Scientific Report 2011/2012 by Humanitas Research Hospital

Scientific Report 2011 â&#x20AC;ş2012 Results and Perspectives

Scientific Report 2011 â&#x20AC;ş2012

Scientific Report 2011 â&#x20AC;ş2012 Results and Perspectives

Contents

Istituto Clinico Humanitas: general hospital and research center

International scientific cooperation

Research in Humanitas

Transferring research discoveries to patients

24 Cooperation networks

30 Translation research

80 Departments and teams 80 Clinical Area

29 Clinical-scientific activities

86 Scientific Research and Laboratories 88 Papers published 2011 88 Preclinical Research 96 Translational research 103 Clinical research

Immunity and inflammation

Oncology

Orthopaedics

32 Macrophages as orchestrators

49 Humanization as an

71 Bone, a living tissue

of the cross-talk between immunity and metabolism

interview with alberto mantovani

36 Macrophage polarization

in cancer: the two sides of the coin

interview with antonio sica

indispensable component of the treatment

interview with armando santoro

74 Hip surgery: between conservative approach and prosthesis

57 Intelligent drugs against

a cunning enemy

interview with carmelo carlo-stella

Neurosciences

interview with paolo vezzoni

interview with guido grappiolo

42 A unitary vision of autoimmune and metabolic disease

interview with carlo selmi

45 Thyroid disease: a crossroad for autommunity and metabolism

interview with andrea lania

65 Innovative aspects in spine pathologies from diagnostic tools to surgical procedures

i nterview with maurizio fornari

68 Technology and lab research in oncologic neurosurgery

interview with lorenzo bello

Istituto Clinico Humanitas: general hospital and research center

Humanitas: general hospital and research center

A close integration between assistance, research and training to offer to our patients the world’s best affordable care: this is the challenge at Humanitas. This ambitious aim sees hundreds of professionals – i.e. doctors, researchers, nurses, technicians and other staff – at the frontline every day. “In our work, the patient has always been placed at the center as a person, with his/her own wholeness and complexity, which goes far beyond one single pathology, or a combination of pathologies – says Ivan Colombo, Vice President of Humanitas – Our aim is to cater for the patients’ health needs with an approach that combines cure, pre-clinical and clinical research, specialist competence and multidisciplinary therapeutic pathways. In fact, at Humanitas, the merging of a polyclinic with highly specialised centres as Humanitas Cancer Center, research activity recognised worldwide, as well as a University branch, allows biomedical advancement to be applied to patients straight away within an ongoing innovation and improvement process.

Our effort towards integration is also translated as the ability to create a system and involve different types of competence: this is the reason why we have and promote the coexistence of institutions with specific and apparently very different missions under the same

An integrated general hospital with a high specialisation Emergency Center Humanitas is an Istituto di Ricovero e Cura a carattere scientifico (IRCCS, a Scientific Institute of In-patient Care). In other words, a multi-specialty and highly integrated general hospital with 747 beds (of which 75 are in the medical, surgical, and oncological day-hospital and 28 in the intensive care unit, while 120 beds are reserved to cardioortho-neuro-motor rehabilitation in a separate building), 24 operating theatres, 5 angiographic rooms, and 120 outpatients clinics. Istituto Clinico Humanitas is accredited by the Italian National Health Service. Its diagnostic and therapeutic activities meet people’s requirements at a local, national, and international level with over 140,000 patients from all Italian Regions and from abroad followed each year. Moreover, it is equipped with a high specialisation Emergency Center, attended by over 55,000 patients every year. The “Humanitas case study” was presented to Harvard University MBA students in the framework of its “Innovations in Health Care” course on the planning and management of high-quality healthcare services.

Humanitas: general hospital and research center

Quality and International accreditation Humanitas is the first Italian general hospital to have been certified by Joint Commission International. Since December 2002, it obtained this international certification as a result of reaching the highest standards in healthcare facilities from the points of view of both patients and public healthcare systems.

On the patientsâ&#x20AC;&#x2122; side Istituto Clinico 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.

Logo Fondazione Humanitas roof, i.e. Humanitas and Humanitas Cancer Center as far as assistance is concerned, but Logo ARIEL also Humanitas and Ariel Foundations for care and support, and the UniversitĂ di Milano for teaching and training (including the new international degree course), as well as the Consiglio nazionale delle ricerche (which presence at Humanitas has notably increased during 2011) and the Humanitas Foundation for Research in the research sectorâ&#x20AC;?.

Technology and Innovation Humanitas is a general hospital with a strong tendency for an interdisciplinary, integrated approach and high specialization. From cardiac surgery to orthopaedics, from oncosurgery to neurosurgery, the most advanced standards at an international level are offered, as well as up to date technologies. Among these, radiotherapy, with last generation nuclear accelerators â&#x20AC;&#x201C; which include TrueBeam â&#x20AC;&#x201C; operating at high speed and allowing for an extremely fast and precise treatment. Moreover, Humanitas is equipped with a robotic surgical system to treat cardiac arrhythmias, a 3 Tesla nuclear magnetic resonance, an open-bore NMR and a PET-CT. As well as with an innovative EOS system, the first and only in Italy, that enables an accurate assessment of vertebral column and lower limbs in weight-bearing standing position and reduces the radiation dose considerably. It offers surgeons and orthopaedics a big amount of relevant clinical information to manage each case appropriately and with minimal invasivity. Humanitas also stands out because of the role of robotic surgery, which represents the new frontier in minimally invasive surgery.

Humanitas Cancer Center Within the Istituto Clinico Humanitas operates the Humanitas Cancer Center, a specialist center for cancer research and cure. Specialist rooms, and therapeutic paths geared around the patients’ needs combine with state-of-theart technology and personalized therapies, with a 360-degree assistance. Multidisciplinary cooperation is fundamental, not only at an oncological level, but also between all the specialists who may intervene in the cure process. Humanitas Cancer Center gathers highly specialized experts in oncology. The Polyclinic is able to cater for all the patients’ needs – be they cardiologic, rehabilitative or emergencyrelated – and is organized so as to guarantee support to relatives and continuous care – even after dismissal – through home-hospitalization and cooperation with local hospices. In addition, special attention is given to people who were healed from cancer, whose number is increasing nowadays, and who may need to follow a specific path which is both medical- and assistancerelated, as well as psychological, thanks to specifically designed medical rooms and pathways. At Humanitas, research – which is fundamental for the improvement of the cure quality and results – encompasses all the areas of the curing process: prevention, screening, development of new drugs and support therapies, laparoscopic and robotic surgery, radiotherapy. All this without leaving out pre-clinical research and focusing on the mechanisms where oncologic diseases originate. A specific website – www.cancercenter.it – presents the activities of the Centre, clinical trials, the initiatives for screening and prevention, and patient support services, as well as the latest news from the Oncology world.

Humanitas Cancer Centerâ&#x20AC;&#x2122;s figures 200 health professionals (physicians, surgeons, psychologists, physicists, and biologists) 200 nursing professionals 200 clinical and basic researchers 30,000 patients per year, 40% from Regions other than Lombardy 300 clinical trials and projects aimed to develop new therapeutical options in the last 3 years

The Center 30,000 sqm 300 beds 120 outpatient clinics 20 operating theatres 1 Translational Research Center with a Biobank, Molecular Biology and Clinical Pharmacology labs

Last generation technology equipment for diagnosis and treatment 4 linear accelerators for Radiotherapy, included the innovative TrueBeam accelerator PET-CT and a cyclotron for radiopharmaceutical production 4 CTs 5 NMRs, included a 3 Tesla NMR and an openbore NMR 1 Da Vinci Surgical System

International scientific cooperation The challenge of integrating assistance, research and training is played on international grounds: “this means being confronted with the best international institutions at all levels (i.e. assistance, research and training) in order to attract and train the best minds, whether from Italy or elsewhere, who are going to be the doctors and researchers of the future” – explains Alberto Mantovani, Scientific Director of Humanitas.

There is a closed link between quality of therapy, research and training. Generally speaking, patients are expected to be treated better where research is performed and centers of clinical excellence are thus also dedicated to training and research. Offering patients the best assistance means attracting the most talented researchers from all over the world and offering young doctors international training. This is the best way to get in touch with most advanced progress and to keep up-to-date and develop critical thinking.

This is why we have been strongly committed with the Università di Milano (in fact some University courses take place at Humanitas) in order to create the International Medical

Humanitas Cancer Center Advisory Board Members 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

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

New York University School of Medicine

Humanitas: general hospital and research center

School (MIMed), an international degree course in Medicine and Surgery in English has been active for two years and is a great opportunity for Italian students who are stimulated by colleagues from all over the world to open their minds to different views and to broaden their own perspective”. The teaching approach of the International Medical School (MIMed) is characterised by an approach that is completely new to Italy: “The different subjects – explains the coordinator Gianluca Vago – are integrated with multidisciplinary cooperation. This reduces the con-

straints of the traditional teacher-student approach and allows the students’ active involvement through active learning approaches like problem-based learning, which promotes cooperation and team work, as well as critical thinking. The whole process takes place under a tutor’s guidance and supervision. The tutor is one of the fundamental roles at MiMed, especially during the years at the clinic, where the first students will be admitted from next September: the introduction of a tutor every two students will allow to plan and simulate bedside clinical activities more carefully, and to organize work in small groups. The aim of this is to allow progressive operational autonomy. The international character of this degree course however, is not only limited to the teaching approach. In fact, the educational model

Humanitas Lectures include a series of top level scientific meetings organised in partnership with the Università degli Studi di Milano. 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 (in the picture with Prof. Alberto Mantovani) are worth mentioning.

“MIMed”, International Medical School “MIMed” was designed to combine academic training, experience in hospital, and research laboratory environments. Adopting an innovative approach, at least in traditional Italian teaching, but in line with the most advanced international academic standards, the study course combines lectures held in English with original teaching methods where students play an active role and are largely responsible for their own learning. Interactions with teachers, a broad spectrum of experience in the field, a solid clinical tutoring system, small study groups, problem-based learning and problem-solving are the main features of the learning process. Info at www.mimed.it

The hospital as a teaching site Humanitas is a teaching center of the Università degli Studi di Milano. Specifically, it hosts the courses of the University School of Medicine, the International Medical School (www.mimed.it), the courses in Biotechnology and Nursing Schools.

Humanitas: general hospital and research center

and the use of the English language allowed to attract a number of foreign students on one hand, and to start International cooperation on the other, so as to promote exchanges with European and American Universities. A key characteristic of this degree course is to provide students with the opportunity to come into contact with prestigious research environments abroad. We have already contacted Pittsburgh University and Trinity College Dublin formally, and this is only the starting point for further extension of our cooperation network, and to join the international training circuit. In addition, we are in close contact with the NBME (National Board of Medical Examiners, the organisation which deals with medical professional certification in the USA), so that our students are able to meet the strict criteria required to be admitted to specialization schools in the USA”.

“The International background represents a commitment and a constant challenge towards top-level training – continues Mantovani – including the environment of research, where we are actively involved in International PhD course. Principally, the Open University one in the UK, as well as the PhD in pathology at the Università di Milano.

germany

Geographical distribution of foreign researchers at Humanitas, from January 1st 2011 to February 28th 2012

canada

Hungary

france usa

colombia

romania switzerland

spain cuba

Brazil

poland

Taiwan india

Fondazione Humanitas per la Ricerca 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 Prof. Rolf Zinkernagel.

Italian researchers who returned after an abroad experience Total 11

Humanitas: general hospital and research center

Research in Humanitas Scientific research is the field where the power of Humanitas is tested to be well-known internationally. Mantovani continues: “We have had positive results so far. Scientists from all over the world are hosted in our laboratories (see map). The year 2011, not differently from 2010, saw our scientific productivity increase constantly in quality, so that quality levels remained very high, as indicated by the bibliometric indexes: 1,875 Impact Factor points (1,750 in 2010), with a consistent focus on the immunodegenerative area, where we are recognized as an IRCCS. We are convinced that this is a crucial field for contemporary medicine, in that it has a strong impact on different clinical areas, ranging from cancer to cardiovascular diseases, inflammatory and autoimmune diseases. We obtained important results which include laboratory discoveries and quality clinical studies which analyze and validate diagnostic and therapeutic procedures. Thanks to the use of genomics techniques in different sectors at the patient’s service, it has been possible to identify possible targets in areas of diagnostic and therapeutic intervention for autoimmune diseases and to validate targeted therapies which – in the case of tumours – are guided by molecular characteristics. One of the challenges of the years to come is to turn advancements made in genomics and post-genomics into diagnostic and therapeutic innovation at the patient’s service. Another challenge is to focus on gender medicine, which deals with gender-related problems and differences, with particular reference to the female sex. The results we have obtained so far tell us that we are on the right track using bi-directional cooperation between research, benchside and bedside. In other words, we must transfer laboratory data to patients and let patients drive our lab efforts”.

Research and Teaching Center At the University Research and Teaching Center which is fully integrated with the Clinical Institute counterpart, over 200 researchers have been working with cutting-edge technology, such as the recently acquired two-photon microscope, and a cell factory. The group operates in close collaboration with the hospital (over 600 physicians on the identification of inflammation mechanisms at the outset of the processes) and in the area of development of various diseases that range from tumours, through to disorders of the gastrointestinal tract, and to cardiovascular diseases e.g. myocardial infarction and stroke.

Translational research Humanitasâ&#x20AC;&#x2122; scientific and research activity has always been characterised by an enormous potential for transferring findings from benchside to bedside, implying a close integration and exchange of data between laboratory and hospital wards, crucial to promptly transfer the results of its reasearch into everyday clinical practice.

Humanitas: general hospital and research center

Transferring research discoveries to patients

In the last years, the introduction and development of increasingly sophisticated research technologies – both basic and clinical – have allowed to reduce the time span between scientific discovery and practical application, i.e. daily practice in ambulatories or wards. “It has become fundamental to guarantee that lab results are transferred to the patients rapidly. This is in fact the main aim of research which is referred to as translational research, which is based on close integration and ongoing information exchange between laboratories and clinical practitioners. Therefore it is fundamental to guarantee training for professionals who are competent scientific researchers and work in close contact with patients at the same time: MDs and researchers (PhDs) who work both in hospitals and labs, combining the strict rigor of research with the ongoing relationship with patients who benefit from the most advanced research outcomes and discoveries. This is why the challenge ahead of us – once more together with Università di Milano – is to provide targeted training for MDs and researchers, as is the case internationally.

We are firm believers in this “bridging” between the lab and the bedside, a basic tenet of translational research. Humanitas believes so firmly in this research, that it has invested in it in spite of the strong economic crisis of the country, and has doubled available space. We have now eight new research groups so as to improve innovative studies in the oncologic, cardiovascular and neurologic fields by studying thoroughly the degenerative mechanisms

which underlie such different pathologies.

bulgarY

italy austria

france belgium

sybilla

uk ireland

netherlands germany sweden

finland

germany

italy

france

greece

italy

switzerland

france

israel

italy

france

spain

israel

italy

ATTACK

india

tolerage

spain france switzerland italy austria czech republic

netherlands germany sweden

france switzerland

spain

INNOCHEM

usa uk

italy austria

switzerland

france

belgium netherlands germany czech rep.

spain UK

denmark germany sweden

netherlands

usa

hungary

germany

netherlands

belgium denmark germany poland austria

The network of the EU-sponsored research projects

MUGEN IBDCHIP

moodinflame

Humanitas: general hospital and research center

Cooperation networks Scientific research grows naturally in a natural dimension (which is boundless by nature), and progresses in the cure of patients. This is why it is fundamental that Humanitas takes part in global cooperation networks. As Ivan Colombo explains, â&#x20AC;&#x153;we want to be challenged on this field, where a big effort has been made over the past few years, from the point of view of assessment as well. For us, assessment is not only passion, but true culture. 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 Prof. Rolf Zinkernagel. The international Advisory Board includes doctors and researchers from the most important Cancer Centers in the world, with which we share clinical and research activities of the Humanitas Cancer Center.

The intensity and proactive character of international relationships at Humanitas is illustrated by the ability to be part (or promoters, or leaders) of highly competitive European projects. Projects that are subsidized by the European Union represent only a small portion of our international dimension. We are currently working on projects with the United States and with Eastern countries, in particular with Singapore.

Moreover, we have established structured collaborations with international centers into the wordlwide research scenery, e.g. Brazilâ&#x20AC;?.

Timer On January 1st 2012, the collaborative research programme TargetIng novel MEchanisms of Resolution in inflammation (TIMER) has started in order to accelerate the development of novel and powerful strategies to fight inflammation. TIMER is co-funded with 3 million Euro by the European Commission to establish robust collaboration with Brazil in the strategic area of inflammatory disorders with high socioeconomic impact. This research programme covers a wide range of crucial aspects leading to resolution of 24

ireland UK

sweden

denmark

belgium

Countries involved in international cooperation networks

netherlands germany austria

usa

portugal

inflammation; from the discovery of novel natural compounds and basic research to clinical trials. Scientists from 9 research partners in 4 European countries and in Brazil will collaborate in this new programme. Participants: • Fondazione Humanitas per la Ricerca, Italy • Universidade Federal de Minas Gerais, Brazil • Universidade of Sao Paulo, Brazil • Fundacao Oswaldo Cruz, Brazil • Fondazione per l’Istituto di Ricerca in

switzerland

france

croatia

japan

Biomedicina, Switzerland • University of Glasgow, United Kingdom • Telormedix SA, Switzerland • The Provost Fellows & Scholars of the Holy and Undivided • Trinity of Queen Elizabeth near Dublin, Ireland • Merck Serono SA, Switzerland • ALTA Ricerca e Sviluppo in Biotecnologie S.r.l.u., Italy Coordinator: Alberto Mantovani, Fondazione Humanitas per la Ricerca 25

Humanitas: general hospital and research center

Collaboration at an international level is fundamental even in clinical practice. In recent years, the collaboration with national and international top-ranking hospitals and the constant effort to implement the most advanced technologies has led to outstanding results in the treatment of neoplastic, gastrointestinal, cardiovascular, neurological and immunological diseases.

Concerning our mission against cancer, plenty of clinical research trials designed for the application and testing of new drugs, rely on scientific collaboration with important centers both in the US and Europe: New York, Boston, Tampa, Stanford, Amsterdam, Dublin, Marseille.

The Grant Office The Grant Office acts as a connection between researches and funding institutions, either public or private and represents a strategic support able to allocate funding opportunities and to optimize the management of grants already awarded.

Grant Office is active in the following areas/fields: • continuous scouting of funding opportunities together with evaluation

and selection of those which comply to Humanitas researchers’ projects and strategies; • assistance to the reasearcher in preparing the formal proposal and the project, planning and budget development, and the provision of legal interpretation according to the funding institutions which present the project; • once the funds have been obtained, formal and administrative management according to the tender procedure.

Castellanza Humanitas Mater Domini

Bergamo Humanitas Gavazzeni

www.materdomini.it

www.humanitasgavazzeni.it

Research Fondazione Humanitas per la Ricerca www.humanitasricerca.org

Torino Clinica Cellini www.clinicacellini.it

Take care Fondazione Humanitas www.fondazionehumanitas.it Fondazione Ariel www.fondazioneariel.it

Rozzano Istituto Clinico Humanitas www.humanitas.it

Catania Humanitas Centro Catanese di Oncologia www.humanitascatania.it

The Humanitas Group in Italy The Istituto Clinico Humanitas is the flagship of the Humanitas Group, an Italian hospital network distinguished by its quality, research, high specialisation, common medical culture and emphasis on the humanization of care.

Clinical-scientific activities Clinical activities Outpatients 2009

Inpatients 2009

1,246,415

2010

1,635,391

2011 1000

1200

1400

1600

1800

2011

50,211 48

1,246

2010

49,720

2011

1,742,004

2009

50,423

thousands of patients

1000

thousands of patients

2008

Humanitasâ&#x20AC;&#x2122; people Total people 2008

1,793

2009

1,811

2010

17,8% 50,4%

1,880

2011

31,8%

1,939

1,000

1,200

1,400

1,600

1,800

2,000

total people

Total 2011 100% = 1,939

2008

Nurses, technicians, biologists and others 978

Physicians Staff and researchers 2009 345 616

Research activities Published papers 2008

Raw impact factor* 2008

197

2009

289

2010 2011 200

300

1,727

2011

363 100

1,587

2010

349

896

400

published papers

1,875 0

400

800

1,200

1,600

2,000

raw impact factor

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

Translational research Immunity and inflammation Oncology Neuroscience Orthopaedics

Immunity and inflammation benchside

Macrophages as orchestrators of the cross-talk between immunity and metabolism Interview with Alberto Mantovani

to initiate and sustain inflammation, and to elicit tumour tissue disruption. A switch towards M2 phenotype is associated to low IL-12 and high IL-10 and TGFβ expression. M2 macrophages promote tissue remodeling and angiogenesis and have immunosuppressive functions. Polarization of macrophages in cancer is discussed exhaustively in the interview with Antonio Sica.

» Immune responses are also activated through pathogens. Do macrophages still undergo polarization in this case?

Professor of General Pathology at the Faculty of Medicine and Surgery at the Università degli Studi di Milano and Scientific Director of Humanitas

Metabolism and immunity have been traditionally regarded as watertight compartments, but the distinction is weakening and a progressive integration, to which research at Humanitas has largely contributed, is gaining ground.

» Which new scientific evidence outlines an increasingly strong connection between metabolic and immune activities?

Let’s consider the binomy pyrexia-temperature, the former being a classical expression of the immune response against pathogens, the latter representing the effect of metabolism finalized to body homeostasis by production of energy, thermal energy included. Recent evidence has shown that metabolism is an integral part of immunity, whereas immune cells orchestrate metabolism. Among immune cells, macrophages may be polarized to different functional states depending on the environment they are in. And their metabolism changes accordingly. They undergo M1 (classical) or M2 (alternative) activation. M1 phenotype is characterized by the expression of high level of proinflammatory cytokines, high production of reactive nitrogen and oxygen intermediates, microbicidal and tumouricidal activity. Thus, the M1 macrophages contribute

As far as the responses to pathogens, M1 oriented macrophages are generally involved in acute infections and in resistance against intracellular agents. Conversely, in experimental and humans parasite infections, M2 macrophages undergo an M2 polarization. Moreover, an M1 to M2 switch is observed during the transition from acute to chronic infection and may protect against overwhelming uncontrolled inflammation. Chronic inflammation and granuloma formation (as it may be seen in tuberculosis) are characterized by the presence of macrophage with M2 phenotype, showing an epithelial morphology and a tendency to fuse with the formation of multinucleated giant cells.

» Which pathways does their metabolism follow? Following M2 polarization – which, as we said, is defensive against parasites but unwanted in cancer as promoting its progression – macrophages make use of amino acids, that can be considered metabolic bricks. In that functional state, macrophages modulate immune responses or tumoural growth using different strategies. For example they affect arginine and cysteine metabolism in order to suppress immune responses. Notably, arginine may exert a dual role, since it may provide killer bullets against cancer or suppress immune responses, via its downstream metabolites like nitric oxide and polyamines. Research at Humanitas has achieved important results in many other areas dealing with metabolism modulation in immune cells. Let me mention those

Immunity and inflammation | Benchside Interview with Alberto Mantovani

carried out by the groups of the Lab of Leukocyte Biology led by Massimo Locati at Humanits and of General Pathology led by Gaetano Cairo at the Università di Milano which joined their respective competences to perform studies on macrophage metabolism. They were able to demonstrate that iron metabolism is differentially regulated in polarized macrophages, a discrete iron load differentially affecting tissues damage, repair, and senescence. In fact, M1 polarized macrophages showed changes in gene expression corresponding to a functional state of iron sequestration and batteriostatic effects, while macrophages with M2 phenotype showed a profile of enhanced iron release promoting cells proliferation.

» So far we have described how metabolism

HIGHLIGHT

changes according to different immune stimuli. What can be said about the reverse process,

Massimo Locati, Principal Investigator of the Leukocyte Biology Research Unit, Professor of the Università di Milano

i.e. the effect of immune cells on general metabolism? This process is even more remarkable and surprising. Recently in fact, data have unexpectedly shown not only that immune cells adapt their metabolism to the contingency, but also that they fulfill homeostatic functions beyond defense including orchestration of metabolic functions. A complete and detailed analysis of these aspects is provided by a review of Subhra Biswas and myself in Cell Metabolism.

» Could you provide some examples? We have already stated that body temperature is an expression of the homeostatic metabolism. And adipose tissue is the elective site of metabolism, either white adipose tissue, which manages energy supplies, or brown adipose tissue whose roles are

New microRNA as endogenous anti-inflammatory players

Acute and chronic inflammatory reactions are complex active biological events based on the induction of distinct set of genes in immune cells activated by infectious agents, or other causes of tissue damage. Several molecular mechanisms are involved in the fine tuning of these transcriptional programs to drive resolution of inflammation, and represent promising targets for innovative strategies to control inflammation. «MicroRNA have recently been discovered as a new layer of control of gene expression mechanisms involved in fundamental physiological and pathological processes, from development to cell transformation. As other epigenetic mechanisms, these short non-coding RNA operate at a global level via complex multitargeting strategies, acting on major molecular pathways, in several cases engaging regulatory networks with key transcription factors. Using high-throughput approaches based on in vitro models we have discovered new microRNA involved in the control of inflammatory reactions. Molecular biology approaches have then allowed the identification of several key signalling pathways and transcription factors associated to leukocyte activation as their specific molecular targets. Finally, evidence that these molecular networks are conserved in evolution has been obtained and the generation of specific gene-targeted models to test their relevance in preclinical settings has been performed. We are now investigating the regulation of these microRNA in clinical conditions, with the final goal to exploit the potential diagnostic, prognostic and therapeutic values of these new anti-inflammatory tools.»

fuel combustion and temperature maintainance. Adipose tissue macrophages (ATMs) are a major component of both types of body fat where they orchestrate metabolism. For years, the cascade of thermoregulation has been thought as dependent on the central nervous system – pyrexia may be triggered at this level – but now the contribution of macrophages on the regulation of the “boiler thermostat”, i.e. the brown adipose tissue, has been established.

» Of course this is true in physiological

environments. What happens, however, in pathological conditions?

This is the point, since macrophages play a primary part when the amount of adipose tissue is unbalanced. The example of obesity is appropriate and particularly relevant nowadays, since this condition is reaching worldwide epidemic proportions – even Italy lost the enviable attribute of “lean country” and the figures of younger generations are tragic in terms of body mass index

and nutritional habits – and is commonly referred to as globesity. In obesity, the abundance of adipose tissue and the adipocyte size is related to the macrophage number. Moreover, these cells show an impaired activity, I would say a confused behavior. They are M1 polarized, thus producing inflammatory cytokines which counteract the insulin-sensitizing action of adiponectin and leptin, leading to insulin resistance.

» When does the actual metabolic pathology come into play?

In type 2 diabetes, ATMs are characterized by a M1 phenotype and release high levels of cytokines which, again, induce insulin-resistance and counteract adipokines activity. Notably, thiazolidinediones (glitazones), largely used in the treatment of diabetes, promote M2 polarization, i.e. a homeostatic and anti-inflammatory state of ATMs promoting insulin sensitization. On the other hand, ATMs infiltration and accumulation is orchestrated by selected chemokines. In contrast, ATMs from lean experimental models express high levels of M2 phenotype genes. Weight loss is associated with a shift back to M2like macrophages which promotes lypolisis. It may be supposed that M2-like cells in non obese individuals are involved in maintaining adipose tissue homeostasis, preventing inflammation and insulin resistance. Obesity-associated insulin resistance, diabetic and metabolic syndrome are sustained by chronic subclinical inflammation. In summary, also in obesity and associated disorders, macrophages play a metabolic homeostatic role, as cells capable of reorienting their own metabolic activity and of orchestrating general metabolism. A similar picture may be drawn in cardiovascular disease with modulation of antinflammatory macrophage program.

» The last chapter regards the relationships

between metabolism and oncology, where immunology – once again – may act as a link.

Metabolism may be reconsidered under an oncological view. Apart from the research data,

Immunity and inflammation | Benchside Interview with Alberto Mantovani

this intuition arises from historical empirical observations. Typically, the cachexia associated to cancer and chronic diseases, e.g. that described in African trypanosomiasis, both in humans and in animals at the beginning of the XX century. The isolation of tumour necrosis factor-alpha (TNF-α), which was termed cachectic factor was a later discovery, but it’s consistent with the progressive advances of knowledge. Another dated – even if not outdated – evidence of connections between metabolism and oncology through immunology consists in the metabolic pathways of glucose metabolism. Otto Warburg, a German physiologist and Nobel laureate in 1931, first observed an anomaly in cancer cells metabolism. Differently to normal cells which mainly generate energy from oxidative breakdown of pyruvate, the end product of glycolisis, cancer cells reprogram their glucose metabolism and thus their energy production, by limiting their energy metabolism largely to glycolisis, leading to a state that has been termed anaerobic glycolisis. This metabolic switch, even if less efficient, is oxygen-independent and may favour the adaptation and growth of neoplastic cells in relative hypoxic tissues.

Let me make a digression to remind that cancer cell glycolysis, now better known as Warburg phenomenon is the basis of positron emission tomography (18-FDG PET), the medical imaging technology whose tracer fluorodeoxyglucose (FDG), radiolabels neoplastic tissues relying on this differential metabolic behaviour. In the last few years, the Warburg effect has been reconsidered in the light of oncogenic mechanisms. It has been shown that, while tumour cells, doing without oxygen, are able to build more bricks and to grow faster, macrophages are affected by the hypoxiyc microenvironment. Hypoxia-inducible factors are expressed differently in M1 and M2 polarized macrophages, M2 phenotype being characterized by a preferential localization in hypoxic areas of the tumour and an upregulation of glycolitic enzymes. Thus the ecological niche composed of immune cells helps cooperate with cancer cells in building the bricks for tumour growth. The immunity-metabolism connection is therefore emerging as one of the links between obesity and increased risk not only of diabetes and cardiovascular pathology, but also of cancer.

top paper Mantovani A, Cassatella MA, Costantini C, Jaillon S.

Neutrophils in the activation and regulation of innate and adaptive immunity Nat Rev Immunol. 2011 Jul 25;11(8):519-31. doi: 10.1038/nri3024 Abstract Neutrophils have long been viewed as the final effector cells of an acute inflammatory response, with a primary role in the clearance of extracellular pathogens. However, more recent evidence has extended the functions of these cells. The newly discovered repertoire of effector molecules in the neutrophil armamentarium includes a broad array of cytokines, extracellular traps and effector molecules of the humoral arm of the innate immune system. In addition, neutrophils are involved in the activation, regulation and effector functions of innate and adaptive immune cells. Accordingly, neutrophils have a crucial role in the pathogenesis of a broad range of diseases, including infections caused by intracellular pathogens, autoimmunity, chronic inflammation and cancer. 36

Macrophage polarization in cancer: the two sides of the coin Interview with Antonio Sica

functional states are characterized by M1 (classical) or M2 (alternative) phenotypes, respectively. More in depth, M2 macrophages are involved in cancer progression through promotion of angiogenesis, tissue remodeling by extra-cellular matrix digestion, and suppression of T- lymphocytes antitumoural activity.

