuseppina Mastrototaro Fabio Piaser SIGNAL TRANSDUCTION IN CARDIAC PATHOLOGY principal investigator: Daniele Catalucci

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Papers published 2013

Papers published 2013 As of 31 January 2014 * = Corresponding author

P r e c l i n i c a l Adaptive Immunity

Eleuteri E, Mezzani A, Di Stefano A, Vallese D, Gnemmi I, Delle Donne L, Taddeo A, Della Bella S, Giannuzzi P.

Kallikourdis M*, Trovato AE, Anselmi F, Sarukhan A, Roselli G, Tassone L, Badolato R, Viola A.

Aerobic training and angiogenesis activation in patients with stable chronic heart failure: a preliminary report.

The CXCR4 mutations in WHIM syndrome impair the stability of the T cell immunological synapse.

Biomarkers 2013;18(5):418-24.

Raw IF: 1.879 Normalized IF: 1

Blood 2013;122(5):666-73.

Raw IF: 9.06 Normalized IF: 8

Galluzzi L, Lugli E*.

Meisel M, Hermann-Kleiter N, Hinterleitner R, Gruber T, Wachowicz K, Pfeifhofer-Obermair C, Fresser F, Leitges M, Soldani C, Viola A, Kaminski S, Baier G.

The kinase PKCÎą selectively upregulates Interleukin-17A during Th17 Cell immune responses.

Immunity 2013;38(1):41-52.

Raw IF: 19.795 Normalized IF: 7.5

Clinical and Experimental Immunology Colombo E, Calcaterra F, Cappelletti M, Mavilio D, Della Bella S*.

Comparison of fibronectin and collagen in supporting the isolation and expansion of endothelial progenitor cells from human adult peripheral blood.

PLoS One 2013;8(6):e66734.

Raw IF: 3.73 Normalized IF: 6

Colombo E, Marconi C, Taddeo A, Cappelletti M, Villa ML, Marzorati M, Porcelli S, Vezzoli A, Della Bella S*.

Fast reduction of peripheral blood endothelial progenitor cells in healthy humans exposed to acute systemic hypoxia.

The Journal of Physiology 2012; 590(pt 3):519-32.

Raw IF: 4.38 Normalized IF: 6

76

R e s e a r c h Lugli E*, Dominguez MH, Gattinoni L, Chattopadhyay PK, Bolton DL, Song K, Klatt NR, Brenchley JM, Vaccari M, Gostick E, Price DA, Waldmann TA, Restifo NP, Franchini G, Roederer M.

Superior T memory stem cell persistence supports long-lived T cell memory.

Journal of Clinical Investigation 2013; 123(2):594-9.

Raw IF: 12.812 Normalized IF: 10

Rejuvenated T cells attack old tumors.

Oncoimmunology 2013;2(2):e24103.

Raw IF: 0 Normalized IF: 0

Galluzzi L, Lugli E*.

Cancer immunotherapy turns viral.

Oncoimmunology 2013;2(4):e24802.

Raw IF: 0 Normalized IF: 0

Giuliani A, Moroncini F, Mazzoni S, Belicchi ML, Villa C, Erratico S, Colombo E, Calcaterra F, Brambilla L, Torrente Y, Albertini G, Della Bella S.

Polyglycolic Acid-Polylactic Acid scaffold response to different progenitor cell in vitro cultures: a demonstrative and comparative X-Ray synchrotron radiation phase-contrast microtomography study.

Tissue Engineering, part C, Methods 2014;20(4):308-16.

Raw IF: 0 Normalized IF: 0

Hudspeth K, Pontarini E, Tentorio P, Cimino M, Donadon M, Torzilli G, Lugli E, Della Bella S, Gershwin ME, Mavilio D*.

The role of natural killer cells in autoimmune liver disease: a comprehensive review.

Journal of Autoimmunity 2013;46:55-65.

Raw IF: 8.145 Normalized IF: 8

Hudspeth K, Silva-Santos B, Mavilio D*.

Natural cytotoxicity receptors: broader expression patterns and functions in innate and adaptive immune cells.

Frontiers in Immunology 2013;4:69.

Raw IF: 0 Normalized IF: 0

Mahnke YD, Brodie TM, Sallusto F, Roederer M, Lugli E.

The whoâ&#x20AC;&#x2122;s who of T-cell differentiation: human memory T-cell subsets.

European Journal of Immunology 2013;43(11):2797-809.

Raw IF: 4.97 Normalized IF: 6

Matera I, Musso M, Griseri P, Rusmini M, Di Duca M, So MT, Mavilio D, Miao X, Tam PH, Ravazzolo R, Ceccherini I, GarciaBarcelo M.

Allele-specific expression at the RET locus in blood and gut tissue of individuals carrying risk alleles for Hirschsprung disease.

Human Mutation 2013;34(5):754-62.

Raw IF: 5.213 Normalized IF: 3

Mavilio D, Galluzzi L, Lugli E*.

Novel multifunctional antibody approved for the treatment of breast cancer.

Oncoimmunology 2013;2(3):e24567.

Raw IF: 0 Normalized IF: 0

Mavilio D, Lugli E*.

Inhibiting the inhibitors: checkpoints blockade in solid tumors.

Oncoimmunology 2013;2(9):e26535.

Raw IF: 0 Normalized IF: 0

Pini Prato A, Rossi V, Mosconi M, Holm C, Lantieri F, Griseri P, Ceccherini I, Mavilio D, Jasonni V, Tuo G, Derchi M, Marasini M, Magnano G, Granata C, Ghiggeri G, Priolo E, Sposetti L, Porcu A, Buffa P, Mattioli G.

Villa M, Black S, Groth N, Rothman KJ, Apolone G, Weiss NS, Aquino I, Boldori L, Caramaschi F, Gattinoni A, Malchiodi G, Crucitti A, Della Cioppa G, Scarpini E, Mavilio D, Mannino S.

A prospective observational study of associated anomalies in Hirschsprung’s disease.

Safety of MF59-adjuvanted influenza vaccination in the elderly: results of a comparative study of MF59-adjuvanted vaccine versus nonadjuvanted influenza vaccine in Northern Italy.

Orphanet Journal of Rare Diseases 2013; 8:184.

Raw IF: 4.316 Normalized IF: 3

Rusmini M, Griseri P, Lantieri F, Matera I, Hudspeth KL, Roberto A, Mikulak J, Avanzini S, Rossi V, Mattioli G, Jasonni V, Ravazzolo R, Pavan WJ, Pini-Prato A, Ceccherini I, Mavilio D*.

Induction of RET dependent and independent pro-inflammatory programs in human peripheral blood mononuclear cells from Hirschsprung patients.

PLoS One 2013;8(3):e59066.

Raw IF: 3.73 Normalized IF: 6

Varchetta S, Lusso P, Hudspeth K, Mikulak J, Mele D, Paolucci S, Cimbro R, Malnati M, Riva A, Maserati R, Mondelli MU, Mavilio D*.

Sialic acid-binding Ig-like lectin-7 interacts with HIV-1 gp120 and facilitates infection of CD4pos T cells and macrophages.

Retrovirology 2013;10:154.

Raw IF: 5.657 Normalized IF: 6

Varchetta S, Oliviero B, Mavilio D, Mondelli MU.

Different combinations of cytokines and activating receptor stimuli are required for human natural killer cell functional diversity.

Cytokine 2013;62(1):58-63.

Raw IF: 2.518 Normalized IF: 1

American Journal of Epidemiology 2013;178(7):1139-45.

Raw IF: 4.78 Normalized IF: 3

Human Genome; Medical Biotechnologies Ficara F, Crisafulli L, Lin C, Iwasaki M, Smith KS, Zammataro L, Cleary ML.

Pbx1 restrains myeloid maturation while preserving lymphoid potential in haematopoietic progenitors.

Journal of Cell Science 2013; 126(pt 14):3181-91.

Raw IF: 5.877 Normalized IF: 6

Mégarbané A, Pangrazio A, Villa A, Chouery E, Maarawi J, Sabbagh S, Lefranc G, Sobacchi C.

Homozygous stop mutation in the SNX10 gene in a consanguineous Iraqi boy with osteopetrosis and corpus callosum hypoplasia.

European Journal of Medical Genetics 2013;56(1):32-5.

Raw IF: 1.685 Normalized IF: 2

Pangrazio A, Puddu A, Oppo M, Valentini M, Zammataro L, Vellodi A, Gener B, Llano-Rivas I, Raza J, Atta I, Vezzoni P, Superti-Furga A, Villa A, Sobacchi C*.

Exome sequencing identifies CTSK mutations in patients originally diagnosed as intermediate osteopetrosis.

Bone 2014;59:122-6.

Raw IF: 3.823

Normalized IF: 4

Santin G, Paulis M, Vezzoni P, Pacchiana G, Bottiroli G, Croce AC.

Autofluorescence properties of murine embryonic stem cells during spontaneous differentiation phases.

Lo Iacono N, Pangrazio A, Abinun M, Bredius R, Zecca M, Blair HC, Vezzoni P, Villa A, Sobacchi C.

Lasers in Surgery and Medicine 2013;45(9):597-607.

Raw IF: 2.455 Normalized IF: 6

RANKL cytokine: from pioneer of the osteoimmunology era to cure for a rare disease.

Sobacchi C, Schulz A, Coxon FP, Villa A, Helfrich MH.

Clinical & Developmental Immunology 2013;2013:412768.

Raw IF: 3.064 Normalized IF: 4

Maina V, Marrella V, Mantero S, Cassani B, Fontana E, Anselmo A, Del Prete A, Sozzani S, Vezzoni P, Poliani PL, Villa A*.

Hypomorphic mutation in the RAG2 gene affects dendritic cell distribution and migration.

Journal of Leukocyte Biology 2013;94(6):1221-30.

Raw IF: 4.568 Normalized IF: 6

Osteopetrosis: genetics, treatment and new insights into osteoclast function.

Nature Reviews. Endocrinology 2013;9(9):522-36.

Raw IF: 11.025 Normalized IF: 8

Yokoyama A, Ficara F, Murphy MJ, Meisel C, Hatanaka C, Kitabayashi I, Cleary ML.

MLL becomes functional through intramolecular interaction not by proteolytic processing.

PLoS One 2013;8(9):e73649.

Raw IF: 3.73 Normalized IF: 6

77

Papers published 2013

Inflammation and Immunology in Cardiovascular Bye A, Røsjø H, Aspenes ST, Condorelli G, Omland T, Wisløff U.

Circulating MicroRNAs and aerobic fitness - The HUNT-Study.

PLoS One 2013;8(2):e57496.

Raw IF: 3.73 Normalized IF: 3 Catalucci D, Condorelli G.

HEXIM1: a new player in myocardial hypertrophy?

Cardiovascular Research 2013;99(1):41699.

Raw IF: 5.94 Normalized IF: 6

Cavarretta E, Chiariello GA, Condorelli G*.

Platelets, endothelium, and circulating microRNA-126 as a prognostic biomarker in cardiovascular diseases: per aspirin ad astra.

Adult c-kit(pos) cardiac stem cells are necessary and sufficient for functional cardiac regeneration and repair.

Cell 2013;154(4):827-42.

Raw IF: 31.957 Normalized IF: 7.5

Hausenloy DJ, Erik Bøtker H, Condorelli G, Ferdinandy P, Garcia-Dorado D, Heusch G, Lecour S, van Laake LW, Madonna R, Ruiz-Meana M, Schulz R, Sluijter JP, Yellon DM, Ovize M.

Translating cardioprotection for patient benefit: position paper from the Working Group of Cellular Biology of the Heart of the European Society of Cardiology.

Priori SG, Napolitano C, Di Pasquale E, Condorelli G.

Induced pluripotent stem cell-derived cardiomyocytes in studies of inherited arrhythmias.

Journal of Clinical Investigation 2013;123(1):84-91.

Raw IF: 13 Normalized IF: 10

Rivera NV, Carreras-Torres R, Roncarati R, Viviani-Anselmi C, De Micco F, Mezzelani A, Koch W, Hoppmann P, Kastrati A, Stewart AF, Chen L, Roberts R, Karssen LC, Amin N, Trimarco V, Izzo R, Iaccarino G, Condorelli G, Puca AA, Pagnotta P, Airoldi F, Trimarco B, van Duijn CM, Condorelli G, Briguori C.

Assessment of the 9p21 3 locus in severity of coronary artery disease in the presence and absence of type 2 diabetes.

Cardiovascular Research 2013;98(1):7-27.

Raw IF: 5.94 Normalized IF: 3

BMC Medical Genetics 2013;14 11.

Raw IF: 3 Normalized IF: 2

European Heart Journal 2013;34(44):3400-2.

Raw IF: 14.097 Normalized IF: 10

Latronico MVG , Condorelli G*.

Curcio A, Torella D, Iaconetti C, Pasceri E, Sabatino J, Sorrentino S, Giampà S, Micieli M, Polimeni A, Henning BJ, Leone A, Catalucci D, Ellison GM, Condorelli G, Indolfi C.

Circulation Research 2013;113(10):1099-101.

Raw IF: 11.861 Normalized IF: 8

Roncarati R, Viviani Anselmi C, Krawitz P, Lattanzi G, von Kodolitsch Y, Perrot A, di Pasquale E, Papa L, Portararo P, Columbaro M, Forni A, Faggian G, Condorelli G*, Robinson PN.

MicroRNA-1 downregulation increases connexin 43 displacement and induces ventricular tachyarrhythmias in rodent hypertrophic hearts.

PLoS One 2013;8(7):e70158.

Raw IF: 3.73 Normalized IF: 3

Di Pasquale E, Lodola F, Miragoli M, Denegri M, Avelino-Cruz JE, Buonocore M, Nakahama H, Portararo P, Bloise R, Napolitano C, Condorelli G*, Priori SG.

CAMKII inhibition rectifies arrhythmic phenotype in a patient-specific model of Catecholaminergic Polymorphic Ventricular Tachycardia.

Cell Death and Disease 2013;4:E843.

Raw IF: 6.044 Normalized IF: 6

Di Pasquale E*, Song B, Condorelli G.

Generation of human cardiomyocytes: a differentiation protocol from feeder-free human induced pluripotent stem cells.

Journal of Visualized Experiments 2013;76.

Raw IF: 0

78

Ellison GM, Vicinanza C, Smith AJ, Aquila I, Leone A, Waring CD, Henning BJ, Stirparo GG, Papait R, Scarfò M, Agosti V, Viglietto G, Condorelli G, Indolfi C, Ottolenghi S, Torella D, Nadal-Ginard B.

Normalized IF: 0

MicroRNA-dependent control of the cardiac fibroblast secretome.

Papait R*, Cattaneo P, Kunderfranco P, Greco C, Carullo P, Guffanti A, Viganò V, Stirparo GG, Latronico MV, Hasenfuss G, Chen J, Condorelli G.

Genome-wide analysis of histone marks identifying an epigenetic signature of promoters and enhancers underlying cardiac hypertrophy.

Pnas 2013;110(50):20164-9.

Raw IF: 9.737 Normalized IF: 8

Papait R*, Greco C, Kunderfranco P, Latronico MV, Condorelli G.

Epigenetics: a new mechanism of regulation of heart failure?

Basic Research in Cardiology 2013;108(4):361.

Raw IF: 5.904 Normalized IF: 6

Papait R*, Kunderfranco P, Stirparo GG, Latronico MV, Condorelli G*.

Long noncoding RNA: a new player of heart failure?

Journal of Cardiovascular Translational Research 2013;6(6):876-83.

Raw IF: 3.062 Normalized IF: 4

Doubly heterozygous LMNA and TTN mutations revealed by exome sequencing in a severe form of dilated cardiomyopathy.

European Journal of Human Genetics 2013;21(10):1105-11.

Raw IF: 4.319 Normalized IF: 6

Roncarati R, Viviani Anselmi C, Losi MA, Papa L, Cavarretta E, Da Costa Martins P, Saccani Jotti G, Franzone A, Galastri L, Latronico MVG, Imbriaco M, Esposito G, De Windt L, Betocchi S, Condorelli G*.

Circulating miR-29 is a biomarker of hypertrophy and fibrosis in patients with hypertrophic cardiomyopathy.

Journal of American College of Cardiology 2014;63(9):920-7.

Raw IF: 14.086 Normalized IF: 10

Varrone F, Gargano B, Carullo P, Di Silvestre D, De Palma A, Grasso L, Di Somma C, Mauri P, Benazzi L, Franzone A, Jotti GS, Bang ML, Esposito G, Colao A, Condorelli G*, Catalucci D*.

The circulating level of FABP3 is an indirect biomarker of microRNA-1.

Journal of American College of Cardiology 2013;61(1):88-95.

Raw IF: 14.086 Normalized IF: 10

Viviani Anselmi C, Briguori C, Roncarati R, Papa L, Visconti G, Focaccio A, De Micco F, Latronico MVG, Pagnotta P, Condorelli G.

Routine assessment of on-clopidogrel platelet reactivity and gene polymorphisms in predicting clinical outcome following drug-eluting stent implantation in patients with stable coronary artery disease.

Journal of American College of Cardiology 2013;6(11):1166-75.

Raw IF: 14.086 Normalized IF: 10

Yamamoto DL, Vitiello C, Zhang J, Gokhin DS, Castaldi A, Coulis G, Piaser F, Filomena MC, Eggenhuizen PJ, Kunderfranco P, Camerini S, Takano K, Endo T, Crescenzi M, Luther P, Lieber RL, Chen J, Bang ML*.

The nebulin SH3 domain is dispensable for normal skeletal muscle structure but is required for effective active load bearing in mouse.

Journal of Cell Science 2013; 126(pt 23):5477-89.

Raw IF: 5.877 Normalized IF: 6

Leukocyte Biology Bachelerie F, Ben-Baruch A, Burkhardt AM, Combadiere C, Farber JM, Graham GJ, Horuk R, Sparre-Ulrich AH, Locati M, Luster AD, Mantovani A, Matsushima K, Murphy PM, Nibbs R, Nomiyama H, Power CA, Proudfoot AE, Rosenkilde MM, Rot A, Sozzani S, Thelen M, Yoshie O, Zlotnik A.

International Union of Pharmacology LXXXIX Update on the extended family of chemokine receptors and introducing a new nomenclature for atypical Q:1 chemokine receptors.

Pharmacological Reviews 2013;66(1):1-79.

Raw IF: 22.345 Normalized IF: 15

Borroni EM, Cancellieri C, Vacchini A, Benureau Y, Lagane B, Bachelerie F, Arenzana-Seisdedos F, Mizuno K, Mantovani A, Bonecchi R*, Locati M.

ฮฒ-arrestin-dependent activation of the cofilin pathway is required for the scavenging activity of the atypical chemokine receptor D6.

Science Signaling 2013;6(273):ra30.111,S1-3.

Raw IF: 7.648 Normalized IF: 8

Cancellieri C, Vacchini A, Locati M*, Bonecchi R, Borroni EM.

Atypical chemokine receptors: from silence to sound.

Biochemical Society Transactions 2013;41(1):231-6.

Raw IF: 2.587 Normalized IF: 2

Curtale G, Mirolo M, Renzi T, Rossato M, Bazzzoni F, Locati M.

Negative regulation of Toll-Like Receptor 4 signalling by the IL-10dependent microRNA-146b.

Pnas 2013;110(28):11499-504.

Raw IF: 9.737 Normalized IF: 8

Del Prete A, Bonecchi R, Vecchi A, Mantovani A, Sozzani S*.

CCRL2, a fringe member of the atypical chemoattractant receptor family.

European Journal of Immunology 2013;43(6):1418-22.

Raw IF: 4.97 Normalized IF: 6

Iborra M. Bernuzzi F, Correale C, Vetrano S, Fiorino G, Beltrรกn B, Marabita F, Locati M, Spinelli A, Nos P, Invernizzi P, Danese S.

Identification of serum and tissue micro-RNA expression profiles in different stages of the inflammatory bowel disease.

Clinical & Experimental Immunology 2013;173(2):250-8.

Raw IF: 3.409 Normalized IF: 4

Locati M, Mantovani A*, Sica A.

Macrophage activation and polarization as an adaptive component of innate immunity.

Advances in Immunology 2013;120:163-84.

Raw IF: 7.256 Normalized IF: 8

Sfondrini L, Sommariva M, Tortoreto M, Meini A, Piconese S, Calvaruso M, Van Rooijen N, Bonecchi R, Zaffaroni N, Colombo MP, Tagliabue E, Balsari A.

Anti-tumor activity of CpG-ODN aerosol in mouse lung metastases.

International Journal of Cancer 2013;133(2):383-93.

Raw IF: 6.198 Normalized IF: 3

Leukocyte Migration Bachelerie F, Ben-Baruch A, Burkhardt AM, Combadiere C, Farber JM, Graham GJ, Horuk R, Sparre-Ulrich AH, Locati M, Luster AD, Mantovani A, Matsushima K, Murphy PM, Nibbs R, Nomiyama H, Power CA, Proudfoot AE, Rosenkilde MM, Rot A, Sozzani S, Thelen M, Yoshie O, Zlotnik A.

International Union of Pharmacology LXXXIX Update on the extended family of chemokine receptors and introducing a new nomenclature for atypical Q:1 chemokine receptors.

Pharmacological Reviews 2013;66(1):1-79.

Raw IF: 22.345 Normalized IF: 15

Del Prete A, Bonecchi R, Vecchi A, Mantovani A, Sozzani S*.

CCRL2, a fringe member of the atypical chemoattractant receptor family.

European Journal of Immunology 2013;43(6):1418-22.

Raw IF: 4.97 Normalized IF: 6

Fรถrster R, Sozzani S.

Emerging aspects of leukocyte migration.

Mantovani A*, Locati M.

European Journal of Immunology 2013;43(6):1404-6.

Raw IF: 4.97 Normalized IF: 6

Tumor-associated macrophages as a paradigm of macrophage plasticity, diversity, and polarization: lessons and open questions.

Maina V, Marrella V, Mantero S, Cassani B, Fontana E, Anselmo A, Del Prete A, Sozzani S, Vezzoni P, Poliani PL, Villa A*.

Arteriosclerosis, Thrombosis, and Vascular Biology 2013;33(7):1478-83.

Raw IF: 6.338 Normalized IF: 6

Hypomorphic mutation in the RAG2 gene affects dendritic cell distribution and migration.

Recalcati S, Locati M, Cairo G.

Journal of Leukocyte Biology 2013;94(6):1221-30.

Raw IF: 4.568 Normalized IF: 6

Systemic and cellular consequences of macrophage control of iron metabolism.

Seminars in Immunology 2013;24(6):393-8.

Raw IF: 5.926 Normalized IF: 6

79

Papers published 2013

Parola C, Salogni L, Vaira X, Scutera S, Somma P, Salvi V, Musso T, Tabbia G, Bardessono M, Pasquali C, Mantovani A, Sozzani S, Bosisio D.

Pharmacology and Brain Pathology

Selective activation of human dendritic cells by OM-85 through a NF-kB and MAPK dependent pathway.

Antonucci F, Corradini I, Morini R, Fossati G, Menna E, Pozzi D, Pacioni S, Verderio C, Bacci A, Matteoli M*.

PLoS One 2013;8(12):e82867.

Raw IF: 3.73 Normalized IF: 3

Reduced SNAP-25 alters short-term plasticity at developing glutamatergic synapses.

Raccosta L, Fontana R, Maggioni D, Lanterna C, Villablanca EJ, Paniccia A, Musumeci A, Chiricozzi E, Trincavelli ML, Daniele S, Martini C, Gustafsson JA, Doglioni C, Feo SG, Leiva A, Ciampa MG, Mauri L, Sensi C, Prinetti A, Eberini I, Mora JR, Bordignon C, Steffensen KR, Sonnino S, Sozzani S, Traversari C, Russo V.

EMBO Reports 2013;14(7):645-51.

Raw IF: 7.189 Normalized IF: 8

The oxysterol-CXCR2 axis plays a key role in the recruitment of tumorpromoting neutrophils.

Journal of Experimental Medicine 2013;210(9):1711-28.

Raw IF: 13.214 Normalized IF: 5

Salvi V, Scutera S, Rossi S, Zucca M, Alessandria M, Greco D, Bosisio D, Sozzani S, Musso T.

Dual regulation of osteopontin production by TLR stimulation in dendritic cells.

Journal of Leukocyte Biology 2013; 94(1):147-58.

Raw IF: 4.568 Normalized IF: 3

Molecular Immunology Locati M, Mantovani A*, Sica A.

Macrophage activation and polarization as an adaptive component of innate immunity.

Advances in Immunology 2013;120:163-84.

Raw IF: 7.256 Normalized IF: 8

Mantovani A, Sica A, Invernizzi P.

Macrophage plasticity and polarizaton in liver homeostasis and pathology.

Hepatology 2014;59(5):2034-42.

Raw IF: 12.003 Normalized IF: 10

80

Menna E, Zambetti S, Morini R, Donzelli A, Disanza A, Calvigioni D, Braida D, Nicolini C, Orlando M, Fossati G, Cristina Regondi M, Pattini L, Frassoni C, Francolini M, Scita G, Sala M, Fahnestock M, Matteoli M*.

Eps8 controls dendritic spine density and synaptic plasticity through its actincapping activity.

EMBO Journal 2013;32(12):1730-44.

Raw IF: 9.822 Normalized IF: 8

Prada I, Furlan R, Matteoli M, Verderio C. Bossio C, Mastrangelo R, Morini R, Tonna N, Coco S, Verderio C, Matteoli M, Bianco F.

Classical and unconventional pathways of vesicular release in microglia.

A simple method to generate adipose stem cell-derived neurons for screening purposes.

Glia 2013;61(7).

Raw IF: 5.066

Journal of Molecular Neuroscience 2013;51(2):274-81.

Raw IF: 2.891 Normalized IF: 2

Ricotti L, Fujie T, Vaz達o H, Ciofani G, Marotta R, Brescia R, Filippeschi C, Corradini I, Matteoli M, Mattoli V, Ferreira L, Menciassi A.

De Astis S, Corradini I, Morini R, Rodighiero S, Tomasoni R, Lenardi C, Verderio C, Milani P, Matteoli M*.

Boron nitride nanotube-mediated stimulation of cell co-culture on microengineered hydrogels.

Nanostructured TiO2 surfaces promote polarized activation of microglia, but not astrocytes, toward a proinflammatory profile.

PLoS One 2013;8(8):e71707.

Raw IF: 3.73 Normalized IF: 3

Nanoscale 2013;5(22):10963-74.

Raw IF: 6.233 Normalized IF: 6 Delamarche E, Tonna N, Lovchik RD, Bianco F, Matteoli M.

Pharmacology on microfluidics: multimodal analysis for studying cell-cell interaction.

Current Opinion in Pharmacology 2013;13(5):821-8.

Raw IF: 5.443 Normalized IF: 6

Joshi P, Turola E, Ruiz A, Bergami A, Dalla Libera D, Benussi L, Giussani P, Magnani G, Comi G, Legname G, Ghidoni R, Furlan R, Matteoli M, Verderio C*.

Microglia convert aggregated amyloidbeta into neurotoxic forms through microvesicle shedding.

Cell Death and Differentiation 2014;21(4):582-93.

Raw IF: 8.371 Normalized IF: 8

Normalized IF: 6

Tomasoni R, Repetto D, Morini R, Elia C, Gardoni F, Di Luca M, Turco E, Defilippi P, Matteoli M*.

SNAP-25 regulates spine formation through postsynaptic binding to p140Cap. Nature Communications 2013;4:2136.

Raw IF: 10.015 Normalized IF: 8

Sarcomeres in Cardiac Pathology Varrone F, Gargano B, Carullo P, Di Silvestre D, De Palma A, Grasso L, Di Somma C, Mauri P, Benazzi L, Franzone A, Jotti GS, Bang ML, Esposito G, Colao A, Condorelli G*, Catalucci D*.

The circulating level of FABP3 is an indirect biomarker of microRNA-1.

Journal of American College of Cardiology 2013;61(1):88-95.

Raw IF: 14.086 Normalized IF: 10

Yamamoto DL, Vitiello C, Zhang J, Gokhin DS, Castaldi A, Coulis G, Piaser F, Filomena MC, Eggenhuizen PJ, Kunderfranco P, Camerini S, Takano K, Endo T, Crescenzi M, Luther P, Lieber RL, Chen J, Bang ML*.

The nebulin SH3 domain is dispensable for normal skeletal muscle structure but is required for effective active load bearing in mouse.

Journal of Cell Science 2013; 126(pt 23):5477-89.

Raw IF: 5.877 Normalized IF: 6

Scientific Research Laboratories Allavena P*, Germano G, Belgiovine C, D’Incalci M, Mantovani A.

Trabectedin: a drug from the sea that strikes tumor-associated macrophages.

Oncoimmunology 2013;2(6):e24614.

Raw IF: 0 Normalized IF: 0

Ascierto PA, Grimaldi AM, Acquavella N, Borgognoni L, Calabrò L, Cascinelli N, Cesano A, Del Vecchio M, Eggermont AM, Faries M, Ferrone S, Fox BA, Gajewski TF, Galon J, Gnjatic S, Gogas H, KashaniSabet M, Kaufman HL, Larkin J, Lo RS, Mantovani A, Margolin K, Melief C, McArthur G, Palmieri G, Puzanov I, Ribas A, Seliger B, Sosman J, Suenaert P, Tarhini AA, Trinchieri G, Vidal-Vanaclocha F, Wang E, Ciliberto G, Mozzillo N, Marincola FM, Thurin M.

Future perspectives in melanoma research Meeting report from the “Melanoma Bridge Napoli, December 2nd-4th 2012”.

Journal of Translational Medicine 2013; 11:137.

Raw IF: 3.459 Normalized IF: 3

Bachelerie F, Ben-Baruch A, Burkhardt AM, Combadiere C, Farber JM, Graham GJ, Horuk R, Sparre-Ulrich AH, Locati M, Luster AD, Mantovani A, Matsushima K, Murphy PM, Nibbs R, Nomiyama H, Power CA, Proudfoot AE, Rosenkilde MM, Rot A, Sozzani S, Thelen M, Yoshie O, Zlotnik A.

International Union of Pharmacology LXXXIX Update on the extended family of chemokine receptors and introducing a new nomenclature for atypical Q:1 chemokine receptors.

Pharmacological Reviews 2013;66(1):1-79.

Raw IF: 22.345 Normalized IF: 15

Bally I, Ancelet S, Moriscot C, Gonnet F, Mantovani A, Daniel R, Schoehn G, Arlaud GJ, Thielens NM.

Expression of recombinant human complement C1q allows identification of the C1r/C1s-binding sites.

Pnas 2013;110(21):8650-5.

Raw IF: 9.737 Normalized IF: 4

Barry J, Loh Z, Collison A, Mazzone S, Lalwani A, Zhang V, Davidson S, Wybacz E, Garlanda C, Mantovani A, Mattes J, Foster PS, Phipps S.

Absence of Toll-IL-1 receptor 8/SIGIRR reduces house dust mite-induced allergic airways inflammation in mice.

American Journal of Respiratory Cell and Molecular Biology 2013;49(3):481-90.

Raw IF: 4.148 Normalized IF: 3

Biswas SK, Allavena P, Mantovani A.

Celesti G, Di Caro G, Bianchi P, Grizzi F, Basso G, Marchesi F, Doni A, Marra G, Roncalli M, A. Mantovani A, Malesci A*, Laghi L.

Presence of Twist1-positive neoplastic cells in the stroma of chromosomeunstable colorectal tumors.

Gastroenterology 2013;145(3):647-57.

Raw IF: 12.821 Normalized IF: 10

Celesti G, Di Caro G, Bianchi P, Grizzi F, Marchesi F, Basso G, Rahal D, Delconte G, Catalano M, Cappello P, Roncalli M, Zerbi A, Montorsi M, Novelli F, Mantovani A, Allavena P, Malesci A*, Laghi L. (Celesti and Di Caro contributed equally to this work)

Early expression of the fractalkine receptor CX3CR1 in pancreatic carcinogenesis.

British Journal of Cancer 2013;109(9):2424-33.

Raw IF: 5.082 Normalized IF: 6

Tumor-associated macrophages: functional diversity, clinical significance and open questions.

Christersdottir Björklund T, Reilly SJ, Gahm C, Bottazzi B, Mantovani A, Tornvall P, Halle M.

Seminars in Immunopathology 2013;35(5):585-600.

Raw IF: 5.379 Normalized IF: 6

Increased long-term expression of pentraxin 3 in irradiated human arteries and veins compared to internal controls from free tissue transfers.

Borroni EM, Cancellieri C, Vacchini A, Benureau Y, Lagane B, Bachelerie F, Arenzana-Seisdedos F, Mizuno K, Mantovani A, Bonecchi R*, Locati M.

Journal of Translational Medicine 2013;11(1):223.

Raw IF: 3.459 Normalized IF: 3

β-arrestin-dependent activation of the cofilin pathway is required for the scavenging activity of the atypical chemokine receptor D6.

Del Prete A, Bonecchi R, Vecchi A, Mantovani A, Sozzani S*.

Science Signaling 2013; 6(273):ra30.1-11,S1-3.

Raw IF: 7.648

Normalized IF: 8

CCRL2, a fringe member of the atypical chemoattractant receptor family.

European Journal of Immunology 2013;43(6):1418-22.

Raw IF: 4.97 Normalized IF: 6

Cardoso AP, Pinto ML, Pinto AT, Oliveira MI, Pinto MT, Gonçalves R, Relvas JB, Figueiredo C, Seruca R, Mantovani A, Mareel M, Barbosa MA, Oliveira MJ.

Di Caro G, Marchesi F, Laghi L, Grizzi F.

Macrophages stimulate gastric and colorectal cancer invasion through EGFR Y1086, c-Src, Erk1/2 and Akt phosphorylation and smallGTPase activity.

Journal of Cellular and Molecular Medicine 2013;17(9):1088-95.

Raw IF: 4.753 Normalized IF: 6

Oncogene 2014;33(16):2123-33.

Raw IF: 7.357 Normalized IF: 4

Immune cells: plastic players along colorectal cancer progression.

Gaetani P*, Pisano P, Solinas G, Colombo P, Destro A, Levi D, Aimar E, Rodriguez R, Baena Y, Allavena P.

Immunohistohemical expression of the chemokine fractalkine and its receptor in the human brain cortex after severe traumatic brain injury and brain hemorrhage.

Journal of Neurosurgical Sciences 2013;57(1):55-62.

Raw IF: 0.53 Normalized IF: 1

81

Papers published 2013

Garlanda C, Dinarello CA, Mantovani A*.

The interleukin-1 family: back to the future.

Immunity 2013;39(6):1003-18.

Raw IF: 19.795 Normalized IF: 15

Garlanda C, Mantovani A*.

Ligands and receptors of the interleukin-1 family in immunity and disease.

Frontiers in Immunology 2013;4:296.

Raw IF: 0 Normalized IF: 0

Garlanda C*, Riva F, Bonavita E, Gentile S, Mantovani A.

Decoys and regulatory “Receptors” of the IL-1/Toll-Like receptor superfamily.

Frontiers in Immunology 2013;4:180.

Raw IF: 0 Normalized IF: 0

Garlanda C*, Riva F, Bonavita E, Mantovani A.

Negative regulatory receptors of the IL-1 family.

Seminars in Immunology 2013;25(6):408-15.

Raw IF: 5.926 Normalized IF: 6

Germano G, Frapolli R, Belgiovine C, Anselmo A, Pesce S, Liguori M, Erba E, Uboldi S, Zucchetti M, Pasqualini F, Nebuloni M, van Rooijen N, Mortarini R, Beltrame L, Marchini S, Fuso Nerini I, Sanfilippo R, Casali PG, Pilotti S, Galmarini CM, Anichini A, Mantovani A, D’Incalci M, Allavena P*.

Role of macrophage targeting in the antitumor activity of trabectedin.

Cancer Cell 2013;24(2):249-62.

Raw IF: 24.755 Normalized IF: 15

Giannice R, Erreni M, Allavena P, Buscaglia M, Tozzi R.

Chemokines mRNA expression in relation to the Macrophage Migration Inhibitory Factor (MIF) mRNA and Vascular Endothelial Growth Factor (VEGF) mRNA expression in the microenvironment of endometrial cancer tissue and normal endometrium: a pilot study.

Cytokine 2013;64(2):509-15.

Raw IF: 2.518 Normalized IF: 2

Proteolytic cleavage of the long pentraxin PTX3 in the airways of cystic fibrosis patients.

Innate Immunity 2013;19(6):611-22.

Raw IF: 2.682 Normalized IF: 2

Hollan I, Nebuloni M, Bottazzi B, Mikkelsen K, Førre OT, Almdahl SM, Mantovani A, Fagerland MW, Aukrust P, Meroni PL; on behalf of the Feiring Heart Biopsy Study Group.

Pentraxin 3, a novel cardiovascular biomarker, is expressed in aortic specimens of patients with coronary artery disease with and without rheumatoid arthritis.

Cardiovascular Pathology 2013;22(5):324-31.

Raw IF: 2.352 Normalized IF: 4

Inforzato A, Doni A, Barajon I, Leone R, Garlanda C, Bottazzi B, Mantovani A*.

PTX3 as a paradigm for the interaction of pentraxins with the complement system.

Seminars in Immunology 2013;25(1):79-85.

Raw IF: 5.926 Normalized IF: 6

Inforzato A, Reading PC, Barbati E, Bottazzi B, Garlanda C*, Mantovani A.

The “sweet” side of a long pentraxin: how glycosylation affects PTX3 functions in innate immunity and inflammation.

Frontiers in Immunology 2013;3:407.

Raw IF: 0 Normalized IF: 0

Jaillon S, Galdiero MR, Del Prete D, Cassatella MA, Garlanda C, Mantovani A*.

Neutrophils in innate and adaptive immunity.

Seminars in Immunopathology 2013;35(4):377-94.

Raw IF: 5.379 Normalized IF: 6

Jaillon S, Mancuso G, Hamon Y, Beauvillain C, Cotici V, Midiri A, Bottazzi B, Nebuloni M, Garlanda C, Frémaux I, Gauchat JF, Descamps P, Beninati C, Mantovani A, Jeannin P, Delneste Y.

Aegean reflections on innate immunity.

Prototypic long pentraxin PTX3 is present in breast milk, spreads in tissues, and protects neonate mice from pseudomonas aeruginosa lung infection.

Nature Immunology 2013;14(10):1025-9.

Raw IF: 26.199 Normalized IF: 15

Journal of Immunology 2013;191(4):1873-82.

Raw IF: 5.52 Normalized IF: 6

Hajishengallis G, Mantovani A, Moretta A, Lambris JD.

82

Hamon Y, Jaillon S, Person C, Giniès JL, Garo E, Bottazzi B, Ghamrawi S, Urban T, Subra JF, Bouchara JP, Mantovani A, Jeannin P, Delneste Y.

Job ER, Bottazzi B, Gilbertson B, Edenborough KM, Brown LE, Mantovani A, Brooks AG, Reading PC.

Serum amyloid P is a sialylated glycoprotein inhibitor of influenza A viruses.

PLoS One 2013;8(3):e59623.

Raw IF: 3.73 Normalized IF: 6

Lech M, Römmele C, Gröbmayr R, Eka Susanti H, Kulkarni OP, Wang S, Gröne HJ, Uhl B, Reichel C, Krombach F, Garlanda C, Mantovani A, Anders HJ.

Endogenous and exogenous pentraxin-3 limits postischemic acute and chronic kidney injury.

Kidney International 2013;83(4):647-61.

Raw IF: 7.916 Normalized IF: 4

Locatelli M, Ferrero S, Martinelli Boneschi F, Boiocchi L, Zavanone M, Maria Gaini S, Bello L, Valentino S, Barbati E, Nebuloni M, Mantovani A, Garlanda C*.

The long pentraxin PTX3 as a correlate of cancer-related inflammation and prognosis of malignancy in gliomas.

Journal of Neuroimmunology 2013; 260(1-2):99-106.

Raw IF: 3.033 Normalized IF: 4

Locati M, Mantovani A*, Sica A.

Macrophage activation and polarization as an adaptive component of innate immunity.

Advances in Immunology 2013;120:163-84.

Raw IF: 7.256 Normalized IF: 8

Ma YJ, Doni A, Romani L, Jürgensen HJ, Behrendt N, Mantovani A, Garred P.

Ficolin-1-PTX3 complex formation promotes clearance of altered self-cells and modulates IL-8 production.

Journal of Immunology 2013;191(3):1324-33.

Raw IF: 5.52 Normalized IF: 6

Maina V, Marrella V, Mantero S, Cassani B, Fontana E, Anselmo A, Del Prete A, Sozzani S, Vezzoni P, Poliani PL, Villa A*.

Hypomorphic mutation in the RAG2 gene affects dendritic cell distribution and migration.

Journal of Leukocyte Biology 2013;94(6):1221-30.

Raw IF: 4.568 Normalized IF: 6

Mantovani A*, Garlanda C.

Platelet-macrophage partnership in innate immunity and inflammation.

Nature Immunology 2013;14(8):768-70.

Raw IF: 26.199 Normalized IF: 15

Mantovani A*, Locati M.

Tumor-associated macrophages as a paradigm of macrophage plasticity, diversity, and polarization: lessons and open questions.

Arteriosclerosis, Thrombosis, and Vascular Biology 2013;33(7):1478-83.

Raw IF: 6.338 Normalized IF: 6

Ronca R, Alessi P, Coltrini D, Salle ED, Giacomini A, Leali D, Corsini M, Belleri M, Tobia C, Garlanda C, Bonomi E, Tardanico R, Vermi W, Presta M.

Long Pentraxin-3 as an epithelialstromal Fibroblast Growth Factortargeting inhibitor in prostate cancer.

Journal of Pathology 2013;230(2):228-38.

Raw IF: 7.585 Normalized IF: 4

Russell SE, Stefanska AM, Kubica M, Horan RM, Mantovani A, Garlanda C, Fallon PG, Walsh PT.

Mantovani A, Sica A, Invernizzi P.

Toll IL-1R8/single Ig IL-1-related receptor regulates psoriasiform inflammation through direct inhibition of innate IL-17A expression by γδ T cells.

Macrophage plasticity and polarizaton in liver homeostasis and pathology.

Journal of Immunology 2013;191(6):3337-46.

Raw IF: 5.52 Normalized IF: 3

Hepatology 2014;59(5):2034-42.

Raw IF: 12.003 Normalized IF: 10

Mantovani A*, Valentino S, Gentile S, Inforzato A, Bottazzi B, Garlanda C.

The long pentraxin PTX3: a paradigm for humoral pattern recognition molecules.

Annals of the New York Academy of Sciences 2013;1285:41640.

Raw IF: 4.375 Normalized IF: 6

Parola C, Salogni L, Vaira X, Scutera S, Somma P, Salvi V, Musso T, Tabbia G, Bardessono M, Pasquali C, Mantovani A, Sozzani S, Bosisio D.

Selective activation of human dendritic cells by OM-85 through a NF-kB and MAPK dependent pathway.

PLoS One 2013;8(12):e82867.

Raw IF: 3.73 Normalized IF: 3

Romano M, Frapolli R, Zangarini M, Bello E, Porcu L, Galmarini CM, GarcíaFernández LF, Cuevas C, Allavena P, Erba E, D’Incalci M.

Shafiani S, Dinh C, Ertelt JM, Moguche AO, Siddiqui I, Smigiel KS, Sharma P, Campbell DJ, Way SS, Urdahl KB.

Pathogen-specific Treg cells expand early during mycobacterium tuberculosis infection but are later eliminated in response to Interleukin-12.

Immunity 2013;38(6):1261-70.

Raw IF: 19.795 Normalized IF: 7.5

Suzuki S, Shishido T, Funayama A, Netsu S, Ishino M, Kitahara T, Sasaki T, Katoh S, Otaki Y, Watanabe T, Shibata Y, Mantovani A, Takeishi Y, Kubota I.

Long pentraxin PTX3 exacerbates pressure overload-induced left ventricular dysfunction.

PLoS One 2013;8(1):e53133.

Raw IF: 3.73 Normalized IF: 3

Curcio A, Torella D, Iaconetti C, Pasceri E, Sabatino J, Sorrentino S, Giampà S, Micieli M, Polimeni A, Henning BJ, Leone A, Catalucci D, Ellison GM, Condorelli G, Indolfi C.

MicroRNA-1 downregulation increases connexin 43 displacement and induces ventricular tachyarrhythmias in rodent hypertrophic hearts.

PLoS One 2013;8(7):e70158.

Raw IF: 3.73 Normalized IF: 3

Papait R*, Cattaneo P, Kunderfranco P, Greco C, Carullo P, Guffanti A, Viganò V, Stirparo GG, Latronico MV, Hasenfuss G, Chen J, Condorelli G.

Genome-wide analysis of histone marks identifying an epigenetic signature of promoters and enhancers underlying cardiac hypertrophy.

Pnas 2013;110(50):20164-9.

Raw IF: 9.737 Normalized IF: 8

Tritsch E, Mallat Y, Lefebvre F, Diguet N, Escoubet B, Blanc J, De Windt LJ, Catalucci D, Vandecasteele G, Li Z, Mericskay M.

An SRF/miR-1 axis regulates NCX1 and Annexin A5 protein levels in the normal and failing heart.

Cardiovascular Research 2013;98(3):372-80.

Raw IF: 5.94 Normalized IF: 3

Varrone F, Gargano B, Carullo P, Di Silvestre D, De Palma A, Grasso L, Di Somma C, Mauri P, Benazzi L, Franzone A, Jotti GS, Bang ML, Esposito G, Colao A, Condorelli G*, Catalucci D*.

The circulating level of FABP3 is an indirect biomarker of microRNA-1.

Journal of American College of Cardiology 2013;61(1):88-95.

Raw IF: 14.086 Normalized IF: 10

Signal Transduction in Cardiac Pathology

Comparison of in vitro and in vivo biological effects of trabectedin, lurbinectedin (PM01183) and Zalypsis® (PM00104).

Catalucci D, Condorelli G.

International Journal of Cancer 2013;133(9):2024-33.

Raw IF: 6.198 Normalized IF: 3

Cardiovascular Research 2013;99(1):41699.

Raw IF: 5.94 Normalized IF: 6

HEXIM1: a new player in myocardial hypertrophy?

Yildirim SS, Akman D, Catalucci D, Turan B.

Relationship between downregulation of miRNAs and increase of oxidative stress in the development of diabetic cardiac dysfunction: Junctin as a target protein of miR-1.

Cell Biochemistry and Biophysics 2013;67(3):1397-1408.

Raw IF: 1.912 Normalized IF: 1

83

Papers published 2013 * = Corresponding author

T r a n s l a t i o n a l

Cellular and Molecular Endocrinology Beck-Peccoz P, Lania A, Beckers A, Chatterjee K, Wemeau JL.

2013 European Thyroid Association guidelines for the diagnosis and treatment of Thyrotropin-secreting pituitary tumors.

European Thyroid Journal 2013;2(2):76-82.

Raw IF: 0 Normalized IF: 0

Felisati G, Lenzi R, Pipolo C, Maccari A, Messina F, Revay M, Lania A, Cardia A, Lasio G.

Endoscopic expanded endonasal approach: preliminary experience with the new 3D endoscope.

Acta Otorhinolaryngologica Italica 2013;33(2):102-6.

Raw IF: 0.786 Normalized IF: 1

Filopanti M, Barbieri AM, Mantovani G, Corbetta S, Gasco V, Ragonese M, Martini C, Bogazzi F, Colao AA, Ferone D, Peri A, Pigliaru F, Angeletti G, Arosio M, BeckPeccoz P, Lania A, Spada A.

Lopci E*, Colombo P, Rodari M, Lania A, Vitobello D, Leonardi L, Chiti A.

Imaging struma ovarii by means of 124INa PET/CT. Nuclear Medicine Review, Central & Eastern Europe 2013;16(2):95-6.

Raw IF: 0 Normalized IF: 0

Peverelli E, Busnelli M, Vitali E, Giardino E, Galés C, Lania AG, Beck-Peccoz P, Chini B, Mantovani G, Spada A.

Specific roles of Gi protein family members revealed by dissecting SST5 coupling in human pituitary cells.

Journal of Cell Science 2013;126(pt 2):638-44.

Raw IF: 5.877 Normalized IF: 3

Peverelli E, Mantovani G, Lania A, Spada A.

cAMP in the pituitary: an old messenger for multiple signals.

Journal of Molecular Endocrinology 2013;52(1):R67-7.

Raw IF: 3.577 Normalized IF: 2

Clinical Immunology and Autoimmunity and Metabolism

Liu JZ, Hov JR, Folseraas T, Ellinghaus E, Rushbrook SM, Doncheva NT, Andreassen OA, Weersma RK, Weismüller TJ, Eksteen B, Invernizzi P, Hirschfield GM, Gotthardt DN, Pares A, Ellinghaus D, Shah T, Juran BD, Milkiewicz P, Rust C, Schramm C, Müller T, Srivastava B, Dalekos G, Nöthen MM, Herms S, Winkelmann J, Mitrovic M, Braun F, Ponsioen CY, Croucher PJ, Sterneck M, Teufel A, Mason AL, Saarela J, Leppa V, Dorfman R, Alvaro D, Floreani A, Onengut-Gumuscu S, Rich SS, Thompson WK, Schork AJ, Næss S, Thomsen I, Mayr G, König IR, Hveem K, Cleynen I, GutierrezAchury J, Ricaño-Ponce I, van Heel D, Björnsson E, Sandford RN, Durie PR, Melum E, Vatn MH, Silverberg MS, Duerr RH, Padyukov L, Brand S, Sans M, Annese V, Achkar JP, Boberg KM, Marschall HU, Chazouillères O, Bowlus CL, Wijmenga C, Schrumpf E, Vermeire S, Albrecht M; UK-PSCSC Consortium; International IBD Genetics Consortium, Rioux JD, Alexander G, Bergquist A, Cho J, Schreiber S, Manns MP, Färkkilä M, Dale AM, Chapman RW, Lazaridis KN; International PSC Study Group, Franke A, Anderson CA, Karlsen TH.

Dense genotyping of immune-related disease regions identifies nine new risk loci for primary sclerosing cholangitis.

Role of uridine diphosphate-5’glucuronosyltransferase type 1A (UGT1A1) and alcohol dehydrogenase (ADH) gene polymorphisms in pegvisomant-induced liver toxicity in acromegalic patients.

Avrameas S, Selmi C.

European Journal of Endocrinology 2014;170(2):247-54.

Raw IF: 3.136 Normalized IF: 2

Journal of Autoimmunity 2013;41:46-9.

Raw IF: 8,145 Normalized IF: 8

The limitations and hidden gems of the epidemiology of primary biliary cirrhosis.

De Santis M, Crotti C, Selmi C.

Journal of Autoimmunity 2013;46:81-7.

Raw IF: 8,145 Normalized IF: 8

Giavoli C, Profka E, Sala E, Filopanti M, Barbieri AM, Bergamaschi S, Ferrante E, Arosio M, Ambrosi B, Lania A, Spada A, Beck-Peccoz P.

Impact of IGF(CA)19 gene polymorphism on the metabolic response to GH therapy in adult GH Deficient (GHD) patients.

European Journal of Endocrinology 2014;170(2):273-81.

Raw IF: 3.136 Normalized IF: 2

84

R e s e a r c h

Natural autoantibodies in the physiology and pathophysiology of the immune system.

Liver abnormalities in connective tissue diseases.