» So, how shall the presence of macrophages in tumoural tissue be interpreted?

Principal Investigator of the Molecular Immunology Research Unit, Associate Professor of Pathology, Università degli Studi del Piemonte Orientale

Immunity and inflammation have a broad impact on a spectrum of diseases, cancer included. The cross-talk between neoplastic cells and inflammatory cells may be understood analyzing the two opposite phenotypes of macrophages, which represent the extremes of a continuum of activation states.

» Within the continuous progress made in the

know-how of cross-talk between immunity and cancer, the research at Humanitas has provided an important contribution about the role of macrophages. Shall we lay out the most interesting aspects and the latest data?

The microenvironment surrounding cancer is rich in immune-competent cells: dendritic cells, neutrophils, lymphocytes and macrophages. The latter – also termed tumour-associated macrophages (TAMs) – being the most abundant population and the major players in orchestration of inflammatory circuits associated with cancer growth. Diversity and plasticity are hallmarks of the monocytemacrophage lineage. While appropriately activated macrophages are endowed with antitumoural activity via cytotoxicity and production of inflammatory mediators, a switch to an acquired protumoural activity, which is of great advantage for the neoplasm itself, is described in cancer. These different

There is a continuum from M1 to M2 phenotypes, since TAMs with various functional states can coexist in the same tumour. Studying the molecular events which drive macrophage switch inside a tumour, we have shown that resting TAMs display a higher expression of genes coding for immunosuppressive cytokines, phagocytosis-related receptors, and inflammatory chemokines and a defective activation of NFκB. This molecule belongs to a family of factors, whose production and activation in various dimeric conformations is essential for activation and resolution of inflammation. A further interesting model to understand the role of macrophages is wound healing, a process during which these cells undergo dynamic changes. Namely, M1 polarized macrophages mediate tissue damage and initiate inflammatory responses, while macrophages with M2 phenotype infiltrate the skin after wounding from the earliest stages of the repair. But their depletion inhibits the formation of a highly vascularized cellular granulation tissue, and of scar tissues. Under these conditions, the removal of apoptotic cells and the presence of Tumour Growth Factor β may skew macrophage function. A correspondence may be found between M2 polarization and growth and progression of the disease, suggesting that cancer may be considered as a wound where healing has failed.

» Are these data simply referred to experimental models or also to human studies?

It has been seen in experimental cancer models and also in humans, that macrophage infiltration is a biomarker of risk and macrophage number in neoplastic tissues is associated to a worst prognosis.

Immunity and inflammation | Benchside Interview with Antonio Sica

HIGHLIGHT

This has been proven true for Hodgkin lymphoma, glioma, colangiocarcinoma, prostate carcinoma, and breast carcinoma. Evidence of macrophage polarization as a dynamic process during cancer development and progression is being gathered in humans, as well. An example comes from one of the most largely used drugs ever: aspirin, whose protective antitumoural activity has already been demonstrated by clinical trials in colon cancer and breast cancer. Aspirin acts via an inhibition of inflammatory mediators, mainly cytokines expressed by M1 polarized macrophages, thus turning off inflammation. However, it has to be pointed out that this preventive effect takes place in the earliest phases of cancer induction, where M1 inflammation (e.g. TNF) may support cancerogenesis. In an oncologic patient we generally observe more advanced stages, where the switch to M2 phenotype has already occurred. Thus, we see the expression

Humanitas hosts the Cure and Research Center for Inflammatory Bowel Disease, led by Silvio Danese. The center is part of the Gastroenterology Department, led by Alberto Malesci.

» So, are there no practical implications as yet? On the contrary. The identification and knowledge of the various cellular and molecular pathways that participate in inflammation in different human cancers may be transferred to meaningful therapeutic advances. The assumption is that there are two strategies, not mutually exclusive: attacking the neoplastic cells – the traditional approach – or modulating the inflammatory microenvironment surrounding them – the alternative emerging approach. There is evidence, also from studies performed at Humanitas, that targeting key molecules involved in macrophage M2 polarization may enable to reorient and reshape macrophages towards M1

Inflammatory Bowel Disease pathophysiology: from the bench to the bedside

«It is now clear that Crohn’s disease (CD) and ulcerative colitis (UC) represent two distinct entities of chronic inflammatory bowel disease (IBD) and, as such, have different causes and pathogenic mechanisms. Our laboratory is actively investigating several aspects of these diseases. We are actively investigating the role of the lymphatic system in their pathogenesis, and its relation to progression to colitis-associated colon cancer. In addition, we are actively investigating several molecules involved in controlling epithelial barrier function such as Junction Adhesion Molecule-A, and the protein C. Finally, we are studying stem-cell homing, and are currently trying to understand the mechanisms of stem cell recruitment in the inflamed intestine, in order to improve the engraftment and their homing to the gut. All these areas of investigation are carried out at bench level, with a translational perspective, with the ambitious aim of developing novel therapeutic approaches for CD and UC patients.»

Danese S, Fiocchi C. 38

of immunosuppressive genes (e.g. IL-10 and TGFβ) and low levels of those cytokines which, conversely, support the initial transformation (e.g. TNF).

Ulcerative colitis

N Engl J Med. 2011 Nov 3;365(18):1713-25

top paper Carbone A, Santoro A.

How I treat: diagnosing and managing “in situ” lymphoma Blood. 2011 Apr 14;117(15):3954-60. Epub 2011 Jan 11. Source: Division of Pathology, Centro di Riferimento Oncologico Aviano, Istituto Nazionale Tumori, Istituto di Ricovero e Cura a Carattere Scientifico, Aviano, Italy. acarbone@cro.it Abstract

The “in situ” lymphomas are often incidental findings in an otherwise reactive-appearing lymph node. Notably, the risk of progression to clinically appreciable lymphoma is not yet fully known. The diagnosis of “in situ” lymphoma is feasible when immunohistochemical characterization is carried out and genetic abnormalities are assessed. “In situ” follicular lymphoma is characterized by the presence within the affected germinal centers of B cells that strongly express BCL2 protein, a finding that supports their neoplastic nature, in the absence of interfollicular infiltration. In “in situ” mantle cell lymphoma, the lymphoma involvement is typically limited to the inner mantle zone, where lymphoma cells are cyclin D1(+) and weakly BCL2(+), CD5(+). A staging workup to exclude other site of involvement is highly recommended for the possible coexistence of an overt lymphoma. Biopsy of all sites of suspicious involvement should be mandatory. No evidence for starting therapy also in the presence of multifocal “in situ” lymphoma exists, and a “wait-and-see policy” is strongly suggested. A follow-up strategy reserving imaging evaluation only in the presence of disease-related symptoms or organ involvement appears to be a reasonable option. For patients with concomitant overt lymphoma, staging and treatment procedures must be done according to malignant counterpart.

Intelligent drugs against a cunning enemy

Interview with Carmelo Carlo-Stella

Principal Investigator of the Experimental Therapeutics Unit, Professor of the Università di Milano

The last three decades have witnessed remarkable progresses towards understanding the hallmarks of cancer, defined by Douglas Hanahan and Bob Weinberg as the biological capabilities to be progressively acquired by normal cells during the multistep development of human tumours. The progress of research into the mechanisms of cancer pathogenesis translated into the development of mechanism-based targeted therapies to treat human cancers, i.e., the availability of new drugs specifically targeting neoplastic cells and capable of converting the strengths of cancer cells into weaknesses.

» Now that science has reached a more in-

depth knowledge of cancer cells, is it possible to outline the main characteristics which differentiate cancer cells from normal cells?

During the multistep progression towards cancer, normal cells acquire distinctive biological behaviours which include sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, and activating invasion and metastasis. Moreover, cancer cells show the capability to modify their cellular metabolism in order to support neoplastic cell proliferation most effectively. These features qualify cancer cells as intelligent,

opportunistic and aggressive. The dimension of tumour complexity also include additional elements, such as genetic instability, tumour-promoting inflammation, escaping the immune system as well as normal-to-cancer cell interactions within tumour microenvironment. Indeed, cancer biology cannot be fully appreciated if tumour microenvironment – the place where “normal” cells induce tumour promotion rather than tumour regression – is not appropriately considered. The reductionist view of a tumour as a collection of relatively homogeneous cancer cells is no longer appropriate. In fact, tumour complexity and heterogeneity may even exceed that of normal healthy tissues. In addition to a variety of normal cell types of the tumour microenvironment and a large amount of cancer cells, tumour tissue include a few cancer stem cells (a new dimension of cancer heterogeneity).

» You have described cancer as an “intelligent”

“opportunistic” and “aggressive” enemy whose hallmarks allow its cells to survive, proliferate and disseminate.

Actually, we are playing a game of chess against this enemy, during which we have to face the innate ability of cancer cells to bypass any obstacle and must anticipate each move. We need intelligence to defeat cunning. For this reason, intelligent mechanism-based targeted drugs have been developed in the last decade which exert their therapeutical effects on one or more hallmark capabilities and are directed towards specific molecular targets.

» Can you give us an example? The historical case comes from the discovery of the Philadelphia chromosome in 1960 by Peter Nowell and David Hungerford who showed that this abnormal chromosome was the result of a reciprocal translocation between chromosome 9 and 22 and was associated with Chronic Myelogenous Leukaemia (CML). It then took more than 20 years to clone the BCR/ABL hybrid gene generated by the juxtaposition of the BCR (Breakpoint Cluster Region) gene on chromosome 22 and the ABL (Abelson) gene on chromosome 9. This fusion gene is not only a powerful diagnostic marker detectable in more than

Oncology | Benchside Interview with Carmelo Carlo-Stella

95% of cases of CML, but it is also translated into a fusion protein with costitutive tyrosine kinase activation of ABL gene. What this story taught was the first direct link between chromosomal abnormalities to any malignancy. What it suggested, was the need for developing drugs capable of targeting (and blocking) the costitutive tyrosine kinase activation of ABL. Imatinb, a gene-targeting drug that is the paradigm of a new generation of “smart” drugs, was the first tyrosine kinase inhibitor to be developed in the late Nineties. Ten years later, the natural history of CML – formerly an incurable disease – has dramatically changed. Treated with a non-toxic oral drug, more than 75% of patients diagnosed with CML now achieve a durable complete cytogenetic remission. With the disease in long-term remission (inactive, but not necessarily cured) many CML patients can now expect a normal life span. Imatinib represented a new way to think about treating cancer patients. In fact, other tyrosine

kinase inhibitors (such as nilotinib, dasatinib, sunitinib) were developed and are now important drugs not only for CML but also for a variety of other cancers, including Gastro-Intestinal Stromal Tumours (GISTs) or Philadelphia-positive acute lymphoblastic leukemia.

» Does this lesson apply to any form of cancer? The CML/imatinib story – involving the identification of a cancer-driving genetic lesion and the generation of gene-targeting drugs – has been tentatively extended to almost all neoplastic diseases; however, the unprecedented therapeutic success of imatinib as a specific molecularly targeted therapy for CML has rarely been reproduced. Nevertheless, the availability of a variety of small molecules inhibiting signal transduction as well as of monoclonal antibodies has resulted in significant effects on clinical outcome (survival or progression-free

HIGHLIGHT

As part of the Division of General Surgery III, Humanitas Cancer Center hosts the Pancreatic Surgery Unit led by Alessandro Zerbi

Pancreas: a hostile enemy, but with increasing hope

ÂŤPancreatic cancer is the fourth cause of death for neoplasm in Western countries. It is characterized by a poor prognosis and the only chance of cure is offered by surgery. Its removal is obtained by means of complex surgical procedures, whose results have been improving in the last years both in the immediate postoperative period (especially in high-volume centers) and in the long-term (thanks to the combination with new chemotherapic and radiotherapic regimens). Clinical studies evaluating the role of neoadjuvant chemo/radiotherapy are ongoing, in order to increase the number of resectable tumours and to improve overall survival. It is then important to differentiate pancreatic cancer from other pancreatic neoplasms (such as endocrine and cystic tumours), more rare and characterized by a better prognosis, which require different surgical and adjuvant treatments.Âť

Oncology | Benchside Interview with Carmelo Carlo-Stella

survival) of several hematopoietic cancers (such as acute promyelocytic leukemia, acute lymphoblastic leukemia, multiple myeloma, and B-cell non-Hodgkin lymphoma), as well as solid tumours (such as breast cancer, GISTs, renal cell carcinoma). Although stories of therapeutic successes using targeted agents are increasing, a real clinical efficacy of single targeted agents is difficult to conceive for solid tumours as well as hematological malignancies whose pathogenesis involves multiple genetic defects. To face genetic redundancy, an attack on multiple battlefronts and in distinct phases, i.e. the development of several targeted drugs to be used sequentially or in combination, is indeed required for efficiently co-targeting mutiple cancer-driving lesions thereby overcoming redundant signaling of tumour cells and eventually preventing the development of adaptative resistance.

» How can you summarize the lessons we have learned by targeted therapies?

Development of targeted therapies has substantially contributed to enforce the role and relevance of translational research and to change the way we face cancer treatment. In this respect, GISTs represent another successful paradigm for targeted therapy. GISTs are in fact driven by the costitutive activation of tyrosine kinases (preclinical lesson: investigating disease pathogenesis). These kinases are different from those of CML, but anyway responsive to imatinib that has indeed improved clinical outcome of GIST patients significantly (clinical lesson: performing clinical trials). Response of GISTs to imatinib may be eventually limited by cancer-driven selection of imatinib-resistant clones that can indeed be efficiently controlled by switching from imatinib to other kinase inhibitors (translational lesson: from bed to bench and back).

» There certainly is a wide range of options. Yet, it seems complex to manage them.

We cannot afford empirism, which is inefficient

and may be dangerous. We have to follow rigorous principles that are able to provide a logical framework for the management of each distinct cancer. A priority is sparing health because a single targeted drug is not dramatically toxic, but their combination may be associated to an increasing toxicity. Another mainstay is establishing diagnostic, therapeutical and prognostic markers. The traditional histological and cytological criteria are no longer adequate to establish the indications of targeted drugs. To obtain this kind of information, new biomarkers are needed, which are able to offer a genetic, epigenetic and biomolecular characterization in order to tailor the appropriate treatment for each patient. Which – notably – is also considerably expensive: another good reason to make an informed choice. There is a crucial need for identification of predictive biomarkers of response and identification of possible negative interactions between targeted agents to select better the patients likely to respond to treatment. Developing strong translational research programs combining early pre-clinical drug development with early phase clinical development is the strategy to be pursued to face the challenge of reconciling three main issues: (1) the huge amount of information generated by basic science, (2) the rapidly growing armamentarium of targeted therapeutics, (3) the validation of truly relevant, noncosmetic antitumour effects. The bench-to-bedside interplay of translational research will allow (1) to understand how to switchoff cancer driving genetic and epigenetic lesions, (2) to identify new indications (eventually, for old drugs), (3) to better select patients who can benefit of a given targeted agent, (4) to identify the right place of a treatment within the personalized therapeutic program of each patient. By setting up laboratories of molecular and cellular biology, clinical pharmacology, and pharmacogenomics, an extensive program of biobanking as well as clinical units devoted to drug development in Oncology and Hematology, Humanitas Cancer Center stands at the forefront of translational research.

HIGHLIGHT

Follow-up for complex patients

Rita Mazza, Medical Oncology Division

The majority of hematological malignancies occur in patients who are older than 65 years. These patients typically have poorer outcomes because of the presence of concomitant disease and diminished organ function. However, aging is a heterogeneous process that is not merely captured by chronological age, and valid tools to accurately assess who might benefit from therapy according to disease and to patientsâ&#x20AC;&#x2122; characteristics are needed. ÂŤAt Humanitas a clinical project is ongoing, aimed at improving management of hematological patients who are considered complex due to comorbidity, older age and/or disease-related conditions, through a global and systematic evaluation of fitness status and degree of frailty. The application of comorbidity score in younger patients (such as HCT-CI), and the employment of comprehensive geriatric assessment are designed to capture the functional status of patients other than disease-specific prognostic index. The prospective application of these scores at diagnosis and at transplant may improve the ability of therapeutic decisions regarding the intensity of chemotherapy and/or the activation of a transplant program. Another goal is the quantification of frailty and comorbidity prevalence in hematologic patients. This analysis is essential for the creation of an integrated multitasking approach in the evaluation and management of preexistent and overcoming comorbidity and in the monitoring of foreseeable early and late toxic effects of treatments. We therefore aimed to assess the correlation between comorbidity or frailty status and adherence, and to plan treatment. These data will be a guide to design patient-oriented strategies which may account for better adherence to treatment and for improvement of life quality.Âť

top paper De Vincenzo F, Zucali PA, Ceresoli GL, Colombo P, Simonelli M, Lorenzi E, Perrino M, Gianoncelli L, De Sanctis R, Graziotti P, Santoro A.

Response to Sunitinib in an Adult Patient With Rhabdoid Renal Renal Cell Carcinoma J Clin Oncol. 2011 Jun 20;29(18):e529-31. Epub 2011 Apr 11.

Identifying the players in immune reconstitution and homeostasis Enrico Lugli, PhD in Medical Biotechnologies, works at a project which aims at studying how the immune system is reconstituted after bone marrow transplant, so as to enhance its natural capacity to kill cancer cells.

Gerry Scotti supports 4 research projects Fondazione Humanitas per la Ricerca Four grants for four talented young researchers. Gerry Scotti, one of the most famous TV presenters, “adopted” four young researchers at Humanitas, and is financing their research studies against cancer for a year. Four cheques accounting for € 25,000 each, for a total of € 100,000 have been donated by the presenter to Giovanna Finocchiaro, Enrico Lugli, Federica Marchesi and Luca Toschi, who practised their skills and experience in prestigious structures abroad. Their research projects address fundamental challenges in Oncology, i.e. to improve the quality of the cure with increasingly targeted therapies and to take advantage of our natural defense mechanisms against big killers like pancreas and lung cancer.

«The normal immune system is characterized by hundreds of populations of cells with specific functions in physiology, pathology and homeostasis. Recent data from our and other laboratories suggest that subsets of the immune system do not have the same potential of rebuilding the immune system itself after acute injury. For example, in T cells, the T memory stem cells (TSCM) recently discovered by our laboratory has superior reconstitution capacity in immunodeficient hosts. In collaboration with the Hematology Department at Istituto Clinico Humanitas, the Vaccine Research Center at the NIH, USA and the Cardiff University in the UK, we intend to study the contribution of discrete populations of the blood to this process following a new, innovative protocol of bone marrow transplantation (BMT) with low incidence of infections and graft versus host disease. By using advanced polychromatic flow cytometry technology, we will determine the characteristics (activation, proliferation and effector function) of the immune cell populations undergoing recovery in order to identify the key players in this process, with particular focus on TSCM. Moreover, we will determine the contribution of antigen-specific immunity in protection from diseases that commonly reactivate in immunodeficiency such as CMV, EBV and influenza. Identifying the key populations involved in the immune reconstitution process is be important to design better therapeutic strategies for the treatment of immunodeficiencies, cancer and infectious diseases».

Sox2 and Fgfr1 gene copy number in surgically resected non-small cell lung cancer Luca Toschi and Giovanna Finocchiaro, MDs specialized in Oncology, work at Humanitas focussing on lung cancer with particular reference to clinical and traslational research. Their project aims at finding new therapeutical approaches against this big killer.

«Lung cancer is the leading cause of cancer death worldwide and survival rates are poor. In the last few years progress in the knowledge of non-small cell lung cancer (NSCLC) biology led to the identification of activated oncogenes (EGFR, ALK) that can be therapeutically targeted by novel agents, offering new hope to lung cancer patients. The dismal prognosis of NSCLC, even when diagnosed at an early stage, prompted the identification of new oncogenes involved in lung carcinogenesis that might serve as prognostic indicators or new targets for novel molecules. SOX2 is a member of the SRY-related HMG-box family of transcription factors and has been shown to be frequently amplified and overexpressed in squamous cell lung cancer, with conflicting results regarding its prognostic relevance. Similarly, FGFR1, a transmembrane tyrosine kinase receptor belonging to the fibroblast growth factor receptor family, has been recently reported to be amplified in squamous cell lung carcinomas, suggesting a potential role for FGFR1 as a therapeutic target in NSCLC. We are currently evaluating SOX2 and FGFR1 gene copy number in a large cohort of surgically resected NSCLCs to investigate their prognostic relevance and to assess their association with clinico-pathological characteristics and with other biomarkers status. Our study has the potential to identify patients with a higher risk of relapse that might deserve further treatment after surgery, and to spare treatment toxicity for those patients with a more indolent disease».

Frontline against pancreas cancer Federica Marchesi, a graduate in Medical Biotechnologies contributed to the identification of one of the molecular bases which lead pancreas cancer to spread and invade the surrounding nerves. She continues the same studies at Humanitas with the aim of understanding whether and how the organisation of immune cells in pancreas cancer affects the clinical progression of the disease. «Over the past ten years, accumulating evidence have indicated that cellular mediators of the immune system are a critical constituent of the tumour microenvironment. Their role is however paradoxical, and often their deregulated function contributes to tumour progression instead of tumour eradication. Elucidation of the clinical relevance of tumour immune infiltrate would have important implications for cancer prevention and treatment; in fact, stimulating the patient’s immune system to attack malignant tumour cells, reverting the compromised immune response to tumours, is considered a promising therapeutic strategy to treat cancer. My research is focused on the adenocarcinoma of the pancreas, a devasting disease highly resistant to available therapeutic options, but in which an important inflammatory infiltrate is present. My project aims at analyzing how cellular mediators of the immune system organize in the tumour environment and influence the development, growth and dissemination of the tumour. The assumption is that a better knowledge of the role of immune infiltration into pancreatic adenocarcinoma may help the design of successful alternative strategies targeting the immune system, to cure pancreatic cancer».

Neuroscience

Innovative aspects in spine pathologies from diagnostic tools to surgical procedures Interview with Maurizio Fornari

between the surrounding functional and anatomic structures during surgery.

» How did these advances in diagnostics and

imaging change interventional procedures?

Director of the Neurosurgery Division

High level technologies and competence are needed to perform surgical interventions on vertebral column where a minimal error margin is tolerated.

» Which important innovations have been registered in spinal neurosurgery?

The main revolution over the last 10-15 years has been instrumented surgery. It has gone side-byside with better knowledge of spinal anatomy and biomechanics. In fact, non invasive imaging, e.g. computed tomography and magnetic resonance have definitely made some aspects of neuraxial diseases clearer, both for degenerative and neoplastic ones, thanks to 3D anatomical reconstruction and kinematic models. A special mention has to be reserved to spinal navigation, a technology initially developed for intracerebral surgery and lately extended to other districts of neurosurgical interest. The neuronavigation system comprises computer-assisted technology enabling the integration of threedimensional anatomical and functional data and preoperative imaging data with the intraoperative identification of a target. A spatial relationship is established between preoperative imaging data and the corresponding intraoperative anatomy. Thus it helps to localize its target and its relationship

An extraordinary step forward has been represented by microsurgery, and by mininvasive endoscopic surgery. For example a minimally invasive surgical technique for lumbar decompression offers significant improvement for patients with degenerative spinal stenosis, together with a low rate of complications. This technique represents the alternative to traditional surgical decompression by laminectomy – which is invasive and prone to causing postoperative instability – in cases with moderate to severe impairment and where symptoms do not respond to conservative therapy. It can be performed in patients with multilevel disease, poor health, and advanced age. Generally they can leave within 24 hours after surgery.

» Does this mean that nowadays neurosurgery operations are less demanding and carry a lower risk for patients?

It has to be so, since our patients tend to be older due to the increased average lifespan. A quarter of the Italian population is over 65 years and has a higher life expectancy – we are the most long-lived population together with the Japanese –; and both trends will continue. This demographic transition has, consequently, changed the case records towards an impressive predominance of degenerative diseases. Among these, degenerative spondylolisthesis is an alarming condition, diagnosed – but often undiagnosed – when a forward motion (slip) of one or more vertebral body/ies – generally at L3-L5 levels – occurs. It’s a consequence of the aging process in which spinal bones, joints, and ligaments become weaker and unable to maintain column alignment. Its frequency increases with age, starting from the fifth decade and peaking after 65 years, and shows a female to male prevalence ratio as high as 3:1. Typical distressing symptoms include low back pain, muscle spasms, thigh or leg pain, and weakness. The

Neuroscience | Interview with Maurizio Fornari

inability to maintain a steady standing posture may be seen in most severe cases. The treatment consists in titanium pedicle screw insertion in order to realign and stabilize the column. At present, surgery has become safer and less invasive, thanks to innovative TC techniques and computer-assisted surgical navigation systems.

» What does innovation in TC technologies consist in?

This technology, called O-Arm™, is based on an intraoperative CT scan acquired in prone position with the O-Arm™ Imaging system (it takes approximately 17 seconds for the acquisition) and automatically transferred to a navigation system. The recognition and merging of the images with the surgical anatomy are automatic and in real time. After positioning the screws, a second intraoperative CT scan with the O-Arm™ is performed. The main advantages are the possibility of generating the imaging set for spinal neuronavigation after the final positioning of the patient, thereby minimizing inaccuracy, and of checking the position of the screws during the surgical procedure, thus avoiding the need for revision surgery. Operating times are significantly shortened and patients’ discharge is anticipated.

» Osteoporosis is another disorder strongly

associated to senescence. When are surgery or medical therapy most recommended?

In Europe, vertebral fragility fractures account for an estimated annual incidence of about a million cases. These consequences, even serious, may be treated with minimally invasive stabilization systems and instrumented surgery. Vertebroplasty and kyphoplasty represent alternative options to surgery and involve the injection of an acrylic cement under local anesthesia and imaging guidance to control the pain of vertebral fractures. Moreover, innovative drugs to treat osteoporosis have been developed. Meanwhile we can afford to intervene also in elderly patients. The surgery is still engaging and difficult in

terms of site, but we are advantaged by the dramatic reduction of operating and recovering times, which is of absolute relevance to a patient aged 70 or 80. On the other hand, waiving surgery in presence of a medullary compression is endowed with the progression to a less or more pronounced disability.

» Are there any other emerging degenerative pathologies?

We have “discovered” a new condition, actually we have verified that a well known condition, such as scoliosis may occur much later than expected, in the seventh decade. In this case, a sagittal imbalance may be involved. In fact, the function of the spine depends upon its proper alignment, where lordoses and kyphoses of the spinal regions are in balance and the body’s center of gravity insists on hips and pelvis. If balance is preserved, the erect posture requires minimal muscular effort as the skeleton resists the gravitational force. Disruption of the normal sagittal alignment can occur due to one of several conditions, including degenerative ageing processes with loss of paravertebral muscles strength. Non-operative management can, in some cases, help to ameliorate patients’ symptoms, but surgery is often necessary. Preoperatively, an accurate analysis of skeletal segment (especially spine and hip) is crucial, but has been understood only recently. It can be obtained thanks to the new EOS system that enables a fullbody assessment of balance and posture in standing, weight bearing position as well as a 3D bone imaging, and automatically provides the orthopedic surgeon with more than 100 clinical parameters for diagnosis and surgical planning. Notably, the use of this technology reduces the radiation dose considerably, resulting in 7-9 times less than a standard X-ray and 90% less than a CT scan. EOS was developed from a Nobel Prize-winning technology by a team of engineers, orthopedic surgeons and radiologists as a complete orthopedic imaging solution. This last innovative technological system has been operational at Humanitas since Spring 2011.

HIGHLIGHT

Paola Allavena, Principal Investigator of Cellular Immunology Unit

New markers for glioblastoma

Glioblastoma multiforme, the most aggressive form of glioma tumours of the central nervous system, represents an unmet clinical challenge for its fast progression and resistance to treatment. This tumour is characterized by a marked infiltration of adjacent normal brain parenchyma. Among the factors that contribute to the invasive phenotype of neoplastic cells, increasing attention has been directed to chemotactic cytokines (chemokines), small proteins that elicit cell mobilization and regulate tissue trafficking. ÂŤWe have recently discovered (Erreni et al, European J. Cancer, Dec. 2010) that glioblastoma cells are producing high amounts of the chemokine CX3CL1, which is absent in normal brain, and is produced at only low levels in other less aggressive glioma tumours. The neoplastic cells also express the cognate receptor for this chemokine: the molecule CX3CR1, suggesting that a functional axis between the ligand and its receptor may be involved in the malignant behaviour of these tumours. As for other solid tumours, glioblastoma contains a small fraction of Cancer Stem Cells (CSCs), responsible for tumour initiation, progression and disease recurrence. Also the CSC isolated from glioblastoma and grown in culture, as neurosphere, are characterized by the expression of the receptor CX3CR1 and the chemokine ligand CX3CL1. The identification of CSCs specific markers and of the molecular mechanisms supporting their invasive phenotype and tumourigenic potential is of great importance for the design of innovative and more efficacious treatments.Âť

Neuroscience | Interview with Lorenzo Bello

Technology and lab research in oncologic neurosurgery Interview with Lorenzo Bello

Head of Oncologic Neurosurgery Unit, Professor of the Università di Milano

Clinical activity with the aid of technology versus experimental laboratory: two main, and yet not isolated branches, which allow us to obtain synergy and the best integration of knowledge and competence.

» What are the news in oncological neurosurgery and where is it heading?

Clinical reasearch is working on exploring brain functional anatomy in order to obtain a map of brain function, in addition such a map should be customized for each single patient. We can’t count on any previous reference since current knowledge is changing, via a process of continuous deconstruction and reconstruction. Anyway, we are confident in acquiring more information about a question – I would say the question – that has always been crucial for neurology professionals: “How does the brain work?” and in using the answer also to optimize neurosurgical strategies, e.g. to identify more clearly which eloquent areas to preserve during tissue removal.

» Could you provide some examples of

innovation in brain mapping research in terms of neurophysiology and neuropsychology?

In the study of functional brain mapping, the

identification of specific subcortical functional structures is of particular interest. Among these, the cortico-spinal tract has to be more deeply investigated in humans, since most data arise from experimental models. Moreover, in order to reach a better knowledge of language networks studies are ongoing on the inferior and superior longitudinal fasciculus, a ventral stream structures which differentiate humans from primates, thus likely explaining the relevant difference in language evolution.

» What can be said about application of clinical research data to neurosurgery?

It has to be pointed out that there is a need of close integration of different highly specialized competence – neuroimaging, neurophysiology, and neuropsychology – especially intraoperatively, when surgery with the aid of brain mapping is performed. Neurophysiologists and neuropsychologists are present in the operating room, where they interpret patient’s responses and reactions, so as to orient surgical procedure. I would like to mention ACTIVE, a European Commission clinical research project coordinated by the Bioengineering Department of Politecnico di Milano and managed by a multidisciplinary consortium. It’s committed to exploit ICT technologies and various engineering methods to develop an integrated multi-robotic platform for neurosurgery, particularly for surgical treatment of epilepsy which accounts for approximately 10,000 to 24,000 candidate patients per year in Europe. We are involved particularly for those procedures performed when the patient is awake. In brain surgery, motion, even minimal, arising from the patient, the operator or a brain tissues deformation is a main problem. In ACTIVE project, cooperating robots and an advanced processing unit for pre- and intra-operative control will interact with the brain that will deform for the tool contact, blood pressure, breathing and deliquoration. Operator movements will be monitored and corrected in real time and on the field by a novel technological interface for tele-manipulation. The patient’s head movement or any unpredictable patient motion will be filtered and compensated by a control system.