Best Practice & Research Clinical Gastroenterology 2013;27(4):543-51.

Raw IF: 3,155 Normalized IF: 4

Insawang T, Selmi C, Cha’on U, Gershwin ME, Yongvanit P, Prasongwattana V.

Response to Dr Roger’s letter: Further studies are necessary in order to conclude a causal association between the consumption of monosodium L-glutamate (MSG) and the prevalence of metabolic syndrome in the rural Thai population.

Nutrition and Metabolism 2013;10(1) 10.

Raw IF: 3,156 Normalized IF: 2

Nature Genetics 2013;45(6):670-5.

Raw IF: 35,209 Normalized IF: 15

Podda M, Selmi C, Lleo A, Moroni L, Invernizzi P*.

Selmi C*, Crotti C, Meroni PL.

Less-traveled roads in clinical immunology and allergy: the cases of drug reactions and environmental influence.

Clinical Reviews in Allergy and Immunology 2013;45(1):1-5.

Raw IF: 5.59 Normalized IF: 6

Selmi C*.

Autoimmunity in 2012.

Clinical Reviews in Allergy and Immunology 2013;45(2):290-301.

Raw IF: 5.59 Normalized IF: 6

Sharma A, Prasongwattana V, Cha’on U, Selmi C, Hipkaeo W, Boonnate P, Pethlert S, Titipungul T, Intarawichian P, Waraasawapati S, Puapiroj A, Sitprija V, Reungjui S.

Monosodium glutamate(MSG) consumption is associated with urolithiasis and urinary tract obstruction in rats.

PLoS One 2013;8(9):e75546.

Raw IF: 3.73

Normalized IF: 3

Sumida K, Shimoda S, Iwasaka S, Hisamoto S, Kawanaka H, Akahoshi T, Ikegami T, Shirabe K, Shimono N, Maehara Y, Selmi C, Gershwin ME, Akashi K.

Characteristics of splenic CD8＋ T cell exhaustion in patients with hepatitis C. Clinical & Experimental Immunology 2013;174(1):172-8.

Raw IF: 3.409

Normalized IF: 2

Tsuneyam K, Baba H, Kikuchi K, Nishida T, Nomoto K, Hayashi S, Miwa S, Nakajima T, Nakanishi Y, Masuda S, Terada M, Imura J, Selmi C.

Autoimmune features in metabolic liver disease: a single-center experience and review of the literature.

Clinical Reviews in Allergy and Immunology 2013;45(1):143-8.

Raw IF: 5.59

Normalized IF: 6

Gastrointestinal Immunopathology Allocca M, Fiorino G, Danese S.

Commentary: Antibodies reacting with the infliximab Fab portion - something new?

Alimentary Pharmacology & Therapeutics 2013;38(5):552.

Raw IF: 4.548

Normalized IF: 6

Allocca M, Jovani M, Fiorino G, Schreiber S, Danese S*.

Anti-IL-6 treatment for Inflammatory Bowel Diseases: next cytokine, next target.

Current Drug Targets 2013;14(12):1508-21.

Raw IF: 3.848

Normalized IF: 6

Armuzzi A, Biancone L, Daperno M, Coli A, Pugliese D, Annese V, Aratari A, Ardizzone S, Balestrieri P, Bossa F, Cappello M, Castiglione F, Cicala M, Danese S, D’Incà R, Dulbecco P, Feliciangeli G, Fries W, Genise S, Gionchetti P, Gozzi S, Kohn A, Lorenzetti R, Milla M, Onali S, Orlando A, Papparella LG, Renna S, Ricci C, Rizzello F, Sostegni R, Guidi L, Papi C.

Adalimumab in active ulcerative colitis: A “real-life” observational study.

Digestive and Liver Disease 2013; 45(9):738-43.

Raw IF: 3.162 Normalized IF: 4

Armuzzi A, Pugliese D, Danese S, Rizzo G, Felice C, Marzo M, Andrisani G, Fiorino G, Sociale O, Papa A, De Vitis I, Rapaccini GL, Guidi L.

Infliximab in steroid-dependent Ulcerative Colitis: effectiveness and predictors of clinical and endoscopic remission.

Inflammatory Bowel Diseases 2013;19(5):1065-72.

Raw IF: 5.119 Normalized IF: 6

Barello S, Leone D, Danese S, Vegni E.

Inflammatory bowel diseases and psychological issues: a new approach for a systematic analysis of the academic debate.

Psychology, Health and Medicine Epub 2013 Nov 12.

Raw IF: 1.375 Normalized IF: 1

Cammarota T, Ribaldone DG, Resegotti A, Repici A, Danese S, Fiorino G, Sarno A, Robotti D, Debani P, Bonenti G, Pellicano R, Andrealli A, Sapone N, Simondi D, Bresso F, Astegiano M.

Role of bowel ultrasound as a predictor of surgical recurrence of Crohn’s disease.

Cesarini M, Katsanos K, Papamichael K, Ellul P, Lakatos PL, Caprioli F, Kopylov U, Tsianos E, Mantzaris GJ, Ben-Horin S, Danese S, Fiorino G*.

Dose optimization is effective in ulcerative colitis patients losing response to infliximab: a collaborative multicentre retrospective study.

Digestive and Liver Disease 2014;46(2):135-9.

Raw IF: 3.162 Normalized IF: 4

D’Alessio S*, Tacconi C*, Fiocchi C, Danese S.

Advances in therapeutic interventions targeting the vascular and lymphatic endothelium in Inflammatory Bowel Disease.

Current Opinion in Gastroenterology 2013;29(6):608-13.

Raw IF: 4.103 Normalized IF: 6

Danese S.

IBD: golimumab in ulcerative colitis: a ‘ménage à trois’ of drugs.

Nature Reviews. Gastroenterology & Hepatology 2013;10(9):511-12.

Raw IF: 10.426 Normalized IF: 8

Danese S.

Comparison between 1 5 and 3 0 Tesla Magnetic Resonance Enterography for the assessment of disease activity and complications in ileo-colonic Crohn’s disease.

Digestive Diseases and Sciences 2013;58(11):3246-55.

Raw IF: 2.26 Normalized IF: 4

Danese S*, Colombel JF, Peyrin-Biroulet L, Rutgeerts P, Reinisch W.

Review article: the role of anti-TNF in the management of ulcerative colitis past, present and future.

Scandinavian Journal of Gastroenterology 2013;48(5):552-5.

Raw IF: 2.156 Normalized IF: 4

Alimentary Pharmacology & Therapeutics 2013; 37(9):855-66.

Raw IF: 4.548 Normalized IF: 6

Cesarini M, Fiorino G*.

Danese S*, Gomollon F; Governing Board and Operational Board of ECCO.

Leukocyte traffic control: a novel therapeutic strategy for inflammatory bowel disease: an update.

Expert Review of Clinical Immunology 2013;9(4):301-6.

Raw IF: 2.89 Normalized IF: 4

ECCO position statement. The use of biosimilar medicines in the treatment of inflammatory bowel disease (IBD).

Journal of Crohn’s & Colitis 2013;7(7):586-9.

Raw IF: 3.385 Normalized IF: 6

85

Papers published 2013

Danese S, Peyrin Biroulet L.

Fries W, Belvedere A, Vetrano S*.

Jovani M, Fiorino G, Danese S*.

New mechanisms and targets for IBD therapy: translational gastroenterology comes of age guests.

Sealing the broken barrier in IBD: intestinal permeability, epithelial cells and junctions.

Anti-IL-13 in Inflammatory Bowel Disease: from the bench to the bedside.

Current Drug Targets 2013;14(12):1377-8.

Raw IF: 3.848 Normalized IF: 6

Current Drug Targets 2013;14(12):1460-70.

Raw IF: 3.848 Normalized IF: 6

Feagan BG, Rutgeerts P, Sands BE, Hanauer S, Colombel JF, Sandborn WJ, Van Assche G, Axler J, Kim HJ, Danese S, Fox I, Milch C, Sankoh S, Wyant T, Xu J, Parikh A; GEMINI 1 Study Group.

(Collaborators: Danese S).

Guidi L, Felice C, Procoli A, Bonanno G, Martinelli E, Marzo M, Mocci G, Pugliese D, Andrisani G, Danese S, De Vitis I, Papa A, Armuzzi A, Rutella S.

Current Drug Targets 2013;14(12):1444-52.

Raw IF: 3.848 Normalized IF: 6

Niess JH, Danese S.

Vedolizumab as induction and maintenance therapy for ulcerative colitis.

New England Journal of Medicine 2013;369(8):699-710.

Raw IF: 51.658 Normalized IF: 15

Ferrante M, Colombel JF, Sandborn WJ, Reinisch W, Mantzaris GJ, Kornbluth A, Rachmilewitz D, Lichtiger S, D’Haens GR, van der Woude CJ, Danese S, Diamond RH, Oortwijn AF, Tang KL, Miller M, Cornillie F, Rutgeerts PJ.

Validation of endoscopic activity scores in patients with Crohn’s disease based on a post-hoc analysis of data from SONIC. Gastroenterology 2013;145(5):978-86.e5.

Raw IF: 12.821 Normalized IF: 10

Fiocchi C, Danese S.

Ulcerative colitis. The authors reply.

New England Journal of Medicine 2012;366(9):862-3.

Raw IF: 51.658 Normalized IF: 7.5

Fiorino G, Allocca MA, Danese S*.

Commentary: anaemia in inflammatory bowel disease – the most common and ignored extra intestinal manifestation.

Alimentary Pharmacology & Therapeutics 2014;39(2):227-8.

Raw IF: 4.548 Normalized IF: 6

Fiorino G, Danese S*, Pariente B, Allez M.

Paradoxical immune-mediated inflammation in inflammatory bowel disease patients receiving anti-TNF-α agents.

Autoimmunity Reviews 2014;13(1):15-9.

Raw IF: 7.975 Normalized IF: 8

86

FOXP3(+) T Regulatory Cell modifications in Inflammatory Bowel Disease patients treated with anti-TNFα agents.

BioMed Research International 2013;2013:286368.

Raw IF: 2.88 Normalized IF: 2

Iborra M, Bernuzzi F, Correale C, Vetrano S, Fiorino G, Beltrán B, Marabita F, Locati M, Spinelli A, Nos P, Invernizzi P, Danese S.

Identification of serum and tissue microRNA expression profiles in different stages of the inflammatory bowel disease.

Clinical & Experimental Immunology 2013;173(2):250-8.

Raw IF: 3.409 Normalized IF: 4

Indriolo A, Fagiuoli S, Pasulo L, Fiorino G, Danese S, Ravelli P.

Letter: Infliximab therapy in inflammatory bowel disease patients after liver transplantation.

Alimentary Pharmacology & Therapeutics 2013;37(8):840-2.

Raw IF: 4.548 Normalized IF: 3

Jovani M, Danese S.

Anti-TNF and skin inflammation in IBD: a new paradox in gastroenterology?

Gut 2014;63(4):533-5.

Raw IF: 10.732

Normalized IF: 8

Panes J, Bouhnik Y, Reinisch W, Stoker J, Taylor SA, Baumgart DC, Danese S, Halligan S, Marincek B, Matos C, PeyrinBiroulet L, Rimola J, Rogler G, van Assche G, Ardizzone S, Ba-Ssalamah A, Bali MA, Bellini D, Biancone L, Castiglione F, Ehehalt R, Grassi R, Kucharzik T, Maccioni F, Maconi G, Magro F, Martín-Comín J, Morana G, Pendsé D, Sebastian S, Signore A, Tolan D, Tielbeek JA, Weishaupt D, Wiarda B, Laghi A.

Imaging techniques for assessment of inflammatory bowel disease: Joint ECCO and ESGAR evidence-based consensus guidelines.

Journal of Crohn’s & Colitis 2013;7(7):556-85.

Raw IF: 3.385 Normalized IF: 3

Peyrin-Biroulet L, Danese S.

Tofacitinib: janus bifrons in ulcerative colitis treatment.

Gastroenterology 2013;144(5):1136-8.

Raw IF: 12.821 Normalized IF: 10

Peyrin-Biroulet L, Fiorino G, Buisson A, Danese S*.

Surveillance for colorectal cancer in inflammatory bowel disease.

First-line therapy in adult Crohn’s disease: who should receive anti-TNF agents?

Giornale Italiano di Endoscopia Digestiva 2013;36(3):191-7.

Raw IF: 0 Normalized IF: 0

Nature Reviews. Gastroenterology & Hepatology 2013;10(6):345-51.

Raw IF: 10.426 Normalized IF: 8

Jovani M, Danese S.

Reinisch W, Chowers Y, Danese S, Dignass A, Gomollón F, Haagen Nielsen O, Lakatos PL, Lees CW, Lindgren S, Lukas M, Mantzaris GJ, Michetti P, Moum B, Peyrin-Biroulet L, Toruner M, van der Woude J, Weiss G, Stoevelaar H.

Vedolizumab for the treatment of IBD: a selective therapeutic approach targeting pathogenic a4b7 cells.

Current Drug Targets 2013;14(12):1433-43.

Raw IF: 3.848 Normalized IF: 6

Jovani M*, Fiorino G, Danese S.

Commentary: associations between immune activation, intestinal permeability and irritable bowel syndrome.

Alimentary Pharmacology & Therapeutics 2013;37(2):277-8.

Raw IF: 4.548 Normalized IF: 6

The management of iron deficiency in inflammatory bowel disease - an online tool developed by the RAND/UCLA appropriateness method.

Alimentary Pharmacology & Therapeutics 2013;38(9):1109-18.

Raw IF: 4.548 Normalized IF: 3

Roblin X, Danese S, Peyrin-Biroulet L.

Tilg H, Danese S.

Does anti-TNF therapy cost so many COINs?

Roseburia hominis: a novel guilty player in ulcerative colitis pathogenesis?

Gastroenterology 2014;146(1):309-11.

Raw IF: 12.821 Normalized IF: 10

Gut Epub 2013;Oct 6.

Raw IF: 10.732

Saibeni S, Etchevers MJ, Tassies D, Panés J, Reverter JC, Danese S, Piqué JM, Bruno S, Vecchi M, Gasbarrini A, Sans M.

Torres J, Danese S, Colombel JF.

Antimitochondrial antibody heterogeneity and the xenobiotic etiology of primary biliary cirrhosis.

Assessment of anti-prothrombin antibodies in thrombosis complicating inflammatory bowel diseases.

New therapeutic avenues in ulcerative colitis: thinking out of the box.

Hepatology 2013;57(4):1498-508.

Raw IF: 12.003 Normalized IF: 5

Gut 2013;62(11):1642-52.

Raw IF: 10.732 Normalized IF: 8

International Journal of Colorectal Disease 2013;28(9):1281-6.

Raw IF: 2.238 Normalized IF: 2

Sandborn WJ, Feagan BG, Rutgeerts P, Hanauer S, Colombel JF, Sands BE, Lukas M, Fedorak RN, Lee S, Bressler B, Fox I, Rosario M, Sankoh S, Xu J, Stephens K, Milch C, Parikh A; GEMINI 2 Study Group.

(Collaborators: Danese S).

Vedolizumab as induction and maintenance therapy for Crohn’s disease.

New England Journal of Medicine 2013;369(8):711-21.

Raw IF: 51.658 Normalized IF: 3

Sebastian S, Hernández V, Myrelid P, Kariv R, Tsianos E, Toruner M, MartiGallostra M, Spinelli A, van der Meulen-de Jong AE, Yuksel ES, Gasche C, Ardizzone S, Danese S.

Colorectal cancer in inflammatory bowel disease: results of the 3rd ECCO pathogenesis scientific workshop (I).

Normalized IF: 8

Travis SP, Danese S, Kupcinskas L, Alexeeva O, D’Haens G, Gibson PR, Moro L, Jones R, Ballard ED, Masure J, Rossini M, Sandborn WJ.

Preoperative magnetic resonance enterography in predicting findings and optimizing surgical approach in Crohn’s disease.

Journal of Gastrointestinal Surgery 2014;18(1):83-90.

Raw IF: 2.361 Normalized IF: 6

Stein J, Bager P, Befrits R, Gasche C, Gudehus M, Lerebours E, Magro F, Mearin F, Mitchell D, Oldenburg B, Danese S.

Anemia management in patients with inflammatory bowel disease: routine practice across nine European countries.

European Journal of Gastroenterology & Hepatology 2013;25(12):1456-63.

Raw IF: 1.915 Normalized IF: 1

Iborra M, Bernuzzi F, Correale C, Vetrano S, Fiorino G, Beltrán B, Marabita F, Locati M, Spinelli A, Nos P, Invernizzi P, Danese S.

Identification of serum and tissue microRNA expression profiles in different stages of the inflammatory bowel disease.

Once-daily budesonide MMX in active, mild-to-moderate ulcerative colitis: results from the randomised CORE II study.

Clinical & Experimental Immunology 2013;173(2):250-8.

Raw IF: 3.409 Normalized IF: 4

Gut 2014;63(3):433-41.

Raw IF: 10.732

Invernizzi P*.

Normalized IF: 8

Tursi A, Brandimarte G, Elisei W, Picchio M, Forti G, Pianese G, Rodino S, D’Amico T, Sacca N, Portincasa P, Capezzuto E, Lattanzio R, Spadaccini A, Fiorella S, Polimeni F, Polimeni N, Stoppino V, Stoppino G, Giorgetti GM, Aiello F, Danese S.

Randomised clinical trial: mesalazine and/or probiotics in maintaining remission of symptomatic uncomplicated diverticular disease - a double-blind, randomised, placebo-controlled study.

Alimentary Pharmacology & Therapeutics 2013;38(7):741-51.

Raw IF: 4.548 Normalized IF: 6

Journal of Crohn’s & Colitis 2014;8(1):5-18.

Raw IF: 3.385 Normalized IF: 6

Spinelli A*, Fiorino G, Bazzi P, Sacchi M, Bonifacio C, De Bastiani S, Malesci A, Balzarini L, Peyrin-Biroulet L, Montorsi M, Danese S.

Chen RC, Naiyanetr P, Shu SA, Wang J, Yang GX, Kenny TP, Guggenheim KC, Butler JD, Bowlus C, Tao MH, Kurth MJ, Ansari AA, Kaplan M, Coppel RL, Lleo A, Gershwin ME, Leung PS.

Hepatobiliary Immunopathology Ando Y, Yang GX, Kenny TP, Kawata K, Zhang W, Huang W, Leung PS, Lian ZX, Okazaki K, Ansari AA, He XS, Invernizzi P, Ridgway WM, Lu Q, Gershwin ME.

Overexpression of microRNA-21 is associated with elevated proinflammatory cytokines in dominantnegative TGF-β receptor type II mouse.

Journal of Autoimmunity 2013;41:111-9.

Raw IF: 8.145 Normalized IF: 4

Intrahepatic cholestasis of pregnancy: a further important step in dissecting its genetic architecture.

Digestive and Liver Disease 2013; 45(3):266-7.

Raw IF: 3.162 Normalized IF: 4

Invernizzi P*.

Liver auto-immunology: the paradox of autoimmunity in a tolerogenic organ.

Journal of Autoimmunity 2013;46:41791.

Raw IF: 8.145 Normalized IF: 8

Invernizzi P, Bernuzzi F, Lleo A, Pozzoli V, Bignotto M, Zermiani P, Crosignani A, Battezzati PM, Zuin M, Podda M, Raggi C*.

Telomere dysfunction in peripheral blood mononuclear cells from patients with primary biliary cirrhosis.

Digestive and Liver Disease 2014; 46(4):363-8.

Raw IF: 3.162 Normalized IF: 4

Invernizzi P*, Bossuyt X, Bogdanos DP.

Serum autoantibodies: from identification to clinical relevance.

Clinical & Developmental Immunology 2013:382069.

Raw IF: 1.838 Normalized IF: 1

Bogdanos DP, Smyk DS, Invernizzi P, Rigopoulou EI, Blank M, Sakkas L, Pouria S, Shoenfeld Y.

Invernizzi P, Gershwin ME.

Tracing environmental markers of autoimmunity: introducing the infectome.

Liver International 2014;34(2):167-70.

Raw IF: 3.87 Normalized IF: 6

Immunologic Research 2013;56(2-3):220-40.

Raw IF: 2.963 Normalized IF: 2

New therapeutics in primary biliary cirrhosis: will there ever be light?

87

Papers published 2013

Kar SP, Seldin MF, Chen W, Lu E, Hirschfield GM, Invernizzi P, Heathcote J, Cusi D; the Italian PBC Genetics Study Group, Almasio PL, Alvaro D, Andreone P, Andriulli A, Barlassina C, Benedetti A, Bernuzzi F, Bianchi I, Bragazzi M, Brunetto M, Bruno S, Caliari L, Casella G, Coco B, Colli A, Colombo M, Colombo S, Cursaro C, Croce LS, Crosignani A, Donato F, Elia G, Fabris L, Floreani A, Galli A, Grattagliano I, Lazzari R, Lleo A, Macaluso F, Marra F, Marzioni M, Mascia E, Mattalia A, Montanari R, Morini L, Morisco F, Muratori L, Muratori P, Niro G, Picciotto A, Podda M, Portincasa P, Prati D, Raggi C, Rosina F, Rossi S, Sogno I, Spinzi G, Strazzabosco M, Tarallo S, Tarocchi M, Tiribelli C, Toniutto P, Vinci M, Zuin M, Gershwin ME, Siminovitch KA, Amos CI.

Pathway-based analysis of primary biliary cirrhosis genome-wide association studies.

Genes and Immunity 2013;14(3):179-86.

Raw IF: 3.675 Normalized IF: 6

Liu JZ, Hov JR, Folseraas T, Ellinghaus E, Rushbrook SM, Doncheva NT, Andreassen OA, Weersma RK, Weismüller TJ, Eksteen B, Invernizzi P, Hirschfield GM, Gotthardt DN, Pares A, Ellinghaus D, Shah T, Juran BD, Milkiewicz P, Rust C, Schramm C, Müller T, Srivastava B, Dalekos G, Nöthen MM, Herms S, Winkelmann J, Mitrovic M, Braun F, Ponsioen CY, Croucher PJ, Sterneck M, Teufel A, Mason AL, Saarela J, Leppa V, Dorfman R, Alvaro D, Floreani A, Onengut-Gumuscu S, Rich SS, Thompson WK, Schork AJ, Næss S, Thomsen I, Mayr G, König IR, Hveem K, Cleynen I, GutierrezAchury J, Ricaño-Ponce I, van Heel D, Björnsson E, Sandford RN, Durie PR, Melum E, Vatn MH, Silverberg MS, Duerr RH, Padyukov L, Brand S, Sans M, Annese V, Achkar JP, Boberg KM, Marschall HU, Chazouillères O, Bowlus CL, Wijmenga C, Schrumpf E, Vermeire S, Albrecht M; UK-PSCSC Consortium; International IBD Genetics Consortium, Rioux JD, Alexander G, Bergquist A, Cho J, Schreiber S, Manns MP, Färkkilä M, Dale AM, Chapman RW, Lazaridis KN; International PSC Study Group, Franke A, Anderson CA, Karlsen TH.

Dense genotyping of immune-related disease regions identifies nine new risk loci for primary sclerosing cholangitis.

Nature Genetics 2013;45(6):670-5.

Raw IF: 35.209 Normalized IF: 15

Lleo A, Oertelt-Prigione S, Bianchi I, Caliari L, Finelli P, Miozzo M, Lazzari R, Floreani A, Donato F, Colombo M, Gershwin ME, Podda M, Invernizzi P*.

Y chromosome loss in male patients with primary biliary cirrhosis.

Journal of Autoimmunity 2013;41:87-91.

Raw IF: 8.145 Normalized IF: 8

Mantovani A, Sica A, Invernizzi P.

Macrophage plasticity and polarizaton in liver homeostasis and pathology.

Hepatology 2014;59(5):2034-42.

Raw IF: 12.003 Normalized IF: 10

Podda M, Selmi C, Lleo A, Moroni L, Invernizzi P*.

The limitations and hidden gems of the epidemiology of primary biliary cirrhosis.

Journal of Autoimmunity 2013;46:81-7.

Raw IF: 8.145 Normalized IF: 8

Raggi C*, Invernizzi P.

Methylation and liver cancer.

Clinics and Research in Hepatology and Gastroenterology 2013;37(6):564-71.

Raw IF: 1.348 Normalized IF: 1

Molecular Gastroenterology Celesti G, Di Caro G, Bianchi P, Grizzi F, Basso G, Marchesi F, Doni A, Marra G, Roncalli M, Mantovani A, Malesci A*, Laghi L.

Presence of Twist1-positive neoplastic cells in the stroma of chromosomeunstable colorectal tumors.

Gastroenterology 2013;145(3):647-57.

Raw IF: 12.821 Normalized IF: 10

Celesti G, Di Caro G, Bianchi P, Grizzi F, Marchesi F, Basso G, Rahal D, Delconte G, Catalano M, Cappello P, Roncalli M, Zerbi A, Montorsi M, Novelli F, Mantovani A, Allavena P, Malesci A*, Laghi L.

Early expression of the fractalkine receptor CX3CR1 in pancreatic carcinogenesis.

British Journal of Cancer 2013;109(9):2424-33.

Raw IF: 5.082 Normalized IF: 6

Lleo A*, Invernizzi P.

88

Apotopes and innate immune system: novel players in the primary biliary cirrhosis scenario.

Di Caro G, Marchesi F, Laghi L, Grizzi F.

Digestive and Liver Disease 2013; 45(8):630-6.

Raw IF: 3.162 Normalized IF: 4

Journal of Cellular and Molecular Medicine 2013;17(9):1088-95.

Raw IF: 4.753 Normalized IF: 6

Immune cells: plastic players along colorectal cancer progression.

Di Ieva A, Bruner E, Davidson J, Pisano P, Haider T, Stone SS, Cusimano MD, Tschabitscher M, Grizzi F.