» From what you have said so far, it appears that imaging techniques have a vital role which goes beyond a mere anatomic definition.

Magnetic resonance imaging with its different acquisition methods – for example measures of anisotropy and diffusivity, both based on the analysis of Brownian motion of water molecules – offers a great deal of precious information. Related to our clinical studies on the cortico-spinal tract, subcortical white matter tracts are being investigated by means of diffusion-tensor imaging (DTI) and fibre tractography reconstruction (FT). Both are magnetic resonance methods based on the concept of anisotropic water diffusion in myelinated fibers, which enable 3D reconstruction and visualization of white matter tracts. The development of novel advanced tractographic alghoritms will favour a better understanding of the several tracts, involved either in the phonological or semantic components of language. Another type of magnetic resonance data acquisition and processing (isotropic and anisotropic diffusion mapping) can provide an intraoperative brain mapping able to define tumoural extension and invasion – also guiding tissue sampling – and to establish the extent of resection. Thus, safe and effective surgical removal of tumours located within functional brain areas is nowadays more feasible. Indeed, the extent of resection is proven to be significantly related to overall and progression-free survival. Anisotropic mapping (specifically, a change in isotropic component) also contributes to the evaluation of the effect of chemotherapy, showing how tumoural tissues change in response to a definite pharmacological treatment. This research is being carried out in cooperation with the Neuroradiology of the Fondazione San Raffaele. Moreover, working with the research group of Nuclear Medicine led by Arturo Chiti and Riccardo Soffietti (Neurooncology, Università di Torino), we are trying to establish a correlation between findings on the response to chemotherapy obtained by magnetic resonance and data about methionine or tyrosine captation by brain tumour tissues provided by positron emission tomography.

A third important project is dealing with neuropsychology, specifically the impairment of working memory processes in surgically resected tumours affecting limbic and paralimbic areas and in surgically treated patients with epilepsy. Our studies, in collaboration with the Università di Milano Bicocca, are going to explore syntactic and verbal organization at cortical and subcortical levels and to analyze how neuropsychological tests are impaired in the early phases of the disease, anticipating imaging changes and predicting a relapse.

» The last point to discuss remains lab research. Where studies on angiogenesis and tumoural progression and invasion are being performed. In particular, we are deepening our understanding of mechanisms of resistance to angiogenesis inhibitors, whose use has been established also in brain tumours. A first project is committed to evaluating – by means of cancer stem cells models – which genes are activated by the various drugs and whether a different constitutive genic expression by different tumours might affect the outcome, thus being of predictive value. Another research project, supported by a grant from Fondazione Berlucchi at the Università di Milano is developing a proteomic and transcriptomic study on determinants in development and progression of lowgrade brain tumours.

Orthopaedics benchside

Bone, a living tissue

Interview with Paolo Vezzoni

in osteoclasts function or differentiation. The first example is provided by a rare form of osteopetrosis with can be treated with a cytokine, the same present in our body, where it is produced mainly by bone marrow mesenchimal cells. Stem cells represent the second example, being the therapeutic option for the treatment of genetic bone diseases. The possibility to cure both immune systemic diseases and genetic bone disease with stem cells transplant is becoming more and more evident.

» A new and larger view of bone role? Principal Investigator of Medical Biotechnologies Unit, CNR

Bone has to be considered no longer as a static and merely supportive structure, but rather a metabolically active compartment and a living tissue able to generate stem cells. Bone genetic diseases offer a good model in which unindifferentiated cells can be used for therapeutic aims.

» Your team has been working for years on genetic bone diseases which represent a particular challenge for the translational research.

The most relevant problem we have to face with genetic diseases is the dichotomy between the possibility to make a brilliant diagnosis, accurately reconstruct the pathogenetic mechanisms, and the few or even null chances of treatment. Actually, what I’ve described is the traditional scenario, while lately we have looked for and found some promising therapeutical opportunities which – interestingly – arise from the bone.

ould you explain what these opportunities C consist of?

Two good examples can be mentioned, both referring to osteopetrosis, a term including a group of rare heritable diseases that share a common feature – increased bone density with severe clinical consequences – and a common mechanism – a defect

Bone has to be observed as a living tissue with a multiplicity of functions, starting from the bestknown metabolic activities, above all calcium metabolism. I would like to emphasize its dynamism, with significant changes according to the variable needs during lifespan, e.g. during the growth and the development of the human body or in case of unexpected events like fractures, or even in physiological more demanding situations like pregnancy. Bone tissue is not only a field of study for orthopaedists, neither exclusively for metabolists, but increasingly for immunologists. Bone and immunity are strictly linked to the extent that a new field of study, whose name is osteoimmunology, has recently come into existence.

» How can this link be outlined briefly? This link may be easily explained considering the common origin of bone and immune cells. Osteoclasts, the large multinuclear cells, are physiologically involved in bone remodeling processes and share with monocytes-macrophages a common precursor, the haematopoietic stem cell.

» Also, are some therapeutic procedures the

demonstration of this common background?

Treating Severe Combined Immunodeficiency (SCID), a severe form of heritable immunodeficiency, is possible thanks to bone marrow transplant. Compared to organ transplant, bone marrow transplant is less critical in terms of donor availability, since it is relatively easy to obtain hematopoietic

Orthopaedics | Benchside Interview with Paolo Vezzoni

stem cells from peripheral blood. On the other hand, rejection is a troublesome aspect. In fact, in bone marrow transplant not only the transplanted tissue may be rejected by the recipient’s immune system, but also the transplanted tissue may reject the recipient. This latter condition is described as Graft Versus Host Disease (GVHD) and represents a truly limiting factor in the possibility to perform a bone marrow transplant which so far has to be reserved to patients with a matched donor.

» Are new perspectives coming into play? Yes, and they are hopeful perspectives. In the last 5 years procedures have been developed which make it possible to derive pluripotent cells from adult cells. Even if they’re still stem cells, we can circumvent the ethical concern of using embryos as source of human Embryonic Stem Cells (hESCs) or of performing a “therapeutic cloning”. Moreover, the clinical problem of transplant rejection can be solved, since they derive from the patient him/herself and are fully compatible. We have the possibility to obtain multiple somatic cell types – bone marrow hematopoietic cells included– of patients cells: they’re taken from the patient him/herself, “corrected” in vitro and “given back”, i.e. reinfused, to the patient. These cells, molecularly and functionally similar to hESCs – although not identical – are called induced Pluripotent Cells (iPSCs). This is a very promising model, which applies to several genetic disorders. Notably, iPSCs have a

great potential in orphan or rare disease (for their low incidence and scarce therapeutical options).

» And does it also apply to bone heritable

diseases, you have been studying for a long time?

No doubt. We derive iPCSs by reprogramming them to the undifferentiated stage from an experimental mouse model which carries the same genetic disease and correct in vitro the genetic defect. In osteopetrosis, we can take advantage of the strict similarity of the experimental model with the human disease. That increases the probability of positive results in a near future. Until now, no patients with osteopetrosis have been cured in this way, but we are confident.

» The internationally recognised experience of

your group in bone genetic disease makes you a point of reference for this new research branch?

While our research on iPSCs proceeds, we are continuing on the traditional activity of diagnosis and translational research. We have collected hundreds of DNA samples in our biobank, covering most Italian cases and a significant amount of cases from all over the world, being part of the European Group for Blood and Marrow Transplantation (EBMT). We collaborate with the department of Pediatrics in Brescia to transplant patients with osteopetrosis, since the procedure needs to be performed in childhood.

HIGHLIGHT

Alessandro Castagna, Director of Shoulder, Elbow and Foot Surgery Division

Translational research in rotator cuff pathology

Rotator cuff pathology is a common condition involving especially middle aged and mature people. It may lead to significant symptoms and functional impairment. For these reasons it is among the most prevalent reasons of medical consultation for problems involving the shoulder. «As is typical of many orthopaedic issues, rotator cuff pathology was originally related to some mechanical effects on the tendons strength evolving through the years into a final failure of the sophisticated system represented by the cuff. Impingement against the acromial arch, overuse and stress forces were some of the most frequent causes advocated as starter of the rotator cuff tendons lesions. As a consequence, the treatment was mostly focused into a mechanical correction of the causes including acromionplasty and reinserting of the torn tendons. Unfortunately the recurrence rate of these procedures was relatively high after an adequate follow-up. This observation drew the attention of some researchers and the most active surgeons to seek for rotator cuff failure causes other than the simple mechanical attrition. In recent years many studies were performed in order to understand the subtle biological border between a healthy and a weak tendon or an healing tendon and a non-healing – as we are used to say – tendon after surgery. Our Unit is very active in this research field trying to explore the multiple directions that may affect rotator cuff tendons vitality. Namely we are following four basic research lines: • understanding why a rotator cuff tendon is prone to tear. Many factors may potentially influence the cellular activity of the tenocytes but what arises from our research is that potentially in some cases it could be an impairment in the metabolic activity of the cells rather than a mechanical consequence: • following the previous hypothesis, trying to detect potential markers able to indicate the real beginning of the degenerative process and, consequently, developing a therapy to prevent the disease evolution. Unfortunately, this option is a long way ahead; • understanding why surgically repaired rotator cuff tears may not completely heal (we introduced in the scientific community the term of non-healing instead of retear as more appropriate in many cases; • biological supporting the healing process after surgical repair, by the use of different extra-cellular matrix scaffolds, and the identification (and selection) of the best sources (allograft or xenograft) and of the clinical relevance for the patient. The aim of our research is to improve the quality of the treatment of rotator cuff pathology, transferring the basic science achievements into the daily activity of our Unit: the best possible care of our patients.»

Orthopaedics | Benchside Interview with Paolo Vezzoni

Hip surgery: between conservative approach and prosthesis Interview with Guido Grappiolo

Director of the Hip and Knee Prosthetic Surgery Division

Hip prostheses have improved the lives of so many patients, preventing pain and functional impairment, but their efficiency and durability are still time-related and alternative options are needed.

» What is the current stage of hip prostheses long-term reliability?

At the moment we can rely on 15-30 years of excellent performance, followed by hardly predictable outcomes. It’s easy to conclude that even the most advanced hip prostheses can’t cover the life course of our youngest patients. Notably, patients are younger and younger and consequently we have to face more demanding clinical cases, in terms of load, solicitation, and wear.

» So, is this a particularly difficult framework?

This is certainly a complex and challenging scenery, but I usually compare the hip joint prosthesis to a vehicle’s wheel which has components endowed with different durability. Some of them require periodical replacements, others are everlasting. What’s is crucial is the timeliness, starting from the diagnosis onwards. Very accurate imaging tools – above all arthroMRI (magnetic resonance imaging) – are available, which are able to detect the initial phases of hip joint and arthroplasty degeneration and to show

both anatomical and functional alterations. Only an early diagnosis makes conservative surgery feasible. Then, if we need a prosthesis, it has to be considered that prosthetic failure is silent and painless for a while, this increasing the diagnostic value of imaging. Carrying on with the wheel metaphor, if a tyre wears off you can change it, but if the rim wears off you have to substitute the wheel.

» Which approach and strategies are necessary when hip surgery is essential?

The conservative approach is mandatory, because of the limited longevity of a hip prosthesis we have discussed. A reappraisal of the “old” conservative surgery is taking place. At the time, osteotomy was performed for recentering and redistributing loads in severe hip dysplasia. Now conservative joint surgery can prolongs the survival of the native joint and postpones arthroplasty for a period of around 10 years with a relative minimally invasive procedures (arthroscopy). If prostheses is the only solution to effectively manage the pain it may be recommended to start with a less extensive procedure, simply coating the femoral head, then following with the replacement of head itself. Step by step more extensive components are substituted. The advantage derives from sparing the patient’s tissues and maintaining the possibility of future repeated interventions.

» Does a conservative approach imply minimal invasivity, i.e. arthroscopy?

Arthroscopy (i.e. closed mini invasive surgery) is a valuable technology and is appropriate for remodeling small bone sections (trimming of the acetabular rim and reshaping of the head) in patients with mild to moderate damage. But a open-surgery with a wider operatory field and a larger room for manoeuvre ensure higher precision in severe or complex cases especially dedicated to

young patients with a higher regenerative potential. In surgery (opened or closed), a major concern is the preservation of the blood vessels.

» And does a conservative approach also mean staminal cells?

Staminal cells are another promising option, but a distinction is needed. If bone marrow adult stem cells are able to generate new bone and, consequently utilised for supporting repair processes especially in hip revision arthroplasty, their use to achieve regeneration of the articular cartilage has not yet provided conclusive results with immediate therapeutic perspectives.

» What happens at the time when hip prosthesis can no longer be put off?

Keeping always in mind that the arthroplasty is a point of no return, we have to improve tribology. Tribology is a branch of engineering which specifically studies the behaviour of the prosthetic articulation in terms of lubrication, friction and wear. Wear is the loss of material from the surface and the detached material (debris) is one of the main causes of prosthetic failure. Especially in young patient wear has to be contained, the optimal tribology has to be pursued through materials; the most promising solutions are: metal-on-metal bearings, ceramic-onceramic bearings and last generation of polyethylene versus ceramic. Compared to polyethylene used in the first Charnley prostheses, this component now available as highly cross-linked Ultra-High Molecular Weight Polyethylen, shows a negligible wear of acetabular components during an expected clinical lifespan and has been added with vitamin E to prevent oxidation and consequent ageing. Nowadays this is considered the most reliable solution in total hip arthroplasty; concerns have risen reagarding metal-on-metal and the last version of ceramic-on-ceramic is too recent to provide a conclusive reliabilty.

Orthopaedics | Benchside Interview with Piero Volpi

Technology without forgetting the human factor Interview with Piero Volpi

porous titanium and trabecular titanium have been developed. In particular, trabecular titanium with its three-dimensional highly porous structure imitates the cell structure of the cancellous bone. Thus, it enables an excellent osteointegration at the tissue-prosthesis interface to ensure stability and long-term survival rate of the implants. Preliminary results are satisfactory, but the final judgment about the success or failure of a knee arthroplasty depends upon time.

» What about the other research branch: Director of the Knee and Orthopaedics and Sport Traumatology Division

New biomaterials and innovative technologies are currently being introduced in knee surgery. A relevant fact that can be of net benefit only if combined with the experience and the skill of the operator.

» Which challenges and needs does modern surgery, and specifically modern knee prosthetic surgery, pose?

Essentially, the patient’s profile is changing. The raise of the average age generates a larger elderly population which principally needs a good quality of life. It means integrity, or at least an adequate preservation of cognitive functions and, notably, of motility. Moreover, an increasing amount of complex clinical cases is coming under observation in orthopaedic departments: relevant axial deformities, repeated surgical procedures, allergy to metals (e.g. nickel or chromium).

» Which answer and solutions are today available?

Special biomaterials and new prosthetic designs are recommended in those cases. The research on materials is directed towards biocompatibility and similarity to bone extracellular matrix, onto which cells attach, multiply, migrate and function. In the latest years trabecular tantalium,

prosthetic design?

Research on prosthetic design has been happening for a long time, and big efforts have been made by the industry, obtaining an even more complete and wider offer of prosthesic implants, among which I would like to mention the femoro-patellar prostheses and the gender-specific total knee prostheses. In these latter, the size of the implant is slightly different to accommodate for the slightly different size of the bones between genders. The design of a gender specific prosthesis better replicates the normal feminine anatomy with a 5 degree valgism. However the best in personalized design has been obtained thanks to custom-made prostheses.

» The trend towards customized interventions is

becoming common practice in orthopaedics, as well as in several medical specialties. Which are the more important advantages in yours?

In joint replacement, custom-made implants may allow for better function, as well as improved durability. We can optimize these results respecting anatomy and biomechanic of the knee joint. To this aim, our research and activity are constantly oriented towards performing biological reconstructions of joints’ components, tipically menisci, cartilages and anterior cruciate ligaments, either injured or removed following a previous surgical intervention. Stem cells and growth factors represent other biological therapeutic options, with a great potentiality to be developed in the near future. At the moment, several cartilage damages and meniscal tears can be treated with stem cells injections or

In vitro differentiated osteoclast

using scaffolds loaded with autologous marrowderived mesenchymal stem cells.

Âť A minimally invasive approach. Is it so crucial? Minimally invasive and progressively more anatomical interventions are of utmost importance. This is true also for arthroscopic techniques. Let me explain with a couple of examples. The anterior cruciate ligament reconstruction consists of a surgical tissue graft replacement (usually tendons taken from the knee itself) of this ligament. Recently, the double-bundle anterior cruciate ligament reconstruction has been shown to better replicate the native anatomy and results in better outcomes. Thus, the historically standard technique, the single-bundle reconstruction, is being progressively abandoned. All-inside reconstruction is another innovative approach which is characterized by minimal invasivity. It requires a few small arthroscopy incisions, maintains the integrity of the tibial and spare cancellous tibial bone.

Âť This leaves us with a quick reference to knee

surgery technologies. Thanks to the availability of the da Vinci surgical system, Humanitas performs state-of-the-art robotic surgery. Can the advantages of the same technology be applied to knee surgery as well? Apart from the da Vinci system, which has different applications, computed assisted surgery has been used for a long time exclusively in prosthetic surgery to evaluate joint kinematic. More recently, navigator assisted surgery has begun to be used more extensively in orthopaedic surgery, e.g. in ligament reconstructions or in osteotomies in order to optimize the orientation of the surgical incision and of the bone tunnels in real time, and to fit the individual patientâ&#x20AC;&#x2122;s anatomy. With a warning. Technological innovations are a powerful opportunity to support surgery, and specifically knee surgery, provided that individual experience and appropriateness criteria are considered central and given utmost priority. This is an absolute requirement to get good outcomes, independently of all other variables, most advanced technologies included.

Clinical & Research Departments

Board of Directors President

Scientific Superintendent

Gianfelice Rocca

Nicola Dioguardi

Vice President

Scientific Director

Ivan Colombo

Alberto Mantovani

Chief Executive Officer

Clinical Research Director Humanitas Cancer Center Director

Luciano Ravera

Armando Santoro Medical Director

Norberto Silvestri

Education

Research Advisory Board

Piero Melodia

Rolf Zinkernagel (President) Charles Dinarello Fabio Cominelli Lorenzo Moretta

Departments and teams Clinical Area Updated to March 2012

Cancer Center director: Armando Santoro 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

(*) Physician dealing with activity in the Research laboratories too (**) Research staff (***) Research nurse (•) Head of unit (°) Consultant

■ Divisions that join in the Humanitas Cancer Center

Antonella Anastasia Margherita Autuori Monica Balzarotti Elena Bergamaschi (**) Monica Bertossi (**) Alexia Francesca Bertuzzi Stefania Bramanti Ettore Brusamolino (•) Carmelo Carlo-Stella (•) (*) Carlo Carnaghi Luca Castagna Carolina Cauchi Raffaele Cavina (•) Elisa Crotti (**) Fabio De Vincenzo Gabriella Delvecchio (**) Giovanna Finocchiaro Isabella Garassino Milena Gasco Laura Giordano (**) Barbara Ercoli (**) Rita Finotto (**) Adalberto Ibatici Nathalia Locopo (**) Massimo Magagnoli Giovanna Masci Elisa Mauro Rita Mazza Emanuela Mencaglia Lucio Morabito Simona Naimo Andrea Nozza Nicola Personeni Tiziana Pressiani Lorenza Rimassa (•) Luca Rubino (**)

Barbara Sarina Nadia Sessarego (**) Matteo Simonelli Licia Siracusano Orsola Sironi Elisabetta Todisco Rosalba Torrisi (•) Luca Toschi Maria Chiara Tronconi Laura Velutti Paolo Andrea Zucali (•) Monica Zuradelli PET AND NUCLEAR MEDICINE division director: Arturo Chiti Lidja Antunovic Egesta Lopci Giovanna Pepe Marcello Rodari Giovanni Tosi RADIOTHERAPY AND RADIOSURGERY division director: Marta Scorsetti Filippo Alongi Stefano Arcangeli Anna Maria Ascolese Simona Castiglioni Maddalena Catalano Elena Clerici Francesca Lobefalo Pietro Mancosu Pierina Navarria Chiara Pellegrini Sara Pentimalli Giacomo Reggiori Angelo Tozzi THORACIC SURGERY division director: Marco Alloisio Umberto Cariboni Valentina Errico Giorgio Maria Ferraroli Maurizio Valentino Infante (•) Alberto Testori (•) Roberto Travaglini (°)

Cardiovascular Department director: Ettore Vitali CARDIac SURGERY division director: Giuseppe Tarelli Alessio Basciu Alessandro Barbone Antioco Cappai Enrico Citterio Pietro Malvindi Diego Ornaghi (•) Giuseppe Raffa Fabrizio Settepani CLINICAL CARDIOLOGY division director: Maddalena Lettino Tiziana Anita Ammaturo Laura Ardino (***) Monica Bocciolone (•) Margherita Calcagnino Alessio Cappelleri Franco Fea Augusto Foresti (°) Veronica Fusi Daniela Guiducci Maurizio Mangiavacchi Manuel Marconi (•) Giuseppe Mariani Barbara Nardi Roberta Paliotti Daniela Pini Sergio Potenza (°) Michele Randazzo Cinzia Santucciu Maria Luisa Stella Luisa Ulian ECHOCARDIOGRAPHY division director: Renato Maria Bragato Sara Anna Cioccarelli (°) Mirko Curzi Aurelio Sgalambro

ELECTROPHYSIOLOGY AND ELECTROSTIMULATION division director: Maurizio Gasparini Carlo Ceriotti Paola Galimberti Edoardo Gandolfi HAEMODYNAMICS, INVASIVE CARDIOLOGY AND CORONARY CARE division director: Patrizia Presbitero Cristina Barbaro Guido Belli (•) Elena Corrada (coronary care) (•) Giuseppe Ferrante (*) Gabriele Luigi Gasparini Veronica Lisignoli Marco Mennuni Nicoletta Monzini (**) Paolo Pagnotta (•) Marco Luciano Rossi Dennis Zavalloni Parenti VASCULAR SURGERY I division director: Pier Luigi Giorgetti Elisa Casabianca Andrea Odero Giorgio Luca Poletto Athos Popovich VASCULAR SURGERY II division director: M. Grazia Bordoni Giuseppe Carella Vittorio Danesino Paolo Spada ANAESTHESIA AND CARDIOSURGERY INTENSIVE CARE division director: Angelo Bandera

Diagnostic Imaging Department director: Giorgio Brambilla DIAGNOSTIC radiology division director: Luca Balzarini Alberto Bizzi (neuroradiology) (•) Cristiana Bonifacio Francesco Cabras Mariagiorgia Farina Sara Imparato Romano Lutman (•) Paolo Malerba (•) Lorenzo Monti Federica Mrakic Sposta Maria Alessandra Pestalozza Manuel Profili Felice Rognone (•) ECHOGRAPHY division director: Paola Magnoni Manuela Cira De Crescenzo Pasquale De Nittis Jean Claude Foteuh Margherita Lunelli Caterina Claudia Pedicino Laura Saltarin Chiara Valsania Vascular & Interventional Radiology division director: Giorgio Brambilla Vittorio Pedicini (•) Dario Poretti

Graziano Cortis Pietro Ferrara Licia Melis Maria Cristina Soriano Rodrigo Paolo Francesco Tosi Maria Maddalena Visigalli (•)

Diagnostic Laboratory Services Department director: Gianluca Vago LABORATORY TESTS division director: Alessandro Montanelli Barbara Barbieri Daniela Bettio Simona Brambilla Elena Bredi Erminia Anna Casari Elisabetta Corsi Concetta De Luca Antonella Ferrario Rossana Mineri Marta Noemi Monari Carla Barbara Ripamonti PATHOLOGY division director: Massimo Roncalli Silvia Armenia Andrea Bornati Paola Bossi Tatiana Brambilla Piergiuseppe Colombo (•) Annarita Destro Luca Di Tommaso Bethania Fernandes Barbara Fiamengo Chiara Lo Russo Sofia Manara Cornelia Navligu Daoud Rahal (•) Paola Spaggiari Gaia Spagnuolo

(*) Physician dealing with activity in the Research laboratories too (**) Research staff (***) Research nurse (•) Head of unit (°) Consultant

■ Divisions that join in the Humanitas Cancer Center

Gastroenterology Department director: Alberto Malesci GASTROENTEROLOGY AND DIGESTIVE ENDOSCOPY division director: Alberto Malesci Elisa Carlani Silvio Danese (*) Chiara De Cassan Gionata Fiorino Luigi Laghi (*) Paolo Dario Omodei (•) Paoletta Preatoni Beatrice Salvioli Orsola Sociale (***) DIGESTIVE ENDOSCOPY service division director: Alessandro Repici Alessandra Carlino Fiorentina Frattolillo Nico Pagano Giacomo Rando Fabio Romeo Giuseppe Strangio Eva Maria Vitetta GENERAL MEDICINE AND HEPATOLOGY division director: Maurizio Tommasini Roberto Ceriani (•) Luca Contu Giovanni Covini (•) Maria Gioia Lea Pich

General Anaesthesia and Intensive Care Department director: Giovanni Bordone General anaesthesia and intensive care Department Enrico Arosio (•) Jana Balazova Gian Michele Battistini Francesca Belforti Gabriella Brancato Stefania Brusa Stefania Cantoni Cristina Carlino Vincenzo Cesina Francesco Corazzi Paola Matilde De Pietri Orazio Difrancesco Cristina Dominoni Andrea Forastieri Molinari Nadia Fusilli Alessandro Gaggianese Donatella Girardello (•) Enrico Giustiniano Yari Gollo Stefania Grimaldi Valeria Lascari Sabrina Malara Silvia Eleonora Malossini Juan Carlos Pastore Francesco Pellegrino Laura Rocchi Nadia Ruggieri Giorgio Signoroni Maria Rosaria Spoto (•) Guido Paolo Turio Paola Cosma Zito Anaesthesia I division director: Franco Cancellieri Anaesthesia II division director: Valentina Bellato Anaesthesia III division director: Vittorio Gavazzeni

General Surgery Department director: Marco Montorsi GENERAL AND MINIMALLY INVASIVE SURGERY division director: Riccardo Rosati Fabio Baticci (•) Martina Ceolin Ugo Elmore (•) Uberto Fumagalli Romario (•) Pietro Dante Muselli Alberto Peracchia (°) Matteo Porta GENERAL AND ONCOLOGIC SURGERY division director: Vittorio Quagliuolo Antonella Ardito Pietro Francesco Bagnoli Andrea Brocchi Luca Cozzaglio (•) Leandro Gennari (°) Chiara Erminia Mussi GENERAL SURGERY III division director: Marco Montorsi Stefano Bona (•) Florin Botea Daniele Del Fabbro Matteo Donadon Francesca Gavazzi Angela Palmisano Cristina Ridolfi Antonino Spinelli Guido Torzilli (liver surgery) (•) Alessandro Zerbi (pancreatic surgery) (•)

Gynaecology Department director: Paolo E. Levi Setti GYNAECOLOGY division director: Domenico Vitobello Antonio Accardi Barbara Bianchini Gianluigi Bresciani Cinzia Bulletti Nicoletta Iedà Gabriele Siesto GYNAECOLOGY AND REPRODUCTIVE MEDICINE division director: Paolo Emanuele Levi Setti Elena Albani Annamaria Baggiani Renzo Benaglia Raffaella De Cesare Alessia De Mita Luisa Delle Piane Alessandra Drovanti Valeria Liprandi Luciano Negri Maria Rosaria Parisen Toldin Laura Sacchi Elena Zannoni Irene Zerbetto

Internal Medicine Department director: Mauro Podda vice director: Salvatore Badalamenti ACCIDENT & EMERGENCY UNIT division directors: Salvatore Badalamenti, Antonio Voza Andrea Annoni Giuseppe Biancofiore Gianluigi Citterio Carlo Fedeli Giovanni Giorgino Nicolaos Geroutis Hayato Kurihara Elisabetta Lavezzi Alfonso Maiorino Silvia Oldani Stefano Ottolini Marta Ripoll Pons DERMATOLOGY division director: Marcello Monti Luca Livio Mancini Francesco Sacrini ENDOCRINOLOGY AND DIABETOLOGY division director: Andrea Lania Paolo Colombo Pietro Travaglini (°) GENERAL MEDICINE AND pneumology division director: Michele Ciccarelli Maria Francesca Barmina Massimo Crippa Alberto Grassi Alessandra Ibba Francesca Puggioni Lucia Testoni

INTERNAL MEDICINE division director: Raffaello Furlan Ilaria Bianchi (*) Enrico Brunetta (*) Maria De Santis (*) Pietro Invernizzi (*) Ana Lleo De Nalda (*) Francesca Meda (*) Carlo Francesco Selmi (•) (*) NEPHROLOGY AND DIALYSIS division director: Salvatore Badalamenti Claudio Angelini (•) Paola Arosio Cesare Berra (•) Albania Calvetta Silvia Finazzi Giorgio Graziani (°) Marco Mirani Rosa Pedale Silvia Santostasi Rossella Valentino Simona Verdesca RHEUMATOLOGY division director: Bianca Marasini Laura Belloli Marco Sergio Massarotti Francesca Uboldi THROMBOSIS Centre division director: Lidia Rota Monica Bacci Anna Colombo Monica Demarco Paola Ferrazzi Luca Librè Corrado Lodigiani Grazia Loredana Mendolicchio Ilaria Quaglia

Neuroscience Area

Orthopaedic Area

EMERGENCY NEUROLOGY AND STROKE UNIT division director: Simona Marcheselli

Arthroscopic SURGERY of the knee division director: Enrico Arnaldi

Beatrice Albano Manuel Corato Lara Fratticci Federico Torelli

Andrea Bruno Massimo De Donato Paolo Dupplicato Alexander Kirienko Paolo Pesenti

NEUROLOGY II division director: Eduardo Nobile Orazio

HAND SURGERY division director: Alberto Lazzerini

Francesca Gallia Claudia Giannotta (**) Elda Judica Fabrizia Terenghi Mauro Toffetti NEUROSURGERY division director: Maurizio Fornari Luca Attuati Andrea Cardia (•) Francesco Costa Giovanni Battista Lasio (•) Davide Milani Alessandro Ortolina Federico Pessina Stefania Radice Riccardo Rodriguez Y Baena (°) Lorenzo Bello (oncologic neurosurgery) (•) Enrica Maria Fava

Alessandra Martano Luciana Marzella Ilaria Papini Zorli Angela Trabucco Fabiana Zura Puntaroni HIP AND KNEE PROsTHEtIC SURGERY division director: Guido Grappiolo Franco Astore Andrea Baldini Emanuele Caldarella Gianluca Cusmà Dovico Guatteri Federico Della Rocca Matteo Carlo Ferrari Antonino Gurgone Giuseppe Mazziotta Damiano Ricci Giuseppe Santoro Marco Scardino Francesco Traverso knee ORTHOPAEDICS and sport traumatology division director: Piero Volpi co-head: Matteo G.M. Denti