Cranial sutures: a multidisciplinary review.

Child’s Nervous System 2013;29(6):893-905.

Raw IF: 1.241 Normalized IF: 2

Di Ieva A, Bruner E, Widhalm G, Minchev G, Tschabitscher M, Grizzi F.

Computer-assisted and fractalbased morphometric assessment of microvascularity in histological specimens of gliomas.

Scientific Reports 2012;2:429.

Raw IF: 2.927 Normalized IF: 6

Di Ieva A, Grizzi F, Jelinek H, Pellionisz AJ, Losa AG.

Fractals in the neurosciences, part I: general principles and basic neurosciences.

Neuroscientist Epub 2013;Dec 20.

Raw IF: 5.633 Normalized IF: 6

Di Ieva A, Esteban FJ, Grizzi F, MartínLandrove M, Klonowski W.

Fractals in the neurosciences, part II: clinical applications and future perspectives.

Neuroscientist Epub 2013;Dec 20.

Raw IF: 5.633 Normalized IF: 3

Di Ieva A, Weckman A, Di Michele J, Rotondo F, Grizzi F, Kovacs K, Cusimano MD.

Microvascular morphometrics of the hypophysis and pituitary tumors: From bench to operating theatre.

Microvascular Research 2013;89:41821.

Raw IF: 2.929 Normalized IF: 2

Galon J, Mlecnik B, Bindea G, Angell HK, Berger A, Lagorce C, Lugli A, Zlobec I, Hartmann A, Bifulco C, Nagtegaal ID, Palmqvist R, Masucci GV, Botti G, Tatangelo F, Delrio P, Maio M, Laghi L, Grizzi F, Asslaber M, D’Arrigo C, VidalVanaclocha F, Zavadova E, Chouchane L, Ohashi PS, Hafezi-Bakhtiari S, Wouters BG, Roehrl M, Nguyen L, Kawakami Y, Hazama S, Okuno K, Ogino S, Gibbs P, Waring P, Sato N, Torigoe T, Itoh K, Patel PS, Shukla SN, Wang Y, Kopetz S, Sinicrope FA, Scripcariu V, Ascierto PA, Marincola FM, Fox BA, Pagès F.

Towards the introduction of the Immunoscore in the classification of malignant tumors.

Journal of Pathology 2014;232(2):199-209.

Raw IF: 7.585 Normalized IF: 4

Grizzi F, Bianchi P, Malesci A, Laghi L.

Taverna G, Grizzi F, Colombo P, Graziotti P.

Prognostic value of innate and adaptive immunity in colorectal cancer.

Is angiogenesis a hallmark of prostate cancer?

World Journal of Gastroenterology 2013;19(2):174-84.

Raw IF: 2.547 Normalized IF: 4

Frontiers in Oncology 2013;3:15.

Raw IF: 0 Normalized IF: 0

Grizzi F, Chiriva-Internati M.

Translating sperm protein 17 as a target for immunotherapy from the bench to the bedside in the light of cancer complexity.

Tissue Antigens 2013;81(2):116-8.

Raw IF: 2.934 Normalized IF: 3

Grizzi F, Di Biccari S, Fiamengo B, Štifter S, Colombo P.

Pituitary tumor-transforming gene 1 is expressed in primary ductal breast carcinoma, lymph node infiltration and distant metastases.

Disease Markers 2013;35(4):267-72.

Raw IF: 2.14 Normalized IF: 4

Grizzi F, Di Caro G, Laghi L, Hermonat P, Mazzola P, Nguyen DD, Radhi S, Figueroa JA, Cobos E, Annoni G, Chiriva-Internati M.

Mast cells and the liver aging process.

Immunity and Ageing 2013;10(1):9.

Raw IF: 0 Normalized IF: 0

Taverna G*, Magnoni P, Giusti G, Seveso M, Benetti A, Hurle R, Colombo P, Minuti F, Grizzi F, Graziotti P.

Impact of real-time elastography versus systematic prostate biopsy method on cancer detection rate in men with a serum Prostate-Specific Antigen between 2 5 and 10 ng/mL. ISRN Oncology 2013;584672.

Raw IF: 0 Normalized IF: 0

Wouters MM, Lambrechts D, Becker J, Cleynen I, Tack J, Vigo AG, Ruiz de León A, Urcelay E, Pérez de la Serna J, Rohof W, Annese V, Latiano A, Palmieri O, Mattheisen M, Mueller M, Lang H, Fumagalli U, Laghi L, Zaninotto G, Cuomo R, Sarnelli G, Nöthen MM, Vermeire S, Knapp M, Gockel I, Schumacher J, Boeckxstaens GE.

Genetic variation in the lymphotoxin-α (LTA)/tumour necrosis factor-α (TNFα) locus as a risk factor for idiopathic achalasia.

Gut Epub 2013;Nov 20.

Raw IF: 10.732

Normalized IF: 4

Grizzi F*, Di Ieva A.

Rethinking immunotherapy for brain cancers in the light of cancer complexity.

Indian Journal of Medical Research 2013;137(5):871-3.

Raw IF: 2.061 Normalized IF: 6

Piazzi G, Selgrad M, Garcia M, Ceccarelli C, Fini L, Bianchi P, Laghi L, D’Angelo L, Paterini P, Malfertheiner P, Chieco P, Boland CR, Bazzoli F, Ricciardiello L.

Van-Gogh-like 2 antagonises the canonical WNT pathway and is methylated in colorectal cancers.

British Journal of Cancer 2013;108(8):1750-6.

Raw IF: 5.082 Normalized IF: 3

Taverna G, Giusti G, Seveso M, Hurle R, Colombo P, Stifter S, Grizzi F*.

Mast cells as a potential prognostic marker in prostate cancer.

Disease Markers 2013;35(6):711-20.

Raw IF: 2.14 Normalized IF: 4

Oncology Experimental Therapies Carlo-Stella C*, Locatelli SL, Giacomini A, Cleris L, Saba E, Righi M, Guidetti A, Gianni AM.

Sorafenib inhibits lymphoma xenografts by targeting MAPK/ERK and AKT pathways in tumor and vascular cells.

PLoS One 2013;8(4):e61603.

Raw IF: 3.73 Normalized IF: 6

Devizzi L, Guidetti A, Seregni E, Passera R, Maccauro M, Magni M, Testi A, Di Nicola M, Tarella C, Matteucci P, Viviani S, Ruella M, Carlo-Stella C, Chiesa C, Cox MC, Bombardieri E, Gianni AM.

Long-term results of autologous haematopoietic stem-cell transplantation after high-dose 90Y-ibritumomab tiuxetan for patients with poor-risk non-Hodgkin lymphoma not eligible for high-dose BEAM. Journal of Clinical Oncology 2013;31(23):2974-6.

Raw IF: 18.038 Normalized IF: 7.5

Farina L, Spina F, Guidetti A, Longoni P, Ravagnani F, Dodero A, Montefusco V, Carlo-Stella C, Corradini P.

Peripheral blood CD34+ cell monitoring after cyclophosphamide and granulocyte-colony-stimulating factor: an algorithm for the pre-emptive use of plerixafor.

Leukemia and Lymphoma 2014;55(1):331-6.

Raw IF: 2.301 Normalized IF: 1

Giacomini A, Righi M, Cleris L, Locatelli SL, Mitola S, Daidone MG, Gianni AM, Carlo-Stella C*.

Induction of death receptor 5 expression in tumor vasculature by perifosine restores the vascular disruption activity of TRAIL-expressing CD34+ cells.

Angiogenesis 2013;16(3):707-22.

Raw IF: 3.972 Normalized IF: 6

Locatelli SL, Giacomini A, Guidetti A, Cleris L, Mortarini R, Anichini A, Gianni AM, Carlo-Stella C*.

Perifosine and sorafenib combination induces mitochondrial cell death and antitumor effects in NOD/SCID mice with Hodgkin lymphoma cell line xenografts.

Leukemia 2013;27(8):1677-87.

Raw IF: 10.164 Normalized IF: 8

Marconi M, Ascione B, Ciarlo L, Vona R, Garofalo T, Sorice M, Gianni AM, Locatelli SL, Carlo-Stella C, Malorni W, Matarrese P.

Constitutive localization of DR4 in lipid rafts is mandatory for TRAIL-induced apoptosis in B-cell haematologic malignancies.

Cell Death and Disease 2013;4:e863.

Raw IF: 6.044 Normalized IF: 3

Pierdominici M, Barbati C, Vomero M, Locatelli SL, Carlo-Stella C, Ortona E, Malorni W.

Autophagy as pathogenic mechanism and drug target in lymphoproliferative disorders.

Faseb Journal 2014;28(2):524-35.

Raw IF: 5.704 Normalized IF: 3

Righi M, Giacomini A, Cleris L, CarloStella C.

3D Quantification of tumor vasculature in lymphoma xenografts in NOD/SCID mice allows to detect differences among vascular-targeted therapies.

PLoS One 2013;8(3):e59691.

Raw IF: 3.73 Normalized IF: 6

89

Papers published 2013 * = Corresponding author

C l i n i c a l

Breast Unit Garcia-Etienne CA*, Tomatis M, Heil J, Danaei M, Rageth CJ, Marotti L, Rosselli Del Turco M, Ponti A.

Fluctuating mastectomy rates across time and geography.

Annals of Surgical Oncology 2013;20(7):2114-6.

Raw IF: 4.12 Normalized IF: 6

Gatzemeier W, Bruce Mann G.

Which sentinel lymph-node (SLN) positive breast cancer patient needs an axillary lymph-node dissection (ALND) ACOSOG Z0011 results and beyond.

Breast 2013;22(3):211-6.

Raw IF: 1.967

Normalized IF: 4

Heil J, Rauch G, Szabo AZ, Garcia-Etienne CA, Golatta M, Domschke C, Badiian M, Kern P, Schuetz F, Wallwiener M, Sohn C, Fries H, von Minckwitz G, Schneeweiss A, Rezai M.

Breast cancer mastectomy trends between 2006 and 2010: association with magnetic resonance imaging, immediate breast reconstruction, and hospital volume.

Annals of Surgical Oncology 2013;20(12):3839-46.

Raw IF: 4.12 Normalized IF: 6

Tinterri C, Gatzemeier W*, Costa A, Gentilini MA, Zanini V, Regolo L, Pedrazzoli C, Rondini E, Amanti C, Gentile G, Taffurelli M, Fenaroli P, Tondini C, Sacchetto G, Sismondi P, Murgo R, Orlandi M, Cianchetti E, Andreoli C.

Breast-conservative surgery with and without radiotherapy in patients aged 55-75 years with early-stage breast cancer: a prospective, randomized, multicenter trial analysis after 108 months of median follow-up.

Annals of Surgical Oncology 2014;21(2):408-15.

Raw IF: 4.12 Normalized IF: 6

R e s e a r c h

Torrisi R*, Garcia-Etienne CA, Losurdo A, Morenghi E, Di Tommaso L, Gatzemeier W, Sagona A, Fernandes B, Rossetti C, Eboli M, Rubino A, Barbieri E, Andreoli C, Orefice S, Gandini C, Rota S, Zuradelli M, Masci G, Santoro A, Tinterri C.

Potential impact of the 70-gene signature in the choice of adjuvant systemic treatment for ER positive, HER2 negative tumors: a single institution experience.

Breast 2013;22(4):419-24.

Raw IF: 1.967 Normalized IF: 4

cardiac surgery Barbone A, Pini D, Rega F, Ornaghi D, Vitali E, Meyns B.

Circulatory support in elderly chronic heart failure patients using the CircuLite(R) Synergy(R) system.

European Journal of Cardio-Thoracic Surgery 2013;44(2):207-12.

Raw IF: 2.674 Normalized IF: 6

Gaita F, Ebrille E, Scaglione M, Caponi D, Garberoglio L, Vivalda L, Barbone A, Gallotti R.

Very long-term results of surgical and transcatheter ablation of long-standing persistent atrial fibrillation.

Reoperation after acute type a aortic dissection repair: a series of 104 patients.

Annals of Thoracic Surgery 2013;95(3):922-7.

Raw IF: 3.454 Normalized IF: 6

Raffa GM, Malvindi PG, Ornaghi D, Citterio E, Cappai A, Basciu A, Barbone A, Fossati F, Tarelli G, Settepani F.

Minimally invasive direct coronary artery bypass in the era of percutaneous coronary intervention.

Journal of Cardiovascular Medicine Epub 2013;Jul 19.

Raw IF: 2.657 Normalized IF: 4

Raffa GM*, Settepani F.

Conversion to sternotomy during sternal-sparing coronary artery surgery.

Journal of Cardiac Surgery 2013;28(4):386-7.

Raw IF: 1.351 Normalized IF: 2

Raffa GM*, Tarelli G, Balzarini L, Torta D, Monti L.

Hamartoma of mature cardiac myocytes: a cardiac tumour with preserved contractility.

European Heart Journal Cardiovascular Imaging 2013;14(12):1216.

Raw IF: 0 Normalized IF: 0

Annals of Thoracic Surgery 2013;96(4):1273-8.

Raw IF: 3.454 Normalized IF: 3

Malvindi PG*, Cappai A, Raffa GM, Barbone A, Basciu A, Citterio E, Ornaghi D, Tarelli G, Settepani F.

Analysis of postsurgical aortic false aneurysm in 27 patients.

Texas Heart Institute Journal 2013; 40(3):274-80.

Raw IF: 0.674 Normalized IF: 1

Malvindi PG*, Raffa GM, Cappai A, Barbone A, Basciu A, Settepani F, Citterio E, Ornaghi D, Tarelli G, Vitali E.

Mitral and aortic valve prosthetic endocarditis after percutaneous closure of mitral paravalvular leak.

90

Malvindi PG*, van Putte BP, Sonker U, Heijmen RH, Schepens MA, Morshuis WJ.

Annals of Thoracic Surgery 2013;95(2):e45-6.

Raw IF: 3.454 Normalized IF: 6

Clinical Cardiology Barbone A, Pini D, Rega F, Ornaghi D, Vitali E, Meyns B.

Circulatory support in elderly chronic heart failure patients using the CircuLite(R) Synergy(R) system.

European Journal of Cardio-Thoracic Surgery 2013;44(2):207-12.

Raw IF: 2.674 Normalized IF: 6

Coronary Care Corrada E, Mennuni MG, Grieco N, Sesana G, Beretta G, Presbitero P.

Neurological recovery after outof-hospital cardiac arrest: hospital admission predictors and one-year survival in an urban cardiac network experience.

Minerva Cardioangiologica 2013;61(4): 451-60.

Raw IF: 0.427 Normalized IF: 1

Zavalloni D*, Lisignoli V, Barbaro C, Mennuni M, Tosi P, Marcheselli S, Presbitero P.

Platypnoea-orthodeoxia syndrome secondary to patent foramen ovale (PFO): a challenging subset for PFO percutaneous closure.

Heart, Lung & Circulation 2013;22(8):642-6.

Raw IF: 1.254 Normalized IF: 2

Diagnostic Radiology Appleby BS, Lu M, Bizzi A, Phillips MD, Berri SM, Harbison MD, Schonberger LB.

Iatrogenic Creutzfeldt-Jakob disease from commercial cadaveric human growth hormone.

Emerging Infectious Diseases 2013;19(4):682-4.

Raw IF: 5.993 Normalized IF: 3

Field JK, van Klaveren R, Pedersen JH, Pastorino U, Paci E, Becker N, Infante M, Oudkerk M, de Koning HJ; on behalf of the European Randomized Screening Trial Group. (Collaborators: Brambilla G, Lutman F, Santoro A, Chiti A, Morenghi E, Destro A, Roncalli M, Marco Alloisio).

European randomized lung cancer screening trials: post NLST. Journal of Surgical Oncology 2013;108(5):280-6.

Raw IF: 2.644 Normalized IF: 3

Jovani M, Baticci F, Bonifacio C, Omodei PD, Malesci A*.

Abdominal cocoon or idiopathic encapsulating peritoneal sclerosis: magnetic resonance imaging.

Spinelli A*, Fiorino G, Bazzi P, Sacchi M, Bonifacio C, De Bastiani S, Malesci A, Balzarini L, Peyrin-Biroulet L, Montorsi M, Danese S.

Digestive and Liver Disease 2014;46(2):192-3.

Raw IF: 3.162 Normalized IF: 2

Preoperative magnetic resonance enterography in predicting findings and optimizing surgical approach in Crohn’s disease.

Lopci E*, Monti L, Balzarini L, Chiti A.

Journal of Gastrointestinal Surgery 2014;18(1):83-90.

Raw IF: 2.361 Normalized IF: 6

Cardiac and acoustic metastases in relapsing melanoma.

Clinical Nuclear Medicine 2013;38(2):e85-8.

Raw IF: 2.955 Normalized IF: 6

Mauri G, Michelozzi C, Melchiorre F, Poretti D, Tramarin M, Pedicini V, Solbiati L, Cornalba G, Sconfienza LM.

Biodegradable biliary stent implantation in the treatment of benign bilioplasticrefractory biliary strictures: preliminary experience.

Digestive Endoscopy Service Annese V, Daperno M, Rutter MD, Amiot A, Bossuyt P, East J, Ferrante M, Götz M, Katsanos KH, Kießlich R, Ordás I, Repici A, Rosa B, Sebastian S, Kucharzik T, Eliakim R; ECCO.

European Radiology 2013;23(12):3304-10.

Raw IF: 3.548 Normalized IF: 6

European evidence based consensus for endoscopy in inflammatory bowel disease.

Raffa GM*, Tarelli G, Balzarini L, Torta D, Monti L.

Journal of Crohn’s and Colitis 2013;7(12):982-1018.

Raw IF: 3.385 Normalized IF: 3

Hamartoma of mature cardiac myocytes: a cardiac tumour with preserved contractility.

European Heart Journal Cardiovascular Imaging 2013;14(12):1216.

Raw IF: 0 Normalized IF: 0

Rimassa L*, Pressiani T, Boni C, Carnaghi C, Rota Caremoli E, Fagiuoli S, Foa P, Salvagni S, Cortesi E, Chiara Tronconi M, Personeni N, Bozzarelli S, Chiara Banzi M, Fanello S, Romano Lutman F, Giordano L, Santoro A.

A phase II randomized dose escalation trial of sorafenib in patients with advanced hepatocellular carcinoma.

Oncologist 2013;18(4):379-80.

Raw IF: 4.095 Normalized IF: 6

Cammarota T, Ribaldone DG, Resegotti A, Repici A, Danese S, Fiorino G, Sarno A, Robotti D, Debani P, Bonenti G, Pellicano R, Andrealli A, Sapone N, Simondi D, Bresso F, Astegiano M.

Role of bowel ultrasound as a predictor of surgical recurrence of Crohn’s disease.

Scandinavian Journal of Gastroenterology 2013;48(5):552-5.

Raw IF: 2.156 Normalized IF: 4

Fuccio L, Hassan C, Laterza L, Correale L, Pagano N, Bocus P, Fabbri C, Maimone A, Cennamo V, Repici A, Costamagna G, Bazzoli F, Larghi A.

The role of K-ras gene mutation analysis in EUS-guided FNA cytology specimens for the differential diagnosis of pancreatic solid masses: a meta-analysis of prospective studies.

Gastrointestinal Endoscopy 2013; 78(4):596-608.

Raw IF: 5.21 Normalized IF: 3

91

Papers published 2013

Hassan C, Pooler BD, Kim DH, Rinaldi A, Repici A, Pickhardt PJ.

Ricci E*, Hassan C, Petruzziello L, Bazzoli F, Repici A, Di Giulio E.

Computed tomographic colonography for colorectal cancer screening: risk factors for the detection of advanced neoplasia.

Inter-centre variability of the adenoma detection rate: a prospective, multicentre study.

Cancer 2013;119(14):2549-54.

Raw IF: 5.201 Normalized IF: 3

Hassan C, Repici A, Zullo A, Kanakadandi V, Sharma P.

Colonic polyps : are we ready to resect and discard?

Gastrointestinal Endoscopy Clinics of North America 2013;23(3):663-78.

Raw IF: 0 Normalized IF: 0

Sharma P, Gupta N, Kuipers EJ, Repici A, Wallace M.

Advanced imaging in colonoscopy and its impact on quality.

ISRN Oncology 2013;584672.

Raw IF: 0 Normalized IF: 0

Gastrointestinal Endoscopy 2014;79(1):28-36.

Raw IF: 5.21 Normalized IF: 3

Hassan C, Repici A, Zullo A, Sharma P.

New paradigms for colonoscopic management of diminutive colorectal polyps: predict, resect, and discard or do not resect?

Complications of endoscopic ultrasound fine needle aspiration on pancreatic cystic lesions: final results from a large prospective multicenter study.

Clinical Endoscopy 2013;46(2):130-7.

Raw IF: 0 Normalized IF: 0

Digestive and Liver Disease 2014;46(1):41-4.

Raw IF: 3.162 Normalized IF: 4

Repici A, Hassan C, Radaelli F, Occhipinti P, De Angelis C, Romeo F, Paggi S, Saettone S, Cisarò F, Spaander M, Sharma P, Kuipers EJ.

Tringali A, Didden P, Repici A, Spaander M, Bourke MJ, Williams SJ, Spicak J, Drastich P, Mutignani M, Perri V, Roy A, Johnston K, Costamagna G.

Accuracy of narrow-band imaging in predicting colonoscopy surveillance intervals and histology of distal diminutive polyps: results from a multicenter, prospective trial.

Endoscopic treatment of malignant gastric and duodenal strictures: a prospective, multicenter study.

Repici A, Pagano N, Rando G, Carlino A, Vitetta E, Ferrara E, Strangio G, Zullo A, Hassan C.

A retrospective analysis of early and late outcome of biodegradable stent placement in the management of refractory anastomotic colorectal strictures.

Birnie D, Lemke B, Aonuma K, Krum H, Lee KL, Gasparini M, Starling RC, Milasinovic G, Gorcsan J 3rd, Houmsse M, Abeyratne A, Sambelashvili A, Martin DO.

Clinical outcomes with synchronized left ventricular pacing: analysis of the adaptive CRT trial.

Heart Rhythm 2013;10(9):1368-74.

Raw IF: 5.045 Normalized IF: 3

Boriani G, Glotzer TV, Santini M, West TM, De Melis M, Sepsi M, Gasparini M, Lewalter T, Camm JA, Singer DE.

Zullo A, Hassan C, Repici A, Annibale B.

Intestinal metaplasia surveillance: searching for the road-map.

European Heart Journal 2014;35(8):508-16.

Raw IF: 14.097 Normalized IF: 5

World Journal of Gastroenterology 2013;19(10):1523-6.

Raw IF: 2.547 Normalized IF: 2

Zullo A, Hassan C, Repici A, Bruzzese V.

Helicobacter pylori eradication and reflux disease onset: did gastric acid get “crazy”?

Repici A, Zullo A, Hassan C, Spaggiari P, Strangio G, Vitetta E, Ferrara E, Malesci A.

World Journal of Gastroenterology 2013;19(6):786-9.

Raw IF: 2.547 Normalized IF: 2

European Journal of Gastroenterology & Hepatology 2013;25(11):1261-4.

Raw IF: 1.915 Normalized IF: 2

Electrophysiology and Electrostimulation

Device-detected atrial fibrillation and risk for stroke: an analysis of >10 000 patients from the SOS AF project (Stroke preventiOn Strategies based on Atrial Fibrillation information from implanted devices).

Gastrointestinal Endoscopy 2014;30(1):66-75.

Raw IF: 5.21 Normalized IF: 3

Surgical Endoscopy 2013;27(7):2487-91.

Raw IF: 3.427 Normalized IF: 6

Endoscopic submucosal dissection of early gastric neoplastic lesions: a western series.

Taverna G*, Magnoni P, Giusti G, Seveso M, Benetti A, Hurle R, Colombo P, Minuti F, Grizzi F, Graziotti P.

Impact of real-time elastography versus systematic prostate biopsy method on cancer detection rate in men with a serum Prostate-Specific Antigen between 2 5 and 10 ng/mL.

Tarantino I, Fabbri C, Di Mitri R, Pagano N, Barresi L, Mocciaro F, Maimone A, Curcio G, Repici A, Traina M.

Gastrointestinal Endoscopy 2013;78(1):106-14.

Raw IF: 5.21 Normalized IF: 6

92

Digestive and Liver Disease 2013;45(12):1022-7.

Raw IF: 3.162 Normalized IF: 2

Echography

Gasparini M*.

Letter to the Editor: Survival after shock therapy in ICD and CRT-D recipients according to rhythm shocked: ALTITUDE Survival by Rhythm Study.

Journal of American College of Cardiology 2013;62(18):1674-9.

Raw IF: 14.086 Normalized IF: 5

Gasparini M, Boriani G.

Letter by Gasparini and Boriani regarding the article: Cardiac resynchronization therapy in patients with permanent atrial fibrillation: results from the Resynchronization for Ambulatory Heart Failure Trial (RAFT).

Circulation. Heart Failure 2013;6(2):e22.

Raw IF: 6.684 Normalized IF: 3

Gasparini M*, Galimberti P.

Device therapy in heart failure: has CRT changed “the sickest benefit the most” to “the healthiest benefit the most?”

Journal of the American College of Cardiology 2013;61(9):945-7.

Raw IF: 14.086 Normalized IF: 10

Gasparini M, Leclercq C, Yu CM, Auricchio A, Steinberg JS, Lamp B, Klersy C, Leyva F.

Absolute survival after cardiac resynchronization therapy according to baseline QRS duration: a multi-national, ten-year experience data from the MULIN-CRT (Multicenter International -CRT) Study.

American Heart Journal 2014;167(2):203-9.e1.

Raw IF: 4.497 Normalized IF: 6

Gasparini M, Proclemer A, Klersy C, Kloppe A, Lunati M, Ferrer JB, Hersi A, Gulaj M, Wijfels MC, Santi E, Manotta L, Arenal A.