(*) Physician dealing with activity in the Research laboratories too (**) Research staff (***) Research nurse (•) Head of unit (°) Consultant

■ Divisions that join in the Humanitas Cancer Center

Corrado Bait Matteo Cervellin Emanuele Prospero

PEDIATRIC AND NEUROORTHOPAEDICS SURGERY division director: Nicola Portinaro Maurizio Mori Silvia Mulas Artemisia Panou Pierluigi Terranegra shoulder, elbow and foot surgery division director: Alessandro Castagna Ignazio Bagnoli Mario Borroni Giacomo Delle Rose Antonio Giardella Leonardo Maradei (•) Nikolaos Markopoulos Luigi Milano (foot surgery) (•) Mario Randelli (°) Paolo Renato Rolla TRAUMATOLOGY division director: Marco Berlusconi Luca Berni Matteo Cavanna Federico Chiodini Lorenzo Di Mento Davide Marchettini Antonella Pieroni Josè Antonio Puchol Incertis Ivano Scarabello

Rehabilitation Department director: Stefano Respizzi Cardiac & Respiratory Rehabilitation division director: Stefano Aglieri Anna Beretta Alessandro Eusebio Ornella Riccardi Neurologic Rehabilitation division director: Bruno Bernardini Carla Corsini Sara Ghirmai Marco Augusto Pagani Orthopaedic Rehabilitation division director: Stefano Respizzi Barbara Baroni Maria Cristina D’Agostino Elisabetta Faucher Gianluca Galimberti (•) Marco Salvucci Elisabetta Tibalt

Specialised Divisions of Surgery OPHTHALMOLOGY division director: Paolo Vinciguerra Elena Albè Laura Balia Fabrizio Ivo Camesasca Carlo Castellani Marco Criscito (°) Alessandra Di Maria Marco Gramigna Emanuela Legrottaglie Alessandro Randazzo Mario Romano Pietro Rosetta Maria Ingrid Torres Munoz Rosario Urso Josè Luis Vallejo Garcia Pietro Paolo Vico OTORHINOLARYNGOLOGY division director: Arturo Poletti Filippo Barucca Fabio Bertone Giovanni Colombo Gioavanni Cugini Susanna Di Pietro Luca Malvezzi Stefano Miceli Vanessa Rossi PLASTIC SURGERY I division director: Simone Grappolini

SURGICAL DAY HOSPITAL division director: Roberta Monzani Marco Aldo Babbini Diego Beltrutti (°) Francesco Carrera Aljosa Ciarloni Laura Crozzoli Michele De Ruvo Chiara Ferrari Stefania Gherardi Fabio Intelligente (°) Annarita Larocca Marco Maiola Oreste Davide Montino Rossana Peretti 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 Mauro Seveso Gianluigi Taverna (•) Silvia Zandegiacomo De Zorzi

Alessandra Veronesi PLASTIC SURGERY II division director: Marco Klinger Silvia Giannasi Ombretta Nucca

Departments and teams Scientific Research and Laboratories Updated to March 2012

Scientific Superintendence director: Nicola Dioguardi Sonia Di Biccari Barbara Franceschini Carlo Russo

Scientific Direction and Research Laboratories director: Alberto Mantovani Annunciata Vecchi

Clinical trials office director: Michele Tedeschi Alessandra Giampà Francesco Minuti Emanuela Morenghi Megan Rosalind Roberts

Adaptive Immunity principal investigator: Antonella Viola junior principal investigator: Marinos Kallikourdis Javier Cibella Stefano Garetto Cristina Mazzon Cristina Ploia Giuliana Roselli Cristiana Soldani Anna Elisa Trovato Chiu-Hui Wang Lucia Zanotti ANATOMY AND IMAGING principal investigator: Cristiano Rumio Stefania Recalcati CELLULAR AND MOLECULAR ENDOCRINOLOGY principal investigator: Andrea Lania (3) Valeria Cambiaghi CELLULAR IMMUNOLOGY principal investigator: Paola Allavena Paola Allavena Cristina Belgiovine Francesca Bergomas Marco Erreni Manuela Liguori Federica Marchesi Samantha Angela Pesce Imran Siddiqui

Silvia Della Bella (•) Francesca Calcaterra Kelly Lorraine Hudspeth Irene Mattiola Joanna Mikulak Elena Pontarini Alessandra Roberto Paolo Francesco Tintorio CLINICAL IMMUNOLOGY AND AUTOIMMUNITY AND METABOLISM principal investigator: Carlo Francesco Selmi (2) Francesca Cavaciocchi Maria De Santis (2) Francesca Meda (2) EXPERIMENTAL IMMUNOPATHOLOGY principal investigator: Cecilia Garlanda Elisa Barbati Eduardo Bonavita Davide Del Prete Julio Raul Fernandez Masso Francesca Feruglio Maria Rosaria Galdiero Stefania Gentile Sebastien Jaillon Fabio Pasqualini Nadia Polentarutti Marcello Rubino GASTROINTESTINAL IMMUNOPATHOLOGY principal investigator: Silvio Danese (1)

Grant office Danilo Petroni Monica Di Meglio (•) group leader (1) MD-PhD. In addition to research s/he works as a clinician in Gastroenterology (2) MD-PhD. In addition to research s/he works as a clinician in Internal Medicine (3) MD-PhD. In addition to research s/he works as a clinician in Endocrinology

CLINICAL AND EXPERIMENTAL IMMUNOLOGY principal investigator: Domenico Mavilio

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

Carmen Correale Silvia D’Alessio Alessandro Gandelli Marco Genua Patrizia Naccarato Raffaella Onori Emanuela Sala Carlotta Tacconi Stefania Vetrano

HEPATOBILIARY IMMUNOPATHOLOGY principal investigator: Pietro Invernizzi (2) Francesca Bernuzzi Ilaria Bianchi (2) Fabiola Civardi Ana Lleo De Nalda (2) IMMUNOPHARMACOLOGY principal investigator: Barbara Bottazzi Patrick Brennecke Ivan Cuccovillo Antonio Inforzato Ilaria Laface Marina Sironi Sonia Valentino LEUKOCYTE BIOLOGY principal investigator: Massimo Locati Raffaella Bonecchi (•) Nicoletta Caronni Graziella Curtale Massimiliano Mirolo Bedsheba Nachimuthu Matthieu Florian Pesant Tiziana Renzi Benedetta Savino Federica Tomay Rafal Bartlomiej Tusinski

MOLECULAR IMMUNOLOGY principal investigator: Antonio Sica Stefania Banfi Sara Morlacchi Gabor Szebeni Maria Grazia Totaro ONCOLOGY EXPERIMENTAL THERAPIES principal investigator: Carmelo Carlo-Stella (4) Irene Bertolini Alessandra Inguscio Silvia Laura Locatelli PHARMACOLOGY AND BRAIN PATHOLOGY principal investigator: Michela Matteoli Giuliana Fossati Elisabetta Menna Raffaella Morini Romana Tomasoni Claudia Verderio Stefania Zambetti PHYSIOLOGY principal investigator: Elisabetta Cerri

LEUKOCYTE MIGRATION principal investigator: Silvano Sozzani Annalisa Del Prete MOLECULAR GASTROENTEROLOGY principal investigator: Luigi Laghi (1) Gianluca Basso Paolo Bianchi Giuseppe Celesti Giuseppe Di Caro Fabio Grizzi

BIOBANK Daniela Pistillo Giorgia Ceva Grimaldi Nina Patricia Machado Torres Valentina Paleari Alice Pezzoni COMMON RESEARCH SERVICES Achille Anselmo Chiara Buracchi Andrea Doni Gianpaolo Milite Diego Morone Monica Rimoldi Silvia Tartari

NATIONAL RESEARCH COUNCIL (CNR) HUMAN GENOME AND MEDICAL BIOTECHNOLOGIES principal investigators: Paolo Vezzoni, Anna Villa Maria Elena Caldana Alessandra Castelli Laura Crisafulli Francesca Ficara Maria Luisa Focarelli Michela Lizier Nadia Lo Iacono Virginia Maina Stefano Mantero Veronica Marrella Sharon Muggeo Tui Anna Neri Giovanni Pacchiana Alessandra Pangrazio Marianna Paulis Cristina Sobacchi Dario Strina Lucia Susani INFLAMMATION AND IMMUNOLOGY IN CARDIOVASCULAR Pierluigi Carullo Paola Luisa Cattaneo Elisa Di Pasquale Leonardo Elia Carolina Greco Michele Latronico Roberto Papait (•) Manuela Quintavalle Alessandra Rodanò sarcomers in CARDIAC PATHOLOGY ) principal investigator: Marie Louise Bang Enrica Marmonti SIGNAL TRANSDUCTION IN CARDIAC PATHOLOGY principal investigator: Daniele Catalucci Barbara Gargano

Papers published 2011

Papers published 2011 At 31 January 2012 * = Corresponding author

P r e c l i n i c a l GASTROENTEROLOGY AND DIGESTIVE ENDOSCOPY

R e s e a r c h Gadaleta RM, van Erpecum KJ, Oldenburg B, Willemsen EC, Renooij W, Murzilli S, Klomp LW, Siersema PD, Schipper ME, Danese S, Penna G, Laverny G, Adorini L, Moschetta A, Mil SW.

Angulo S, Morales A, Danese S, Llacuna L, Masamunt MC, Pultz N, Cifone MG, De Simone C, Delgado S, Vila J, Panés J, Donskey C, Fernández-Checa JC, Fiocchi C, Sans M.

Farnesoid X receptor activation inhibits inflammation and preserves the intestinal barrier in inflammatory bowel disease.

Probiotic Sonicates Selectively Induce Mucosal Immune Cells Apoptosis through Ceramide Generation via Neutral Sphingomyelinase.

Gut. 2011 Apr;60(4):463-72. Raw IF: 10.614

PLoS One. 2011 Mar 9;6(3):e16953. Raw IF: 4.411

Werner L, Berndt U, Paclik D, Danese S, Schirbel A, Sturm A.

Normalized IF: 3

Danese S.

Immune and non-immune components orchestrate the pathogenesis of inflammatory bowel disease. Am J Physiol Gastrointest Liver Physiol. 2011 May;300(5):G716-22. Epub 2011 Jan 13. Raw IF: 3.522 Normalized IF: 6 Danese S.

Role of the vascular and lymphatic endothelium in the pathogenesis of inflammatory bowel disease: ‘brothers in arms’. Gut. 2011 Jul;60(7):998-1008. Epub 2011 Jan 6. Raw IF: 10.614 Normalized IF: 8

Normalized IF: 4

TNFα inhibitors restrict T cell activation and cycling via Notch-1 signalling in inflammatory bowel disease. Gut. 2011 Nov 7. [Epub ahead of print]. Raw IF: 10.614

Normalized IF: 4

GENERAL MEDICINE AND HEPATOLOGY Carcamo WC, Satoh M, Kasahara H, Terada N, Hamazaki T, Chan JY, Yao B, Tamayo S, Covini G, von Mühlen CA, Chan EK.

Induction of cytoplasmic rods and rings structures by inhibition of the CTP and GTP synthetic pathway in mammalian cells. PLoS One. 2011;6(12):e29690. Epub 2011 Dec 29. Raw IF: 4.411 Normalized IF: 3

Fava F, Danese S*.

Intestinal microbiota in inflammatory bowel disease: Friends or foes? World J Gastroenterol. 2011 February 7; 17(5): 557-566 Raw IF: 2.24 Normalized IF: 4 Fini L, Piazzi G, Daoud Y, Selgrad M, Maegawa S, Garcia M, Fogliano V, Romano M, Graziani G, Vitaglione P, Carmack SW, Gasbarrini A, Genta RM, Issa JP, Boland CR, Ricciardiello L.

Chemoprevention of Intestinal Polyps in ApcMin/+ Mice Fed with Western or Balanced Diets by Drinking. Annurca Apple Polyphenol Extract. Cancer Prev Res (Phila). 2011 Jun;4(6):907-15. Epub 2011 Mar 7. Raw IF: 4.978 Normalized IF: 6 Peyrin-Biroulet L, Ferrante M, Magro F, Campbell S, Franchimont D, Fidder H, Strid H, Ardizzone S, VeeremanWauters G, Chevaux JB, Allez M, Danese S, Sturm A.

INTERNAL MEDICINE Bianchi I, Lleo A, Gershwin ME, Invernizzi P.*

The X chromosome and immune associated genes. J Autoimmun. 2011 Dec 15. [Epub ahead of print]. Raw IF: 8.136 Normalized IF: 8 Demorrow S, Onori P, Venter J, Invernizzi P, Frampton G, White M, Franchitto A, Kopriva S, Bernuzzi F, Francis H, Coufal M, Glaser S, Fava G, Meng F, Alvaro D, Carpino G, Gaudio E, Alpini G.

Neuropeptide Y inhibits cholangiocarcinoma cell growth and invasion. Am J Physiol Cell Physiol. 2011 May;300(5):C1078-89. Epub 2011 Jan 26. Raw IF: 3.817 Normalized IF: 3

Results from the 2nd Scientific Workshop of the ECCO (I): Impact of mucosal healing on the course of inflammatory bowel disease.

Folci M, Meda F, Gershwin ME, Selmi C.*

J Crohns Colitis. 2011 Oct;5(5):477-83. Epub 2011 Aug 3. Raw IF: 2.628 Normalized IF: 2

Clin Rev Allergy Immunol. 2011 Jan 18. [Epub ahead of print]. Raw IF: 3.435 Normalized IF: 6

Cutting-Edge Issues in Primary Biliary Cirrhosis.

Frampton G, Invernizzi P, Bernuzzi F, Pae HY, Quinn M, Horvat D, Galindo C, Huang L, McMillin M, Cooper B, Rimassa L, Demorrow S.

Rong G, Zhong R, Lleo A, Leung PS, Bowlus CL, Yang GX, Yang CY, Coppel RL, Ansari AA, Cuebas DA, Worman HJ, Invernizzi P, Gores GJ, Norman G, He XS, Gershwin ME.

Interleukin-6-driven progranulin expression increases cholangiocarcinoma growth by an Akt-dependent mechanism.

Epithelial cell specificity and apotope recognition by serum autoantibodies in primary biliary cirrhosis.

Gut. 2012 Feb;61(2):268-77. Epub 2011 Nov 7. Raw IF: 10.614 Normalized IF: 8

Hepatology. 2011 Jul;54(1):196-203. Raw IF: 10.885

Normalized IF: 4

Selmi C*, De Santis M, Cavaciocchi F, Gershwin ME. Hashimoto N, Shimoda S, Kawanaka H, Tsuneyama K, Uehara H, Akahoshi T, Kinjo N, Taketomi A, Shirabe K, Akashi K, Lleo A, Ansari AA, Gershwin ME, Maehara Y.

Modulation of CD4(+) T cell responses following splenectomy in hepatitis C virus-related liver cirrhosis. Clin Exp Immunol. 2011 Aug;165(2):243-50. Epub 2011 May 25. Raw IF: 3.134 Normalized IF: 2 Hirschfield GM, Invernizzi P.

Progress in the genetics of primary biliary cirrhosis. Semin Liver Dis. 2011 May;31(2):147-56. Epub 2011 May 2. Raw IF: 5.286 Normalized IF: 6 Invernizzi P.

Human leukocyte antigen in primary biliary cirrhosis: An old story now reviving. Hepatology. 2011 Aug;54(2):714-23. Raw IF: 10.885

Normalized IF: 8

Lleo A, Gershwin ME, Mantovani A, Invernizzi P.*

Towards Common Denominators in Primary Biliary Cirrhosis: The Role of IL-12. J Hepatol. 2011 Oct 14. [Epub ahead of print] No abstract available. Raw IF: 9.334 Normalized IF: 8

Infectious agents and xenobiotics in the etiology of primary biliary cirrhosis. Dis Markers. 2010;29(6):287-99. Raw IF: 1.723

Normalized IF: 2

Shimoda S, Selmi C, Gershwin ME.

Fractalkine and Other Chemokines in Primary Biliary Cirrhosis Int J Hepatol. 2012;2012:102839. Epub 2011 Aug 9. Raw IF: 0 Normalized IF: 0.1 Smyck DS, Mytilinaiou MG, Milkiewicz P, Rigopoulou EI, Invernizzi P, Bogdanos DP.

Towards systemic sclerosis and away from primary biliary cirrhosis:the case of PTPN22. Autoimmun Highlights 2012,3(1):1-9. Raw IF: 0

Normalized IF: 0.1

Tanaka A, Ohira H, Kikuchi K, Nezu S, Shibuya A, Bianchi I, Podda M, Invernizzi P, Takikawa H.

Genetic association of Fc receptor-like 3 polymorphisms with susceptibility to primary biliary cirrhosis: ethnic comparative study in Japanese and Italian patients. Tissue Antigens. 2011 Mar;77(3):239-43. Raw IF: 3.024

Normalized IF: 6

Meda F, Folci M, Baccarelli A, Selmi C.*

MEDICAL ONCOLOGY AND HAEMATOLOGY

The epigenetics of autoimmunity. Cell Mol Immunol. 2011 May;8(3):226-36. Epub 2011 Jan 31. Raw IF: 2.026 Normalized IF: 2 Mitchell MM, Lleo A, Zammataro L, Mayo MJ, Invernizzi P, Bach N, Shimoda S, Gordon S, Podda M, Gershwin ME, Selmi C, Lasalle JM.

Epigenetic investigation of variably X chromosome inactivated genes in monozygotic female twins discordant for primary biliary cirrhosis. Epigenetics. 2011 Jan 1;6(1):95-102. Raw IF: 4.622

Normalized IF: 6

Le贸n LG, Giovannetti E, Alecci C, Giancola F, Funel N, Zucali P, Peters GJ, Padr贸n JM.

Antiproliferative effects of novel aliphatic acetogenin analogs against aggressive solid tumor cell lines. In Vivo. 2011 Mar-Apr;25(2):203-7. Raw IF: 1.159

Normalized IF: 1

Frampton G, Invernizzi P, Bernuzzi F, Pae HY, Quinn M, Horvat D, Galindo C, Huang L, McMillin M, Cooper B, Rimassa L, Demorrow S.

Interleukin-6-driven progranulin expression increases

Papers published 2011

cholangiocarcinoma growth by an Akt-dependent mechanism. Gut. 2012 Feb;61(2):268-77. Epub 2011 Nov 7. Raw IF: 10.614 Normalized IF: 8 Giovannetti E, Zucali PA, Assaraf YG, Leon LG, Smid K, Alecci C, Giancola F, Destro A, Gianoncelli L, Lorenzi E, Roncalli M, Santoro A, Peters GJ.

Preclinical emergence of vandetanib as a potent antitumour agent in mesothelioma: molecular mechanisms underlying its synergistic interaction with pemetrexed and carboplatin. Br J Cancer. 2011 Nov 8;105(10):1542-53. Epub 2011 Oct 4. Raw IF: 4.831 Normalized IF: 6

Chemokine nitration prevents intratumoral infiltration of antigen-specific T cells. J Exp Med. 2011 Sep 26;208(10):1949-62. Epub 2011 Sep 19. Raw IF: 14.776 Normalized IF: 10 Roncalli M*, Terracciano L, Di Tommaso L, David E, Colombo M; Gruppo Italiano Patologi Apparato Digerente (GIPAD); Società Italiana di Anatomia Patologica e Citopatologia Diagnostica/International Academy of Pathology, Italian division (SIAPEC/IAP).

Liver precancerous lesions and hepatocellular carcinoma: the histology report. Dig Liver Dis. 2011 Mar;43 Suppl 4:S361-72. Raw IF: 2.805 Normalized IF: 4

PATHOLOGY Kasic T, Colombo P, Soldani C, Wang CM, Miranda E, Roncalli M, Bronte V, Viola A*.

Modulation of human T cell functions by reactive nitrogen species. Eur J Immunol. 2011 Jul;41(7):1843-9. Raw IF: 4.942

Molon B, Ugel S, Del Pozzo F, Soldani C, Zilio S, Avella D, De Palma A, Mauri P, Monegal A, Rescigno M, Savino B, Colombo P, Jonjic N, Pecanic S, Lazzarato L, Fruttero R, Gasco A, Bronte V, Viola A.

Normalized IF: 6

Furlan A, Stagni V, Hussain A, Richelme S, Conti F, Prodosmo A, Destro A, Roncalli M, Barilà D, Maina F.

REPRODUCTIVE MEDICINE Criado E*, Moalli F, Polentarutti N, Albani E, Morreale G, Menduni F, Levi-Setti PE.

Experimental contamination assessment of a novel closed ultravitrification device. Fertil Steril. 2011 Apr;95(5):1777-9. Raw IF: 3.958

Normalized IF: 6

Abl interconnects oncogenic Met and p53 core pathways in cancer cells. Cell Death Differ. 2011 Oct;18(10):1608-16. Epub 2011 Apr 1. Raw IF: 9.05 Normalized IF: 4 Giovannetti E, Zucali PA, Assaraf YG, Leon LG, Smid K, Alecci C, Giancola F, Destro A, Gianoncelli L, Lorenzi E, Roncalli M, Santoro A, Peters GJ.

RESEARCH LABORATORIES OF SCIENTIFIC DIRECTION Allavena P*, Chieppa M, Bianchi G, Solinas G, Fabbri M, Laskarin G, Mantovani A.

Engagement of the mannose receptor by tumoral mucins activates an immune suppressive phenotype in human tumor-associated macrophages. Clin Dev Immunol. 2010;2010:547179. Raw IF: 2.263

Normalized IF: 2

Allavena P, Germano G, Marchesi F, Mantovani A*.

Chemokines in cancer related inflammation. Mazzon C*, Anselmo A, Cibella J, Soldani C, Destro A, Kim N, Roncalli M, Burden SJ, Dustin ML, Sarukhan A, Viola A.

The critical role of agrin in the hematopoietic stem cell niche. 90

Blood. 2011 Sep 8;118(10):2733-42. Epub 2011 Jun 7. Raw IF: 10.558 Normalized IF: 8

Exp Cell Res. 2011 Mar 10;317(5):664-73. Raw IF: 3.609

Normalized IF: 6

Baldini M, Maugeri N, Ramirez GA, Giacomassi C, Castiglioni A, Prieto-González S, Corbera-Bellalta M, Di Comite G, Papa I, Dell’Antonio G, Ammirati E, Cuccovillo I, Vecchio V,

Mantovani A, Rovere-Querini P, Sabbadini MG, Cid MC, Manfredi AA.

Selective upregulation of the soluble pattern recognition receptor PTX3 and of VEGF in giant cell arteritis: Relevance for recent optic nerve ischemia. Arthritis Rheum. 2011 Oct 11 [Epub ahead of print]. Raw IF: 8.435 Normalized IF: 4 Bertilaccio MT, Simonetti G, Dagklis A, Rocchi M, Rodriguez TV, Apollonio B, Mantovani A, Ponzoni M, Ghia P, Garlanda C, Caligaris-Cappio F, Muzio M.

Lack of TIR8/SIGIRR triggers progression of chronic lymphocytic leukemia in mouse models. Blood. 2011 Jul 21;118(3):660-9. Epub 2011 Jun 7. Raw IF: 10.558 Normalized IF: 4 Bertini R, Barcelos LS, Beccari AR, Cavalieri B, Moriconi A, Bizzarri C, Di Benedetto P, Di Giacinto C,Gloaguen I, Galliera E, Corsi MM, Russo RC, Andrade SP, Cesta MC, Nano G, Aramini A, Cutrin JC, Locati M, Allegretti M, Teixeira MM.

Receptor binding mode and pharmacological characterization of a potent and selective dual CXCR1/ CXCR2 non-competitive allosteric inhibitor.

Bason C, Molinari A, Maric D, Tosato G, Berardi AC.

Adult human circulating CD34-Lin-CD45-CD133- cells can differentiate into hematopoietic and endothelial cells. Blood. 2011 Aug 25;118(8):2105-15. Epub 2011 Jun 29. Raw IF: 10.558 Normalized IF: 8 Correia DV, Fogli M, Hudspeth K, da Silva MG, Mavilio D°, Silva-Santos B°. ° These authors equally contributed to this work

Differentiation of human peripheral blood V{delta}1+ T cells expressing the natural cytotoxicity receptor NKp30 for recognition of lymphoid leukemia cells. Blood. 2011 Jul 28;118(4):992-1001. Epub 2011 Jun 1. Raw IF: 10.558 Normalized IF: 8 Costello DA, Watson MB, Cowley TR, Murphy N, Murphy Royal C, Garlanda C, Lynch MA.

Interleukin-1{alpha} and HMGB1 Mediate Hippocampal Dysfunction in SIGIRR-Deficient Mice. J. Neurosci. 2011 Mar 9;31(10):3871-9. Raw IF: 7.271

Normalized IF: 4

Br J Pharmacol. 2012 Jan;165(2):436-454. Epub 2011 Jun 30. Raw IF: 4.925 Normalized IF: 3

Criado E*, Moalli F, Polentarutti N, Albani E, Morreale G, Menduni F, Levi-Setti PE.

Bonecchi R, Locati M, Mantovani A*.

Fertil Steril. 2011 Apr;95(5):1777-9. Raw IF: 3.958

Chemokines and cancer: a fatal attraction. Cancer Cell. 2011 Apr 12;19(4):434-5. Raw IF: 26.925

Normalized IF: 15

Bosschaerts T, Morias Y, Stijlemans B, Hérin M, Porta C, Sica A, Mantovani A, De Baetselier P, Beschin A.

IL-10 limits production of pathogenic TNF by M1 myeloid cells through induction of nuclear NF-kB p50 member in Trypanosoma congolense infection resistant C57BL/6 mice. Eur J Immunol. 2011 Nov;41(11):3270-80. Raw IF: 4.942

Normalized IF: 3

Experimental contamination assessment of a novel closed ultravitrification device. Normalized IF: 6

Davey MS, Tamassia N, Rossato M, Bazzoni F, Calzetti F, Bruderek K, Sironi M, Zimmer L, Bottazzi B, Mantovani A, Brandau S, Moser B, Eberl M, Cassatella MA.

Failure to detect production of IL-10 by activated human neutrophils. Nat Immunol. 2011 Oct 19;12(11):1017-8. Raw IF: 25.668 Normalized IF: 7.5 De Palma G, Castellano G, Del Prete A, Sozzani S, Fiore N, Loverre A, Parmentier M, Gesualdo L, Grandaliano G, Schena FP.

Cairo G, Recalcati S, Mantovani A, Locati M.

The possible role of ChemR23/chemerin axis in the recruitment of dendritic cells in lupus nephritis.

Iron trafficking and metabolism in macrophages: contribution to the polarized phenotype.

Kidney Int. 2011 Jun;79(11):1228-35. Epub 2011 Feb 23. Raw IF: 6.105 Normalized IF: 3

Trends Immunol. 2011 Jun;32(6):241-7. Epub 2011 Apr 21. Raw IF: 9.533 Normalized IF: 8 Ciraci E, Della Bella S, Salvucci O, Rofani C, Segarra M,

Del Prete A*, Allavena P, Santoro G, Fumarulo R, Corsi MM, Mantovani A.

Molecular pathways in cancer-related inflammation |

Papers published 2011

Molekularni putovi u upali povezanoj s karcinomom. Biochemia Medica 2011 vol. 21 (3). Raw IF: 1.085

Normalized IF: 6

Normalized IF: 2

Dolzani P, Assirelli E, Pulsatelli L, Addimanda O, Mancarella L, Peri G, Mantovani A, Facchini A, Meliconi R.

Systemic inflammation and antibodies to citrullinated peptides in hand osteoarthritis. Clin Exp Rheumatol. 2011 Nov-Dec;29(6):1006-9. Epub 2011 Dec 22. Raw IF: 2.358 Normalized IF: 1

Gout E, Moriscot C, Doni A, Dumestre-Pérard C, Lacroix M, Pérard J, Schoehn G, Mantovani A, Arlaud GJ, Thielens NM.

M-Ficolin Interacts with the Long Pentraxin PTX3: A Novel Case of Cross-Talk between Soluble PatternRecognition Molecules. J Immunol. 2011 May 15;186(10):5815-22. Epub 2011 Apr 13. Raw IF: 5.745 Normalized IF: 3 Ievoli E, Lindstedt R, Inforzato A, Camaioni A, Palone F, Day AJ, Mantovani A, Salvatori G, Salustri A.

Erreni M, Mantovani A, Allavena P*.

Tumor-associated macrophages (TAM) and inflammation in colorectal cancer. Cancer Microenvironment 2011 vol. 4(2) 141-154 Raw IF: 0 Normalized IF: 0.1 Faggioli F, Vezzoni P*, Montagna C.

Single-cell analysis of ploidy and centrosomes underscores the peculiarity of normal hepatocytes. PLoS One. 2011;6(10):e26080. Epub 2011 Oct 12. Raw IF: 4.411 Normalized IF: 6 Ferratini M, Ripamonti V, Masson S, Grati P, Racca V, Cuccovillo I, Raimondi E, Capomolla S, Macchi C, Coruzzi P, Vago T, Calvo M, Mantovani A, Latini R.

Pentraxin-3 predicts functional recovery and 1-year major adverse cardiovascular events after rehabilitation of cardiac surgery patients. J Cardiopulm Rehabil Prev 2012 Jan;32(1):17-24. Epub 2011 Dec 21. Raw IF: 1.415 Normalized IF: 2 Garlanda C, Bottazzi B, Moalli F, Deban L, Molla F, Latini R, Mantovani A*.

Pentraxins and Atherosclerosis: The Role of PTX3. Curr Pharm Des. 2011;17(1):38-46. Raw IF: 4.774

Eur J Immunol. 2011 Sep;41(9):2470-2. Raw IF: 4.942

Normalized IF: 6

Implication of the oligomeric state of the N-terminal PTX3 domain in cumulus matrix assembly. Matrix Biol. 2011 Jun;30(5-6):330-7. Epub 2011 May 18. Raw IF: 3.328 Normalized IF: 2 Inforzato A, Jaillon S, Moalli F, Barbati E, Bonavita E, Bottazzi B, Mantovani A, Garlanda C*.

The long pentraxin PTX3 at the crossroads between innate immunity and tissue remodelling. Tissue Antigens. 2011 Apr;77(4):271-82. Raw IF: 3.024

Normalized IF: 6

Kasic T, Colombo P, Soldani C, Wang CM, Miranda E, Roncalli M, Bronte V, Viola A*.

Modulation of human T cell functions by reactive nitrogen species. Eur J Immunol. 2011 Jul;41(7):1843-9. Raw IF: 4.942

Normalized IF: 6

Lech M, Römmele C, Kulkarni OP, Susanti HE, Migliorini A, Garlanda C, Mantovani A, Anders HJ.

Lack of the Long Pentraxin PTX3 Promotes Autoimmune Lung Disease but not Glomerulonephritis in Murine Systemic Lupus Erythematosus. PLoS One. 2011;6(5):e20118. Epub 2011 May 27. Raw IF: 4.411 Normalized IF: 3

Germano G, Mantovani A, Allavena P*.

Targeting of the innate immunity/inflammation as complementary anti-tumor therapies. Ann Med. 2011 Dec;43(8):581-93. Epub 2011 Jul 14. Raw IF: 4.323 Normalized IF: 6

Gordon S, Mantovani A*.