Effect of long-detection interval vs standard-detection interval for implantable cardioverter-defibrillators on antitachycardia pacing and shock delivery: the ADVANCE III randomized clinical trial.

JAMA 2013;309(18):1903-11.

Raw IF: 29.978 Normalized IF: 15

Morani G, Gasparini M, Zanon F, Casali E, Spotti A, Reggiani A, Bertaglia E, Solimene F, Molon G, Accogli M, Tommasi C, Paoletti Perini A, Ciardiello C, Padeletti L.

Cardiac resynchronization therapydefibrillator improves long-term survival compared with cardiac resynchronization therapy-pacemaker in patients with a class IA indication for cardiac resynchronization therapy: data from the Contak Italian Registry.

Europace 2013;15(9):1273-9.

Raw IF: 3 Normalized IF: 4

Emergency Neurology and Stroke Unit

Cappellari M, Bovi P, Moretto G, Zini A, Nencini P, Sessa M, Furlan M, Pezzini A, Orlandi G, Paciaroni M, Tassinari T, Procaccianti G, Di Lazzaro V, Bettoni L, Gandolfo C, Silvestrelli G, Rasura M, Martini G, Melis M, Calloni MV, ChiodoGrandi F, Beretta S, Guarino M, Altavista MC, Marcheselli S, Galletti G, Adobbati L, Del Sette M, Mancini A, Orrico D, Monaco S, Cavallini A, Sciolla R, Federico F, Scoditti U, Brusaferri F, Grassa C, Specchio L, Bongioanni MR, Sparaco M, Zampolini M, Greco G, Colombo R, Passarella B, Adami A, Consoli D, Toni D.

Celesti G, Di Caro G, Bianchi P, Grizzi F, Marchesi F, Basso G, Rahal D, Delconte G, Catalano M, Cappello P, Roncalli M, Zerbi A, Montorsi M, Novelli F, Mantovani A, Allavena P, Malesci A*, Laghi L. (Celesti and Di Caro contributed equally to this work)

The THRombolysis and STatins (THRaST) study.

Grizzi F*, Bianchi P, Malesci A, Laghi L.

Neurology 2013;80(7):655-61.

Raw IF: 8.249 Normalized IF: 8

Cavallini A, Tartara E, Marcheselli S, Agostoni E, Quaglini S, Micieli G.

Improving thrombolysis for acute ischemic stroke in Lombardia stroke centers.

Neurological Sciences 2013;34(7):1227-33.

Raw IF: 1.412 Normalized IF: 2

Ciccone A, Valvassori L, Nichelatti M, Sgoifo A, Ponzio M, Sterzi R, Boccardi E; SYNTHESIS Expansion Investigators.

(Collaborators: Marcheselli S, Stival B, Presbitero P, Rossi ML, Belli G).

Endovascular treatment for acute ischemic stroke.

New England Journal of Medicine 2013;368(10):904-13.

Raw IF: 51.658 Normalized IF: 3

Zavalloni D*, Lisignoli V, Barbaro C, Mennuni M, Tosi P, Marcheselli S, Presbitero P.

Platypnoea-orthodeoxia syndrome secondary to patent foramen ovale (PFO): a challenging subset for PFO percutaneous closure.

Heart, Lung & Circulation 2013;22(8):642-6.

Raw IF: 1.254 Normalized IF: 2

Berk JL, Suhr OB, Obici L, Sekijima Y, Zeldenrust SR, Yamashita T, Heneghan MA, Gorevic PD, Litchy WJ, Wiesman JF, Nordh E, Corato M, Lozza A, Cortese A, Robinson-Papp J, Colton T, Rybin DV, Bisbee AB, Ando Y, Ikeda S, Seldin DC, Merlini G, Skinner M, Kelly JW, Dyck PJ; Diflunisal Trial Consortium.

Celesti G, Di Caro G, Bianchi P, Grizzi F, Basso G, Marchesi F, Doni A, Marra G, Roncalli M, A. Mantovani A, Malesci A*, Laghi L.

Repurposing diflunisal for familial amyloid polyneuropathy: a randomized clinical trial.

Presence of Twist1-positive neoplastic cells in the stroma of chromosomeunstable colorectal tumors.

JAMA 2013;310(24):2658-67.

Raw IF: 29.978 Normalized IF: 15

Gastroenterology 2013;145(3):647-57.

Raw IF: 12.821 Normalized IF: 10

Gastroenterology and Digestive Endoscopy

Early expression of the fractalkine receptor CX3CR1 in pancreatic carcinogenesis.

British Journal of Cancer 2013;109(9):2424-33.

Raw IF: 5.082 Normalized IF: 6

Prognostic value of innate and adaptive immunity in colorectal cancer.

World Journal of Gastroenterology 2013;19(2);174-84.

Raw IF: 2.547 Normalized IF: 4

Grizzi F, Di Biccari S, Fiamengo B, Štifter S, Colombo P.

Pituitary tumor-transforming gene 1 is expressed in primary ductal breast carcinoma, lymph node infiltration and distant metastases.

Disease Markers 2013;35(4):267-72.

Raw IF: 2.14 Normalized IF: 4

Jovani M, Baticci F, Bonifacio C, Omodei PD, Malesci A*.

Abdominal cocoon or idiopathic encapsulating peritoneal sclerosis: magnetic resonance imaging.

Digestive and Liver Disease 2014;46(2);192-3.

Raw IF: 3.162 Normalized IF: 2

Repici A, Pagano N, Rando G, Carlino A, Vitetta E, Ferrara E, Strangio G, Zullo A, Hassan C.

A retrospective analysis of early and late outcome of biodegradable stent placement in the management of refractory anastomotic colorectal strictures.

Surgical Endoscopy 2013;27(7):2487-91.

Raw IF: 3.427 Normalized IF: 6

Repici A*, Zullo A, Hassan C, Spaggiari P, Strangio G, Vitetta E, Ferrara E, Malesci A.

Endoscopic submucosal dissection of early gastric neoplastic lesions: a western series.

European Journal of Gastroenterology & Hepatology 2013;25(11):1261-4.

Raw IF: 1.915 Normalized IF: 2

93

Papers published 2013

Salvioli B*, Pellicciari A, Iero L, Di Pietro E, Moscano F, Gualandi S, Stanghellini V, De Giorgio R, Ruggeri E, Franzoni E.

Audit of digestive complaints and psychopathological traits in patients with eating disorders: a prospective study.

Digestive and Liver Disease 2013;45(8):639-44.

Raw IF: 3.162 Normalized IF: 4

Spinelli A*, Fiorino G, Bazzi P, Sacchi M, Bonifacio C, De Bastiani S, Malesci A, Balzarini L, Peyrin-Biroulet L, Montorsi M, Danese S.

Preoperative magnetic resonance enterography in predicting findings and optimizing surgical approach in Crohn’s disease.

Journal of Gastrointestinal Surgery 2014;18(1):83-90.

Raw IF: 2.361 Normalized IF: 6

General and Minimally Invasive Surgery Fumagalli U*, Bersani M, Russo A, Melis A, de Pascale S, Rosati R.

Graziani G*, Cucchiari D, Podestà MA, Quagliuolo V, Montanelli A.

Volume and outcomes after esophageal cancer surgery: the experience of the Region of Lombardy-Italy.

Abdominal pain and increased CA19-9.

Updates Surgery 2013;65(4):271-5.

Raw IF: 0 Normalized IF: 0

Jovani M, Baticci F, Bonifacio C, Omodei PD, Malesci A*.

Abdominal cocoon or idiopathic encapsulating peritoneal sclerosis: magnetic resonance imaging.

Digestive and Liver Disease 2014;46(2):192-3.

Raw IF: 3.162 Normalized IF: 2

Siesto G*, Ieda N, Rosati R, Vitobello D.

Robotic surgery for deep endometriosis: a paradigm shift.

General Anaesthesia and Intensive Care Giustiniano E*, Malossini SE, Pellegrino F, Cancellieri F.

Subarachnoid fluid lactate and paraplegia after descending aorta aneurysmectomy: two compared case reports.

Case Reports in Anesthesiology; 2013:925739.

Raw IF: 0 Normalized IF: 0

Giustiniano E, Ruggieri N*, Battistini GM, Fusilli N, Pellegrino F, Giorgetti P, Bordoni MG, Bellato V, Bordone G.

May transient Positive End-Expiratory Pressure ameliorate hemodynamic setting and outcome after aortic surgery?

Journal of Anesthesia & Clinical Research 2012;3(11):1-5.

Raw IF: 0 Normalized IF: 0

Marchi A, Colombo R, Guzzetti S, Bari V, Bassani T, Raimondi F, Porta A.

Characterization of the cardiovascular control during modified head-up tilt test in healthy adult humans.

Autonomic Neuroscience: Basic & Clinical 2013;179(1-2):166-9.

Raw IF: 1.846 Normalized IF: 2

94

General and Oncologic Surgery

The International Journal of Medical Robotics + Computer Assisted Surgery: MRCAS Epub 2013;June 13.

Raw IF: 1.488 Normalized IF: 4

Spinelli A*, Fiorino G, Bazzi P, Sacchi M, Bonifacio C, De Bastiani S, Malesci A, Balzarini L, Peyrin-Biroulet L, Montorsi M, Danese S.

Preoperative magnetic resonance enterography in predicting findings and optimizing surgical approach in Crohn’s disease.

Journal of Gastrointestinal Surgery 2014;18(1):83-90.

Raw IF: 2.361 Normalized IF: 6

Wouters MM, Lambrechts D, Becker J, Cleynen I, Tack J, Vigo AG, Ruiz de León A, Urcelay E, Pérez de la Serna J, Rohof W, Annese V, Latiano A, Palmieri O, Mattheisen M, Mueller M, Lang H, Fumagalli U, Laghi L, Zaninotto G, Cuomo R, Sarnelli G, Nöthen MM, Vermeire S, Knapp M, Gockel I, Schumacher J, Boeckxstaens GE.

Genetic variation in the lymphotoxin-α (LTA)/tumour necrosis factor-α (TNFα) locus as a risk factor for idiopathic achalasia.

Gut Epub 2013;Nov 20.

Raw IF: 10.732

Normalized IF: 4

Clinical Chemistry 2013;59(11):1678-9.

Raw IF: 7.149 Normalized IF: 8

Gronchi A, Colombo C, Le Péchoux C, Dei Tos AP, Le Cesne A, Marrari A, Penel N, Grignani G, Blay JY, Casali PG, Stoeckle E, Gherlinzoni F, Meeus P, Mussi C, Gouin F, Duffaud F, Fiore M Bonvalot S; on behalf of ISG and FSG.

Sporadic desmoid-type fibromatosis: a stepwise approach to a nonmetastasising neoplasm. A position paper from the Italian and the French Sarcoma Group.

Annals of Oncology 2014;25(3):578-83.

Raw IF: 7.384 Normalized IF: 4

Jakob J, Mussi C, Ronellenfitsch U, Wardelmann E, Negri T, Gronchi A, Hohenberger P.

Gastrointestinal stromal tumor of the rectum: results of surgical and multimodality therapy in the era of imatinib.

Annals of Surgical Oncology 2013; 20(2):586-92.

Raw IF: 4.12 Normalized IF: 6

General Medicine and Hepatology Bruno S, Saibeni S, Bagnardi V, Vandelli C, De Luca M, Felder M, Fracanzani AL, Prisco C, Vitaliani G, Simone L, Gaeta GB, Stanzione M, Persico M, Furlan C, Stroffolini T, Salerno F, Maisonneuve P, Almasio PL; AISF (Italian Association for the Study of the Liver) – EPA-SCO Collaborative Study Group.

(Collaborators: Tommasini M).

Mortality risk according to different clinical characteristics of first episode of liver decompensation in cirrhotic patients: a nationwide, prospective, 3-year follow-up study in Italy.

American Journal of Gastroenterology 2013;108(7):1112-22.

Raw IF: 7.553 Normalized IF: 1.6

General Medicine and Pneumology Baiardini I, Puggioni F, Menoni S, Boot JD, Diamant Z, Braido F, Canonica GW.

Patient knowledge, perceptions, expectations and satisfaction on allergen-specific immunotherapy: a survey.

Respiratory Medicine 2013;107(3):361-7.

Raw IF: 2.585 Normalized IF: 4

Celesti G, Di Caro G, Bianchi P, Grizzi F, Marchesi F, Basso G, Rahal D, Delconte G, Catalano M, Cappello P, Roncalli M, Zerbi A, Montorsi M, Novelli F, Mantovani A, Allavena P, Malesci A*, Laghi L. (Celesti and Di Caro contributed equally to this work)

Larghi A, Panic N, Capurso G, Leoncini E, Arzani D, Salvia R, Del Chiaro M, Frulloni L, Arcidiacono PG, Zerbi A, Manta R, Fabbri C, Ventrucci M, Tarantino I, Piciucchi M, Carnuccio A, Boggi U, Costamagna G, Delle Fave G, Pezzilli R, Bassi C, Bulajic M, Ricciardi W, Boccia S.

Early expression of the fractalkine receptor CX3CR1 in pancreatic carcinogenesis.

Prevalence and risk factors of extrapancreatic malignancies in a large cohort of patients with intraductal papillary mucinous neoplasm (IPMN) of the pancreas.

British Journal of Cancer 2013;109(9):2424-33.

Raw IF: 5.082 Normalized IF: 6

Donadon M*, Di Tommaso L, Roncalli M, Torzilli G.

General Surgery III; Liver Surgery Balzano G, Maffi P, Nano R, Zerbi A, Venturini M, Melzi R, Mercalli A, Magistretti P, Scavini M, Castoldi R, Carvello M, Braga M, Del Maschio A, Secchi A, Staudacher C, Piemonti L.

Extending indications for islet autotransplantation in pancreatic surgery.

Annals of Surgery 2013;258(2):210-8.

Raw IF: 6.329 Normalized IF: 3

Capurso G, Boccia S, Salvia R, Del Chiaro M, Frulloni L, Arcidiacono PG, Zerbi A, Manta R, Fabbri C, Ventrucci M, Tarantino I, Piciucchi M, Carnuccio A, Boggi U, Leoncini E, Costamagna G, Delle Fave G, Pezzilli R, Bassi C, Larghi A; Italian Association for Study of Pancreas (AISP); Intraductal Papillary Mucinous Neoplasm (IPMN) Study Group.

Risk factors for intraductal papillary mucinous neoplasm (IPMN) of the pancreas: a multicentre case-control study.

American Journal of Gastroenterology 2013;108(6):1003-9.

Raw IF: 7.553 Normalized IF: 8

Castoldi L, De Rai P, Zerbi A, Frulloni L, Uomo G, Gabbrielli A, Bassi C, Pezzilli R; The ProInf-AISP (Progetto Informatizzato Pancreatite Acuta, Associazione Italiana per lo Studio del Pancreas) Study Group.

Long term outcome of acute pancreatitis in Italy: results of a multicentre study.

Digestive and Liver Disease 2013;45(10):827-32.

Raw IF: 3.162 Normalized IF: 4

Multiple focal nodular hyperplasias induced by oxaliplatin-based chemotherapy.

World Journal of Hepatology 2013;5(6):340-4.

Raw IF: 0 Normalized IF: 0

Donadon M, Procopio F, Torzilli G*.

Tailoring the area of hepatic resection using inflow and outflow modulation.

World Journal of Gastroenterology 2013;19(7):1049-55.

Raw IF: 2.547 Normalized IF: 4

Fumagalli U*, Bersani M, Russo A, Melis A, de Pascale S, Rosati R.

Volume and outcomes after esophageal cancer surgery: the experience of the Region of Lombardy-Italy.

Annals of Oncology 2013;24(7):1907-11.

Raw IF: 7.384 Normalized IF: 8

Micheletto G, Danelli P, Morandi A, Panizzo V, Montorsi M.

Gallstone ileus after biliointestinal bypass: report of two cases.

Journal of Gastrointestinal Surgery 2013;17(12):2162-5.

Raw IF: 2.361 Normalized IF: 6

Procopio F, Torzilli G.

Organ targeted mini-invasive approach in the treatment of colorectal cancer liver metastases: role of intraoperative ultrasonography as guidance in liver resection.

Minerva Chirurgica 2013;68(1):41-7.

Raw IF: 0.394 Normalized IF: 1

Updates Surgery 2013;65(4):271-5.

Raw IF: 0 Normalized IF: 0

Scorsetti M, Arcangeli S, Tozzi A, Comito T, Alongi F*, Navarria P, Mancosu P, Reggiori G, Fogliata A, Torzilli G, Tomatis S, Cozzi L.

Hudspeth K, Pontarini E, Tentorio P, Cimino M, Donadon M, Torzilli G, Lugli E, Della Bella S, Gershwin ME, Mavilio D*.

Is stereotactic body radiation therapy an attractive option for unresectable liver metastases? A preliminary report from a phase 2 trial.

The role of natural killer cells in autoimmune liver disease: a comprehensive review.

International Journal of Radiation Oncology, Biology, Physics 2013;86(2):336-42.

Raw IF: 4.524 Normalized IF: 6

Journal of Autoimmunity 2013;46:55-65.

Raw IF: 8.145 Normalized IF: 8

Iborra M, Bernuzzi F, Correale C, Vetrano S, Fiorino G, Beltrán B, Marabita F, Locati M, Spinelli A, Nos P, Invernizzi P, Danese S.

Identification of serum and tissue microRNA expression profiles in different stages of the inflammatory bowel disease.

Sebastian S, Hernández V, Myrelid P, Kariv R, Tsianos E, Toruner M, Marti-Gallostra M, Spinelli A, van der Meulen-de Jong AE, Yuksel ES, Gasche C, Ardizzone S, Danese S.

Colorectal cancer in inflammatory bowel disease: results of the 3rd ECCO pathogenesis scientific workshop (I).

Journal of Crohn’s & Colitis 2014;8(1):5-18.

Raw IF: 3.385 Normalized IF: 6

Clinical & Experimental Immunology 2013;173(2):250-8.

Raw IF: 3.409 Normalized IF: 4

95

Papers published 2013

Spinelli A*, Fiorino G, Bazzi P, Sacchi M, Bonifacio C, De Bastiani S, Malesci A, Balzarini L, Peyrin-Biroulet L, Montorsi M, Danese S.

Preoperative magnetic resonance enterography in predicting findings and optimizing surgical approach in Crohn’s disease.

Journal of Gastrointestinal Surgery 2014;18(1):83-90.

Raw IF: 3.361 Normalized IF: 6

Torzilli G*, Belghiti J, Kokudo N, Takayama T, Capussotti L, Nuzzo G, Vauthey JN, Choti MA, De Santibanes E, Donadon M, Makuuchi M.

Reply to the Letter to the Editor: A snapshot of the effective indications and results of surgery for hepatocellular carcinoma in tertiary referral centers: is it adherent to the EASL/AASLD recommendations? An observational study of the HCC East-West Study Group: When the study setting “ignores” the patients.

Annals of Surgery Epub 2013;Nov 18.

Raw IF: 6.329 Normalized IF: 3

Torzilli G*, Belghiti J, Kokudo N, Takayama T, Capussotti L, Nuzzo G, Vauthey JN, Choti MA, De Santibanes E, Donadon M, Morenghi E, Makuuchi M.

A snapshot of the effective indications and results of surgery for hepatocellular carcinoma in tertiary referral centers: is it adherent to the EASL/AASLD recommendations? An observational study of the HCC East-West Study Group.

Annals of Surgery 2013;257(5):929-37.

Raw IF: 6.329 Normalized IF: 6

Tozzi A, Comito T, Alongi F*, Navarria P, Iftode C, Mancosu P, Reggiori G, Clerici E, Rimassa L, Zerbi A, Fogliata A, Cozzi L, Tomatis S, Scorsetti M.

SBRT in unresectable advanced pancreatic cancer: preliminary results of a mono-institutional experience.

Radiation Oncology 2013;8(1):148.

Raw IF: 2.107 Normalized IF: 4

Zerbi A*, Capitanio V, Boninsegna L, Delle Fave G, Pasquali C, Rindi G, Campana D, Falconi M; AISP-Network Study Group.

Treatment of malignant pancreatic neuroendocrine neoplasms: middleterm (2-year) outcomes of a prospective observational multicentre study.

96

HPB the Official Journal of the International Hepato Pancreato Biliary Association 2013;15(12):935-43.

Raw IF: 1.939 Normalized IF: 4

Gynaecology Lopci E*, Colombo P, Rodari M, Lania A, Vitobello D, Leonardi L, Chiti A.

Imaging struma ovarii by means of 124INa PET/CT. Nuclear Medicine Review. Central & Eastern Europe 2013;16(2):95-6.

Raw IF: 0 Normalized IF: 0

Serati M, Bauer R, Cornu JN, Cattoni E, Braga A, Siesto G, Lizée D, Haab F, Torella M, Salvatore S.

TVT-O for the treatment of pure urodynamic stress incontinence: efficacy, adverse effects, and prognostic factors at 5-year follow-up.

European Urology 2013;63(5):872-8.

Raw IF: 10.476 Normalized IF: 4

Serati M, Braga A, Cattoni E, Siesto G, Cromi A, Ghezzi F, Salvatore S.

Transobturator vaginal tape for the treatment of stress urinary incontinence in elderly women without concomitant pelvic organ prolapse: is it effective and safe?

European Journal of Obstetrics, Gynecology, and Reproductive Biology 2013;166(1):107-10.

Raw IF: 1.843 Normalized IF: 2

Serati M, Braga A, Siesto G, Sorice P, Cattoni E, Uccella S, Cromi A, Salvatore S, Ghezzi F.

Risk factors for the failure of antimuscarinic treatment with solifenacin in women with overactive bladder.

Urology 2013;82(5):1044-8.

Raw IF: 2.424 Normalized IF: 2

Serati M, Braga A, Sorice P, Siesto G, Salvatore S, Ghezzi F.

Solifenacin in women with de novo overactive bladder post TVT-O: is it effective?

Journal of Urology Epub 2013;Oct 19.

Raw IF: 4 Normalized IF: 3

Serati M, Cattoni E, Siesto G, Braga A, Sorice P, Cantaluppi S, Cromi A, Ghezzi F, Vitobello D, Bolis P, Salvatore S.

Urodynamic evaluation: can it prevent the need for surgical intervention in women with apparent pure stress urinary incontinence?

BJU international 2013;112(4):E344-50.

Raw IF: 3.046 Normalized IF: 3

Siesto G*, Ieda N, Rosati R, Vitobello D.

Robotic surgery for deep endometriosis: a paradigm shift.

The International Journal of Medical Robotics + Computer Assisted Surgery: MRCAS Epub 2013;June 13.

Raw IF: 1.488 Normalized IF: 4

Siesto G*, Ornaghi S, Iedà N, Vitobello D.

Robotic surgical staging for endometrial and cervical cancers in medically ill patients.

Gynecologic Oncology 2013;129(3):593-7.

Raw IF: 3.929 Normalized IF: 6

Siesto G*, Vitobello D.

Robotic radical hysterectomy following neoadjuvant chemotherapy in FIGO stage IIIB cervical cancer: a case report.

International Journal of Medical Robotics + Computer Assisted Surgery 2014; 10(1):98-102.

Raw IF: 1.488 Normalized IF: 4

Gynaecology and Reproductive Medicine Levi Setti PE*, Albani E, Morenghi E, Morreale G, Delle Piane L, Scaravelli G, Patrizio P.

Comparative analysis of fetal and neonatal outcome of pregnancies from fresh and cryopreserved/thawed oocytes in the same group of patients.

Fertility and Sterility 2013;100(2):396-401.

Raw IF: 4.174 Normalized IF: 6

Lopci E*, Colombo P, Rodari M, Lania A, Vitobello D, Leonardi L, Chiti A.

Imaging struma ovarii by means of 124INa PET/CT. Nuclear Medicine Review. Central & Eastern Europe 2013;16(2):95-6.

Raw IF: 0 Normalized IF: 0

Matteo M, Greco P, Levi Setti PE, Morenghi E, De Rosario F, Massenzio F, Albani E, Totaro P, Liso A.

Preliminary evidence for high antiPLAC1 antibody levels in infertile patients with repeated unexplained implantation failure.

Placenta 2013;34(4):335-9.

Raw IF: 3.117 Normalized IF: 6

Mehri S, Levi Setti PE, Greco K, Sakkas D, Martinez G, Patrizio P.

Corrada E, Mennuni MG, Grieco N, Sesana G, Beretta G, Presbitero P.

Correlation between follicular diameters and flushing versus no flushing on oocyte maturity, fertilization rate and embryo quality.

Neurological recovery after outof-hospital cardiac arrest: hospital admission predictors and one-year survival in an urban cardiac network experience.

Journal of Assisted Reproduction and Genetics 2014;31(1):73-7.

Raw IF: 1.823 Normalized IF: 4

Negri L*, Patrizio P, Albani E, Morenghi E, Benaglia R, Desgro M, Levi Setti PE.

ICSI outcome is significantly better with testicular spermatozoa in patients with necrozoospermia: a retrospective study.

Gynecological Endocrinology 2014;30(1):48-52.

Raw IF: 1.303 Normalized IF: 2

Revelli A, Porcu E, Levi Setti PE, Delle Piane L, Merlo DF, Anserini P.

Is letrozole needed for controlled ovarian stimulation in patients with estrogen receptor-positive breast cancer?

Gynecological Endocrinology 2013;29(11):993-6.

Raw IF: 1.303 Normalized IF: 1

Haemodynamics, Invasive Cardiology and Coronary Care Bhatt DL, Stone GW, Mahaffey KW, Gibson CM, Steg PG, Hamm CW, Price MJ, Leonardi S, Gallup D, Bramucci E, Radke PW, Widimský P, Tousek F, Tauth J, Spriggs D, McLaurin BT, Angiolillo DJ, Généreux P, Liu T, Prats J, Todd M, Skerjanec S, White HD, Harrington RA; CHAMPION PHOENIX Investigators. (Collaborators: Presbitero P).

Effect of platelet inhibition with cangrelor during PCI on ischemic events.

New England Journal of Medicine 2013;368(14):1303-13.

Raw IF: 52 Normalized IF: 3

Ciccone A, Valvassori L, Nichelatti M, Sgoifo A, Ponzio M, Sterzi R, Boccardi E; SYNTHESIS Expansion Investigators.

(Collaborators: Marcheselli S, Stival B, Presbitero P, Rossi ML, Belli G).

Endovascular treatment for acute ischemic stroke.

New England Journal of Medicine 2013;368(10):904-13.

Raw IF: 51.658 Normalized IF: 3

Minerva Cardioangiologica 2013;61(4):451-60.

Raw IF: 0.427 Normalized IF: 1

D’Ascenzo F, Ballocca F, Moretti C, Barbanti M, Gasparetto V, Mennuni M, D’Amico M, Conrotto F, Salizzoni S, Omedè P, Colaci C, Biondi Zoccai G, Lupo M, Tarantini G, Napodanno M, Presbitero P, Sheiban I, Tamburino C, Marra S, Gaita F.

Inaccuracy of available surgical risk scores to predict outcomes after transcatheter aortic valve replacement.

Journal of Cardiovascular Medicine 2013;14(12):894-8.

Raw IF: 2.657 Normalized IF: 2

D’Ascenzo F, Conrotto F, Giordana F, Moretti C, D’Amico M, Salizzoni S, Omedè P, La Torre M, Thomas M, Khawaja Z, Hildick-Smith D, Ussia G, Barbanti M, Tamburino C, Webb J, Schnabel RB, Seiffert M, Wilde S, Treede H, Gasparetto V, Napodano M, Tarantini G, Presbitero P, Mennuni M, Rossi ML, Gasparini M, Biondi Zoccai G, Lupo M, Rinaldi M, Gaita F, Marra S.

Mid-term prognostic value of coronary artery disease in patients undergoing transcatheter aortic valve implantation: a meta-analysis of adjusted observational results.

International Journal of Cardiology 2013;168(3):2528-32.

Raw IF: 6 Normalized IF: 6

Gasparini GL*, Rossi ML, Presbitero P.

A thirty-four-year-old chronic total occlusion successfully treated by percutaneous coronary intervention.

International Journal of Cardiology 2013;168(2):e55-57.

Raw IF: 5.509 Normalized IF: 3

Lucas G, Lluís-Ganella C, Subirana I, Musameh MD, Gonzalez JR, Nelson CP, Sentí M; 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. (Collaborators: Rossi ML).

Ribichini F, Tomai F, Pesarini G, Zivelonghi C, Rognoni A, De Luca G, Boccuzzi G, Presbitero P, Ferrero V, Ghini AS, Marino P, Vassanelli C; the CEREA-DES Investigators. (Collaborators: Belli G, Rossi ML, Soregaroli D, Zavalloni D).

Long-term clinical follow-up of the multicenter, randomized study to test immunosuppressive therapy with oral prednisone for the prevention of restenosis after percutaneous coronary interventions: Cortisone plus BMS or DES veRsus BMS alone to EliminAte Restenosis (CEREA-DES).

European Heart Journal 2013;34(23):1740-8.

Raw IF: 14.1 Normalized IF: 10

Rivera NV, Carreras-Torres R, Roncarati R, Viviani-Anselmi C, De Micco F, Mezzelani A, Koch W, Hoppmann P, Kastrati A, Stewart AF, Chen L, Roberts R, Karssen LC, Amin N, Trimarco V, Izzo R, Iaccarino G, Condorelli G, Puca AA, Pagnotta P, Airoldi F, Trimarco B, van Duijn CM, Condorelli G, Briguori C.

Assessment of the 9p21 3 locus in severity of coronary artery disease in the presence and absence of type 2 diabetes.

BMC Medical Genetics 2013;14 11.

Raw IF: 3 Normalized IF: 2

Scirica BM, Bhatt DL, Braunwald E, Steg PG, Davidson J, Hirshberg B, Ohman P, Frederich R, Wiviott SD, Hoffman EB, Cavender MA, Udell JA, Desai NR, Mosenzon O, McGuire DK, Ray KK, Leiter LA, Raz I; SAVOR-TIMI 53 Steering Committee and Investigators.

(Collaborators: Presbitero P).

Saxagliptin and cardiovascular outcomes in patients with type 2 diabetes mellitus.

New England Journal of Medicine 2013;369(14):1317-26.

Raw IF: 51.658 Normalized IF: 3

Valgimigli M, Park SJ, Kim HS, Park KW, Park DW, Tricoci P, Ferrante G.

Benefits and risks of long-term duration of dual antiplatelet therapy after drugeluting stenting: a meta-analysis of randomized trials.

International Journal of Cardiology 2013;168(3):2579-87.

Raw IF: 5.509 Normalized IF: 6

Hypothesis-based analysis of genegene interactions and risk of myocardial infarction.

PLoS One 2012;7(8):e41730.

Raw IF: 4 Normalized IF: 1.2

97

Papers published 2013

Viviani Anselmi C , Briguori C, Roncarati R, Papa L, Visconti G, Focaccio A, De Micco F, Latronico MVG, Pagnotta P, Condorelli G.

Routine assessment of on-clopidogrel platelet reactivity and gene polymorphisms in predicting clinical outcome following drug-eluting stent implantation in patients with stable coronary artery disease.

Journal of American College of Cardiology 2013;6(11):1166-75.

Raw IF: 14.086 Normalized IF: 10

Zavalloni D*, De Benedictis M, Pagnotta P, Scrocca I, Presbitero P.

New CoreValve Evolut 23mm technology for treatment of degenerated bioprosthesis.

Heart, Lung & Circulation 2013;23(2):183-5.

Raw IF: 1.254 Normalized IF: 2

Zavalloni D*, Lisignoli V, Barbaro C, Mennuni M, Tosi P, Marcheselli S, Presbitero P.

Platypnoea-orthodeoxia syndrome secondary to patent foramen ovale (PFO): a challenging subset for PFO percutaneous closure.

Heart, Lung & Circulation 2013;22(8):642-6.

Raw IF: 1.254 Normalized IF: 2

Internal Medicine Barbic F*, Dipaola F, Solbiati M, Furlan R.

Do work accidents play any role in the increased risk of death observed in 2544 year old patients after syncope?

Journal of the American College of Cardiology 2013;61(24):2488-9.

Raw IF: 14 Normalized IF: 5

Costantino G, Solbiati M, Casazza G, Bonzi M, Vago T, Montano N, McDermott D, Quinn J, Furlan R.

Usefulness of N-terminal Pro-B-Type Natriuretic Peptide increase as a marker for cardiac arrhythmia in patients with syncope.

American Journal of Cardiology 2014;113(1):98-102.

Raw IF: 3.209 Normalized IF: 4

98

Dalla Vecchia L, Barbic F, Galli A, Pisacreta M, Gornati R, Porretta T, Porta A, Furlan R.

Favorable effects of carotid endarterectomy on baroreflex sensitivity and cardiovascular neural modulation: a 4-month follow up.

American Journal of Physiology. Regulatory, Integrative and Comparative Physiology 2013;304(12):R1114-20.

Raw IF: 3.284 Normalized IF: 6

De Santis M, Crotti C, Selmi C.

Liver abnormalities in connective tissue diseases.

Best Practice & Research Clinical Gastroenterology 2013;27(4):543-51.

Raw IF: 3.155 Normalized IF:4

Dipaola F*, Perego F; Gruppo di Autoformazione Metodologica (GrAM).

Is coronary CT angiography useful in diagnosing acute coronary syndromes in the Emergency Department?

Internal and Emergency Medicine 2013;8(4):345-6.

Raw IF: 2.345 Normalized IF: 6

Invernizzi P, Bernuzzi F, Lleo A, Pozzoli V, Bignotto M, Zermiani P, Crosignani A, Battezzati PM, Zuin M, Podda M, Raggi C*.

Telomere dysfunction in peripheral blood mononuclear cells from patients with primary biliary cirrhosis.

Digestive and Liver Disease 2014;46(4):363-8.

Raw IF: 3.162 Normalized IF: 4

Kar SP, Seldin MF, Chen W, Lu E, Hirschfield GM, Invernizzi P, Heathcote J, Cusi D; the Italian PBC Genetics Study Group, Almasio PL, Alvaro D, Andreone P, Andriulli A, Barlassina C, Benedetti A, Bernuzzi F, Bianchi I, Bragazzi M, Brunetto M, Bruno S, Caliari L, Casella G, Coco B, Colli A, Colombo M, Colombo S, Cursaro C, Croce LS, Crosignani A, Donato F, Elia G, Fabris L, Floreani A, Galli A, Grattagliano I, Lazzari R, Lleo A, Macaluso F, Marra F, Marzioni M, Mascia E, Mattalia A, Montanari R, Morini L, Morisco F, Muratori L, Muratori P, Niro G, Picciotto A, Podda M, Portincasa P, Prati D, Raggi C, Rosina F, Rossi S, Sogno I, Spinzi G, Strazzabosco M, Tarallo S, Tarocchi M, Tiribelli C, Toniutto P, Vinci M, Zuin M, Gershwin ME, Siminovitch KA, Amos CI.

Lleo A, Oertelt-Prigione S, Bianchi I, Caliari L, Finelli P, Miozzo M, Lazzari R, Floreani A, Donato F, Colombo M, Gershwin ME, Podda M, Invernizzi P*.

Y chromosome loss in male patients with primary biliary cirrhosis.

Journal of Autoimmunity 2013;41:87-91.

Raw IF: 8.145 Normalized IF: 8

Perego F, Costantino G, Dipaola F, Scannella E, Borella M, Galli A, Barbic F, Casella F, Solbiati M, Angaroni L, Duca P, Furlan R.

Predictors of hospital admission after syncope: relationships with clinical risk scores.

International Journal of Cardiology 2012;161(3):182-3.

Raw IF: 5.509 Normalized IF: 3

Petix NR, Del Rosso A, Furlan R, Guarnaccia V, Zipoli A.

Nitrate-potentiated Head-Up Tilt testing (HUT) has a low diagnostic yield in patients with likely vasovagal syncope.

Pacing and Clinical Electrophysiology: PACE 2014,37(2):164-72.

Raw IF: 1.746 Normalized IF: 2

Podda M, Selmi C, Lleo A, Moroni L, Invernizzi P*.

The limitations and hidden gems of the epidemiology of primary biliary cirrhosis.

Journal of Autoimmunity 2013;46:81-7.

Raw IF: 8.145 Normalized IF: 8

Selmi C*, Crotti C, Meroni PL.

Less-traveled roads in clinical immunology and allergy: the cases of drug reactions and environmental influence.

Clinical Reviews in Allergy and Immunology 2013;45(1):1-5.

Raw IF: 6 Normalized IF: 6

Knee Orthopaedics and Sport Traumatology Galbusera F, Tornese DZ, Anasetti F, Bersini S, Volpi P, La Barbera L, Villa T.

Pathway-based analysis of primary biliary cirrhosis genome-wide association studies.

Does soccer cleat design influence the rotational interaction with the playing surface?

Genes and Immunity 2013;14(3):179-86.

Raw IF: 4 Normalized IF: 6

Sports Biomechanics 2013;12(3):293-301.

Raw IF: 0.737 Normalized IF: 1

Volpi P.

Why so many injuries in professional football players?

Journal of Sports Medicine and Physical Fitness 2013;53(1):101-2.

Raw IF: 0.73 Normalized IF: 1

Laboratory tests

Medical Oncology and Haematology Agnelli G, Verso M, Mandalà M, Gallus S, Cimminiello C, Apolone G, Di Minno G, Maiello E, Prandoni P, Santoro A, Crinò L, Labianca R.

A prospective study on survival in cancer patients with and without venous thromboembolism.

Alpini C ,Monari M, Montanelli A, Valaperta S.

Internal and Emergency Medicine Epub 2013;Aug 14.

Raw IF: 2.345 Normalized IF: 6

The laboratory in the differential diagnosis between early rheumatoid arthritis and polyarthropathy related to chronic infection with hepatitis C virus.

Bruix J, Tak WY, Gasbarrini A, Santoro A, Colombo M, Lim HY, Mazzaferro V, Wiest R, Reig M, Wagner A, Bolondi L.

Biochimica Clinica 2013;37(2):91-4.

Raw IF: 0 Normalized IF: 0

Graziani G*, Cucchiari D, Podestà MA, Quagliuolo V, Montanelli A.

Abdominal pain and increased CA19-9.

Clinical Chemistry 2013;59(11):1678-9.

Raw IF: 7.149 Normalized IF: 8

Gullo G, Bettio D, Zuradelli M, Masci G, Giordano L, Bareggi C, Tomirotti M, Salvini P, Runza L, La Verde N, Santoro A.

Level of HER2/neu amplification in primary tumours and metastases in HER2-positive breast cancer and survival after trastuzumab therapy.

Breast 2013;22(2):190-3.

Raw IF: 1.967 Normalized IF: 4

Migliavacca R, Nucleo E, Asticcioli S, Casari E, Bracco S, Sironi MC.

Multifocal diffusion of a KPC-3 producing ST512 K pneumoniae clone in Northern Italy.

New Microbiologica 2013;36(1):109-10.

Raw IF: 1.667 Normalized IF: 1

Tortorano AM, Prigitano A, Lazzarini C, Passera M, Deiana ML, Cavinato S, De Luca C, Grancini A, Lo Cascio G, Ossi C, Sala E, Montagna MT.

A 1-year prospective survey of candidemia in Italy and changing epidemiology over one decade.

Infection 2013;41(3):655-62.

Raw IF: 2.44 Normalized IF: 1

Regorafenib as second-line therapy for intermediate or advanced hepatocellular carcinoma: multicentre, open-label, phase II safety study.

European Journal of Cancer 2013;49(16):3412-9.

Raw IF: 5.061 Normalized IF: 6

Campiglio M, Bufalino R, Sasso M, Ferri E, Casalini P, Adamo V, Fabi A, Aiello R, Riccardi F, Valle E, Scotti V, Tabaro G, Giuffrida D, Tarenzi E, Bologna A, Mustacchi G, Bianchi F, Balsari A, Ménard S, Tagliabue E. (Collaborators: Masci G).

Effect of adjuvant trastuzumab treatment in conventional clinical setting: an observational retrospective multicenter Italian study.

Breast Cancer Research and Treatment 2013;141(1):101-10.

Raw IF: 4.469 Normalized IF: 1.2

Castagna L*, Morabito L, Mauro E, Perotti C, Bramanti S, Sarina B, Giordano L, Crocchiolo R, Santoro A.

First line extracorporeal photochemotherapy for acute GVHD after unmanipulated haploidentical bone marrow transplantation following nonmyeloablative conditioning and posttransplantation cyclophosphamide.

Bone Marrow Transplantation 2014;49(1):3178.

Raw IF: 3.541 Normalized IF: 2

Ceresoli GL, Zucali PA, Mencoboni M, Botta M, Grossi F, Cortinovis D, Zilembo N, Ripa C, Tiseo M, Favaretto AG, Soto-Parra H, De Vincenzo F, Bruzzone A, Lorenzi E, Gianoncelli L, Ercoli B, Giordano L, Santoro A.

Cucchiari D, Bertuzzi A, Colombo P, De Sanctis R, Faucher E, Fusco N, Pellegrinelli A, Arosio P, Angelini C.

Juxtaglomerular cell tumor: multicentric synchronous disease associated with paraneoplastic syndrome.

Journal of Clinical Oncology 2013;31(14):e240-2.

Raw IF: 18.038 Normalized IF: 15

Di Bartolomeo M, Pietrantonio F, Perrone F, Dotti KF, Lampis A, Bertan C, Beretta E, Rimassa L, Carbone C, Biondani P, Passalacqua R, Pilotti S, Bajetta E; on behalf of Italian Trials in Medical Oncology (ITMO) Group.

Lack of KRAS, NRAS, BRAF and TP53 mutations improves outcome of elderly metastatic colorectal cancer patients treated with cetuximab, oxaliplatin and UFT. Targeted Oncology Epub 2013;Jul 3.

Raw IF: 2.764 Normalized IF: 2

Field JK, van Klaveren R, Pedersen JH, Pastorino U, Paci E, Becker N, Infante M, Oudkerk M, de Koning HJ; on behalf of the European Randomized Screening Trial Group. (Collaborators: Brambilla G, Lutman F, Santoro A, Chiti A, Morenghi E, Destro A, Roncalli M, Alloisio M).

European randomized lung cancer screening trials: post NLST. Journal of Surgical Oncology 2013;108(5):280-6.

Raw IF: 2.644 Normalized IF: 3

Gigli F, Gardellini A, Babic A, Liptrott SJ, Castagna L, Martinelli G, Laszlo D.

Efficacy of photopheresis extracorporeal procedure as single treatment for severe chronic GVHD: a case report.

Transfusion and Apheresis Science 2013;42(9):205-7.

Raw IF: 1.225 Normalized IF: 0.5

Giovannetti E, Peters GJ, Zucali PA.

“One marker does not fit all”: additional translational and validation studies are needed to identify faithful predictors of pemetrexed activity in mesothelioma.

Journal of Thoracic Oncology 2013; 8(8):e79-80.

Raw IF: 4.473 Normalized IF: 3

Phase II study of pemetrexed and carboplatin plus bevacizumab as first-line therapy in malignant pleural mesothelioma.

British Journal of Cancer 2013;109(3):552-8.

Raw IF: 5.082 Normalized IF: 6

99

Papers published 2013

Gullo G, Bettio D, Zuradelli M, Masci G, Giordano L, Bareggi C, Tomirotti M, Salvini P, Runza L, La Verde N, Santoro A.

Mancosu P*, Navarria P, Castagna L, Reggiori G, Sarina B, Tomatis S, Alongi F, Nicolini G, Fogliata A, Cozzi L, Scorsetti M.

Level of HER2/neu amplification in primary tumours and metastases in HER2-positive breast cancer and survival after trastuzumab therapy.

Interplay effects between dose distribution quality and positioning accuracy in total marrow irradiation with volumetric modulated arc therapy.

Breast 2013;22(2):190-3.

Raw IF: 1.967 Normalized IF: 4

Medical Physics 2013;40(11):111713.

Raw IF: 2.911 Normalized IF: 6

Iacovelli R, Cartenì G, Sternberg CN, Milella M, Santoni M, Di Lorenzo G, Ortega C, Sabbatini R, Ricotta R, Messina C, Lorusso V, Atzori F, De Vincenzo F, Sacco C, Boccardo F, Valduga F, Massari F, Baldazzi V, Cinieri S, Mosca A, Ruggeri EM, Berruti A, Cerbone L, Procopio G.

Martínez C, Canals C, Sarina B, Alessandrino EP, Karakasis D, Pulsoni A, Sica S, Trneny M, Snowden JA, Kanfer E, Milpied N, Bosi A, Guidi S, de Souza CA, Willemze R, Arranz R, Jebavy L, Hellmann A, Sibon D, Oneto R, Luan JJ, Dreger P, Castagna L, Sureda A; for the Lymphoma Working Party of the European Group for Blood and Marrow Transplantation (EBMT) and the Gruppo Italiano Trapianto di Midollo Osseo (GITMO).

Clinical outcomes in patients receiving three lines of targeted therapy for metastatic renal cell carcinoma: results from a large patient cohort.

European Journal of Cancer 2013; 49(9):2134-42.

Raw IF: 5.061 Normalized IF: 6

Identification of prognostic factors predicting outcome in Hodgkin’s lymphoma patients relapsing after autologous stem cell transplantation.

La Verde N, Moretti A, Farina G, Dazzani MC, Gamucci T, Borgonovo K, Botta M, Salesi N, Zuradelli M, Pavese I, Barbieri E, Cretella E, Saladino T, Varese P, Traverso ES, Addamo G, Ciccarese M, Rispoli AI, Pellegrino A, Mentuccia L, Girelli S, Piva S, Maio MD.

Annals of Oncology 2013;24(9):2430-4.

Raw IF: 7.384 Normalized IF: 8

Eribulin in cutaneous breast cancer metastasis treatment: clinical activity and symptom control.

Future Oncology 2013;9(12):1841-8.

Raw IF: 3.202 Normalized IF: 2

Lanza F, Lemoli RM, Olivieri A, Laszlo D, Martino M, Specchia G, Pavone V, Imola M, Pasini A, Milone G, Scortechini I, Todisco E, Guggiari E, Cascavilla N, Martinelli G, Rambaldi A, Bosi A.

Factors affecting successful mobilization with plerixafor: an Italian prospective survey in 215 patients with multiple myeloma and lymphoma.

Transfusion 2014;54(2):331-9.

Raw IF: 3.526 Normalized IF: 4

Luminari S, Biasoli I, Arcaini L, Versari A, Rusconi C, Merli F, Spina M, Ferreri AJ, Zinzani PL, Gallamini A, Mastronardi S, Boccomini C, Gaidano G, D’Arco AM, Di Raimondo F, Carella AM, Santoro A, Musto P, Federico M.

The use of FDG-PET in the initial staging of 142 patients with follicular lymphoma: a retrospective study from the FOLL05 randomized trial of the Fondazione Italiana Linfomi.

100

Annals of Oncology 2013;24(8):2108-12.

Raw IF: 7.384 Normalized IF: 8

Masci G*, Gandini C. Zuradelli M, Losurdo A, Torrisi R, Rota S, Gullo G, Velutti L, Giordano L, Santoro A.

Weekly non-pegylated liposomal doxorubicin chemotherapy in heavily pre-treated patients with metastatic breast cancer.

Anticancer Research 2013;33(10):4603-9.

Raw IF: 1.713 Normalized IF: 2

Passera R, Pollichieni S, Brunello L, Patriarca F, Bonifazi F, Montefusco V, Falda M, Montanari M, Guidi S, Giaccone L, Mordini N, Carella AM, Bavaro P, Milone G, Benedetti F, Ciceri F, Scimè R, Benedetti E, Castagna L, Festuccia M, Rambaldi A, Bacigalupo A, Corradini P, Bosi A, Boccadoro M, Bandini G, Fanin R, Bruno B.

Allogeneic haematopoietic cell transplantation from unrelated donors in multiple myeloma: study from the Italian Bone Marrow Donor Registry.

Biology of Blood and Marrow Transplantation 2013;19(6):940-8.

Raw IF: 3.94 Normalized IF: 6

Personeni N*, Rimassa L, Pressiani T, Destro A, Ligorio C, Tronconi MC, Bozzarelli S, Carnaghi C, Di Tommaso L, Giordano L, Roncalli M, Santoro A.

Molecular determinants of outcome in sorafenib-treated patients with hepatocellular carcinoma.

Journal of Cancer Research and Clinical Oncology 2013;139(7):1179-87.

Raw IF: 2.914 Normalized IF: 4

Petrini I, Wang Y, Zucali PA, Lee HS, Pham T, Voeller D, Meltzer PS, Giaccone G.

Copy number aberrations of genes regulating normal thymus development in thymic epithelial tumors.

Clinical Cancer Research 2013;19(8):1960-71.

Raw IF: 7.837 Normalized IF: 4

Raiola A, Dominietto A, Varaldo R, Ghiso A, Galaverna F, Bramanti S, Todisco E, Sarina B, Giordano L, Ibatici A, Santoro A, Clavio M, Bacigalupo A, Castagna L.

Unmanipulated haploidentical BMT following non-myeloablative conditioning and post-transplantation CY for advanced Hodgkin’s lymphoma.

Bone Marrow Transplantation 2014;49(2):190-4.

Raw IF: 3.541 Normalized IF: 4

Rimassa L*, Bruix J, Broggini M, Santoro A.

Tivantinib (ARQ197) displays cytotoxic activity that is independent of its ability to bind MET-letter.

Clinical Cancer Research 2013;19(15):4290.

Raw IF: 7.837 Normalized IF: 4

Rimassa L*, Personeni N, Simonelli M, Santoro A.

Tivantinib: a new promising mesenchymalepithelial transition factor inhibitor in the treatment of hepatocellular carcinoma.

Future Oncology 2013;9(2):153-65.

Raw IF: 3.202 Normalized IF: 4

Rimassa L*, Pressiani T, Boni C, Carnaghi C, Rota Caremoli E, Fagiuoli S, Foa P, Salvagni S, Cortesi E, Chiara Tronconi M, Personeni N, Bozzarelli S, Chiara Banzi M, Fanello S, Romano Lutman F, Giordano L, Santoro A.

A phase II randomized dose escalation trial of sorafenib in patients with advanced hepatocellular carcinoma.

Oncologist 2013;18(4):379-80.

Raw IF: 4.095 Normalized IF: 6

Rougier P, Riess H, Manges R, Karasek P, Humblet Y, Barone C, Santoro A, Assadourian S, Hatteville L, Philip PA.

Randomised, placebo-controlled, double-blind, parallel-group phase III study evaluating aflibercept in patients receiving first-line treatment with gemcitabine for metastatic pancreatic cancer.

European Journal of Cancer 2013; 49(12):2633-42.

Raw IF: 5.061 Normalized IF: 6

Surbone A, Annunziata MA, Santoro A, Tirelli U, Tralongo P.

Cancer patients and survivors: changing words or changing culture?

Annals of Oncology 2013;24(10):2468-71.

Raw IF: 7.384 Normalized IF: 4

Todisco E, Ciceri F, Oldani E, Boschini C, Micò C, Vanlint MT, Donnini I, Patriarca F, Alessandrino PE, Bonifazi F, Arcese W, Barberi W, Marenco P, Terruzzi E, Cortelazzo S, Santarone S, Proia A, Corradini P, Tagliaferri E, Falcioni S, Irrera G, Dallanegra L, Castagna L, Santoro A, Camboni A, Sacchi N, Bosi A, Bacigalupo A, Rambaldi A*.