Diversity and plasticity of mononuclear phagocytes.

Lee JS, Cella M, McDonald KG, Garlanda C, Kennedy GD, Nukaya M, Mantovani A, Kopan R, Bradfield CA, Newberry RD, Colonna M.

AHR drives the development of gut ILC22 cells and postnatal lymphoid tissues via pathways dependent on and independent of Notch. Nat Immunol. 2012;13(2):144-51. Epub 2011 Nov 20. Raw IF: 25.668 Normalized IF: 7.5

Liguori M, Solinas G, Germano G, Mantovani A, Allavena P.

Tumor-associated macrophages as incessant builders and destroyers of the cancer stroma. Cancers 2011 vol. 3 (4): 3740-3761. Raw IF: 0

Normalized IF: 0.1

Lleo A, Gershwin ME, Mantovani A, Invernizzi P*.

Towards Common Denominators in Primary Biliary Cirrhosis: The Role of IL-12. J Hepatol. 2011 Oct 14. [Epub ahead of print]. Raw IF: 9.334 Normalized IF: 8 Magrini E*, Szabò I, Doni A, Cibella J, Viola A.

Serotonin-Mediated Tuning of Human Helper T Cell Responsiveness to the Chemokine CXCL12. PLoS One. 2011;6(8):e22482. Epub 2011 Aug 10. Raw IF: 4.411 Normalized IF: 6 Mantovani A.

B cells and macrophages in cancer: yin and yang. Nat Med. 2011 Mar;17(3):285-6. Raw IF: 25.43

Normalized IF: 15

Mantovani A.

Tumor-associated macrophages in cancer-related inflammation. Immunotherapy. 2011;3(4 Suppl. 1), 21-22. Raw IF: 0.542 Normalized IF: 1 Mantovani A, Cassatella MA, Costantini C, Jaillon S.

Neutrophils in the activation and regulation of innate and adaptive immunity. Nat Rev Immunol. 2011 Jul 25;11(8):519-31. Raw IF: 35.196 Normalized IF: 15 Mantovani A*, Germano G, Marchesi F, Locatelli M, Biswas SK.

Cancer-promoting tumor-associated macrophages: New vistas and open questions. Eur J Immunol. 2011 Sep;41(9):2522-5. Raw IF: 4.942

Normalized IF: 6

Marfia G, Madaschi L, Marra F, Menarini M, Bottai D, Formenti A, Di Giulio AM, Carelli S, Gorio A.

Adult neural precursors isolated from post mortem brain yield mostly neurons: An erythropoietin-dependent process.

Neurobiol Dis. 2011 Jul;43(1):86-98. Epub 2011 Feb 13. Raw IF: 5.121 Normalized IF: 6 Marrella V, Maina V, Villa A.

Omenn syndrome does not live by V(D)J recombination alone. Curr Opin Allergy Clin Immunol. 2011 Dec;11(6):525-31.Epub 2011 Oct 13. Raw IF: 3.431 Normalized IF: 6 Martinez de la Torre Y, Pregnolato F, D’Amelio F, Grossi C, Disimone N, Pasqualini F, Nebuloni M, Chen P, Pierangeli S, Bassani N, Ambrogi F, Borghi MO, Vecchi A, Locati M, Meroni PL.

Anti-phospholipid induced murine fetal loss: Novel protective effect of a peptide targeting the β2 glycoprotein I phospholipid-binding site. Implications for human fetal loss. J Autoimmun. 2011 Dec 22. [Epub ahead of print]. Raw IF: 8.136 Normalized IF: 8 Mazzon C*, Anselmo A, Cibella J, Soldani C, Destro A, Kim N, Roncalli M, Burden SJ, Dustin ML, Sarukhan A, Viola A.

The critical role of agrin in the hematopoietic stem cell niche. Blood. 2011 Sep 8;118(10):2733-42. Epub 2011 Jun 7. Raw IF: 10.558 Normalized IF: 8 Mikulak J*, Negrini S, Klajn A, D’Alessandro R, Mavilio D, Meldolesi J.

Dual REST-dependence of L1CAM: from gene expression to alternative splicing governed by Nova2 in neural cells. J Neurochem. 2012 Mar;120(5):699-709. Epub 2012 Jan 23. Raw IF: 4.337 Normalized IF: 6 Mirandola L, Chiriva-Internati M, Montagna D, Locatelli F, Zecca M, Ranzani M, Basile A, Locati M, Cobos E, Kast WM, Asselta R, Paraboschi EM, Comi P, Chiaramonte R.

Notch1 regulates chemotaxis and proliferation by controlling the chemokine receptors 5 and 9 in T-cell acute lymphoblastic leukemia. J Pathol. 2011 Oct 7. [Epub ahead of print]. Raw IF: 7.274 Normalized IF: 4 Moalli F, Jaillon S, Inforzato A, Sironi M, Bottazzi B, Mantovani A, Garlanda C*.

Pathogen Recognition by the Long Pentraxin PTX3.

Papers published 2011

J Biomed Biotechnol. 2011;2011:830421. Epub 2011 Jun 2. Raw IF: 1.23 Normalized IF: 2 Molon B, Ugel S, Del Pozzo F, Soldani C, Zilio S, Avella D, De Palma A, Mauri P, Monegal A, Rescigno M, Savino B, Colombo P, Jonjic N, Pecanic S, Lazzarato L, Fruttero R, Gasco A, Bronte V, Viola A.

Regulatory T Cells Target Chemokine Secretion by Dendritic Cells Independently of Their Capacity To Regulate T Cell Proliferation. J Immunol. 2011 Jun 15;186(12):6807-14. Epub 2011 May 13. Raw IF: 5.745 Normalized IF: 6 Morlacchi S, Soldani C, Viola A, Sarukhan A*.

Self-antigen presentation by mouse B cells results in regulatory T-cell induction rather than anergy or clonal deletion.

J Bone Miner Res. 2011 Nov 9. [Epub ahead of print]. Raw IF: 7.056 Normalized IF: 8 Pello OM*, Silvestre C, De Pizzol M, Andrés V.

A glimpse on the phenomenon of macrophage polarization during atherosclerosis. Immunobiology. 2011 Nov;216(11):1172-6. Epub 2011 May 24. Raw IF: 4.114 Normalized IF: 3 Pello OM, De Pizzol M, Mirolo M, Soucek L, Zammataro L, Amabile A, Doni A, Nebuloni M, Swigart LB, Evan GI, Mantovani A, Locati M*.

Role of c-Myc in alternative activation of human macrophages and tumor-associated macrophage biology. Blood. 2012 Jan 12;119(2):411-21. Epub 2011 Nov 8. Raw IF: 10.558 Normalized IF: 8 Porta C, Riboldi E, Totaro MG, Strauss L, Sica A, Mantovani A*.

Macrophages in cancer and infectious diseases: the ‘good’ and the ‘bad’. Immunotherapy. 2011 Oct;3(10):1185-202. Raw IF: 0.542 Normalized IF: 1

Blood. 2011 Jul 28;118(4):984-91. Epub 2011 Jun 7. Raw IF: 10.558 Normalized IF: 8

Quintavalle M, Condorelli G, Elia L.

Naldini A, Morena E, Belotti D, Carraro F, Allavena P, Giavazzi R.

Arterial remodeling and atherosclerosis: miRNAs involvement.

Identification of thrombin-like activity in ovarian cancer associated ascites and modulation of multiple cytokine networks.

Vascul Pharmacol. 2011 Oct;55(4):106-10. Epub 2011 Aug 16. Raw IF: 2.174 Normalized IF: 2

Thromb Haemost. 2011 Sep 27;106(4):705-11. Epub 2011 Aug 11. Raw IF: 4.701 Normalized IF: 3

Riboldi E, Daniele R, Parola C, Inforzato A, Arnold PL, Bosisio D, Fremont DH, Bastone A, Colonna M, Sozzani S.

Pangrazio A, Boudin E, Piters E, Damante G, Lo Iacono N, D’Elia AV, Vezzoni P, Van Hul W, Villa A, Sobacchi C*.

Human C-type lectin domain family 4, member C (CLEC4C/BDCA-2/CD303) is a receptor for asialogalactosyl-oligosaccharides.

Identification of the first deletion in the LRP5 gene in a patient with Autosomal Dominant Osteopetrosis type I. Bone. 2011 Sep;49(3):568-71. Epub 2011 May 11. Raw IF: 4.601 Normalized IF: 6

characterisation of 5 new cases with novel mutations.

Pangrazio A°, Cassani B°, Guerrini MM, Crockett JC, Marrella V, Zammataro L, Strina D, Schulz A, Schlack C, Kornak U, Mellis DJ, Duthie A, Helfrich MH, Durandy A, Moshous D, Vellodi A, Chiesa R, Veys P, Lo Iacono N, Vezzoni P, Fischer A, Villa A*, Sobacchi C. ° These authors equally contributed to this work

RANK-dependent autosomal recessive osteopetrosis:

J Biol Chem. 2011 Oct 14;286(41):35329-33. Epub 2011 Aug 31. Raw IF: 5.328 Normalized IF: 6 Selleri S, Brigida I, Casiraghi M, Scaramuzza S, Cappelli B, Cassani B, Ferrua F, Aker M, Slavin S. Scarselli A, Cancrini C, Marktel S, Grazia Roncarolo M, Aiuti A.

In vivo T-cell dynamics during immune reconstitution after hematopoietic stem cell gene therapy in adenosine deaminase severe combined immune deficiency. J Allergy Clin Immunol. 2011 Jun;127(6):1368-75.e8. Epub 2011 Apr 7. Raw IF: 9.273 Normalized IF: 4

Sica A.

Role of tumour-associated macrophages in cancerrelated inflammation. Exp Oncol. 2010 Sep;32(3):153-8. Raw IF: 0

Normalized IF: 0.1

Sica A*, Melillo G, Varesio L.

Hypoxia: a double-edged sword of immunity. J Mol Med (Berl). 2011 Jul;89(7):657-65. Epub 2011 Feb 19. Raw IF: 5.192 Normalized IF: 6 Sica A*, Porta C, Morlacchi S, Banfi S, Strauss L, Rimoldi M, Totaro MG, Riboldi E.

Origin and Functions of Tumor-Associated Myeloid Cells (TAMCs). Cancer Microenviron. 2011 Sep 24. [Epub ahead of print] Raw IF: 0 Normalized IF: 0.1 Skuginna V, Lech M, Allam R, Ryu M, Clauss S, Susanti HE, RĂśmmele C, Garlanda C, Mantovani A, Anders HJ.

Toll-Like Receptor Signaling and SIGIRR in Renal Fibrosis upon Unilateral Ureteral Obstruction. PLoS One. 2011 Apr 22;6(4):e19204. Raw IF: 4.411

Normalized IF: 3

VĂŠliz Rodriguez T, Moalli F, Polentarutti N, Paroni M, Bonavita E, Anselmo A, Nebuloni M, Mantero S, Jaillon S, Bragonzi A, Mantovani A, Riva F, Garlanda C*.

Role of TIR8/SIGIRR, a Negative Regulator of IL-1R/ TLR Signalling, in Resistance to Acute Pseudomonas aeruginosa Lung Infection. Infect Immun. 2012 Jan;80(1):100-9- Epub 2011 Oct 24. Raw IF: 4.098 Normalized IF: 6

Papers published 2011 * = Corresponding author

T r a s l a t i o n a l ARTHROSCOPIC SURGERY OF THE SHOULDER Fini M, Bondioli E, Castagna A, Torricelli P, Giavaresi G, Rotini R, Marinelli A, Guerra E, Orlandi C, Carboni A, Aiti A, Benedettini E, Giardino R, Melandri D.

Decellularized human dermis to treat massive rotator cuff tears: in vitro evaluations. Connect Tissue Res. 2011 Dec 15. [Epub ahead of print]. Raw IF: 2.093 Normalized IF: 4

DIAGNOSTIC RADIOLOGY Graziani G*, Cucchiari D, Verdesca S, Balzarini L, Montanelli A, Ponticelli C.

Chyluria Associated with Nephrotic-Range Proteinuria: Pathophysiology, Clinical Picture and Therapeutic Options. Nephron Clin Pract. 2011 Sep 14;119(3):c248-c254. [Epub ahead of print]. Raw IF: 1.843 Normalized IF: 2

R e s e a r c h hypothalamic autoimmunity in patients with selective idiopathic hypopituitarism. Clin Endocrinol (Oxf). 2011 Sep;75(3):361-6. Epub 2011 Mar 28. Raw IF: 3.323 Normalized IF: 4 Filopanti M, Olgiati L, Mantovani G, Corbetta S, Arosio M, Gasco V, De Marinis L, Martini C, Bogazzi F, CannavĂ˛ S, Colao A, Ferone D, Arnaldi G, Pigliaru F, Peri A, Angeletti G, Jaffrain-Rea ML, Lania AG, Spada A.

Growth Hormone Receptor Variants and Response to Pegvisomant in Monotherapy or in Combination with Somatostatin Analogs in Acromegalic Patients: A Multicenter Study. J Clin Endocrinol Metab. 2012 feb; 97(2):E165-72; Epub 2011 Dec 7. Raw IF: 6.495 Normalized IF: 6

GASTROENTEROLOGY AND DIGESTIVE ENDOSCOPY Bianchi P, Laghi L, Delconte G, Malesci A.

Graziani G*, Cucchiari D, Verdesca S, Balzarini L, Montanelli A, Ponticelli C.

Looking at appearance of urine before performing a renal biopsy in nephrotic syndrome. J Nephrol. 2011 Sep-Oct; 24(5): 665-8 Epub 2011 May 19. Raw IF: 1.623 Normalized IF: 2

Prognostic Value of Colorectal Cancer Biomarkers. Cancers 2011 vol. 3 (2). Raw IF: 0

Normalized IF: 0.1

Danese S.

IBD: of mice and men-shedding new light on IL-13 activity in IBD. EMERGENCY UNIT Oldani S*, Finazzi S, Bottazzi B, Garlanda C, Baldassarre E, Valaperta S, Cuccovillo I, Albini M, Child M, Montanelli A, Graziani G, Badalamenti S.

Plasma pentraxin-3 as a marker of bioincompatibility in hemodialysis patients. J Nephrol. 2011 Jun 22. pii: 02C3813E-6B05-45B4-9483C25B14801890. Raw IF: 1.623 Normalized IF 2

Nat Rev Gastroenterol Hepatol. 2011 Mar;8(3):128-9. Raw IF: 4.558 Normalized IF: 6 Danese S.

New therapies for inflammatory bowel disease: from the bench to the bedside. Gut. 2011 Nov 23. [Epub ahead of print]. Raw IF: 10.614

Normalized IF: 8

Di Sabatino A, Rovedatti L, Vetrano S, Vidali F, Biancheri P, Rescigno M, Danese S, Macdonald TT, Corazza GR.

ENDOCRINOLOGY AND DIABETOLOGY

Involvement of CD40-CD40 Ligand in Uncomplicated and Refractory Celiac Disease.

De Bellis A, Pane E, Bellastella G, Sinisi AA, Colella C, Giordano R, Giavoli C, Lania A, Ambrosio MR, Di Somma C, Zatelli MC, Arvat E, Colao A, Bizzarro A, Bellastella A; Italian Autoimmune Hypophysitis Network Study.

Am J Gastroenterol. 2011 Mar; 106(3):519-27. Epub 2010 Dec 7. Raw IF: 6.882 Normalized IF: 3

Detection of anti-pituitary and anti-hypothalamus antibodies to investigate the role of pituitary or

Laghi L*, Bianchi P, Grizzi F, Malesci A.

How dense, how intense? Role of tumour-infiltrating

lymphocytes across colorectal cancer stages. Re: Nosho et al. Tumour-infiltrating T-cell subsets, molecular changes in colorectal cancer, and prognosis: cohort study and literature review. J Pathol 2010; 222: 350366. et al. Tumour-infiltrating T-cell subsets, molecular changes in colorectal cancer, and prognosis: cohort study and literature review.

MA, Iavarone M, Di Marco V, Farinati F, Del Poggio P, Borzio F, Borzio M, Caturelli E, Di Nolfo MA, Frigerio M, Brancaccio G, Gaeta GB.

J Pathol. 2011 Dec;225(4):628; author reply 629-30. Epub 2011 Aug 8. Raw IF: 7.274 Normalized IF: 4

Normalized IF: 2

Rutella S, Fiorino G, Vetrano S, Correale C, Spinelli A, Pagano N, Arena V, Maggiano N, Repici A, Malesci A, Danese S*.

Infliximab therapy inhibits inflammation-induced angiogenesis in the mucosa of patients with Crohnâ&#x20AC;&#x2122;s disease. Am J Gastroenterol. 2011 Apr;106(4):762-70. Raw IF: 6.882 Normalized IF: 6 Savarino E, Marabotto E, Zentilin P, Frazzoni M, Sammito G, Bonfanti D, Sconfienza L, Assandri L, Gemignani L, Malesci A, Savarino V.

The added value of impedance-pH monitoring to Rome III criteria in distinguishing functional heartburn from non-erosive reflux disease. Dig Liver Dis. 2011 Jul;43(7):542-7. Epub 2011 Mar 3. Raw IF: 2.805 Normalized IF: 2

Changing aetiological factors of hepatocellular carcinoma and their potential impact on the effectiveness of surveillance. Dig Liver Dis. 2011 Nov;43(11):875-80. Raw IF: 2.805

GENERAL MEDICINE AND NEPHROLOGY Gharavi AG, Kiryluk K, Choi M, Li Y, Hou P, Xie J, Sanna-Cherchi S, Men CJ, Julian BA, Wyatt RJ, Novak J, He JC, Wang H, Lv J, Zhu L, Wang W, Wang Z, Yasuno K, Gunel M, Mane S, Umlauf S, Tikhonova I, Beerman I, Savoldi S, Magistroni R, Ghiggeri GM, Bodria M, Lugani F, Ravani P, Ponticelli C, Allegri L, Boscutti G, Frasca G, Amore A, Peruzzi L, Coppo R, Izzi C, Viola BF, Prati E, Salvadori M, Mignani R, Gesualdo L, Bertinetto F, Mesiano P, Amoroso A, Scolari F, Chen N, Zhang H, Lifton RP.

Genome-wide association study identifies susceptibility loci for IgA nephropathy. Nat Genet. 2011 Mar 13;43(4):321-7. Raw IF: 36.377

Normalized IF: 7.5

Graziani G*, Cucchiari D, Verdesca S, Balzarini L, Montanelli A, Ponticelli C.

Vetrano S, Ploplis VA, Sala E, Sandoval-Cooper M, Donahue DL, Correale C, Arena V, Spinelli A, Repici A, Malesci A, Castellino FJ, Danese S*.

Chyluria Associated with Nephrotic-Range Proteinuria: Pathophysiology, Clinical Picture and Therapeutic Options.

Unexpected role of anticoagulant protein C in controlling epithelial barrier integrity and intestinal inflammation.

Nephron Clin Pract. 2011 Sep 14;119(3):c248-c254. Raw IF: 1.843 Normalized IF: 2

Proc Natl Acad Sci U S A. 2011 Dec 6;108(49):19830-5. Raw IF: 9.771 Normalized IF: 8

Graziani G*, Cucchiari D, Verdesca S, Balzarini L, Montanelli A, Ponticelli C.

Looking at appearance of urine before performing a renal biopsy in nephrotic syndrome. GENERAL MEDICINE AND HEPATOLOGY Covini G*, Carcamo WC, Bredi E, von MĂźhlen CA, Colombo M, Chan EK.

Cytoplasmic rods and rings autoantibodies developed during pegylated interferon and ribavirin therapy in patients with chronic hepatitis C. Antivir Ther. 2011 Dec 1. [Epub ahead of print] Raw IF: 3.774 Normalized IF: 4 Stroffolini T, Trevisani F, Pinzello G, Brunello F, Tommasini

J Nephrol. 2011 Sep-Oct; 24(5): 665-8 Epub 2011 May 19. Raw IF: 1.623 Normalized IF: 2 Oldani S*, Finazzi S, Bottazzi B, Garlanda C, Baldassarre E, Valaperta S, Cuccovillo I, Albini M, Child M, Montanelli A, Graziani G, Badalamenti S.

Plasma pentraxin-3 as a marker of bioincompatibility in hemodialysis patients. J Nephrol. 2011 Jun 22. pii: 02C3813E-6B05-45B4-9483C25B14801890. Raw IF: 1.623 Normalized IF: 2

Papers published 2011

Ponticelli C.

Herpes viruses and tumours in kidney transplant recipients. The role of immunosuppression. Nephrol Dial Transplant. 2011 Jun;26(6):1769-75. Epub 2011 Apr 11. Raw IF: 3.564 Normalized IF: 6 Ponticelli C*, Cucchiari D, Graziani G.

Hypertension in kidney transplant recipients. Transpl Int. 2011 Jun;24(6):523-33. Raw IF: 3.211

GYnaecology Serati M, Salvatore S, Siesto G, Cattoni E, Braga A, Sorice P, Cromi A, Ghezzi F, Bolis P.

Urinary symptoms and urodynamic findings in women with pelvic organ prolapse: is there a correlation? Results of an artificial neural network analysis. Eur Urol 2011;60:253-260. Raw IF: 8.843

Normalized IF: 8

Normalized IF: 6

HAEMODYNAMICS AND INVASIVE CARDIOLOGY GENERAL SURGERY III Han Y, Demorrow S, Invernizzi P, Jing Q, Glaser S, Renzi A, Meng F, Venter J, Bernuzzi F, White M, Francis H, Lleo A, Marzioni M, Onori P, Alvaro D, Torzilli G, Gaudio E, Alpini G.

Melatonin exerts by an autocrine loop antiproliferative effects in cholangiocarcinoma; its synthesis is reduced favoring cholangiocarcinoma growth. Am J Physiol Gastrointest Liver Physiol. 2011 Oct;301(4): G623-33. Epub 2011 Jul 21. Raw IF: 3.522 Normalized IF: 6 Rutella S, Fiorino G, Vetrano S, Correale C, Spinelli A, Pagano N, Arena V, Maggiano N, Repici A, Malesci A, Danese S*.

Infliximab therapy inhibits inflammation-induced angiogenesis in the mucosa of patients with Crohn’s disease. Am J Gastroenterol. 2011 Apr;106(4):762-70. Raw IF: 6.882 Normalized IF: 6 Vetrano S, Ploplis VA, Sala E, Sandoval-Cooper M, Donahue DL, Correale C, Arena V, Spinelli A, Repici A, Malesci A, Castellino FJ°, Danese S°. ° These authors equally contributed to this work

Unexpected role of anticoagulant protein C in controlling epithelial barrier integrity and intestinal inflammation. Proc Natl Acad Sci U S A. 2011 Dec 6;108(49):19830-5. Raw IF: 9.771 Normalized IF: 8

Ardissino D, Berzuini C, Merlini PA, Mannuccio Mannucci P, Surti A, Burtt N, Voight B, Tubaro M, Peyvandi F, Spreafico M, Celli P, Lina D, Notarangelo MF, Ferrario M, Fetiveau R, Casari G, Galli M, Ribichini F, Rossi ML, Bernardi F, Marziliano N, Zonzin P, Mauri F, Piazza A, Foco L, Bernardinelli L, Altshuler D, Kathiresan S; Italian Atherosclerosis, Thrombosis and Vascular Biology Investigators.

Influence of 9p21.3 genetic variants on clinical and angiographic outcomes in early-onset myocardial infarction. J Am Coll Cardiol. 2011 Jul 19;58(4):426-34. Raw IF: 14.292 Normalized IF: 10

INTERNAL MEDICINE De Santis M, Selmi C*.

The Therapeutic Potential of Epigenetics in Autoimmune Diseases. Clin Rev Allergy Immunol 2012 Feb;42(1):92-101. Epub 2011 Dec 13. Raw IF: 3.435 Normalized IF: 6 Han Y, Demorrow S, Invernizzi P, Jing Q, Glaser S, Renzi A, Meng F, Venter J, Bernuzzi F, White M, Francis H, Lleo A, Marzioni M, Onori P, Alvaro D, Torzilli G, Gaudio E, Alpini G.

Melatonin exerts by an autocrine loop antiproliferative effects in cholangiocarcinoma; its synthesis is reduced favoring cholangiocarcinoma growth. Am J Physiol Gastrointest Liver Physiol. 2011 Oct;301(4):G623-33. Epub 2011 Jul 21. Raw IF: 3.522 Normalized IF: 6 Invernizzi P.

Primary sclerosing cholangitis is changing clinical spectrum and old biomarkers disclose an innovative

role: the case of alkaline phosphatase. Dig Liver Dis. 2011 Apr;43(4):268-9. Raw IF: 2.805

Selmi C, Mix E, Zettl UK. Normalized IF: 4

Lleo A, Liao J, Invernizzi P, Zhao M, Bernuzzi F, Ma L, Lanzi G, Ansari AA, Coppel RL, Zhang P, Li Y, Zhou Z, Lu Q, Gershwin ME.

IgM levels inversely correlate with cd40l promoter methylation in patients with primary biliary cirrhosis Hepatology. 2011 Aug 24.Volume 55, Issue 1, January 2012, Pages 153-160. Raw IF: 10.885 Normalized IF: 8 Moroni L, Bianchi I, Lleo A*.

A clear look at the neuroimmunology of multiple sclerosis and beyond. Autoimmun Rev. 2012 Jan;11(3):159-62. Epub 2011 May 23. Raw IF: 6.556 Normalized IF: 6 Smyk DS, Rigopoulou EI, Lleo A, Abeles RD, Mavropoulos A, Billinis C, Invernizzi P, Bogdanos DP.

Immunopathogenesis of primary biliary cirrhosis: an old wives’ tale. Immun Ageing. 2011 Dec 2;8(1):12. Raw IF: 0

Normalized IF: 0.1

Geoepidemiology, gender and autoimmune disease.

Tanaka A, Invernizzi P, Ohira H, Kikuchi K, Nezu S, Kosoy R, Seldin MF, Gershwin ME, Takikawa H.

Autoimmun Rev. 2011 Nov 28. [Epub ahead of print]. Raw IF: 6.556 Normalized IF: 6

Replicated association of 17q12-21 with susceptibility of primary biliary cirrhosis in a Japanese cohort.

Selmi C, De Santis M, Gershwin ME.

Liver involvement in subjects with rheumatic disease. Arthritis Res Ther. 2011 Jun 30;13(3):226. Raw IF: 4.357

Normalized IF: 6

Selmi C, Papini MA, Pugliese P, Alcaro CM, Gershwin ME.

Environmental pathways to autoimmune diseases: the cases of primary biliary cirrhosis and multiple sclerosis. Arch Med Sci. 2011 Jun;7(3):368-80. Epub 2011 Jul 11. Raw IF: 1.199 Normalized IF: 4 Selmi C.

Autoimmunity in 2010.

Tissue Antigens. 2011 Jul;78(1):65-8. Raw IF: 3.024

Normalized IF: 6

Toy E, Balasubramanian S, Selmi C, Li CS, Bowlus CL.

The Prevalence, Incidence and Natural History of Primary Sclerosing Cholangitis in an Ethnically Diverse Population. BMC Gastroenterol. 2011 Jul 18;11(1):83. Raw IF: 2.468

Normalized IF: 2

KNEE ORTHOPAEDICS AND SPORT TRAUMATOLOGY Galliera E, De Girolamo L, Randelli P, Volpi P, Dogliotti G, Quaglia A, Banfi G, Cabitza P, Corsi MM, Denti M.

Autoimmun Rev. 2011 Oct;10(12):725-32. Epub 2011 Jul 6. Raw IF: 6.556 Normalized IF: 6

High articular levels of the angiogenetic factors VEGF and VEGF-receptor 2 as tissue healing biomarkers after single bundle anterior cruciate ligament reconstruction.

Selmi C*, Brunetta E, Raimondo MG, Meroni PL.

J Biol Regul Homeost Agents. 2011 Jan-Mar;25(1):85-91. Raw IF: 2.825 Normalized IF: 6

The X chromosome and the sex ratio of autoimmunity. Autoimmun Rev. 2011 Dec 3. [Epub ahead of print]. Raw IF: 6.556 Normalized IF: 6

Selmi C*, Meroni PL, Gershwin ME.

LABORATORY TESTS Bergamaschi M*, Coccini G.

Primary biliary cirrhosis and Sjögren’s syndrome: Autoimmune epithelitis.

Realistic technician staffing requirements in a histopathology laboratory via an innovative workload method.

J Autoimmun. 2011 Dec 15. [Epub ahead of print]. Raw IF: 8.136 Normalized IF: 8

Pathologica. 2011 Feb;103(1):1-3. Raw IF: 0

Normalized IF: 0.1

Papers published 2011

De Luca C, Casari E, Nucleo E, Ferrario A, Migliavacca R, Pagani L.

Evaluation of to commercially available methods used for the rapid detection of ESBL-producing strains. Microbiologia Medica vol.26 (1) 2011 pag.39-44. Raw IF: 0 Normalized IF: 0.1 Graziani G*, Cucchiari D, Verdesca S, Balzarini L, Montanelli A, Ponticelli C.

Looking at appearance of urine before performing a renal biopsy in nephrotic syndrome. J Nephrol. 2011 Sep-Oct; 24(5): 665-8 Epub 2011 May 19. Raw IF: 1.623 Normalized IF: 2 Monari M, Valaperta S, Garbelli S, Montanelli A.

25-Hydroxyvitamin D levels in the outpatient population of a northern Italy region. Mediterranean Journal of Nutrition and Metabolism; 2011, May 17 [Epub ahead of print]. Raw IF: 0 Normalized IF: 0.1

MEDICAL ONCOLOGY AND HAEMATOLOGY Fogliata A, Cozzi L, Clivio A, Ibatici A, Mancosu P, Navarria P, Nicolini G, Santoro A, Vanetti E, Scorsetti M.

Preclinical Assessment of Volumetric Modulated Arc Therapy for Total Marrow Irradiation. Int J Radiat Oncol Biol Phys. 2011 Jun 1;80(2):628-36. Epub 2011 Jan 27. Raw IF: 4.503 Normalized IF: 6 Zucali PA*, Giovannetti E, Destro A, Mencoboni M, Ceresoli GL, Gianoncelli L, Lorenzi E, De Vincenzo F, Simonelli M, Perrino M, Bruzzone A, Thunnissen E, Tunesi G, Giordano L, Roncalli M, Peters GJ, Santoro A.

Thymidylate syntase and excision repaircross-complementing group-1 as predictors of responsiveness in mesothelioma patients treated with pemetrexed-carboplatin. Clin Cancer Res. 2011 Apr 15;17(8):2581-90. Raw IF: 7.338 Normalized IF: 8

NEUROLOGY II Nobile-Orazio E*, Giannotta C.

Testing for anti-glycolipid IgM antibodies in chronic immune-mediated demyelinating neuropathies. J Peripher Nerv Syst. 2011 Jun;16 Suppl 1:18-23. Raw IF: 3.032 Normalized IF: 4

Monari M, Valaperta S, Montanelli A.