Tralongo P, Annunziata MA, Santoro A, Tirelli U, Surbone A.

Beyond semantics: the need to better categorize patients with cancer.

Journal of Clinical Oncology 2013;31(20):2637-8.

Raw IF: 18.038 Normalized IF: 7.5

Varesco L, Viassolo V, Viel A, Gismondi V, Radice P, Montagna M, Alducci E, Della Puppa L, Oliani C, Tommasi S, Caligo MA, Vivanet C, Zuradelli M, Mandich P, Tibiletti MG, Cavalli P, Lucci Cordisco E, Turchetti D, Boggiani D, Bracci R, Bruzzi P, Bonelli L.

Performance of BOADICEA and BRCAPRO genetic models and of empirical criteria based on cancer family history for predicting BRCA mutation carrier probabilities: a retrospective study in a sample of Italian cancer genetics clinics.

Breast 2013;22(6):1130-5.

Raw IF: 1.967 Normalized IF: 2

Zinzani PL, Viviani S, Anastasia A, Vitolo U, Luminari S, Zaja F, Corradini P, Spina M, Brusamolino E, Gianni AM, Santoro A, Botto B, Derenzini E, Pellegrini C, Argnani L.

Cucchiari D*, Graziani G, Ponticelli C.

The dialysis scenario in patients with systemic lupus erythaematosus.

Nephrology, Dialysis, Transplantation Epub 2013;Oct 28.

Raw IF: 3.371 Normalized IF: 6

Graziani G*, Cucchiari D, Podestà MA, Quagliuolo V, Montanelli A.

Abdominal pain and increased CA19-9.

Clinical Chemistry 2013;59(11):1678-9.

Raw IF: 7.149 Normalized IF: 8

Moroni G, Longhi S, Giglio E, Messa P, Ponticelli C.

What happens after complete withdrawal of therapy in patients with lupus nephritis.

Clinical and Experimental Rheumatology 2013;31(4s78):S75-81.

Raw IF: 2.655 Normalized IF: 4

Moroni G, Quaglini S, Gallelli B, Banfi G, Messa P, Ponticelli C.

Progressive improvement of patient and renal survival and reduction of morbidity over time in patients with lupus nephritis (LN) followed for 20 years.

The CIBMTR score predicts survival of AML patients undergoing allogeneic transplantation with active disease after a myeloablative or reduced intensity onditioning: a retrospective analysis of the Gruppo Italiano Trapianto Di Midollo Osseo (GITMO).

Brentuximab vedotin in relapsed/ refractory Hodgkin’s lymphoma: Italian experience and results of the use in the daily clinic outside clinical trials.

Haematologica 2013;98(8):1232-6.

Raw IF: 5.935 Normalized IF: 3

Ponticelli C.

Leukemia 2013;27(10):2086-91.

Raw IF: 10.164 Normalized IF: 8

Zucali PA*, Perrino M, Lorenzi E, Ceresoli GL, De Vincenzo F, Simonelli M, Gianoncelli L, De Sanctis R, Giordano L, Santoro A.

Expert Opinion on Drug Safety 2014;13(3):373-81.

Raw IF: 2.621 Normalized IF: 4

Torrisi R*, Garcia-Etienne CA, Losurdo A, Morenghi E, Di Tommaso L, Gatzemeier W, Sagona A, Fernandes B, Rossetti C, Eboli M, Rubino A, Barbieri E, Andreoli C, Orefice S, Gandini C, Rota S, Zuradelli M, Masci G, Santoro A, Tinterri C.

Vinorelbine in pemetrexed-pretreated patients with malignant pleural mesothelioma.

Ponticelli C*, Glassock RJ.

Potential impact of the 70-gene signature in the choice of adjuvant systemic treatment for ER positive, HER2 negative tumors: a single institution experience.

Breast 2013;22(4):419-24.

Raw IF: 1.967 Normalized IF: 4

Tozzi A, Comito T, Alongi F*, Navarria P, Iftode C, Mancosu P, Reggiori G, Clerici E, Rimassa L, Zerbi A, Fogliata A, Cozzi L, Tomatis S, Scorsetti M.

SBRT in unresectable advanced pancreatic cancer: preliminary results of a mono-institutional experience.

Radiation Oncology 2013;8(1):148.

Raw IF: 2.107 Normalized IF: 4

Lung Cancer Epub 2013;Nov 20.

Raw IF: 3.392 Normalized IF: 6

Lupus 2013;22(8):810-8.

Raw IF: 2.783

Normalized IF: 4

Basiliximab: efficacy and safety evaluation in kidney transplantation.

Treatment of membranous nephropathy in patients with renal insufficiency: what regimen to choose?

Journal of Nephrology 2013;26(3):427-9.

Raw IF: 2.015 Normalized IF: 4

Nephrology and Dialysis Cucchiari D, Bertuzzi A, Colombo P, De Sanctis R, Faucher E, Fusco N, Pellegrinelli A, Arosio P, Angelini C.

Juxtaglomerular cell tumor: multicentric synchronous disease associated with paraneoplastic syndrome.

Journal of Clinical Oncology 2013;31(14):e240-2.

Raw IF: 18.038 Normalized IF: 15

Ponticelli C, Glassock RJ.

Glomerular diseases: membranous nephropathy. A modern view.

Clinical Journal of the American Society of Nephrology 2014;9(3):609-16.

Raw IF: 5.068 Normalized IF: 6

Ponticelli C*, Graziani G.

Current and emerging treatments for idiopathic focal and segmental glomerulosclerosis in adults.

Expert Review of Clinical Immunology 2013;9(3):251.

Raw IF: 2.89 Normalized IF: 4

101

Papers published 2013

Neurology Galeotti F, Massari M, D’Alessandro R, Beghi E, Chiò A, Logroscino G, Filippini G, Benedetti MD, Pugliatti M, Santuccio C, Raschetti R; ITANG study group.

(Collaborators: Nobile-Orazio E, Terenghi F).

Risk of Guillain-Barré syndrome after 2010-2011 influenza vaccination.

European Journal of Epidemiology 2013;28(5):433-44.

Raw IF: 5.118 Normalized IF: 1.2

Nobile-Orazio E*.

Neuropathy and monoclonal gammopathy.

Handbook of Clinical Neurology 2013;115:443-59.

Raw IF: 0 Normalized IF: 0

Nobile-Orazio E.

Treatment of chronic immune-mediated neuropathies: impact of the rare diseases centers network in Italy.

Revue Neurologique 2013;169(S1):S33-8.

Raw IF: 0.51 Normalized IF: 1

Nobile-Orazio E*, Gallia F.

Multifocal motor neuropathy: current therapies and novel strategies.

Drugs 2013;73(5):397-406.

Raw IF: 4.633 Normalized IF: 6

Nobile-Orazio E*, Giannotta C, Musset L, Messina P, Léger JM. (Collaborators: Gallia F, Costa RG).

Sensitivity and predictive value of antiGM1/galactocerebroside IgM antibodies in multifocal motor neuropathy.

Journal of Neurology, Neurosurgery, and Psychiatry Epub 2013;Aug 1.

Raw IF: 4.924 Normalized IF: 6

Neurosurgery Costa F*, Fornari M, Felisati G, Maccari A, Bauer D, Lasio G.

Epidermoid cyst of the pituitary stalk: case report and review of the literature.

Neurosurgery Quarterly 2013;23(2):108-11.

Raw IF: 0,089 Normalized IF: 1

Costa F*, Ortolina A, Tomei M, Cardia A, Zekay E, Fornari M.

Instrumented fusion surgery in elderly patients (over 75 years old): clinical and radiological results in a series of 53 patients.

European Spine Journal 2013;22 Suppl 6:S910-3.

Raw IF: 2,133 Normalized IF: 4

Costa F*, Porazzi E, Restelli U, Foglia E, Cardia A, Ortolina A, Tomei M, Fornari M, Banfi G.

Economic study: a cost-effectiveness analysis of an intra-operative compared with a pre-operative image guided system in lumbar pedicle screw fixation in patients with degenerative spondylolisthesis.

Spine Journal Epub 2013;Oct 30.

Raw IF: 3,22 Normalized IF: 6

Costa F*, Villa T, Anasetti F, Tomei M, Ortolina A, Cardia A, La Barbera L, Fornari M, Galbusera F.

Primary stability of pedicle screws depends on the screw positioning and alignment.

The long pentraxin PTX3 as a correlate of cancer-related inflammation and prognosis of malignancy in gliomas.

Journal of Neuroimmunology 2013; 260(1-2):99-106.

Raw IF: 3.033 Normalized IF: 4

Vallar G, Bello L, Bricolo E, Castellano A, Casarotti A, Falini A, Riva M, Fava E, Papagno C.

Cerebral correlates of visuospatial neglect: a direct cerebral stimulation study.

Human Brain Mapping 2013;35(4):1334-50.

Raw IF: 6.878 Normalized IF: 6

Nuclear Medicine Alongi F, De Bari B, Campostrini F, Arcangeli S, Matei DV, Lopci E, Petralia G, Bellomi M, Chiti A, Magrini SM, Scorsetti M, Orecchia R, Jereczek-Fossa BA.

Spine Journal 2013; 13(12):1934-9.

Raw IF: 3.355 Normalized IF: 6

Salvage therapy of intraprostatic failure after radical external-beam radiotherapy for prostate cancer: a review.

Felisati G, Lenzi R, Pipolo C, Maccari A, Messina F, Revay M, Lania A, Cardia A, Lasio G.

Critical Reviews in Oncology/Haematology 2013;88(3):550-63.

Raw IF: 4.637 Normalized IF: 6

Endoscopic expanded endonasal approach: preliminary experience with the new 3D endoscope.

Acta Otorhinolaryngologica Italica 2013;33(2):102-6.

Raw IF: 0.786 Normalized IF: 1

Gaetani P*, Pisano P, Solinas G, Colombo P, Destro A, Levi D, Aimar E, Rodriguez R, Baena Y, Allavena P.

Immunohistohemical expression of the chemokine fractalkine and its receptor in the human brain cortex after severe traumatic brain injury and brain hemorrhage.

Journal of Neurosurgical Sciences 2013;57(1):55-62.

Raw IF: 0.53 Normalized IF: 1

Galbusera F, Wilke HJ, Brayda-Bruno M, Costa F, Fornari M.

Influence of sagittal balance on spinal lumbar loads: a numerical approach.

Clinical Biomechanics 2013;28(4):370-7.

Raw IF: 1.869 Normalized IF: 4

102

Locatelli M, Ferrero S, Martinelli Boneschi F, Boiocchi L, Zavanone M, Maria Gaini S, Bello L, Valentino S, Barbati E, Nebuloni M, Mantovani A, Garlanda C*.

Alongi F*, Liardo RL, Iftode C, Lopci E, Villa E, Comito T, Tozzi A, Navarria P, Ascolese AM, Mancosu P, Tomatis S, Bellorofonte C, Chiti A, Scorsetti M.

11C choline PET guided salvage radiotherapy with volumetric modulation arc therapy and hypofractionation for recurrent prostate cancer after HIFU failure: preliminary results of tolerability and acute toxicity.

Technology in Cancer Research & Treatment Epub 2013;Aug 31.

Raw IF: 1.943 Normalized IF: 2

Chiti A*, Kirienko M, Incerti E, Picchio M.

Writing PET into existence.

European Journal of Nuclear Medicine and Molecular Imaging 2014;41(1):7-10.

Raw IF: 5.114 Normalized IF: 6

Field JK, van Klaveren R, Pedersen JH, Pastorino U, Paci E, Becker N, Infante M, Oudkerk M, de Koning HJ; on behalf of the European Randomized Screening Trial Group. (Collaboratoris: Brambilla G, Lutman F, Santoro A, Chiti A, Morenghi E, Destro A, Roncalli M, Alloisio M).

European randomized lung cancer screening trials: post NLST. Journal of Surgical Oncology 2013;108(5):280-6.

Raw IF: 2.644 Normalized IF: 3

Jamar F, Buscombe J, Chiti A, Christian PE, Delbeke D, Donohoe KJ, Israel O, Martin-Comin J, Signore A.

EANM/SNMMI guideline for 18F-FDG use in inflammation and infection.

Journal of Nuclear Medicine 2013; 54(4):647-58.

Raw IF: 5.774 Normalized IF: 3

Jereczek-Fossa BA, Rodari M, Bonora M, Fanti P, Fodor C, Pepe G, Lopci E, Zerini D, Vischioni B, Baroni G, Matei DV, De Cobelli O, Chiti A, Orecchia R.

[11C]choline PET/CT impacts treatment decision making in patients with prostate cancer referred for radiotherapy.

Clinical Genitourinary Cancer Epub 2013;Nov 12.

Raw IF: 1.429 Normalized IF: 2

Lopci E*, Colombo P, Rodari M, Lania A, Vitobello D, Leonardi L, Chiti A.

Imaging struma ovarii by means of 124INa PET/CT. Nuclear Medicine Review. Central & Eastern Europe 2013;16(2):95-6.

Raw IF: 0 Normalized IF: 0

Lopci E*, Monti L, Balzarini L, Chiti A.

Cardiac and acoustic metastases in relapsing melanoma.

Clinical Nuclear Medicine 2013;38(2):e85-8.

Raw IF: 2.955 Normalized IF: 6

Lopci E*, Rodari M, Pepe G, Antunovic L, Chiti A.

Imaging acute spinal myelitis with 18F-FDG PET/CT. European Journal of Nuclear Medicine and Molecular Imaging 2014;41(2):399-400.

Raw IF: 5.114 Normalized IF: 6

Lopci E, Zanoni L, Fanti S, Ambrosini V, Castellani MR, Aktolun C, Chiti A*.

Gallium-68 DOTANOC imaging in paraganglioma/pheochromocytoma: presentation of sample cases and review of the literature.

Quarterly Journal of Nuclear Medicine and Molecular Imaging 2013;57(2):134-45.

Raw IF: 1.918 Normalized IF: 4

Piccardo A, Lopci E, Conte M, Cabria M, Cistaro A, Garaventa A, Villavecchia G.

Bone and lymph node metastases from neuroblastoma detected by 18F-DOPAPET/CT and confirmed by posttherapy 131I-MIBG but negative on diagnostic 123I-MIBG scan.

Clinical Nuclear Medicine 2014;39(1):e80-3.

Raw IF: 2.955 Normalized IF: 6

Piccardo A, Lopci E, Conte M, Foppiani L, Garaventa A, Cabria M, Villavecchia G, Fanti S, Cistaro A.

PET/CT imaging in neuroblastoma.

Quarterly Journal of Nuclear Medicine and Molecular Imaging 2013;57(1):29-39.

Raw IF: 1.918 Normalized IF: 4

Piccardo A, Lopci E, Foppiani L, Morana G, Conte M.

18F-DOPA PET/CT for assessment of response to induction chemotherapy in a child with high-risk neuroblastoma.

Pediatric Radiology 2014;44(3):355-61.

Raw IF: 1.565 Normalized IF: 4

Quartuccio N, Treglia G, Salsano M, Mattoli MV, Muoio B, Piccardo A, Lopci E, Cistaro A.

The role of Fluorine-18Fluorodeoxyglucose positron emission tomography in staging and restaging of patients with osteosarcoma.

Radiology and Oncology 2013;47(2):97-102.

Raw IF: 1.602 Normalized IF: 1

Ophthalmology Agarwal A, Jacob S, Tamayo G, Vinciguerra P, Wilson SE, Netto MV, Izquierdo L, Smadja D, Tomita M, Fontes BM, Ali贸 JL.

Refractive surgical problem: June consultation.

Journal of Cataract and Refractive Surgery 2013;39(6):958-65.

Raw IF: 2.527 Normalized IF: 3

Pellegrini G, Rama P, Matuska S, Lambiase A, Bonini S, Pocobelli A, Colabelli RG, Spadea L, Fasciani R, Balestrazzi E, Vinciguerra P, Rosetta P, Tortori A, Nardi M, Gabbriellini G, Traverso CE, Macaluso C, Losi L, Percesepe A, Venturi B, Corradini F, Panaras A, Di Rocco A, Guatelli P, De Luca M.

Biological parameters determining the clinical outcome of autologous cultures of limbal stem cells.

Regenerative Medicine 2013;8(5):553-67.

Raw IF: 3.873 Normalized IF: 3

Romano MR*, Vallejo-Garcia JL, Romano V, Angi M, Vinciguerra P, Costagliola C.

Thermodynamics of vitreoretinal surgery.

Current Eye Research 2013;38(3):371-4.

Raw IF: 1.71 Normalized IF: 4

Romano MR, Vinciguerra R, Vinciguerra P.

Sutureless silicone oil removal: a quick and safe technique.

Retina 2013;33(5):1090-1.

Raw IF: 0 Normalized IF: 0

Romano V, Angi M, Scotti F, del Grosso R, Romano D, Semeraro F, Vinciguerra P, Costagliola C, Romano MR.

Inflammation and macular oedema after pars plana vitrectomy.

Mediators of Inflammation 2013;971758.

Raw IF: 3.882 Normalized IF: 6

Semeraro F, Romano MR, Duse S, Costagliola C.

Quality of vision in patients implanted with aspherical and spherical intraocular lens: intraindividual comparison.

Indian Journal of Ophthalmology Epub 2013;Sep 6.

Raw IF: 0.797 Normalized IF: 1

Vinciguerra P*.

The efficacy of corneal cross-linking shows a sudden decrease with very high intensity UV light and short treatment time.

Investigative Ophthalmology & Visual Science 2013;54(2):1181.

Raw IF: 3.441 Normalized IF: 6

Vinciguerra P, Rechichi M, Rosetta P, Romano MR, Mastropasqua L, Scorcia V, Azzolini C, Vinciguerra R.

High fluence iontophoretic corneal collagen cross-linking: in vivo OCT imaging of riboflavin penetration.

Journal of Refractive Surgery 2013; 29(6):376-7.

Raw IF: 2.474 Normalized IF: 3

103

Papers published 2013

Vinciguerra R, Romano MR, Camesasca FI, Azzolini C, Trazza S, Morenghi E, Vinciguerra P.

Corneal cross-linking as a treatment for keratoconus: four-year morphologic and clinical outcomes with respect to patient age.

Ophthalmology 2013;120(5):908-16.

Raw IF: 5.563 Normalized IF: 6

Vinciguerra R, Rosetta P, Romano MR, Azzolini C, Vinciguerra P.

Treatment of refractory infectious keratitis with corneal collagen crosslinking window absorption.

Cornea 2013;32(6):e139-40.

Raw IF: 1.746 Normalized IF: 2

May autonomic indices from cardiovascular variability help identify hypertension?

Journal of Hypertension 2014;32(2):363-73.

Raw IF: 3.806 Normalized IF: 6

Menon A, Pettinari L, Martinelli C, Colombo G, Portinaro N, Dalle-Donne I, d’Agostino MC, Gagliano N.

New insights in extracellular matrix remodeling and collagen turnover related pathways in cultured human tenocytes after ciprofloxacin administration.

Muscles Ligaments and Tendons Journal 2013;3(3):122-31.

Raw IF: 0 Normalized IF: 0

Paediatric and NeuroOrthopaedics Surgery

Castagna A, Borroni M, Garofalo R, Rose GD, Cesari E, Padua R, Conti M, Gumina S.

Deep partial rotator cuff tear: transtendon repair or tear completion and repair? A randomized clinical trial.

Menon A, Pettinari L, Martinelli C, Colombo G, Portinaro N, Dalle-Donne I, d’Agostino MC, Gagliano N.

Knee Surgery, Sports Traumatology, Arthroscopy Epub 2013;May 21.

Raw IF: 2.676 Normalized IF: 6

New insights in extracellular matrix remodeling and collagen turnover related pathways in cultured human tenocytes after ciprofloxacin administration.

Castagna A, Cesari E, Garofalo R, Gigante A, Conti M, Markopoulos N, Maffulli N.

Muscles Ligaments and Tendons Journal 2013;3(3):122-31.

Raw IF: 0 Normalized IF: 0

Matrix metalloproteases and their inhibitors are altered in torn rotator cuff tendons, but also in the macroscopically and histologically intact portion of those tendons.

Muscles Ligaments and Tendons Journal 2013;3(3):132-8.

Raw IF: 0 Normalized IF: 0

Castagna A, Cesari E, Gigante A, Conti M, Garofalo R.

Metalloproteases and their inhibitors are altered in both torn and intact rotator cuff tendons.

Musculoskeletal Surgery 2013;97(suppl1):39-47.

Raw IF: 0

Cucchiari D, Bertuzzi A, Colombo P, De Sanctis R, Faucher E, Fusco N, Pellegrinelli A, Arosio P, Angelini C.

Juxtaglomerular cell tumor: multicentric synchronous disease associated with paraneoplastic syndrome.

Journal of Clinical Oncology 2013;31(14):e240-2.

Raw IF: 18.038 Normalized IF: 15

Di Tommaso L, Sangiovanni A, Borzio M, Nyun Park Y, Farinati F, Roncalli M.

Advanced precancerous lesions in the liver.

Best Practice & Research Clinical Gastroenterology 2013;27(2):269-84.

Raw IF: 3.155 Normalized IF: 4

Donadon M*, Di Tommaso L, Roncalli M, Torzilli G.

Orthopaedic Rehabilitation

Normalized IF: 0

Giussani M, Antolini L, Brambilla P, Pagani M, Zuccotti G, Valsecchi MG, Lucini D, Genovesi S.

Cardiovascular risk assessment in children: role of physical activity, family history and parental smoking on BMI and blood pressure.

104

Lucini D*, Solaro N, Pagani M.

Journal of Hypertension 2013;31(5):983-92.

Raw IF: 3.806 Normalized IF: 3

Pathology Celesti G, Di Caro G, Bianchi P, Grizzi F, Basso G, Marchesi F, Doni A, Marra G, Roncalli M, Mantovani A, Malesci A*, Laghi L.

Presence of Twist1-positive neoplastic cells in the stroma of chromosomeunstable colorectal tumors.

Gastroenterology 2013;145(3):647-57.

Raw IF: 13 Normalized IF: 10

Celesti G, Di Caro G, Bianchi P, Grizzi F, Marchesi F, Basso G, Rahal D, Delconte G, Catalano M, Cappello P, Roncalli M, Zerbi A, Montorsi M, Novelli F, Mantovani A, Allavena P, Malesci A*, Laghi L. (Celesti and Di Caro contributed equally to this work)

Early expression of the fractalkine receptor CX3CR1 in pancreatic carcinogenesis.

British Journal of Cancer 2013;109(9):2424-33.

Raw IF: 5.082 Normalized IF: 6

Multiple focal nodular hyperplasias induced by oxaliplatin-based chemotherapy.

World Journal of Hepatology 2013;5(6):340-4.

Raw IF: 0 Normalized IF: 0

Field JK, van Klaveren R, Pedersen JH, Pastorino U, Paci E, Becker N, Infante M, Oudkerk M, de Koning HJ; on behalf of the European Randomized Screening Trial Group. (Collaborators: Brambilla G, Lutman F, Santoro A, Chiti A, Morenghi E, Destro A, Roncalli M, Alloisio M).

European randomized lung cancer screening trials: post NLST. Journal of Surgical Oncology 2013;108(5):280-6.

Raw IF: 2.644 Normalized IF: 3

Gaetani P, Pisano P, Solinas G, Colombo P, Destro A, Levi D, Aimar E, Rodriguez R, Baena Y, Allavena P.

Immunohistohemical expression of the chemokine fractalkine and its receptor in the human brain cortex after severe traumatic brain injury and brain hemorrhage.

Journal of Neurosurgical Sciences 2013;57(1):55-62.

Raw IF: 0.53 Normalized IF: 1

Grizzi F, Di Biccari S, Fiamengo B, Štifter S, Colombo P.

Pituitary tumor-transforming gene 1 is expressed in primary ductal breast carcinoma, lymph node infiltration and distant metastases.

Disease Markers 2013;35(4):267-72.

Raw IF: 2.14 Normalized IF: 4

Personeni N*, Rimassa L, Pressiani T, Destro A, Ligorio C, Tronconi MC, Bozzarelli S, Carnaghi C, Di Tommaso L, Giordano L, Roncalli M, Santoro A.

Molecular determinants of outcome in sorafenib-treated patients with hepatocellular carcinoma.

Journal of Cancer Research and Clinical Oncology 2013;139(7):1179-87.

Raw IF: 2.914 Normalized IF: 4

Pintea B, Di Tommaso L, Destro A, Roncalli M.

Combined hepatocellular carcinoma - cholangiocarcinoma harboring a metastasis of colon adenocarcinoma.

Journal of Gastrointestinal and Liver Diseases 2013;22(3):341-3.

Raw IF: 1.855 Normalized IF: 2

Repici A*, Zullo A, Hassan C, Spaggiari P, Strangio G, Vitetta E, Ferrara E, Malesci A.

Torrisi R*, Garcia-Etienne CA, Losurdo A, Morenghi E, Di Tommaso L, Gatzemeier W, Sagona A, Fernandes B, Rossetti C, Eboli M, Rubino A, Barbieri E, Andreoli C, Orefice S, Gandini C, Rota S, Zuradelli M, Masci G, Santoro A, Tinterri C.

Potential impact of the 70-gene signature in the choice of adjuvant systemic treatment for ER positive, HER2 negative tumors: a single institution experience.

Breast 2013;22(4):419-24.

Raw IF: 1.967 Normalized IF: 4

Plastic Surgery Klinger M*, Caviggioli F, Klinger FM, Giannasi S, Bandi V, Banzatti B, Forcellini D, Maione L, Catania B, Vinci V.

Autologous fat graft in scar treatment.

Endoscopic submucosal dissection of early gastric neoplastic lesions: a western series.

Journal of Craniofacial Surgery 2013;24(5):1610-5.

Raw IF: 0.686 Normalized IF: 1

European Journal of Gastroenterology & Hepatology 2013;25(11):1261-4.

Raw IF: 1.915 Normalized IF: 2

Klinger F , Caviggioli F , Vinci V , Forcellini D , Maione L , Lisa A , Klinger M.

Taverna G, Giusti G, Seveso M, Hurle R, Colombo P, Stifter S, Grizzi F*.

Triple-V flap: nipple reconstruction using a modified C-V flap technique for longlasting improvement of projection.

Mast cells as a potential prognostic marker in prostate cancer.

Disease Markers 2013;35(6):711-20.

Raw IF: 2 Normalized IF: 4

Taverna G, Grizzi F, Colombo P, Graziotti P.

Is angiogenesis a hallmark of prostate cancer?

Frontiers in Oncology 2013;3:15.

Raw IF: 0 Normalized IF: 0

Taverna G*, Magnoni P, Giusti G, Seveso M, Benetti A, Hurle R, Colombo P, Minuti F, Grizzi F, Graziotti P.

Impact of real-time elastography versus systematic prostate biopsy method on cancer detection rate in men with a serum Prostate-Specific Antigen between 2 5 and 10 ng/mL. ISRN Oncology 2013;584672.

Raw IF: 0 Normalized IF: 0

European Journal of Plastic Surgery 2013;36(11):689-92.

Raw IF: 0 Normalized IF: 0

Vinci V, Klinger M, Klinger FM, Forcellini D, Borbon G, Caviggioli F.

Treatment outcomes for keloid scar management in the pediatric burn population.

Burns 2013;39(6):1321-2.

Raw IF: 1.799 Normalized IF: 2

Radiotherapy and Radiosurgery Alongi F*, Cozzi L, Arcangeli S, Iftode C, Comito T, Villa E, Lobefalo F, Navarria P, Reggiori G, Mancosu P, Clerici E, Fogliata A, Tomatis S, Taverna G, Graziotti P, Scorsetti M.

Linac based SBRT for prostate cancer in 5 fractions with VMAT and flattening filter free beams: preliminary report of a phase II study.

Radiation Oncology 2013;8(1):171.

Raw IF: 2.107 Normalized IF: 4

Alongi F*, Cozzi L, Fogliata A, Iftode C, Comito T, Clivio A, Villa E, Lobefalo F, Navarria P, Reggiori G, Mancosu P, Clerici E, Tomatis S, Taverna G, Graziotti P, Scorsetti M.

Hypofractionation with VMAT versus 3DCRT in post-operative patients with prostate cancer.

Anticancer Research 2013;33(10):4537-43.

Raw IF: 1.713 Normalized IF: 2

Alongi F, De Bari B, Campostrini F, Arcangeli S, Matei DV, Lopci E, Petralia G, Bellomi M, Chiti A, Magrini SM, Scorsetti M, Orecchia R, Jereczek-Fossa BA.

Salvage therapy of intraprostatic failure after radical external-beam radiotherapy for prostate cancer: a review.

Critical Reviews in Oncology/Haematology 2013;88(3):550-63.

Raw IF: 4.637 Normalized IF: 6

Alongi F, De Bari B, Franco P, Ciammella P, Chekrine T, Livi L, Jereczek-Fossa BA, Filippi AR; AIRO Young and AIRO Prostate cancer Working Group.

The PROCAINA (PROstate CAncer INdication Attitudes) Project (Part I): a survey among Italian radiation oncologists on postoperative radiotherapy in prostate cancer.

Radiologia Medica 2013;118(4):660-78.

Raw IF: 1.461 Normalized IF: 2

Alongi F*, Liardo RL, Iftode C, Lopci E, Villa E, Comito T, Tozzi A, Navarria P, Ascolese AM, Mancosu P, Tomatis S, Bellorofonte C, Chiti A, Scorsetti M.

11C choline PET guided salvage radiotherapy with volumetric modulation arc therapy and hypofractionation for recurrent prostate cancer after HIFU failure: preliminary results of tolerability and acute toxicity.

Technology in Cancer Research & Treatment Epub 2013;Aug 31.

Raw IF: 1.943 Normalized IF: 2

Cacicedo J, Navarro A, Alongi F, Gómez de Iturriaga A, Del Hoyo O, Boveda E, Casquero F, Perez JF, Bilbao P.

The role of re-irradiation of secondary and recurrent head and neck carcinomas Is it a potentially curative treatment?

A practical approach.

Cancer Treatment Reviews 2014;40(1):178-89.

Raw IF: 6.024 Normalized IF: 3

105

Papers published 2013

Celesti G, Di Caro G, Bianchi P, Grizzi F, Marchesi F, Basso G, Rahal D, Delconte G, Catalano M, Cappello P, Roncalli M, Zerbi A, Montorsi M, Novelli F, Mantovani A, Allavena P, Malesci A*, Laghi L. (Celesti and Di Caro contributed equally to this work)

Early expression of the fractalkine receptor CX3CR1 in pancreatic carcinogenesis.

British Journal of Cancer 2013;109(9):2424-33.

Raw IF: 5.082 Normalized IF: 6

Lobefalo F, Bignardi M, Reggiori G, Tozzi A, Tomatis S, Alongi F, Fogliata A, Gaudino A, Navarria P, Cozzi L, Scorsetti M, Mancosu P*.

Dosimetric impact of inter-observer variability for 3D conformal radiotherapy and volumetric modulated arc therapy: the rectal tumor target definition case.

Radiation Oncology 2013;8(1):176.

Raw IF: 2.107 Normalized IF: 4

Mancosu P*, Navarria P, Castagna L, Reggiori G, Sarina B, Tomatis S, Alongi F, Nicolini G, Fogliata A, Cozzi L, Scorsetti M.

Interplay effects between dose distribution quality and positioning accuracy in total marrow irradiation with volumetric modulated arc therapy.

Medical Physics 2013;40(11):111713.

Raw IF: 2.911 Normalized IF: 6

Mancosu P*, Reggiori G, Alongi F, Cozzi L, Fogliata A, Lobefalo F, Navarria P, Stravato A, Tomatis S, Scorsetti M.

Total monitor units influence on plan quality parameters in volumetric modulated arc therapy for breast case.

Physica Medica 2014;30(3):296-300.

Raw IF: 1.167 Normalized IF: 2

Navarria P*, Ascolese AM, Mancosu P, Alongi F, Clerici E, Tozzi A, Iftode C, Reggiori G, Tomatis S, Infante M, Alloisio M, Testori A, Fogliata A, Cozzi L, Morenghi E, Scorsetti M.

Volumetric modulated arc therapy with flattening filter free (FFF) beams for stereotactic body radiation therapy (SBRT) in patients with medically inoperable early stage non small cell lung cancer (NSCLC).

Radiotherapy and Oncology 2013;107(3):414-8.

Raw IF: 4.52 Normalized IF: 6

106

Scorsetti M, Arcangeli S, Tozzi A, Comito T, Alongi F*, Navarria P, Mancosu P, Reggiori G, Fogliata A, Torzilli G, Tomatis S, Cozzi L.

Is stereotactic body radiation therapy an attractive option for unresectable liver metastases? A preliminary report from a phase 2 trial.

International Journal of Radiation Oncology, Biology, Physics 2013;86(2):336-42.

Raw IF: 4.524 Normalized IF: 6

Tozzi A, Comito T, Alongi F,* Navarria P, Iftode C, Mancosu P, Reggiori G, Clerici E, Rimassa L, Zerbi A, Fogliata A, Cozzi L, Tomatis S, Scorsetti M.

SBRT in unresectable advanced pancreatic cancer: preliminary results of a mono-institutional experience.

Radiation Oncology 2013;8(1):148.

Raw IF: 2.107 Normalized IF: 4

Rheumatology and Clinical Immunology Iagnocco A, Ceccarelli F, Cuomo G, Delle Sedie A, Filippou G, Filippucci E, Grassi W, Porta F, Sakellariou G; Musculoskeletal Ultrasound Study Group of the Italian Society of Rheumatology. (Collaborators: Massarotti M).

Diffusion and applications of musculoskeletal ultrasound in Italian Rheumatology Units.

Reumatismo 2013;65(1):46-7.

Raw IF: 0 Normalized IF: 0

Iagnocco A, Porta F, Cuomo G, Delle Sedie A, Filippucci E, Grassi W, Sakellariou G, Epis O, Adinolfi A, Ceccarelli F, De Lucia O, Di Geso L, Di Sabatino V, Gabba A, Gattamelata A, Gutierrez M, Massaro L, Massarotti M, Perricone C, Picerno V, Ravagnani V, Riente L, Scioscia C, Naredo E, Filippou G; on behalf of the Musculoskeletal Ultrasound Study Group of the Italian Society of Rheumatology.

The Italian MSUS Study Group recommendations for the format and content of the report and documentation in musculoskeletal ultrasonography in rheumatology.

Rheumatology 2014;53(2):367-73.

Raw IF: 4.212 Normalized IF: 6

Shoulder and Elbow Surgery Castagna A, Borroni M, Garofalo R, Rose GD, Cesari E, Padua R, Conti M, Gumina S.

Deep partial rotator cuff tear: transtendon repair or tear completion and repair? A randomized clinical trial.

Knee Surgery, Sports Traumatology, Arthroscopy Epub 2013;May 21.

Raw IF: 2.676 Normalized IF: 6

Castagna A, Cesari E, Garofalo R, Gigante A, Conti M, Markopoulos N, Maffulli N.

Matrix metalloproteases and their inhibitors are altered in torn rotator cuff tendons, but also in the macroscopically and histologically intact portion of those tendons.

Muscles Ligaments and Tendons Journal 2013;3(3):132-8.

Raw IF: 0 Normalized IF: 0

Castagna A, Cesari E, Gigante A, Conti M, Garofalo R.

Metalloproteases and their inhibitors are altered in both torn and intact rotator cuff tendons.

Musculoskeletal Surgery 2013;97(suppl1):39-47.

Raw IF: 0

Normalized IF: 0

Castagna A, Delcogliano M, de Caro F, Ziveri G, Borroni M, Gumina S, Postacchini F, De Biase CF.

Conversion of shoulder arthroplasty to reverse implants: clinical and radiological results using a modular system.

International Orthopaedics 2013; 37(7):1297-305.

Raw IF: 3.319 Normalized IF: 6

De Biase CF, Ziveri G, Delcogliano M, de Caro F, Gumina S, Borroni M, Castagna A, Postacchini R.

The use of an eccentric glenosphere compared with a concentric glenosphere in reverse total shoulder arthroplasty: two-year minimum followup results.

International Orthopaedics 2013;37(10):1949-55.

Raw IF: 2.319 Normalized IF: 3

De Filippo M, Castagna A, Steinbach LS, Silva M, Concari G, Pedrazzi G, Pogliacomi F, Sverzellati N, Petriccioli D, Vitale M, Ceccarelli F, Zompatori M, Rossi C.

Reproducible noninvasive method for evaluation of glenoid bone loss by multiplanar reconstruction curved computed tomographic imaging using a cadaveric model.

Arthroscopy 2013;29(3):471-7.

Raw IF: 3.103 Normalized IF: 6

Galvan A, Frullanti E, Anderlini M, Manenti G, Noci S, Dugo M, Ambrogi F, De Cecco L, Spinelli R, Piazza R, Pirola A, Gambacorti-Passerini C, Incarbone M, Alloisio M, Tosi D, Nosotti M, Santambrogio L, Pastorino U, Dragani TA.

Gene expression signature of noninvolved lung tissue associated with survival in lung adenocarcinoma patients.

Carcinogenesis 2013;34(12):2767-73.

Raw IF: 5.635 Normalized IF: 3

Genovese E, Spanò E, Castagna A, Leonardi A, Angeretti MG, Callegari L, Fugazzola C.

Infante M*, Berghmans T, Heuvelmans MA, Hillerdal G, Oudkerk M.

MR-arthrography in superior instability of the shoulder: correlation with arthroscopy.

Slow-growing lung cancer: an emerging entity from screening to clinical management.

La Radiologia Medica 2013;118(6):1022-33.

Raw IF: 1.461 Normalized IF: 1

The European Respiratory Journal 2013;42(6):1706-22.

Raw IF: 6.355 Normalized IF: 6

Giavaresi G, Bondioli E, Melandri D, Giardino R, Tschon M, Torricelli P, Cenacchi G, Rotini R, Castagna A, Veronesi F, Pagani S, Fini M.

Response of human chondrocytes and mesenchymal stromal cells to a decellularized human dermis.

BMC Musculoskeletal Disorders 2013;14:12.

Raw IF: 1.875 Normalized IF: 2

Gumina S, Carbone S, Campagna V, Castagna A, Rocca CD, Giannicola G. Pigmented villonodular synovitis of the shoulder associated with massive rotator cuff tear treated by arthroscopic synovectomy and debridement.

Musculoskeletal Surgery 2013;97(suppl1):79-84.

Raw IF: 0 Normalized IF: 0

Thoracic Surgery Field JK, van Klaveren R, Pedersen JH, Pastorino U, Paci E, Becker N, Infante M, Oudkerk M, de Koning HJ; on behalf of the European Randomized Screening Trial Group. (Collaborators: Brambilla G, Lutman F, Santoro A, Chiti A, Morenghi A, Destro A, Roncalli M, Alloisio M).

European randomized lung cancer screening trials: post NLST. Journal of Surgical Oncology 2013;108(5):280-6.

Raw IF: 2.644 Normalized IF: 3

Luzzati A, Shah S, Gagliano F, Perrucchini G, Fontanella W, Alloisio M.

4 & 5 levels en bloc spondylectomy for malignant spinal tumors.

Spine 2014;39(2):E129-39.

Raw IF: 2.159 Normalized IF: 4

Navarria P*, Ascolese AM, Mancosu P, Alongi F, Clerici E, Tozzi A, Iftode C, Reggiori G, Tomatis S, Infante M, Alloisio M, Testori A, Fogliata A, Cozzi L, Morenghi E, Scorsetti M.

Volumetric modulated arc therapy with flattening filter free (FFF) beams for stereotactic body radiation therapy (SBRT) in patients with medically inoperable early stage non small cell lung cancer (NSCLC).

Thrombosis Centre Agnelli G, Buller HR, Cohen A, Curto M, Gallus AS, Johnson M, Masiukiewicz U, Pak R, Thompson J, Raskob GE, Weitz JI; AMPLIFY Investigators. (Collaborators: Lodigiani C).

Oral apixaban for the treatment of acute venous thromboembolism.

New England Journal of Medicine 2013;369(9):799-808.

Raw IF: 51.658 Normalized IF: 3

Agnelli G, Buller HR, Cohen A, Curto M, Gallus AS, Johnson M, Porcari A, Raskob GE, Weitz JI; PLIFY-EXT Investigators.

(Collaborators: Lodigiani C).

Apixaban for extended treatment of venous thromboembolism.

New England Journal of Medicine 2013;368(8):699-708.

Raw IF: 51.658 Normalized IF: 3

Becattini C, Agnelli G, Schenone A, Eichinger S, Bucherini E, Silingardi M, Bianchi M, Moia M, Ageno W, Vandelli MR, Grandone E, Prandoni P; WARFASA Investigators. (Collaborators: Lodigiani C).

Aspirin for preventing the recurrence of venous thromboembolism.

New England Journal of Medicine 2012;366(21):1959-67.

Raw IF: 51.658 Normalized IF: 3

Bertoletti L, Quenet S, Laporte S, Sahuquillo JC, Conget F, Pedrajas JM, Martin M, Casado I, Riera-Mestre A, Monreal M; RIETE Investigators. (Collaborators: Rota LL).

Radiotherapy and Oncology 2013;107(3):414-8.

Raw IF: 4.52 Normalized IF: 6

Pulmonary embolism and 3-month outcomes in 4036 patients with venous thromboembolism and chronic obstructive pulmonary disease: data from the RIETE registry.

Testori A, Meroni S, Cariboni U, Errico V, Voulaz E, Infante VM, Alloisio M.

Respiratory Research 2013;14:75.

Raw IF: 3.642 Normalized IF: 1.2

A very elderly lung cancer patient: case report of a long disease free survival.

Annals of Thoracic and Cardiovascular Surgery Epub 2013;Jun 4.

Raw IF: 0.466 Normalized IF: 1

Traumatology Berlusconi M*, Busnelli L, Chiodini F, Portinaro N.

BĂźller HR, Gallus AS, Pillion G, Prins MH, Raskob GE; Cassiopea Investigators.

(Collaborators: Lodigiani C).

Enoxaparin followed by once-weekly idrabiotaparinux versus enoxaparin plus warfarin for patients with acute symptomatic pulmonary embolism: a randomised, double-blind, doubledummy, non-inferiority trial.

Lancet 2012;379(9811):123-9.

Raw IF: 39.06 Normalized IF: 3

To fix or not to fix? The role of fibular fixation in distal shaft fractures of the leg.

Injury 2014;45(2):408-1.

Raw IF: 2.174

Normalized IF: 6

107

Papers published 2013

Cosmi B, Legnani C, Pengo V, Ghirarduzzi A, Testa S, Poli D, Prisco D, Tripodi A, Palareti G; PROLONG Investigators (on behalf of FCSA, Italian Federation of Anticoagulation Clinics). (Collaborators: Rota LL).

The influence of factor V Leiden and G20210A prothrombin mutation on the presence of residual vein obstruction after idiopathic deep-vein thrombosis of the lower limbs.

Thrombosis and Haemostasis 2013; 109(3):510-16.

Raw IF: 6.094 Normalized IF: 1.2

den Exter PL, Gómez V, Jiménez D, Trujillo-Santos J, Muriel A, Huisman MV, Monreal M; Registro Informatizado de la Enfermedad TromboEmbólica (RIETE) Investigators. (Collaborators: Rota LL, Ferrazzi P).

A clinical prognostic model for the identification of low-risk patients with acute symptomatic pulmonary embolism and active cancer.

Chest 2013;143(1):138-45.

Raw IF: 5.854 Normalized IF: 1.2

EINSTEIN–PE Investigators, Büller HR, Prins MH, Lensin AW, Decousus H, Jacobson BF, Minar E, Chlumsky J, Verhamme P, Wells P, Agnelli G, Cohen A, Berkowitz SD, Bounameaux H, Davidson BL, Misselwitz F, Gallus AS, Raskob GE, Schellong S, Segers A. (Collaborators: Lodigiani C).

Oral rivaroxaban for the treatment of symptomatic pulmonary embolism.

New England Journal of Medicine 2012;366(14):1287-97.

Raw IF: 51.658 Normalized IF: 3

Hokusai-VTE Investigators, Büller HR, Décousus H, Grosso MA, Mercuri M, Middeldorp S, Prins MH, Raskob GE, Schellong SM, Schwocho L, Segers A, Shi M, Verhamme P, Wells P. (Collaborators: Lodigiani C).

Edoxaban versus warfarin for the treatment of symptomatic venous thromboembolism.

New England Journal of Medicine 2013;369(15):1406-15.

Raw IF: 51.658 Normalized IF: 3

Lecumberri R, Alfonso A, Jiménez D, Fernández Capitán C, Prandoni P, Wells PS, Vidal G, Barillari G, Monreal M; RIETE investigators. (Collaborators: Rota LL).

Dynamics of case-fatalilty rates of recurrent thromboembolism and major bleeding in patients treated for venous thromboembolism.

Thrombosis and Haemostasis 2013;110(4):834-43.

Raw IF: 6.094 Normalized IF: 1.2

Lussana F, Betti S, D’Angelo A, De Stefano V, Fedi S, Ferrazzi P, Legnani C, Marcucci R, Palareti G, Rota LL, Sampietro F, Squizzato A, Prisco D, Cattaneo M.

Evaluation of the prevalence of severe hyperhomocysteinemia in adult patients with thrombosis who underwent screening for thrombophilia.

Thrombosis Research 2013;132(6):681-4.

Raw IF: 3.133 Normalized IF: 2

Nieto JA, Solano R, Trapero Iglesias N, Ruiz-Giménez N, Fernández-Capitán C, Valero B, Tiberio G, Bura-Riviere A, Monreal M; RIETE Investigators.

(Collaborators: Rota LL).

Validation of a score for predicting fatal bleeding in patients receiving anticoagulation for venous thromboembolism.

Thrombosis Research 2013;132(2):175-9.

Raw IF: 3.133 Normalized IF: 0.8

Otero R, Elías T, Jara L, Trujillo-Santos J, Bertoletti L, Nauffal D, Ruiz-Ruiz J, Blanco-Molina Á, Monreal M; RIETE investigators. (Collaborators: Rota LL, Ferrazzi P).

Factors associated with elevated pulmonary arterial pressure levels on the echocardiographic assessment in patients with prior pulmonary embolism.

Thrombosis Research 2013;131(5):e191-5.

Raw IF: 3.133 Normalized IF: 0.8

Trujillo-Santos J, Schellong S, Falga C, Zorrilla V, Gallego P, Barrón M, Monreal M; RIETE Investigators. (Collaborators: Rota LL).

Low-molecular-weight or unfractionated heparin in venous thromboembolism: the influence of renal function.

American Journal of Medicine 2013;126(5):425-34.e1.

Raw IF: 4.768 Normalized IF: 1.2

108

Urology Alongi F*, Cozzi L, Arcangeli S, Iftode C, Comito T, Villa E, Lobefalo F, Navarria P, Reggiori G, Mancosu P, Clerici E, Fogliata A, Tomatis S, Taverna G, Graziotti P, Scorsetti M.

Linac based SBRT for prostate cancer in 5 fractions with VMAT and flattening filter free beams: preliminary report of a phase II study.

Radiation Oncology 2013;8(1):171.

Raw IF: 2.107 Normalized IF: 4

Alongi F*, Cozzi L, Fogliata A, Iftode C, Comito T, Clivio A, Villa E, Lobefalo F, Navarria P, Reggiori G, Mancosu P, Clerici E, Tomatis S, Taverna G, Graziotti P, Scorsetti M.

Hypofractionation with VMAT versus 3DCRT in post-operative patients with prostate cancer.

Anticancer Research 2013;33(10):4537-43.

Raw IF: 1.713 Normalized IF: 2

Giusti G.

Totally X-ray-free percutaneous nephrolithotomy: caveat emptor.

British Journal of Urology International 2013;112(7):878-9.

Raw IF: 3.046 Normalized IF: 6

Luciani LG, Porpiglia F, Cai T, D’Elia C, Vattovani V, Giusti G, Tiscione D, Chiodini S, Peschechera R, Fiori C, Spina R, Parma P, Celia A, Malossini G.

Operative safety and oncologic outcome of laparoscopic radical nephrectomy for renal cell carcinoma >7 cm: a multicenter study of 222 patients.

Urology 2013;81(6):1239-45.

Raw IF: 2.424 Normalized IF: 4

Taverna G, Giusti G, Seveso M, Hurle R, Colombo P, Stifter S, Grizzi F*.

Mast cells as a potential prognostic marker in prostate cancer.

Disease Markers 2013;35(6):711-20.

Raw IF: 2.14 Normalized IF: 4

Taverna G, Grizzi F, Colombo P, Graziotti P.

Is angiogenesis a hallmark of prostate cancer?

Frontiers in Oncology 2013;3:15.

Raw IF: 0 Normalized IF: 0

Taverna G*, Magnoni P, Giusti G, Seveso M, Benetti A, Hurle R, Colombo P, Minuti F, Grizzi F, Graziotti P.

Impact of real-time elastography versus systematic prostate biopsy method on cancer detection rate in men with a serum Prostate-Specific Antigen between 2 5 and 10â&#x20AC;&#x2030;ng/mL. ISRN Oncology 2013;584672.

Raw IF: 0 Normalized IF: 0

Vascular and Interventional Radiology Field JK, van Klaveren R, Pedersen JH, Pastorino U, Paci E, Becker N, Infante M, Oudkerk M, de Koning HJ; on behalf of the European Randomized Screening Trial Group. (Collaborators: Brambilla G, Lutman F, Santoro A, Chiti A, Morenghi E, Destro A, Roncalli M, Alloisio).

European randomized lung cancer screening trials: post NLST. Journal of Surgical Oncology 2013;108(5):280-6.

Raw IF: 2.644 Normalized IF: 3

Mauri G, Michelozzi C, Melchiorre F, Poretti D, Tramarin M, Pedicini V, Solbiati L, Cornalba G, Sconfienza LM.

Biodegradable biliary stent implantation in the treatment of benign bilioplasticrefractory biliary strictures: preliminary experience.

European Radiology 2013;23(12):3304-10.

Raw IF: 3.548 Normalized IF: 6

Vascular Surgery Giustiniano E, Ruggieri N*, Battistini GM, Fusilli N, Pellegrino F, Giorgetti P, Bordoni MG, Bellato V, Bordone G.

May transient Positive End-Expiratory Pressure ameliorate hemodynamic setting and outcome after aortic surgery?

Journal of Anesthesia & Clinical Research 2012;3(11):1-5.

Raw IF: 0 Normalized IF: 0

109

Scientific Report Š Humanitas June 2014 Scientific Direction: Alberto Mantovani Communication Manager: Walter Bruno Editorial Coordination: Humanitas: Monica Florianello in collaboration with: Michele Tedeschi (Clinical Trials Office) Silvia Marra (Library) Danilo Petroni (Grant Office) Elena Pisano and Annalisa Franceschetti (Human Resources Office) Zadig, Milano: Giulia Candiani in collaboration with: Maria Rosa Valetto and Laura Ferroglio Graphic design: Luisa Goglio, Brescia Photographs: Marco Capovilla, Milano Paolo Carlini, Milano Renzo Chiesa, Milano Humanitas Press Office

Printed in June 2014

by Tipografia F.lli Verderio, Milano

IRCCS Istituto Clinico Humanitas via Manzoni 56 20089 Rozzano (Milano, Italy) Phone +39 02 8224 2445 Fax +39 02 8224 5101 www.humanitas.it