[Parvovirus B19: unexpected epidemiology.] Minerva Ginecol. 2011 Feb;63(1):86. Raw IF: 0

Normalized IF: 0.1

Oldani S*, Finazzi S, Bottazzi B, Garlanda C, Baldassarre E, Valaperta S, Cuccovillo I, Albini M, Child M, Montanelli A, Graziani G, Badalamenti S.

Plasma pentraxin-3 as a marker of bioincompatibility in hemodialysis patients. J Nephrol. 2011 Jun 22. pii: 02C3813E-6B05-45B4-9483C25B14801890. Raw IF: 1.623 Normalized IF: 2 Valaperta S, Alpini C, Bottone MG, Monari M, Assandri R, Montanelli A.

100

NEUROSURGERY Di Ieva A*, Grizzi F, Ceva-Grimaldi G, Aimar E, Serra S, Pisano P, Lorenzetti M, Tancioni F, Gaetani P, Crotti F, Tschabitscher M, Matula C, Rodriguez y Baena R.

The microvascular network of the pituitary gland: a model for the application of fractal geometry to the analysis of angioarchitecture and angiogenesis of brain tumors. J Neurosurg Sci. 2010 Jun;54(2):49-54. Raw IF: 0.64

Normalized IF: 1

NUCLEAR MEDICINE

[Anti-Golgi antibodies: let me look around].

Sclafani F, Carnaghi C, Di Tommaso L, Rodari M, Destro A, Rimassa L, Giordano L, Chiti A, Roncalli M, Santoro A.

Recenti Prog Med. 2011 Jan;102(1):11-3. Raw IF: 0 Normalized IF: 0.1

Detection of somatostatin receptor subtypes 2 and 5 by somatostatin receptor scintigraphy and

immunohistochemistry: clinical implications in the diagnostic and therapeutic management of gastroenteropancreatic neuroendocrine tumors. Tumori. 2011 Sep-Oct;97(5):620-8. Raw IF: 1.014

Normalized IF: 1

PATHOLOGY

The HOX gene network in hepatocellular carcinoma. Int J Cancer. 2011 Dec 1;129(11):2577-87. Epub 2011 May 30. Raw IF: 4.926 Normalized IF: 3

Di Tommaso L, Destro A, Fabbris V, Spagnuolo G, Laura Fracanzani A, Fargion S, Maggioni M, Patriarca C, Maria Macchi R, Quagliuolo M, Borzio M, Iavarone M, Sangiovanni A, Colombo M, Roncalli M*.

Diagnostic accuracy of clathrin heavy chain staining in a marker panel for the diagnosis of small hepatocellular carcinoma. Normalized IF: 8

Yonesaka K, Zejnullahu K, Okamoto I, Satoh T, Cappuzzo F, Souglakos J, Ercan D, Rogers A, Roncalli M, Takeda M, Fujisaka Y, Philips J, Shimizu T, Maenishi O, Cho Y, Sun J, Destro A, Taira K, Takeda K, Okabe T, Swanson J, Itoh H, Takada M, Lifshits E, Okuno K, Engelman JA, Shivdasani RA, Nishio K, Fukuoka M, Varella-Garcia M, Nakagawa K, JĂ¤nne PA.

Activation of ERBB2 Signaling Causes Resistance to the EGFR-Directed Therapeutic Antibody Cetuximab. Sci Transl Med. 2011 Sep 7;3(99):99ra86. Raw IF: 3.292

Klinger FM, Vinci V, Forcellini D, Caviggioli F*.

Basic Science Review on Adipose Tissue for Clinicians. Plast Reconstr Surg. 2011 Sep;128(3):829-830. Raw IF: 2.647 Normalized IF: 3

RADIOTHERAPY AND RADIOSURGERY

Cillo C, Schiavo G, Cantile M, Bihl MP, Sorrentino P, Carafa V, Dâ&#x20AC;&#x2122; Armiento M, Roncalli M, Sansano S, Vecchione R, Tornillo L, Mori L, De Libero G, Zucman-Rossi J, Terracciano L.

Hepatology. 2011 May;53(5):1549-57. Raw IF: 10.885

PLASTIC SURGERY II

Normalized IF: 2

Zucali PA*, Giovannetti E, Destro A, Mencoboni M, Ceresoli GL, Gianoncelli L, Lorenzi E, De Vincenzo F, Simonelli M, Perrino M, Bruzzone A, Thunnissen E, Tunesi G, Giordano L, Roncalli M, Peters GJ, Santoro A.

Tancioni F, Navarria P*, Mancosu P, Pedrazzoli P, Morenghi E, Santoro A, Baena RR, Scorsetti M.

Surgery followed by radiotherapy for the treatment of metastatic epidural spinal cord compression (mescc) from breast cancer. Spine. 2011 Sep 15;36(20):E1352-9. Raw IF: 2.51

Normalized IF: 6

REPRODUCTIVE MEDICINE Criado E.

Reply of the Author. Fertil Steril.Vol 95, Issue 8 , Page e70, 30 June 2011. Epub 2011 May 10. Raw IF: 3.958 Normalized IF: 3 Levi Setti PE*, Bulletti C.

Strategies to improve embryo implantation to supraphysiological rates. Ann N Y Acad Sci. 2011 Mar;1221:75-9. Raw IF: 2.847

Normalized IF:6

Levi Setti PE.

Preface: A window into the reproductive era research. Placenta. 2011 Sep;32 Suppl 3:S223. No abstract available. Raw IF: 2.985 Normalized IF: 6

RESEARCH LABORATORIES SCIENTIFIC DIRECTION Lerzo F, Peri G, Doni A, Bocca P, Morandi F, Pistorio A, Carleo AM, Mantovani A, Pistoia V, Prigione I.

Dexamethasone Prophylaxis in Pediatric Open Heart Surgery Is Associated with Increased Blood Long Pentraxin PTX3: Potential Clinical Implications. Clin Dev Immunol. 2011;2011:730828. Epub 2011 Jul 9. Raw IF: 2.263 Normalized IF: 2

101

Papers published 2011

Maugeri N, Rovere-Querini P, Slavich M, Coppi G, Doni A, Bottazzi B, Garlanda C, Cianflone D, Maseri A, Mantovani A, Manfredi AA.

Smith S, Gabhann JN, Higgs R, Stacey K, Wahren-Herlenius M, Espinosa A, Totaro MG, Sica A, Ball E, Bell A, Johnston J, Browne P, Oâ&#x20AC;&#x2122;Neill L, Kearns G, Jefferies CA.

Early and Transient Release of Leukocyte Pentraxin 3 during Acute Myocardial Infarction.

Enhanced interferon regulatory factor 3 binding to the IL-23p19 promoter correlates with enhanced IL-23 expression in systemic lupus erythematosus.

Immunol. 2011 Jul 15;187(2):970-9. Epub 2011 Jun 15 Raw IF: 5.745 Normalized IF: 3

Arthritis Rheum. 2011 Nov 29. Raw IF: 8.435

Normalized IF: 4

Moalli F, Paroni M, VĂŠliz Rodriguez T, Riva F, Polentarutti N, Bottazzi B, Valentino S, Mantero S, Nebuloni M, Mantovani A, Bragonzi A, Garlanda C.

The Therapeutic Potential of the Humoral Pattern Recognition Molecule PTX3 in Chronic Lung Infection caused by Pseudomonas aeruginosa. J Immunol. 2011 May 1;186(9):5425-34. Epub 2011 Mar 25. Raw IF: 5.745 Normalized IF: 6

Di Ieva A*, Grizzi F, Ceva-Grimaldi G, Aimar E, Serra S, Pisano P, Lorenzetti M, Tancioni F, Gaetani P, Crotti F, Tschabitscher M, Matula C, Rodriguez y Baena R.

Munoz-Suano A, Kallikourdis M, Sarris M, Betz AG.

The microvascular network of the pituitary gland: a model for the application of fractal geometry to the analysis of angioarchitecture and angiogenesis of brain tumors.

Regulatory T cells protect from autoimmune arthritis during pregnancy. J Autoimmun. 2011 Oct 15. [Epub ahead of print]. Raw IF: 8,136 Normalized IF: 8

J Neurosurg Sci. 2010 Jun;54(2):49-54. Raw IF: 0.64

Nur E, van Beers EJ, Martina S, Cuccovillo I, Otten HM, Schnog JJ, Meijers JC, Mantovani A, Brandjes DP, Bottazzi B, Biemond BJ; on behalf of the CURAMA Study Group.

Dioguardi N.

Plasma levels of pentraxin-3, an acute phase protein, are increased during sickle cell painful crisis.

Med Hypotheses. 2011 Dec;77(6):1022-7. Epub 2011 Sep 16. Raw IF: 1.389 Normalized IF: 2

Blood Cells Mol Dis. 2011 Mar 15;46(3):189-194. Epub 2011 Jan 21. Raw IF: 2.716 Normalized IF: 4 Oldani S*, Finazzi S, Bottazzi B, Garlanda C, Baldassarre E, Valaperta S, Cuccovillo I, Albini M, Child M, Montanelli A, Graziani G, Badalamenti S.

Plasma pentraxin-3 as a marker of bioincompatibility in hemodialysis patients. J Nephrol. 2011 Jun 22. pii: 02C3813E-6B05-45B4-9483C25B14801890. Raw IF: 1.623 Normalized IF: 2 Prontera P, Rogaia D, Sobacchi C, Tavares VL, Mazzotta G, Passos-Bueno MR, Donti E.

Craniometaphyseal dysplasia with severe craniofacial involvement shows homozygosity at 6q21-22.1 locus. 102

RESEARCH LABORATORIES SCIENTIFIC SUPERINTENDENCE

Am J Med Genet A. 2011 May;155A(5):1106-8 Raw IF: 2.505 Normalized IF: 2

Normalized IF: 1

Hypothesis for a new method to measure the dynamic patterns of tissue injury.

Laghi L*, Bianchi P, Grizzi F, Malesci A.

How dense, how intense? Role of tumour-infiltrating lymphocytes across colorectal cancer stages. Re: Nosho et al. Tumour-infiltrating T-cell subsets, molecular changes in colorectal cancer, and prognosis: cohort study and literature review. J Pathol 2010; 222: 350366. et al. Tumour-infiltrating T-cell subsets, molecular changes in colorectal cancer, and prognosis: cohort study and literature review. J Pathol. 2011 Dec;225(4):628; author reply 629-30. Epub 2011 Aug 8 Raw IF: 7.274 Normalized IF: 4 Losa GA, Di Ieva A, Grizzi F, De Vico G.

On the fractal nature of nervous cell system. Front Neuroanat. 2011;5:45. Epub 2011 Jul 21. No abstract available. Raw IF: 0 Normalized IF: 0.1

THORACIC SURGERY Frullanti E, Galvan A, Falvella FS, Manenti G, Colombo F, Vannelli A, Incarbone M, Alloisio M, Nosotti M, Santambrogio L, Gonzalez-Neira A, Pastorino U, Dragani TA.

Multiple genetic loci modulate lung adenocarcinoma clinical staging. Clin Cancer Res. 2011 Apr 15;17(8):2410-6. Raw IF: 7.338 Normalized IF: 4

THROMBOSIS CENTRE Zarpellon A, Celikel R, Roberts JR, McClintock RA, Mendolicchio GL, Moore KL, Jing H, Varughese KI, Ruggeri ZM.

Binding of {alpha}-thrombin to surface-anchored platelet glycoprotein Ib{alpha} sulfotyrosines through a twosite mechanism involving exosite I. Proc Natl Acad Sci U S A. 2011 May 24;108(21):8628-33. Epub 2011 May 9. Raw IF: 9.771 Normalized IF: 4

103

Papers published 2011 * = Corresponding author

C l i n i c a l

R e s e a r c h

Nordenson U, Garofalo R, Conti M, Linger E, Classon J, Karlsson J, Castagna A.

ANAESTHESIA Pagano N, Arosio M, Romeo F, Rando G, Del Conte G, Carlino A, Strangio G, Vitetta E, Malesci A, Repici A.

Balanced Propofol Sedation in Patients Undergoing EUS-FNA: A Pilot Study to Assess Feasibility and Safety. Diagn Ther Endosc. 2011 Jul 12 Raw IF: 0

Normalized IF: 0.1

Minor or occult shoulder instability: an intra-articular pathology presenting with extra-articular subacromial impingement symptoms. Knee Surg Sports Traumatol Arthrosc. 2011 Sep;19(9):1570-5. Epub 2011 May 24 Raw IF: 1.857 Normalized IF: 4

Repici A*, Pagano N, Hassan C, Carlino A, Rando G, Strangio G, Romeo F, Zullo A, Ferrara E, Vitetta E, Ferreira Dde P, Danese S, Arosio M, Malesci A.

Padua R, Alviti F, Castagna A, Padua L.

Balanced Propofol Sedation administered by non Anesthesiologists: The first Italian experience

J Shoulder Elbow Surg. 2011 Jun 20(4):e26. Epub 2011 Mar 27 Raw IF: 2.314 Normalized IF: 3

World J Gastroenterol. 2011 Sep 7;17(33):3818-23. Raw IF: 2.24 Normalized IF: 4

Padua R, Padua L, Galluzzo M, Ceccarelli E, Alviti F, Castagna A

Regarding â&#x20AC;&#x153;literature review before questionnaire crosscultural adaptationâ&#x20AC;?.

Position of shoulder arthroplasty and clinical outcome in proximal humerus fractures. ARTHROSCOPIC SURGERY OF THE SHOULDER Chillemi C, Petrozza V, Garro L, Sardella B, Diotallevi R, Ferrara A, Gigante A, Di Cristofano C, Castagna A, Della Rocca C.

Rotator cuff re-tear or non-healing: histopathological aspects and predictive factors. Knee Surg Sports Traumatol Arthrosc. 2011 Sep;19(9):1588-96. Epub 2011 Apr 30. Raw IF: 1.857 Normalized IF: 2 Garofalo R, Conti M, Massazza G, Cesari E, Vinci E, Castagna A.

Subcoracoid impingement syndrome: a painful shoulder condition related to different pathologic factors.

Porcellini G, Castagna A, Cesari E, Merolla G, Pellegrini A, Paladini P.

Partial repair of irreparable supraspinatus tendon tears: clinical and radiographic evaluations at long-term follow-up. J Shoulder Elbow Surg. 2011 Oct;20(7):1170-7. Epub 2011 Feb 1. Raw IF: 2.314 Normalized IF: 6 Rotini R, Marinelli A, Guerra E, Bettelli G, Castagna A, Fini M, Bondioli E, Busacca M.

Musculoskelet Surg. 2011 Jul; 95 Suppl.1:25-9 Raw IF: 0 Normalized IF: 0.1

Human dermal matrix scaffold augmentation for large and massive rotator cuff repairs: preliminary clinical and MRI results at 1-year follow-up.

Garofalo R, Cesari E, Vinci E, Castagna A.

Musculoskelet Surg. 2011 Jul;95 Suppl 1:13-23. Raw IF: 0 Normalized IF: 0.1

Role of metalloproteinases in rotator cuff tear. Sports Med Arthrosc. 2011 Sep;19(3):207-12. Raw IF: 2.043 Normalized IF: 4 Garofalo R, Castagna A, Borroni M, Krishnan SG.

Arthroscopic transosseous (anchorless) rotator cuff repair. Knee Surg Sports Traumatol Arthrosc. 2011 Oct 20. [Epub ahead of print]. Raw IF: 1.857 Normalized IF: 4

104

Musculoskelet Surg. 2011 Jul; 95 Suppl.1:55-8. Raw IF: 0 Normalized IF: 0.1

breast unit Garcia-Etienne CA, Forcellini D, Sagona A, Caviggioli F, Barbieri E, Cornegliani G, Giannasi S, Tinterri C*.

Breast reconstruction: A quality measure for breast cancer care? Breast. 2011 Sep 2. [Epub ahead of print]. Raw IF: 2.089

Normalized IF: 4

Sponga S, Mascioli G, Voisine P, Vitali E.

cardiac surgery Agrifoglio M, Cappai A*, Filippi N, Alamanni F.

Penetrating atherosclerotic ulcer of the ascending aorta: the role of computed tomography scan. J Cardiovasc Med (Hagerstown). 2011 Sep;12(9):671-2. Raw IF: 0.786 Normalized IF: 1

A Case of Inefficient Defibrillation During Thoracotomy. J Card Surg. 2011 May;26(3):338-9. Epub 2011 Jan 14. Raw IF: 1.352 Normalized IF: 2

clinical pharmacology

Barbone A*, Malvindi PG, Ferrara P, Tarelli G.

Carelli S*, Marfia G, Di Giulio AM, Ghilardi G, Gorio A.

Left ventricle unloading by percutaneous pigtail during extracorporeal membrane oxygenation.

Erythropoietin: recent developments in the treatment of spinal cord injury.

Interact Cardiovasc Thorac Surg. 2011 Sep;13(3):293-5. Epub 2011 Jun 16. Raw IF: 0 Normalized IF: 0.1

Neurol Res Int. 2011;2011:453179. Epub 2011 Jul 4. Raw IF: 0 Normalized IF: 0.1

Malvindi PG*, van Putte BP, Leone A, Heijmen RH, Schepens MA, Morshuis WJ.

Aortic reoperation after freestanding homograft and pulmonary autograft root replacement. Ann Thorac Surg. 2011 Apr;91(4):1135-40. Raw IF: 3.792

Normalized IF: 6

Monti L, Mauri G, Balzarini L, Tarelli G, Brambilla G, Vitali E, Ornaghi D, Citterio E, Settepani F*.

Compliance of the Valsalva graft’s pseudosinuses at midterm follow-up with cardiovascular magnetic resonance. Ann Thorac Surg. 2011 Jan;91(1):92-6. Raw IF: 3.792

Normalized IF: 6

Raffa GM*, Cappai A, Tarelli G.

Giant left atrium syndrome. J Cardiovasc Med (Hagerstown). 2011 Oct;12(10):745-6. Raw IF: 0.786 Normalized IF: 1 Raffa GM*, Gaeta R, Carlo P, Marcello S, Viganò M.

Long-Term Patency of Saphenous Vein Patch Plasty for Left Main Coronary Artery Ostial Disease. J Card Surg. 2011 Nov;26(6):629. Epub 2011 Sep 27. Raw IF: 1.352 Normalized IF: 2 Raffa GM*, Malvindi PG, Settepani F, Ornaghi D, Basciu A, Cappai A, Tarelli G.

Aortic Valve Replacement for Paraprosthetic Leak After Transcatheter Implantation. J Card Surg. 2012 Jan;27(1):47-51. Epub 2011 Dec 5. Raw IF: 1.352 Normalized IF: 2

coronary care unit Ferrante G, Presbitero P, Valgimigli M, Morice MC, Pagnotta P, Belli G, Corrada E, Onuma Y, Barlis P, Locca D, Eeckhout E, Di Mario C, Serruys PW.

Percutaneous coronary intervention versus bypass surgery for left main coronary artery disease: a metaanalysis of randomised trials. EuroIntervention. 2011 Oct 30;7(6):738-46 Raw IF: 0 Normalized IF: 0.1 Ferrante G*, Corrada E, Belli G, Zavalloni D, Scatturin M, Mennuni M, Gasparini GL, Bernardinelli L, Cianci D, Pastorino R, Rossi ML, Pagnotta P, Presbitero P.

Impact of Female Sex on Long-Term Outcomes in Patients With ST-Elevation Myocardial Infarction Treated by Primary Percutaneous Coronary Intervention. Can J Cardiol. 2011 Nov;27(6):749-55. Epub 2011 Sep 15. Raw IF: 2.224 Normalized IF: 4

dermatology Bracarda S, Ruggeri EM, Monti M, Merlano M, D’Angelo A, Ferraù F, Cortesi E, Santoro A.

Early detection, prevention and management of cutaneous adverse events due to sorafenib: Recommendations from the Sorafenib Working Group. Crit Rev Oncol Hematol. 2011 Sep 22. [Epub ahead of print] Raw IF: 4.689 Normalized IF: 6

105

Papers published 2011

Monti L, Mauri G, Balzarini L, Tarelli G, Brambilla G, Vitali E, Ornaghi D, Citterio E, Settepani F*.

diagnostic radiology Casella M, Carbucicchio C, Dello Russo A, Tundo F, Bartoletti S, Monti L, Marana I, Giraldi F, Tondo C.

Radiofrequency Catheter Ablation of Life-Threatening Ventricular Arrhythmias Caused by Left Ventricular Metastatic Infiltration. Circ Arrhythm Electrophysiol. 2011 Apr 1;4(2):e7-e10. Raw IF: 4.805 Normalized IF: 3 Cozzaglio L*, Cimino M, Mauri G, Ardito A, Pedicini V, Poretti D, Brambilla G, Sacchi M, Melis A, Doci R.

Percutaneous Transhepatic Biliary Drainage and Occlusion Balloon in the Management of Duodenal Stump Fistula.

Compliance of the Valsalva graft’s pseudosinuses at midterm follow-up with cardiovascular magnetic resonance. Ann Thorac Surg. 2011 Jan;91(1):92-6. Raw IF: 3.792

Normalized IF: 6

Monti L, Haroche J, Sciarra A, Balzarini L, Fiamengo B, Amoura Z, Graziani G.

Interferon-Alpha in Cardiac Erdheim-Chester Disease. J Am Coll Cardiol. 2011 Dec 13;58(25):2695 Raw IF: 14.293 Normalized IF: 5

J Gastrointest Surg. 2011 Nov;15(11):1977-81. Epub 2011 Sep 13. Raw IF: 2.733 Normalized IF: 6

Spinelli A*, Del Fabbro D, Sacchi M, Zerbi A, Torzilli G, Lutman FR, Laghi L, Malesci A, Montorsi M.

Fiorino G, Bonifacio C, Malesci A, Balzarini L, Danese S*.

World J Surg. 2011 Nov;35(11):2521-7. Raw IF: 2.693

MRI in Crohn’s disease-current and future clinical applications. Nat Rev Gastroenterol Hepatol. 2011 Nov 22;9(1):23-31 Raw IF: 4.558 Normalized IF: 6 Livraghi T, Mäkisalo H, Line PD.

Treatment options in hepatocellular carcinoma today. Scand J Surg. 2011;100(1):22-9. Raw IF: 1.08

Normalized IF: 2

Intraoperative Ultrasound with Contrast Medium in Resective Pancreatic Surgery: A Pilot Study. Normalized IF: 6

Tancioni F, Navarria P, Pessina F, Marcheselli S, Rognone E, Mancosu P, Santoro A, Rodriguez y Baena R.

Livraghi T.

Radiofrequency ablation of hepatocellular carcinoma. Surg Oncol Clin N Am. 2011 Apr;20(2):281-99. Raw IF: 1.118 Normalized IF: 2 Livraghi T, Meloni F, Solbiati L, Zanus G; For the Collaborative Italian Group using AMICA system.

Complications of Microwave Ablation for Liver Tumors: Results of a Multicenter Study. Cardiovasc Intervent Radiol. 2011 Aug 11. [Epub ahead of print] Raw IF: 2.003 Normalized IF: 4 Masci G*, Gandini C, Zuradelli M, Pedrazzoli P, Torrisi R, Lutman FR, Santoro A.

Fulvestrant for advanced male breast cancer patients: a case series. 106

Ann Oncol. 2011 Apr;22(4):985. Raw IF: 6.452

Normalized IF: 3

ELECTROPHYSIOLOGY AND ELECTROSTIMULATION Bogale N, Witte K, Priori S, Cleland J, Auricchio A, Gadler F, Gitt A, Limbourg T, Linde C, Dickstein K; on behalf of the Scientific Committee, National coordinators and the investigators (Gasparini M).

The European Cardiac Resynchronization Therapy Survey: comparison of outcomes between de novo cardiac resynchronization therapy implantations and upgrades. Eur J Heart Fail. 2011 Sep;13(9):974-983. Epub 2011 Jul 19. Raw IF: 4.512 Normalized IF: 1.2 Bogale N, Priori S, Gitt A, Alings M, Linde C, Dickstein K; on behalf of the Scientific Committee, National coordinators, and the investigators (Gasparini M).

The European cardiac resynchronization therapy

survey: patient selection and implantation practice vary according to centre volume

adverse outcome in real-world patients with implantable biventricular defibrillators.

Europace. 2011 Oct;13(10):1445-1453. Epub 2011 Jun 28. Raw IF: 1.839 Normalized IF: 0.4

J Am Coll Cardiol. 2011 Jan 11;57(2):167-72. Raw IF: 14.293 Normalized IF: 10

Boriani G, Gasparini M, Landolina M, Lunati M, Proclemer A, Lonardi G, Iacopino S, Rahue W, Biffi M, Distefano P, Grammatico A, Santini M; on behalf of the ClinicalService cardiac centres.

Bianchi S, Ricci RP, Gasparini M, Marconi R, Landolina M, Proclemer A, Botto G, Merico M, Canonaco S, Santini M.

Incidence and clinical relevance of uncontrolled ventricular rate during atrial fibrillation in heart failure patients treated with cardiac resynchronization therapy. Eur J Heart Fail. 2011 Aug;13(8):868-876. Epub 2011 May 10. Raw IF: 4.512 Normalized IF: 6 Boriani G, Gasparini M, Landolina M, Lunati M, Biffi M, Santini M, Padeletti L, Molon G, Botto G, DE Santo T, Valsecchi S; on behalf of the InSync/InSync ICD Italian Registry Investigators.

Impact of Mitral Regurgitation on the Outcome of Patients Treated with CRT-D: Data from the InSync ICD Italian Registry. Pacing Clin Electrophysiol. 2011 Dec 2 [Epub ahead of print] Raw IF: 0 Normalized IF: 0.1 Fumagalli S, Valsecchi S, Boriani G, Gasparini M, Landolina M, Lunati M, Padeletti M, Tronconi F, Marchionni N, Padeletti L.

Comparison of the Usefulness of Cardiac Resynchronization Therapy in Three Age-Groups (<65, 65-74 and ≥75 Years) (from the InSync/InSync ICD Italian Registry). Am J Cardiol. 2011 May 15;107(10):1510-6. Epub 2011 Mar 17. Raw IF: 3.68 Normalized IF: 3 Landolina M, Gasparini M, Lunati M, Iacopino S, Boriani G, Bonanno C, Vado A, Proclemer A, Capucci A, Zucchiatti C, Valsecchi S, Ricci RP, Santini M; on behalf of the Cardiovascular Centers Participating in the ClinicalService Project.

Long-Term Complications Related to Biventricular Defibrillator Implantation: Rate of Surgical Revisions and Impact on Survival: Insights From the Italian ClinicalService Database. Circulation. 2011 Jun 7;123(22):2526-2535. Epub 2011 May 16. Raw IF: 14.432 Normalized IF: 10

Defibrillation testing during implantable cardioverterdefibrillator implantation in Italian current practice: The Assessment of Long-term Induction clinical ValuE (ALIVE) project. Am Heart J. 2011 Aug;162(2):390-7. Epub 2011 Jul 7. Raw IF: 5.052 Normalized IF: 3

emergency neurology and stroke unit Paciaroni M, Balucani C, Agnelli G, Caso V, Silvestrelli G, Grotta JC, Demchuk AM, Sohn SI, Orlandi G, Leys D, Pezzini A, Alexandrov AV, Silvestrini M, Fofi L, Barlinn K, Inzitari D, Ferrarese C, Tassi R, Tsivgoulis G, Consoli D, Baldi A, Bovi P, Luda E, Galletti G, Invernizzi P, Delodovici ML, Corea F, Del Sette M, Monaco S, Marcheselli S, Alberti A, Venti M, Acciarresi M, D’Amore C, Macellari F, Lanari A, Previdi P, Gonzales NR, Pandurengan RK, Vahidy FS, Sline M, Bal SS, Chiti A, Gialdini G, Dumont F, Cordonnier C, Debette S, Padovani A, Cerqua R, Bodechtel U, Kepplinger J, Nesi M, Nencini P, Beretta S, Trentini C, Martini G, Piperidou C, Heliopoulos I, D’Anna S, Cappellari M, Donati E, Bono G, Traverso E, Toni D.

Systemic Thrombolysis in Patients With Acute Ischemic Stroke and Internal Carotid ARtery Occlusion: The ICARO Study. Stroke.2012 Jan;43(1):125-30. Epub 2011 Oct 27. Raw IF: 5.756 Normalized IF: 6 Tancioni F, Navarria P, Pessina F, Marcheselli S, Rognone E, Mancosu P, Santoro A, Baena RR.

endocrinology and diabetology

Santini M, Gasparini M, Landolina M, Lunati M, Proclemer A, Padeletti L, Catanzariti D, Molon G, Botto GL, La Rocca L, Grammatico A, Boriani G; cardiological centers participating in ClinicalService Project.

Filopanti M, Verga U, Ermetici F, Natacci F, Lalatta F, Avignone S, Trespidi L, Beck-Peccoz P, Mantovani G, Lania AG, Spada A.

Device-detected atrial tachyarrhythmias predict

Double pituitary and conserved function in an adult

107

Papers published 2011

patient with neurofibromatosis type 1.

Danese S.

J Clin Endocrinol Metab. 2011 Jul;96(7):1953-4. Raw IF: 6.495 Normalized IF: 3

Adalimumab for ulcerative colitis: A little is better than none? Inflamm Bowel Dis. 2011 May 3. [Epub ahead of print] Raw IF: 4.613 Normalized IF: 6

gastroenterology and digestive endoscopy Boeckxstaens GE, Annese V, des Varannes SB, Chaussade S, Costantini M, Cuttitta A, Elizalde JI, Fumagalli Romario U, Gaudric M, Rohof WO, Smout AJ, Tack J, Zwinderman AH, Zaninotto G, Busch OR; European Achalasia Trial Investigators. Collaborators :(Lei A, Bartelsman J, Hirsch D, KlinkenbergKnol EC, Cuesta MA, Simmermacher RK, Kuipers EJ, Bonjer HJ, Masclee AA, Ringers J, Lerut A, Metman EH, Huten N, Letessier E, Dousset B, Pera M, Perez de la Serna J, Malesci A, Andriulli A, Scaramuzzi G, De Santo E).

Pneumatic dilation versus laparoscopic Heller’s myotomy for idiopathic achalasia. N Engl J Med. 2011 May 12;364(19):1807-16. Raw IF: 53.484 Normalized IF: 15

Bruno M, Carucci P, Repici A, Pellicano R, Mezzabotta L, Goss M, Fagoonee S, Allegranza P, Reggio D, Rizzetto M, De Angelis C.

Negative predictive value of endoscopic ultrasound in patients referred for fine-needle aspiration. Panminerva Med. 2011 Sep;53(3):179-83. Raw IF: 1.957

Normalized IF: 3

Conio M, Repici A, Siersema PD.

Self-expandable plastic stents in pharyngoesophageal strictures: a word of caution. Gastrointest Endosc. 2011 Mar;73(3):642. Raw IF: 5.608

Normalized IF: 3

Danese S, Fiorino G, Reinisch W.

Review article: causative factors and clinical management of patients with Crohn’s disease who lose response to anti-TNF-? therapy. Aliment Pharmacol Ther. 2011 Jul;34(1):1-1. Epub 2011 May 3 Raw IF: 3.861 Normalized IF: 6 Danese S.

Ulcerative Colitis: A Cinderella Story. Curr Drug Targets. 2011 Sep 1;12(10):1372. Raw IF: 3.061

Normalized IF: 4

Danese S, Fiocchi C.

Ulcerative colitis. N Engl J Med. 2011 Nov 3;365(18):1713-25. Raw IF: 53.484 Normalized IF: 15 Danese S*, Malesci A, Vetrano S.

Colitis-associated cancer: the dark side of inflammatory bowel disease. Gut. 2011 Dec;60(12):1609-10. Epub 2011 Oct 13. No abstract available Raw IF: 10.614 Normalized IF: 8 De Angelis C, Pellicano R, Rizzetto M, Repici A.

Role of endoscopy in the management of gastroenteropancreatic neuroendocrine tumours. Minerva Gastroenterol Dietol. 2011 Jun;57(2):129-37. Raw IF: 0 Normalized IF: 0.1

Danese S.

What’s hot in inflammatory bowel disease in 2011? World J Gastroenterol. 2011 Feb 7;17(5):545-6. Raw IF: 2.24 Normalized IF: 4 Danese S*, Colombel JF, Reinisch W, Rutgeerts PJ.

108

Fabro M, Szabo H, Terrosu G, Avellini C, Tabuso M, Sorrentino D.

Acute Severe Colitis: Infliximab and/or Cyclosporine? Curr Drug Targets. 2011 Sep 1;12(10):1448-53. Raw IF: 3.061 Normalized IF: 4

Review article: infliximab for Crohn’s disease treatment - shifting therapeutic strategies after 10 years of clinical experience.

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

Aliment Pharmacol Ther. 2011 Apr;33(8):857-69. Raw IF: 3.861 Normalized IF: 6

Expert Opin Biol Ther. 2011 Jan;11(1):109-16. Raw IF: 3.279 Normalized IF: 6

Adalimumab in ulcerative colitis: hypes and hopes.

Fiorino G, Peyrin-Biroulet L, Naccarato P, Szabò H, Sociale OR, Vetrano S, Fries W, Montanelli A, Repici A, Malesci A, Danese S.

Effects of immunosuppression on immune response to pneumococcal vaccine in inflammatory bowel disease: a prospective study. Inflamm Bowel Dis. 2011 Jun 14.[Epub ahead of print] Raw IF: 4.613 Normalized IF: 6 Fiorino G, Szabò H, Walter F, Malesci A, Peyrin-Biroulet L, Danese S*.

Adalimumab in Crohn’s disease: tips and tricks after 5 years of clinical experience. Curr Med Chem. 2011;18(8):1230-8. Raw IF: 4.63

Normalized IF: 6

Fiorino G, Cesarini M, Danese S*.

Biological Therapy for Ulcerative Colitis: what is after Anti-TNF. Curr Drug Targets. 2011 Sep 1;12(10):1433-9. Raw IF: 3.061 Normalized IF: 4

Meisner S, González-Huix F, Vandervoort JG, Goldberg P, Casellas JA, Roncero O, Grund KE, Alvarez A, García-Cano J, Vázquez-Astray E, Jiménez-Pérez J; WallFlex Colonic Registry Group.

Self-expandable metal stents for relieving malignant colorectal obstruction: short-term safety and efficacy within 30 days of stent procedure in 447 patients. Gastrointest Endosc. 2011 Oct;74(4):876-84. Raw IF: 5.608 Normalized IF: 1.2 Nunes T, Fiorino G, Danese S, Sans M.

Familial aggregation in inflammatory bowel disease: Is it genes or environment? World J Gastroenterol. 2011 Jun 14;17(22):2715-22. Raw IF: 2.24 Normalized IF: 4 Pagano N*, Arosio M, Romeo F, Rando G, Del Conte G, Carlino A, Strangio G, Vitetta E, Malesci A, Repici A.

Balanced Propofol Sedation in Patients Undergoing EUS-FNA: A Pilot Study to Assess Feasibility and Safety. Diagn Ther Endosc. 2011Jul 12 Raw IF: 0

Normalized IF: 0.1

Fiorino G*, Cesarini M, Indriolo A, Malesci A.

Mucosal healing in Ulcerative Colitis: Where do we Stand? Curr Drug Targets. 2011 Sep 1;12(10):1417-23. Raw IF: 3.061 Normalized IF: 4

Peyrin-Biroulet L, Cieza A, Sandborn WJ, Coenen M, Chowers Y, Hibi T, Kostanjsek N, Stucki G, Colombel JF; the International Programme to Develop New Indexes for Crohn’s Disease (IPNIC) group (Danese S., Fiorino G.).

Fiorino G, Bonifacio C, Malesci A, Balzarini L, Danese S*.

Development of the first disability index for inflammatory bowel disease based on the international classification of functioning, disability and health.

MRI in Crohn’s disease-current and future clinical applications Nat Rev Gastroenterol Hepatol. 2011 Nov 22;9(1):23-31 Raw IF: 4.558 Normalized IF: 6 Fumagalli U*, Barbera R, Repici A, Porta M, Malesci A, Rosati R.

Nissen Fundoplication after Failure of Endoluminal Fundoplication: Short-Term Results. J Gastrointest Surg. 2011 Mar;15(3):439-43. Raw IF: 2.733 Normalized IF: 4 Manes G, de Bellis M, Fuccio L, Repici A, Masci E, Ardizzone S, Mangiavillano B, Carlino A, Rossi GB, Occhipinti P, Cennamo V.

Endoscopic Palliation in Patients With Incurable Malignant Colorectal Obstruction by Means of Selfexpanding Metal Stent: Analysis of Results and Predictors of Outcomes in a Large Multicenter Series Arch Surg. 2011 Oct;146(10):1157-62. Raw IF: 4.5

Normalized IF: 3

Gut. 2012 Feb;61(2):241-247. Epub 2011 Jun 5. Raw IF: 10.614 Normalized IF: 1.6 Prantera C, Lochs H, Grimaldi M, Danese S, Scribano ML, Gionchetti P; Retic Study Group (Rifaximin-Eir Treatment in Crohn’s Disease).

Rifaximin-Extended Intestinal Release Induces Remission in Patients With Moderately Active Crohn’s Disease. Gastroenterology. 2011 Dec 6. [Epub ahead of print] Raw IF: 12.032 Normalized IF: 10 Rahier JF, Papay P, Salleron J, Sebastian S, Marzo M, PeyrinBiroulet L, Garcia-Sanchez V, Fries W, van Asseldonk DP, Farkas K, de Boer NK, Sipponen T, Ellul P, Louis E, Peake ST, Kopylov U, Maul J, Makhoul B, Fiorino G, Yazdanpanah Y, Chaparro M; for the European Crohn’s and Colitis Organisation (ECCO).

H1N1 vaccines in a large observational cohort of

109

Papers published 2011

patients with inflammatory bowel disease treated with immunomodulators and biological therapy.

Savarino E, Zentilin P, Tutuian R, Pohl D, Gemignani L, Malesci A, Savarino V.

Gut. 2011 Apr;60(4):456-462. Epub 2011 Jan 26. Raw IF: 10.614 Normalized IF: 8

Impedance-pH reflux patterns can differentiate nonerosive reflux disease from functional heartburn patients.

Repici A*, de Paula Pessoa Ferreira D.

J Gastroenterol. 2011 Oct 25. [Epub ahead of print] Raw IF: 3.61 Normalized IF: 3

Expandable metal stents for malignant colorectal strictures. Gastrointest Endosc Clin N Am. 2011 Jul;21(3):511-33. Raw IF: 0 Normalized IF: 0.1 Repici A, Di Stefano AF, Radicioni MM, Jas V, Moro L, Danese S.

Methylene blue MMX® tablets for chromoendoscopy. Safety tolerability and bioavailability in healthy volunteers. Contemp Clin Trials. 2012 Mar;33(2):260-7. Epub 2011 Nov 11. Raw IF: 1.207 Normalized IF: 2 Repici A*, Pagano N, Hassan C, Carlino A, Rando G, Strangio G, Romeo F, Zullo A, Ferrara E, Vitetta E, Ferreira Dde P, Danese S, Arosio M, Malesci A.

Balanced Propofol Sedation administered by non Anesthesiologists: The first Italian experience

Savarino E, Gemignani L, Zentilin P, De Bortoli N, Malesci A, Mastracci L, Fiocca R, Savarino V.

Achalasia With Dense Eosinophilic Infiltrate Responds to Steroid Therapy. Clin Gastroenterol Hepatol. 2011 Dec;9(12):1104-6. Epub 2011 Aug 11. Raw IF: 5.286 Normalized IF: 3 Spinelli A, Correale C, Szabo H, Montorsi M.

Intestinal fibrosis in Crohn’s disease: medical treatment or surgery? Curr Drug Targets. 2010 Feb;11(2):242-8. Raw IF: 3.061

Normalized IF: 4

World J Gastroenterol. 2011 Sep 7;17(33):3818-23. Raw IF: 2.24 Normalized IF: 4

Spinelli A*, Sacchi M, Fiorino G, Danese S, Montorsi M.

Sanna C, Giordanino C, Giono I, Barletti C, Ferrari A, Recchia S, Reggio D, Repici A, Ricchiuti A, Salizzoniì M, Baldi I, Ciccone G, Rizzetto M, Saracco G.

World J Gastroenterol. 2011 Jul 21;17(27):3213-9. Raw IF: 2.24 Normalized IF: 4

Safety and efficacy of endoscopic retrograde cholangiopancreatography in patients with post-liver transplant biliary complications: results of a cohort study with long-term follow-up. Gut Liver. 2011 Sep;5(3):328-34. Epub 2011 Aug 18. Raw IF: 0.219 Normalized IF: 0.5

Risk of postoperative recurrence and postoperative management of Crohn’s disease.

Spinelli A*, Del Fabbro D, Sacchi M, Zerbi A, Torzilli G, Lutman FR, Laghi L, Malesci A, Montorsi M.

Intraoperative Ultrasound with Contrast Medium in Resective Pancreatic Surgery: A Pilot Study. World J Surg. 2011 Nov;35(11):2521-7. Raw IF: 2.693

Normalized IF: 6

Savarino E, Zentilin P, Dulbecco P, Malesci A, Savarino V.

The role of Acid in functional dyspepsia. Am J Gastroenterol. 2011 Jun;106(6):1168. Raw IF: 6.882 Normalized IF: 3 Savarino E, Gemignani L, Pohl D, Zentilin P, Dulbecco P, Assandri L, Marabotto E, Bonfanti D, Inferrera S, Fazio V, Malesci A, Tutuian R, Savarino V.

Oesophageal motility and bolus transit abnormalities increase in parallel with the severity of gastrooesophageal reflux disease. 110

Aliment Pharmacol Ther. 2011 Aug;34(4):476-86. Raw IF: 3.861 Normalized IF: 3

Spinelli A*, Bazzi P, Spaggiari P, Danese S, Montorsi M.

Surgical conduct in case of intraoperative detection of a Meckel’s diverticulum in Crohn’s disease J Crohns Colitis. 2011 Dec;5(6):647-8. Epub 2011 Sep 9. No abstract available Raw IF: 2.628 Normalized IF: 2 Toskes PP, Secci A, Thieroff-Ekerdt R; ZENPEP Study Group. Collaborators:(Antillon M, Costamagna G, de Iorio F, Milleri A, Doroofyeyev A, Fadeienko G, Hemaidan A, Johlin F, Klyarytska I, Konis G, Malesci A, Nickl N, Pezzilli R, Schmulewitz N, Sontag S, Toskes P, Wo J).

Efficacy of a novel pancreatic enzyme product, EUR1008 (Zenpep), in patients with exocrine pancreatic insufficiency due to chronic pancreatitis. Pancreas. 2011 Apr;40(3):376-82. Raw IF: 2.607

Normalized IF: 2

general and minimally invasive surgery Boeckxstaens GE, Annese V, des Varannes SB, Chaussade S, Costantini M, Cuttitta A, Elizalde JI, Fumagalli Romario U, Gaudric M, Rohof WO, Smout AJ, Tack J, Zwinderman AH, Zaninotto G, Busch OR; European Achalasia Trial Investigators. Collaborators: (Lei A, Bartelsman J, Hirsch D, Klinkenberg- Knol EC, Cuesta MA, Simmermacher RK, Kuipers EJ, Bonjer HJ, Masclee AA, Ringers J, Lerut A, Metman EH, Huten N, Letessier E, Dousset B, Pera M, Perez de la Serna J, Malesci A, Andriulli A, Scaramuzzi G, De Santo E).

Pneumatic dilation versus laparoscopic Heller’s myotomy for idiopathic achalasia. N Engl J Med. 2011 May 12;364(19):1807-16. Raw IF: 53.484 Normalized IF: 15

Liedman B, Lundell L, Babbs C, Attwood S.

Laparoscopic antireflux surgery vs esomeprazole treatment for chronic GERD: the LOTUS randomized clinical trial. JAMA. 2011 May 18;305(19):1969-77. Raw IF: 30.011

Normalized IF: 3

Parise P, Rosati R, Savarino E, Locatelli A, Ceolin M, Dua KS, Tatum RP, Braghetto I, Gyawali CP, Hejazi RA, McCallum RW, Sarosiek I, Bonavina L, Wassenaar EB, Pellegrini CA, Jacobson BC, Canon CL, Badaloni A, Del Genio G.

Barrett’s esophagus: surgical treatments. Ann N Y Acad Sci. 2011 Sep;1232(1):175-195. Raw IF: 2.847 Normalized IF: 6 Rosati R*, Fumagalli Romario U, Elmore U, de Pascale S, Massaron S, Peracchia A.

Long-term results of minimally invasive surgery for symptomatic epiphrenic diverticulum. Am J Surg. 2011 Jan;201(1):132-5. Raw IF: 2.68

Normalized IF: 6

De Ceglie A, Filiberti R, Blanchi S, Fontana V, Fisher DA, Grossi E, Lacchin T, De Matthaeis M, Ignomirelli O, Cappiello R, Casa DD, Foti M, Laterza F, Rosati R, Annese V, Iaquinto G, Conio M.

History of cancer in first degree relatives of Barrett’s esophagus patients: A case-control study. Clin Res Hepatol Gastroenterol. 2011 Dec;35(12):831-8. Epub 2011 Sep 15. Raw IF: 0 Normalized IF: 0,1 Fumagalli Romario U*, Barbera R, Repici A, Porta M, Malesci A, Rosati R.

Nissen Fundoplication after Failure of Endoluminal Fundoplication: Short-Term Results.

general and oncologic surgery Cozzaglio L*, Cimino M, Mauri G, Ardito A, Pedicini V, Poretti D, Brambilla G, Sacchi M, Melis A, Doci R.

Percutaneous Transhepatic Biliary Drainage and Occlusion Balloon in the Management of Duodenal Stump Fistula. J Gastrointest Surg. 2011 Nov;15(11):1977-81. Epub 2011 Sep 13. Raw IF: 2.733 Normalized IF: 6

J Gastrointest Surg. 2011 Mar;15(3):439-43. Raw IF: 2.733 Normalized IF: 4

Cozzaglio L*, Farinella E, Coladonato M, Sciannameo F, Gennari L, Doci R.

Galmiche JP, Hatlebakk J, Attwood S, Ell C, Fiocca R, Eklund S, Långström G, Lind T, Lundell L; LOTUS Trial Collaborators: Miholic J, Hubmann R, Danis J, Tack J, Lerut T, Piessevaux H, Devière J, Buset M, Chioccioli C, De Looze D, Demoulin JC, Louis E, Ghilain JM, Maisin JM, Funch-Jensen P, Nielsen J, Christensen L, Antonsen H, Lauritsen K, Jess P, Wallin L, Naver L, Galmiche JP, Letessier E, Zerbib F, Bonaz B, Bost R, Delchier JC, Fein M, Maroske J, Ell C, Hölscher A, Zornig C, Schneider JH, Hüttl T, Büchler M, Wehrmann U, Kemen M, Layer P, Fuchs KH, Kemen S, Hüppe D, Oddsdóttir M, Thjodleifsson B, Bonavina L, Ancona E, Morino M, Pignata G, Giurissa A, Rossi M, Rosati R, Cestari R, Gooszen H, Hatlebakk J, Tefera S, Johnsen G, Jahnsen J, Sandstad O, Stallemo A, Florholmen J, Tollåli G, Engström C,

Ann Ital Chir. 2010 Jul-Aug;81(4):285-94. Raw IF: 0.225

Current role of surgery in the treatment of digestive fistulas. Normalized IF: 1

Marasini B*, Cozzaglio L, Belloli L, Massarotti M, Ughi N, Pedrazzoli P.

Metastatic melanoma in a young woman treated with TNF-alpha inhibitor for psoriatic arthritis: a case report. Curr Drug Saf. 2011 Sep 1;6(4):275-6. Raw IF: 0

Normalized IF: 0.1

111

Papers published 2011

Mussi C, Colombo P, Bertuzzi A, Coladonato M, Bagnoli P, Secondino S, Navarria P, Morenghi E, Santoro A, Quagliuolo V*.

Retroperitoneal Sarcoma: Is It Time to Change the Surgical Policy? Ann Surg Oncol. 2011 Aug;18(8):2136-42. Epub 2011 May 3. Raw IF: 4.182 Normalized IF: 6

general medicine and hepatology Fabbriciani G, de Socio GV, Massarotti M, Ceriani R, Marasini B.

Adefovir induced hypophosphatemic osteomalacia. Scand J Infect Dis. 2011 Dec;43(11-12):990-2. Epub 2011 May 24. Raw IF: 1.562 Normalized IF: 0.5 Marasini B*, Cozzaglio L, Belloli L, Massarotti M, Ughi N, Pedrazzoli P.

Metastatic melanoma in a young woman treated with TNF-alpha inhibitor for psoriatic arthritis: a case report. Curr Drug Saf. 2011 Sep 1;6(4):275-6. Raw IF: 0

Normalized IF: 0.1

general medicine and nephrology Arnaud L, Hervier B, NĂŠel A, Hamidou MA, Kahn JE, Wechsler B, PĂŠrez-Pastor G, Blomberg B, Fuzibet JG, Dubourguet F, Marinho A, Magnette C, Noel V, Pavic M, Casper J, Beucher AB, Costedoat-Chalumeau N, Aaron L, Salvatierra J, Graux C, Cacoub P, Delcey V, Dechant C, Bindi P, Herbaut C, Graziani G, Amoura Z, Haroche J.

CNS involvement and treatment with interferonalpha are independent prognostic factors in ErdheimChesterdisease: a multicenter survival analysis of 53 patients. Blood. 2011 Mar 10;117(10):2778-82. Raw IF: 10.558

Normalized IF: 8

Balaskas E, Szepietowski JC, Bessis D, Ioannides D, Ponticelli C, Ghienne C, Taberly A, Dupuy P.

Randomized, Double-blind Study with Glycerol and Paraffin in Uremic Xerosis. Clin J Am Soc Nephrol. 2011 Apr;6(4):748-52. Epub 2011 Jan 21. Raw IF: 4.763 Normalized IF: 3

112

Monti L, Haroche J, Sciarra A, Balzarini L, Fiamengo B, Amoura Z, Graziani G.

Interferon-Alpha in Cardiac Erdheim-Chester Disease. J Am Coll Cardiol. 2011 Dec 13;58(25):2695 Raw IF: 14.293 Normalized IF: 5 Ponticelli C*, Salvadori M, Scolari MP, Citterio F, Rigotti P, Veneziano A, Bartezaghi M; on behalf of EVEREST Study.

Everolimus and Minimization of Cyclosporine in Renal Transplantation: 24-Month Follow-Up of the EVEREST Study. Transplantation. 2011 May 27;91(10):e72-e73. Raw IF: 3.676 Normalized IF: 3 Ponticelli C, Moroni G, Glassock RJ.

Recurrence of Secondary Glomerular Disease after Renal Transplantation. Clin J Am Soc Nephrol. 2011 May;6(5):1214-21. Epub 2011 Apr 14. Raw IF: 4.763 Normalized IF: 6 Ponticelli C, Salvadori M, Coppo R.

The Kidney, a Victim and Culprit of Autoimmune and Alloimmune Responses. Nephron Clin Pract. 2011 Aug 11;119(3):c200-c204. Raw IF: 1.843 Normalized IF: 4 Ponticelli C.

Present and future of immunosuppressive therapy in kidney transplantation. Transplant Proc. 2011 Jul-Aug;43(6):2439-40. Raw IF: 0.993 Normalized IF: 2 Ponticelli C.

The mechanisms of acute transplant rejection revisited. J Nephrol. 2011 Nov 16. [Epub ahead of print] Raw IF: 1.623 Normalized IF: 2 Ponticelli C*, Bencini PL.

Nonneoplastic mucocutaneous lesions in organ transplant recipients. Transpl Int. 2011 Nov;24(11):1041-50. Raw IF: 3.211

Normalized IF: 6

general surgery III Botea F*, Torzilli G, Sarbu V.

A simple, effective technique for port-site closure after

laparoscopy. JSLS. 2011 Jan-Mar;15(1):77-80. Raw IF: 0.799

Spinelli A*, Sampietro GM, Bazzi P, Sacchi M, Montorsi M. Normalized IF: 2

Curr Drug Targets. 2011 Sep 1;12(10):1462-6. Raw IF: 3.061 Normalized IF: 4

Donadon M, Torzilli G*.

From mesohepatectomy to mini-mesohepatectomy: evolving the concept of resectability of hepatic tumors at the hepatocaval confluence. Dig Surg. 2011;28(2):109-13. Epub 2011 Apr 29. Raw IF: 1.266 Normalized IF: 2 Personeni N, Torzilli G, Santoro A.

Advanced Colorectal Liver Metastases and Surgery After Preoperative Chemotherapy: Is Response-Based Selection Enough? J Clin Oncol. 2011 Jul 1;29(19):2733-4; author reply 2734-5. Epub 2011 May 23. Raw IF: 18.97 Normalized IF: 7.5 Pezzilli R, Falconi M, Zerbi A, Casadei R, Valli L, Varale R, Armatura G, Felicani C, Morselli-Labate AM.

Clinical and Patient-Reported Outcomes After Pancreatoduodenectomy for Different Diseases: A Follow-Up Study. Pancreas. 2011 Aug;40(6):938-45. Epub 2011 May 10 Raw IF: 2.607 Normalized IF: 2 Ribero D, Nuzzo G, Amisano M, Tomatis M, Guglielmi A, Giulini SM, Aldrighetti L, Calise F, Gerunda GE, Pinna AD, Capussotti L; Italian Chapter of IHPBA.

Comparison of the prognostic accuracy of the sixth and seventh editions of the TNM classification for intrahepatic cholangiocarcinoma. HPB (Oxford). 2011 Mar;13(3):198-205. Raw IF: 1.285

Surgical Approach to Ulcerative Colitis: When is the Best Timing after Medical Treatment?

Spinelli A*, Del Fabbro D, Sacchi M, Zerbi A, Torzilli G, Lutman FR, Laghi L, Malesci A, Montorsi M.

Intraoperative Ultrasound with Contrast Medium in Resective Pancreatic Surgery: A Pilot Study. World J Surg. 2011 Nov;35(11):2521-7. Raw IF: 2.693

Normalized IF: 6

Spinelli A*, Bazzi P, Spaggiari P, Danese S, Montorsi M.

Anatomical right posterior sectionectomy: a further expansion of the ultrasound-guided compression technique. Updates Surg. 2011 Jun;63(2):91-5. Epub 2011 Apr 5. Raw IF: 0 Normalized IF: 0.1 Torzilli G, Procopio F, Palmisano A, Donadon M, Del Fabbro D, Marconi M, Scifo G, Montorsi M.

Total or partial anatomical resection of segment 8 using the ultrasound-guided finger compression technique. HPB (Oxford). 2011 Aug;13(8):586-91. Raw IF: 1.285

Normalized IF: 4

Normalized IF: 2 Torzilli G.

Spinelli A*, Correale C, Szabo H, Montorsi M.

Intestinal fibrosis in Crohn’s disease: medical treatment or surgery? Curr Drug Targets. 2010 Feb;11(2):242-8. Raw IF: 3.061

Normalized IF: 4

Spinelli A*, Sacchi M, Fiorino G, Danese S, Montorsi M.

Advances in the surgical treatment of colorectal cancer liver metastases through ultrasound. Surg Today. 2011 Sep;41(9):1184-9. Epub 2011 Aug 26. Raw IF: 1.057 Normalized IF: 2 Torzilli G*, Procopio F, Donadon M, Del Fabbro D, Cimino M, Montorsi M.

Risk of postoperative recurrence and postoperative management of Crohn’s disease.

Safety of Intermittent Pringle Maneuver Cumulative Time Exceeding 120 Minutes in Liver Resection: A Further Step in Favor of the “Radical but Conservative” Policy

World J Gastroenterol. 2011 Jul 21;17(27):3213-9. Raw IF: 2.24 Normalized IF: 4

Ann Surg. 2012 Feb;255(2):270-80. Raw IF: 7.474

Normalized IF: 8

113

Papers published 2011

gynaecology Salvatore S, Salvatore S, Cattoni E, Siesto G, Serati M, Sorice M, Torella M.

Urinary tract infections in women Eur J Obstet Gynecol Reprod Biol 2011;156:131-136. Raw IF: 1.764 Normalized IF:2

Impact of Drug Eluting Stents and Diabetes Mellitus in Patients With Coronary Bifurcation Lesions: A Survey From the Italian Society of Invasive Cardiology.

Salvatore S, Siesto G, Rizk DEE.

Circ Cardiovasc Interv. 2011 Feb 1;4(1):72-9. Raw IF: 4.364 Normalized IF: 3

Definition of recurrence of pelvic organ prolapse: it is really important? Int Urogyn J 2011; 22:635-636. Raw IF:2.368

Normalized IF:6

Serati M, Cattoni E, Braga A, Siesto G, Salvatore S.

Coital incontinence: relation to detrusor overactivity and stress incontinence. A controversial topic Neurourol Urodynam 2011;30:1415. Raw IF:2.903

Normalized IF:3

Vitobello D*, Siesto G, Bulletti C, Accardi A, Levi Setti PE.

Gynecological fertility-sparing surgery. Placenta. 2011 Sep;32 Suppl 3:S224-31. Epub 2011 Jul 18. Raw IF: 2.985 Normalized IF: 6 Vitobello D, Siesto G, Iedà N, Bulletti C, Accardi A.

Fertility sparing gynecological surgery Placenta 2011;32:s224-231 Raw IF:2.985

Normalized IF:6

Vitobello D*, Siesto G, Bulletti C.

Robotic sacral hysteropexy for pelvic organ prolapse. Int J Med Robot. 2011 Nov 23[Epub ahead of print] Raw IF: 1.257 Normalized IF: 2

HAEMODYNAMICS AND INVASIVE CARDIOLOGY Biondi-Zoccai G, Sheiban I, Romagnoli E, De Servi S, Tamburino C, Colombo A, Burzotta F, Presbitero P,Bolognese L, Paloscia L, Rubino P, Sardella G, Briguori C, Niccoli L, Franco G, Girolamo DD, Piatti L,Greco C, Capodanno D, Sangiorgi G.

Is intravascular ultrasound beneficial for percutaneous coronary intervention of bifurcation lesions? Evidence from a 4,314-patient registry. 114

Capodanno D, Tamburino C, Sangiorgi GM, Romagnoli E, Colombo A, Burzotta F, Gasparini GL, Bolognese L, Paloscia L, Rubino P, Sardella G, Briguori C, Ettori F, Franco G, Di Girolamo D, Sheiban I, Piatti L, Greco C, Petronio AS, Loi B, Lyoi E, Benassi A, Patti A, Gaspardone A, De Servi S; for the I-BIGIS Study Group.

Clin Res Cardiol. 2011 Nov;100(11):1021-8. Epub 2011 Jun 24 Raw IF: 3.466 Normalized IF: 3

Endorsed by the European Society of Gynecology (ESG), the Association for European Paediatric Cardiology (AEPC), and the German Society for Gender Medicine (DGesGM); Authors/ Task Force Members, Regitz-Zagrosek V, Lundqvist CB, Borghi C, Cifkova R, Ferreira R, Foidart JM, Gibbs JS, GohlkeBaerwolf C, Gorenek B, Iung B, Kirby M, Maas AH, Morais J, Nihoyannopoulos P, Pieper PG, Presbitero P, Roos-Hesselink JW, Schaufelberger M, Seeland U, Torracca L; ESC Committee for Practice Guidelines (CPG), Bax J, Auricchio A, Baumgartner H, Ceconi C, Dean V, Deaton C, Fagard R, Funck-Brentano C, Hasdai D, Hoes A, Knuuti J, Kolh P, McDonagh T, Moulin C, Poldermans D, Popescu BA, Reiner Z, Sechtem U, Sirnes PA, Torbicki A, Vahanian A, Windecker S; Document Reviewers, Baumgartner H, Deaton C, Aguiar C, Al-Attar N, Garcia AA, Antoniou A, Coman I, Elkayam U, Gomez-Sanchez MA, Gotcheva N, Hilfiker-Kleiner D, Kiss RG, Kitsiou A, Konings KT, Lip GY, Manolis A, Mebaaza A, Mintale I, Morice MC, Mulder BJ, Pasquet A, Price S, Priori SG, Salvador MJ, Shotan A, Silversides CK, Skouby SO, Stein JI, Tornos P, Vejlstrup N, Walker F, Warnes C.

ESC Guidelines on the management of cardiovascular diseases during pregnancy: The Task Force on the Management of Cardiovascular Diseases during Pregnancy of the European Society of Cardiology (ESC). Eur Heart J. 2011 Dec;32(24):3147-97. Epub 2011 Aug 26. Raw IF: 10.052 Normalized IF: 8 Ferrante G*, Belli G, Presbitero P.

Letter by Ferrante et al regarding article, “impact of collateral flow to the occluded infarct-related artery on clinical outcomes in patients with recent myocardial infarction: a report from the randomized occluded artery trial”. Circulation. 2011 Mar 1;123(8):e256; author reply e257-8. Raw IF: 14.432 Normalized IF: 5 Ferrante G, Barlis P, Niccoli G.

Thrombus-contribution-very-late-restenosis-baremetal-stent-treated-excimer-laser-angioplas. J Invasive Cardiol. 2011 May;23(5):214-5. Raw IF: 1.782

Normalized IF: 2

Ferrante G, Presbitero P, Valgimigli M, Morice MC, Pagnotta P, Belli G, Corrada E, Onuma Y, Barlis P, Locca D, Eeckhout E, Di Mario C, Serruys PW.

Reilly MP, Li M, He J, Ferguson JF, Stylianou IM, Mehta NN, Burnett MS, Devaney JM, Knouff CW, Thompson JR, Horne BD, Stewart AF, Assimes TL, Wild PS, Allayee H, Nitschke PL, Patel RS; Myocardial Infarction Genetics Consortium; Wellcome Trust Case Control Consortium, Martinelli N, Girelli D, Quyyumi AA, Anderson JL, Erdmann J, Hall AS, Schunkert H, Quertermous T, Blankenberg S, Hazen SL, Roberts R, Kathiresan S, Samani NJ, Epstein SE, Rader DJ. (Collaborators: Rossi ML)

Identification of ADAMTS7 as a novel locus for coronary atherosclerosis and association of ABO with myocardial infarction in the presence of coronary atherosclerosis: two genome-wide association studies. Lancet. 2011 Jan 29;377(9763):383-92. Epub 2011 Jan 14. Raw IF: 33.633 Normalized IF: 3 Ribichini F, Tomai F, De Luca G, Boccuzzi G, Presbitero P, Pesarini G, Ferrero V, Ghini AS, Abukaresh R, Aurigemma C, De Luca L, Zavalloni D, Soregaroli D, Marino P, Garbo R, Zanolla L, Vassanelli C; CEREADES investigators.

Immunosuppressive Therapy with Oral Prednisone to Prevent Restenosis after PCI. A Multicenter Randomized Trial.

Percutaneous aortic valve implantation in severe stenosis associated with anomalous origin of the circumflex coronary artery.

Am J Med. 2011 May;124(5):434-43. Raw IF: 5.115

Eur Heart J. 2011 Jul. 32 (13): 1687. Epub 2011 Feb 2. Raw IF: 10.052 Normalized IF: 4

Romagnoli E, Godino C, Ielasi A, Gasparini G, Tzifos V, Sciahbasi A, Lioy E, Presbitero P, Colombo A, Sangiorgi G.

Normalized IF: 6

Resolute italian study in all comers: Immediate and OneYear Outcomes.

Pagnotta P, Ferrante G, Presbitero P*.

Rescue “valve in valve” implantation after late onset corevalve cusp rupture leading to acute massive aortic insufficiency.

Catheter Cardiovasc Interv. 2011 Jul 29. Raw IF: 2.398

Normalized IF: 2

Catheter Cardiovasc Interv. 2011 May 3 [Epub ahead of print] Raw IF: 2.398 Normalized IF: 4

Urban P, Abizaid A, Banning A, Bartorelli AL, Baux AC, Džavík V, Ellis S, Gao R, Holmes D, Jeong MH, Legrand V, Neumann FJ, Nyakern M, Spaulding C, Worthley S; e-SELECT Investigators (Presbitero P).

Previtali M, Repetto A, Camporotondo R, Citro R, Faggiano P, Bovelli D, Baldini E, Pasquetto G, Ascione L, Vignali L, Rosso R, Baralis G, Rossi ML, Ferlini M, Bossone E, Panciroli C, Rovere FD, Visconti LO, Klersy C.

Stent thrombosis and bleeding complications after implantation of sirolimus-eluting coronary stents in an unselected worldwide population: a report from the e-SELECT(Multi-Center Post-Market Surveillance) registry.

Clinical characteristics and outcome of left ventricular ballooning syndrome in a European population.

J Am Coll Cardiol. 2011 Mar 29;57(13):1445-54. Raw IF: 14.292 Normalized IF: 2

Am J Cardiol. 2011 Jan;107(1):120-5. Raw IF: 3.68

Normalized IF: 3

hand surgery Rayoo R, Rayoo M, Ferrante G, Barlis P.

Histological confirmation of hypersensitivity as a contributor to very-late coronary stent thrombosis. Int J Cardiol. 2011 Sep 24. [Epub ahead of print]. Raw IF: 6.802 Normalized IF: 1.2

Riva N, Gallia F, Iannaccone S, Corbo M, Terenghi F, Lazzerini A, Cerri F, Comi G, Quattrini A, Nobile-Orazio E.

Chronic motor axonal neuropathy. J Peripher Nerv Syst. 2011 Dec;16(4):341-346. Raw IF: 3.032 Normalized IF: 4

115

Papers published 2011

internal medicine Lleo A, Moroni L, Caliari L, Invernizzi P*.

Knee Surg Sports Traumatol Arthrosc. 2012 Jan;20(1):114-20. Epub 2011 Jun 16. Raw IF: 1.857 Normalized IF: 4

Autoimmunity and Turner’s syndrome. Autoimmun Rev. 2011 Dec 2. [Epub ahead of print] Raw IF: 6.556 Normalized IF: 6 Montali L, Frigerio A, Riva P, Invernizzi P.

It’s as if PBC didn’t exist’: The illness experience of women affected by primary biliary cirrhosis. Psychol Health. 2011 Nov;26(11):1429-45. Epub 2011 Jun 28. Raw IF: 0 Normalized IF: 0.1 Selmi C*, Affronti A, Ferrari L, Invernizzi P.

Immune-mediated bile duct injury: The case of primary biliary cirrhosis.

Fiorino G, Peyrin-Biroulet L, Naccarato P, Szabò H, Sociale OR, Vetrano S, Fries W, Montanelli A, Repici A, Malesci A, Danese S*.

Effects of immunosuppression on immune response to pneumococcal vaccine in inflammatory bowel disease: A prospective study. Inflamm Bowel Dis. 2011 Jun 14.[Epub ahead of print] Raw IF: 4.613 Normalized IF: 6

MEDICAL ONCOLOGY AND HAEMATOLOGY

World J Gastrointest Pathophysiol. 2010 Oct 15;1(4):11828. Raw IF: 0 Normalized IF: 0.1

Abbadessa G, Rimassa L*, Pressiani T, Carrillo-Infante C, Cucchi E, Santoro A.

Selmi C, Bowlus CL, Gershwin ME, Coppel RL.

Optimized management of advanced hepatocellular carcinoma: Four long-lasting responses to sorafenib.

Primary biliary cirrhosis. Lancet. 2011 May 7;377(9777):1600-9. Epub 2011 Apr 28. Raw IF: 33.633 Normalized IF: 15 Selmi C, Leung PS, Fischer L, German B, Yang CY, Kenny TP, Cysewski GR, Gershwin ME.

World J Gastroenterol. 2011 May 21;17(19):2450-3. Raw IF: 2.24 Normalized IF: 4 Abou-Alfa GK, Amadori D, Santoro A, Figer A, De Greve J, Lathia C, Voliotis D, Anderson S, Moscovici M, Ricci S.

The effects of Spirulina on anemia and immune function in senior citizens.

Safety and Efficacy of Sorafenib in Patients with Hepatocellular Carcinoma (HCC) and Child-Pugh A versus B Cirrhosis.

Cell Mol Immunol. 2011 May;8(3):248-54. Epub 2011 Jan 31. Raw IF: 2.026 Normalized IF: 2

Gastrointest Cancer Res. 2011 Mar;4(2):40-4. Raw IF: 0 Normalized IF: 0.1

Selmi C.

Adamo V, Ricciardi GR, De Placido S, Colucci G, Conte P, Giuffrida D, Gebbia N, Masci G, Cognetti F, Dondi D, Venturini M.

Novel Challenges for the Allergist. Clin Rev Allergy Immunol. 2011 Aug;41(1):1-3. Raw IF: 3.435 Normalized IF: 6

KNEE ORTHOPAEDICS AND SPORT TRAUMATOLOGY Cervellin M, de Girolamo L, Bait C, Denti M, Volpi P*.

116

laboratory test

Autologous platelet-rich plasma gel to reduce donorsite morbidity after patellar tendon graft harvesting for anterior cruciate ligament reconstruction: a randomized, controlled clinical study.

Management and treatment of triple-negative breast cancer patients from the NEMESI study: An Italian experience. Eur J Cancer. 2011 Jul 12. [Epub ahead of print] Raw IF: 4.944 Normalized IF: 3 Alongi F*, Bignardi M, Garassino I, Pentimalli S, Cavina R, Mancosu P, Reggiori G, Poletti A, Ferrari D, Foa P, Bigoni A, Dragonetti A, Salvatori P, Spahiu O, Fogliata A, Cozzi L, Santoro A, Scorsetti M

Prospective phase II trial of cetuximab plus VMATSIB in locally advanced head and neck squamous cell

carcinoma : Feasibility and tolerability in elderly and chemotherapy-ineligible patients. Strahlenther Onkol. 2012 Jan;188(1):49-55. Epub 2011 Dec 24 Raw IF: 3.567 Normalized IF: 4 Arcaini L, Laszlo D, Rizzi S, Balzarotti M, Antoniazzi F, Zilioli VR, Guggiari E, Farina L, Todisco E, Bonfichi M, Alamos SM, Rossi G, Martinelli G, Morra E.

Plerixafor and G-CSF for PBSC mobilization in patients with lymphoma who failed previous attempts with GCSF and chemotherapy: A REL (Rete Ematologica Lombarda) experience. Leuk Res. 2011 Jun;35(6):712-4. Epub 2011 Jan 26. Raw IF: 2.555 Normalized IF: 2 Aschele C, Cionini L, Lonardi S, Pinto C, Cordio S, Rosati G, Artale S, Tagliagambe A, Ambrosini G, Rosetti P, Bonetti A, Negru ME, Tronconi MC, Luppi G, Silvano G, Corsi DC, Bochicchio AM, Chiaulon G, Gallo M, Boni L.

Primary Tumor Response to Preoperative Chemoradiation With or Without Oxaliplatin in Locally Advanced Rectal Cancer: Pathologic Results of the STAR-01 Randomized Phase III Trial. J Clin Oncol. 2011 Jul 10;29(20):2773-80. Epub 2011 May 2 Raw IF: 18.97 Normalized IF: 7.5 Bachner M, Loriot Y, Gross-Goupil M, Zucali PA, Horwich A, Germa-Lluch JR, Kollmannsberger C, Stoiber F, Fléchon A, Oechsle K, Gillessen S, Oldenburg J, Cohn-Cedermark G, Daugaard G, Morelli F, Sella A, Harland S, Kerst M, Gampe J, Dittrich C, Fizazi K, De Santis M.

2-18fluoro-deoxy-D-glucose positron emission tomography (FDG-PET) for postchemotherapy seminoma residual lesions: a retrospective validation of the SEMPET trial. Ann Oncol. 2012 Jan;23(1):59-64. Epub 2011 Apr 2. Raw IF: 6.452 Normalized IF: 3 Bracarda S, Ruggeri EM, Monti M, Merlano M, D’Angelo A, Ferraù F, Cortesi E, Santoro A.

Management of cirrhotic patients with hepatocellular

carcinoma treated with sorafenib. Expert Rev Anticancer Ther. 2011 Dec;11(12):1807-16. Epub 2011 Aug 26. Raw IF: 2.976 Normalized IF: 2 Carbone A, Santoro A.

How I treat: diagnosing and managing “in situ” lymphoma. Blood. 2011 Apr 14;117(15):3954-60. Epub 2011 Jan 11. Raw IF: 10.558 Normalized IF: 8 Carbone A, Gloghini A, Santoro A.

In situ follicular lymphoma: pathologic characteristics and diagnostic features Hematol Oncol. 2011 May 11 [Epub ahead of print] Raw IF: 2.258 Normalized IF: 2 Carnaghi C*, Sclafani F, Basilico V, Doherty M.

Response assessment in oncology: limitations of anatomic response criteria in the era of tailored treatments. Q J Nucl Med Mol Imaging. 2011 Dec;55(6):589-602 Raw IF: 2.537 Normalized IF: 4 Castagna L, Bramanti S, Sarina B, Todisco E, Ibatici A, Santoro A.

ECIL 3-2009 update guidelines for antifungal management. Bone Marrow Transplant. 2011 Aug 8. [Epub ahead of print] Raw IF: 3.66 Normalized IF: 3 Ceresoli GL*, Zucali PA, De Vincenzo F, Gianoncelli L, Simonelli M, Lorenzi E, Ripa C, Giordano L, Santoro A.

Retreatment with pemetrexed-based chemotherapy in patients with malignant pleural mesothelioma. Lung Cancer. 2011 Apr;72(1):73-7. Raw IF: 3.356

Normalized IF: 4

De Vincenzo F, Zucali PA, Ceresoli GL, Colombo P, Simonelli M, Lorenzi E, Perrino M, Gianoncelli L, De Sanctis R, Graziotti P, Santoro A.

Response to Sunitinib in an Adult Patient With Rhabdoid Renal Cell Carcinoma. J Clin Oncol. 2011 Jun 20;29(18):e529-31. Epub 2011 Apr 11. Raw IF: 18.97 Normalized IF: 15 Dellapasqua S, Mazza M, Rosa D, Ghisini R, Scarano E, Torrisi R, Maisonneuve P, Viale G, Cassano E, Veronesi P, Luini A, Goldhirsch A, Colleoni M.

117

Papers published 2011

Pegylated liposomal doxorubicin in combination with low-dose metronomic cyclophosphamide as preoperative treatment for patients with locally advanced breast cancer. Breast. 2011 Aug;20(4):319-23. Epub 2011 Mar 11. Raw IF: 2.089 Normalized IF: 6

Navarria P*, Mancosu P, Alongi F, Pentimalli S, Tozzi A, Reggiori G, Ascolese AM, Arcangeli S, Lobefalo F, Rodriguez y Baena R, Castiglioni S, Pessina F, Tancioni F, Santoro A, Fogliata A, Cozzi L, Scorsetti M.

Lemos C, Giovannetti E, Zucali PA, Assaraf YG, Scheffer GL, van der Straaten T, D’Incecco A, Falcone A, Guchelaar HJ, Danesi R, Santoro A, Giaccone G, Tibaldi C, Peters GJ.

Vertebral metastases reirradiation with volumetricmodulated arc radiotherapy.

Impact of ABCG2 polymorphisms on the clinical outcome and toxicity of gefitinib in non-small-cell lung cancer patients. Pharmacogenomics. 2011 Feb;12(2):159-70. Raw IF: 3.876 Normalized IF: 3 Marasini B*, Cozzaglio L, Belloli L, Massarotti M, Ughi N, Pedrazzoli P.

Metastatic melanoma in a young woman treated with TNF-alpha inhibitor for psoriatic arthritis: a case report. Curr Drug Saf. 2011 Sep 1;6(4):275-6. Raw IF: 0

Normalized IF: 0.1

Marmé F, Werft W, Walter A, Keller S, Wang X, Benner A, Burwinkel B, Sinn P, Hug S, Sohn C, Bretz N, Moldenhauer G, Rupp C, Rupp AK, Biakhov MY, Bottini A, Friedrichs K, Khailenko VA, Manikhas GM, Ruiz A, Sánchez-Rovira P, Santoro A, Segui MA, Villena C, Lichter P, Kristiansen G, Altevogt P, Schneeweiss A.

CD24 Ala57Val polymorphism predicts pathologic complete response to sequential anthracycline- and taxane-based neoadjuvant chemotherapy for primary breast cancer Breast Cancer Res Treat. 2011 Sep 30. [Epub ahead of print] Raw IF: 4.859 Normalized IF: 3 Masci G*, Gandini C, Zuradelli M, Pedrazzoli P, Torrisi R, Lutman FR, Santoro A.

Fulvestrant for advanced male breast cancer patients: a case series. Ann Oncol. 2011 Apr;22(4):985. Raw IF: 6.452

Normalized IF: 3

Mussi C, Colombo P, Bertuzzi A, Coladonato M, Bagnoli P, Secondino S, Navarria P, Morenghi E, Santoro A, Quagliuolo V*.

118

Ann Surg Oncol. 2011 Aug;18(8):2136-42. Epub 2011 May 3. Raw IF: 4.182 Normalized IF: 6

Retroperitoneal Sarcoma: Is It Time to Change the Surgical Policy?

Radiother Oncol. 2011 Dec 20. [Epub ahead of print] Raw IF: 4.337 Normalized IF: 6 Pelagio G, Pistillo D, Mottolese M.

Minimum Biobanking Requirements: Issues in a Comprehensive Cancer Center Biobank Biopreservation and Biobanking Volume 9, Number 2, 2011. Raw IF: 0 Normalized IF: 0.1 Personeni N, Torzilli G, Santoro A.

Advanced Colorectal Liver Metastases and Surgery After Preoperative Chemotherapy: Is Response-Based Selection Enough? J Clin Oncol. 2011 Jul 1;29(19):2733-4; author reply 2734-5. Epub 2011 May 23. Raw IF: 18.97 Normalized IF: 7.5 Reni M, Pasetto LM, Passardi A, Milella M, Mambrini A, Cereda S, Aprile G, Tronconi MC, Berardi R, Cordio S, Sartori N, Rognone A, Pederzoli P, Falconi M.

Treatment trends in metastatic pancreatic cancer patients: Is it time to change? Dig Liver Dis. 2011 Mar;43(3):225-30. Epub 2010 Nov 2. Raw IF: 2.805 Normalized IF: 2 Sartore-Bianchi A, Fieuws S, Veronese S, Moroni M, Personeni N, Frattini M, Torri V, Cappuzzo F, Vander Borght S, Martin V, Skokan M, Santoro A, Gambacorta M, Tejpar S, Varella-Garcia M, Siena S.

Standardisation of EGFR FISH in colorectal cancer: results of an international interlaboratory reproducibility ring study. J Clin Pathol. 2012 Mar;65(3):218-23. Epub 2011 Nov 30. Raw IF: 2.475 Normalized IF: 2 Sclafani F*, Carnaghi C, Di Tommaso L, Rodari M, Destro A, Rimassa L, Giordano L, Chiti A, Roncalli M, Santoro A.

Detection of somatostatin receptor subtypes 2

and 5 by somatostatin receptor scintigraphy and immunohistochemistry: clinical implications in the diagnostic and therapeutic management of gastroenteropancreatic neuroendocrine tumors. Tumori. 2011 Sep-Oct;97(5):620-8. Raw IF: 1.014

Normalized IF: 1

adjuvant therapy in premenopausal women with ER positive locally advanced breast cancer. Breast Cancer Res Treat. 2011 Apr;126(2):431-41. Raw IF: 4.859 Normalized IF: 3 Tronconi MC, Sclafani F, Rimassa L, Carnaghi C, Personeni N, Santoro A.

Scorsetti M, Ceresoli GL, Navarria P, Alongi F, Mancosu P, Santoro A, Fogliata A, Cozzi L.

Fatal Infusion Reaction to Cetuximab: The Need for Predictive Risk Factors and Safer Patient Selection.

In response to dr. Russi and colleagues.

J Clin Oncol. 2011 Aug 10;29(23):e680-1. Epub 2011 Jun 20. Raw IF: 18.97 Normalized IF: 15

Int J Radiat Oncol Biol Phys. 2011 Mar 15;79(4):1279-80 Raw IF: 4.503 Normalized IF: 3 Simonelli M, Rosti G, Banna GL, Pedrazzoli P

Intesified chemotherapy with stem-cell rescue in germcell tumors Annals of Oncology 2011 Sep.; [Epub ahead of print] Raw IF: 6.452 Normalized IF: 6 Tancioni F, Lorenzetti MA*, Navarria P, Pessina F, Draghi R, Pedrazzoli P, Scorsetti M, Alloisio M, Santoro A, Rodriguez y Baena R.

Percutaneous vertebral augmentation in metastatic disease: state of the art. J Support Oncol. 2011 Jan-Feb;9(1):4-10. Raw IF: 0 Normalized IF: 0.1 Tancioni F, Navarria P*, Mancosu P, Pedrazzoli P, Morenghi E, Santoro A, Rodriguez y Baena R, Scorsetti M.

Surgery followed by radiotherapy for the treatment of metastatic epidural spinal cord compression (mescc) from breast cancer. Spine (Phila Pa 1976). 2011 Sep 15;36(20):E1352-9. Raw IF: 2.51 Normalized IF: 6 Tancioni F, Navarria P, Pessina F, Marcheselli S, Rognone E, Mancosu P, Santoro A, Rodriguez y Baena R.

Early Surgical Experience with Minimally Invasive Percutaneous Approach for Patients with Metastatic Epidural Spinal Cord Compression (MESCC) to Poor Prognoses. Ann Surg Oncol. 2012 Jan;19(1):294-300. Epub 2011 Jul 9 Raw IF: 4.182 Normalized IF: 6 Torrisi R*, Bagnardi V, Rotmensz N, Scarano E, Iorfida M, Veronesi P, Luini A, Viale G, Santoro A, Colleoni M, Goldhirsch A.

Letrozole plus GnRH analogue as preoperative and

Visani G, Malerba L, Stefani PM, Capria S, Galieni P, Gaudio F, Specchia G, Meloni G, Gherlinzoni F, Giardini C, Falcioni S, Cuberli F, Gobbi M, Sarina B, Santoro A, Ferrara F, Rocchi M, Ocio EM, Caballero MD, Isidori A.

BeEAM (bendamustine, etoposide, cytarabine, melphalan) prior to autologous stem cell transplant is safe and effective for resistant/relapsed lymphoma patients. Blood. 2011 Sep 22;118(12):3419-25. Epub 2011 Aug 3. Raw IF: 10.558 Normalized IF: 4 Vitolo U, Chiappella A, Ferreri AJ, Martelli M, Baldi I, Balzarotti M, Bottelli C, Conconi A, Gomez H, Lopez-Guillermo A, Martinelli G, Merli F, Novero D, Orsucci L, Pavone V, Ricardi U, Storti S, Gospodarowicz MK, Cavalli F, Sarris AH, Zucca E.

First-Line Treatment for Primary Testicular Diffuse Large B-Cell Lymphoma With Rituximab-CHOP, CNS Prophylaxis, and Contralateral Testis Irradiation: Final Results of an International Phase II Trial. J Clin Oncol. 2011 Jul 10;29(20):2766-72. Epub 2011 Jun 6. Raw IF: 18.97 Normalized IF: 15 Zucali PA*, De Sanctis R, De Vincenzo F, Simonelli M, Lorenzi E, Perrino M, Santoro A.

Treatment of malignant pleural mesothelioma: current status and future directions Clinical Investigation 2011; 1(7): 999-1018 Raw IF: 0 Normalized IF: 0.1 Zucali PA, Simonelli M, Michetti G, Tiseo M, Ceresoli GL, CollovĂ E, Follador A, Lo Dico M, Moretti A, De Vincenzo F, Lorenzi E, Perrino M, Giordano L, Farina G, Santoro A, Garassino M.

Second-line chemotherapy in malignant pleural mesothelioma: Results of a retrospective multicenter survey. Lung Cancer. 2011 Sep 19. [Epub ahead of print] Raw IF: 3.356 Normalized IF: 4

119

Papers published 2011

Zucali PA, Ceresoli GL, De Vincenzo F, Simonelli M, Lorenzi E, Gianoncelli L, Santoro A.

Advances in the biology of malignant pleural mesothelioma. Cancer Treat Rev. 2011 Nov;37(7):543-58. Epub 2011 Feb 1. Raw IF: 6.811 Normalized IF: 6

NUCLEAR MEDICINE Chiti A, Oyen WJ.

Imaging of therapy response in oncology. Q J Nucl Med Mol Imaging. 2011 Dec;55(6):587-8. Raw IF: 2.537 Normalized IF: 4 Fanti S, Krause B, Weber W, Castellucci P, Grosu AL, de Jong IJ, Messa C, Picchio M, Pruim J, Langsteger W, Chiti A*; for the European Association of Nuclear Medicine (EANM), Vienna, Austria. Re: Nicolas Mottet, Joaquim Bellmunt, Michel Bolla, et al. EAU Guidelines on Prostate Cancer. Part II: Treatment of

Advanced, Relapsing, and Castration-Resistant Prostate Cancer. Eur Urol 2011;59:572-83.

Eur Urol. 2011 Nov;60(5):e37-e38. Epub 2011 Aug 16. Raw IF: 8.843 Normalized IF: 4

Immunosuppressive treatment in refractory chronic inflammatory demyelinating polyradiculoneuropathy. A nationwide retrospective analysis. Eur J Neurol. 2011 Dec;18(12):1417-21. Epub 2011 Aug 5. Raw IF: 3.765 Normalized IF: 6 Joint Task Force of the EFNS and the PNS: van Schaik IN, Leger J-M, Nobile-Orazio E, Cornblath DR, Hadden RDM, Koski CL, Pollard JD, Sommer C, Illa I, Spain, van den Bergh P, van Doorn PA.

European Federation of Neurological Societies/ Peripheral Nerve Society Guideline on management of multifocal motor neuropathy. Report of a Joint Task Force of the European Federation of Neurological Societies and the Peripheral Nerve Society – first revision. J Peripher Nerv Syst. 2010 15: 295–301 Raw IF: 3.032

Normalized IF: 4

Peters MJ, van Nes SI, Vanhoutte EK, Bakkers M, van Doorn PA, Merkies IS, Faber CG; PeriNomS Study group. Collaborators (Nobile-Orazio E.).

Revised normative values for grip strength with the Jamar dynamometer. J Peripher Nerv Syst. 2011 Mar;16(1):47-50. Raw IF: 3.032 Normalized IF: 0.8

Grégoire V, Chiti A.

Molecular imaging in radiotherapy planning for head and neck tumors. J Nucl Med. 2011 Mar;52(3):331-4. Epub 2011 Feb 14. Raw IF: 7.022 Normalized IF: 8

Riva N, Gallia F, Iannaccone S, Corbo M, Terenghi F, Lazzerini A, Cerri F, Comi G, Quattrini A, Nobile-Orazio E.

Chronic motor axonal neuropathy. J Peripher Nerv Syst. 2011 Dec;16(4):341-346. Raw IF: 3.032 Normalized IF: 4

Lopci E, Chiti A, Castellani MR, Pepe G, Antunovic L, Fanti S, Bombardieri E.

Matched pairs dosimetry: (124)I/ (131)I metaiodobenzylguanidine and (124)I/ (131)I and (86)Y/ (90)Y antibodies. Eur J Nucl Med Mol Imaging. 2011 May;38 Suppl 1:S28-40. Epub 2011 Apr 12. Raw IF: 5.036 Normalized IF: 6

NEUROLOGY II

120

Cocito D, Grimaldi S, Paolasso I, Falcone Y, Antonini G, Benedetti L, Briani C, Fazio R, Jann S, Matà S, Sabatelli M, Nobile-Orazio E; On behalf of The Italian Network for CIDP Register.

NEUROSURGERY Castellano A, Bello L, Michelozzi C, Gallucci M, Fava E, Iadanza A, Riva M, Casaceli G, Falini A.

Role of diffusion tensor magnetic resonance tractography in predicting the extent of resection in glioma surgery. Neuro Oncol. 2011 Oct 20. [Epub ahead of print] Raw IF: 5.483 Normalized IF: 6 Caviggioli F, Giannasi S, Vinci V, Cornegliani G, Levi D, Gaetani P.

Five-year outcome of surgical treatment of migraine headaches.

Plast Reconstr Surg. 2011 Nov;128(5):564e-5e. Raw IF: 2.635 Normalized IF: 6 Costa F*, Tomei M, Sassi M, Cardia A, Ortolina A, Servello D, Fornari M.

Evaluation of the rate of decompression in anterior cervical corpectomy using an intra-operative computerized tomography scan (O-Arm system). Eur Spine J. 2011 Sep 24. [Epub ahead of print] Raw IF: 1.994 Normalized IF: 6 Giraldi FP, Pagliardini L, Cassarino MF, Losa M, Lasio G, Cavagnini F.

Responses to Crh and Dexamethasone in a Large Series of Human Acth-Secreting Pituitary Adenomas in Vitro Reveal Manifold Corticotroph Tumoural Phenotypes. J Neuroendocrinol. 2011 Dec;23(12):1214-21. Epub 2011 Aug 28. Raw IF: 4.65 Normalized IF: 3 Navarria P*, Mancosu P, Alongi F, Pentimalli S, Tozzi A, Reggiori G, Ascolese AM, Arcangeli S, Lobefalo F, Rodriguez y Baena R, Castiglioni S, Pessina F, Tancioni F, Santoro A, Fogliata A, Cozzi L, Scorsetti M.

Vertebral metastases reirradiation with volumetricmodulated arc radiotherapy. Radiother Oncol. 2011 Dec 20. [Epub ahead of print]. Raw IF: 4.337 Normalized IF: 6 Tancioni F, Lorenzetti MA*, Navarria P, Pessina F, Draghi R, Pedrazzoli P, Scorsetti M, Alloisio M, Santoro A, Rodriguez y Baena R.

Percutaneous vertebral augmentation in metastatic disease: state of the art. J Support Oncol. 2011 Jan-Feb;9(1):4-10. Raw IF: 0 Normalized IF: 0.1

Percutaneous Approach for Patients with Metastatic Epidural Spinal Cord Compression (MESCC) to Poor Prognoses. Ann Surg Oncol. 2012 Jan;19(1):294-300. Epub 2011 Jul 9 Raw IF: 4.182 Normalized IF: 6

OPHTHALMOLOGY Camesasca FI*, Vinciguerra P, Seiler T.

Bilateral Ring-shaped Intrastromal Opacities After Corneal Cross-linking for Keratoconus. J Refract Surg. 2011 Dec;27(12):913-5 Raw IF: 2.491

Normalized IF: 6

Koller T, Pajic B, Vinciguerra P, Seiler T.

Flattening of the cornea after collagen crosslinking for keratoconus. J Cataract Refract Surg. 2011 Aug;37(8):1488-92. Raw IF: 2.942 Normalized IF: 3 Marticorena J, Gómez-Ulla F, Romano MR, Fernández M.

Dye-guided retinal laser and internal drainage for optic pit maculopathy. Graefes Arch Clin Exp Ophthalmol. 2011 Oct 1. Raw IF: 2.158 Normalized IF: 2 Romano MR, Furgiuele D, Bregu M, Costagliola C, Vinciguerra P.

Vitrectomy associated with internal limiting membrane peeling remains a very challenging procedure with variable outcomes. Retina. 2011 Feb;31(2):428-9; autor reply 429-30. Raw IF: 2.774 Normalized IF: 3

Tancioni F, Navarria P, Mancosu P, Pedrazzoli P, Morenghi E, Santoro A, Rodriguez y Baena R, Scorsetti M.

Romano MR*, Angi M, Valldeperas X, Costagliola C, Vinciguerra P.

Surgery followed by radiotherapy for the treatment of metastatic epidural spinal cord compression (mescc) from breast cancer.

Twenty-three-gauge pars plana vitrectomy, densiron-68, and 360° endolaser versus combined 20-gauge pars plana vitrectomy, scleral buckle, and sf6 for pseudophakic retinal detachment with inferior retinal breaks.

Spine (Phila Pa 1976). 2011 Sep 15;36(20):E1352-9. Raw IF: 2.51 Normalized IF: 6 Tancioni F, Navarria P*, Pessina F, Marcheselli S, Rognone E, Mancosu P, Santoro A, Rodriguez y Baena R.

Early Surgical Experience with Minimally Invasive

Retina. 2011 Apr;31(4):686-91. Raw IF: 2.774

Normalized IF: 6

Romano MR, Vinciguerra P, Radice P, Scialdone A, Valldeperas

121

Papers published 2011

X, Romano V, Romano F, Costagliola C.

Outer retinal layers. Ophthalmology. 2011 May;118(5):1006-1006.e2 Raw IF: 5.017 Normalized IF: 3

Monti L, Haroche J, Sciarra A, Balzarini L, Fiamengo B, Amoura Z, Graziani G.

Interferon-Alpha in Cardiac Erdheim-Chester Disease. J Am Coll Cardiol. 2011 Dec 13;58(25):2695 Raw IF: 14.293 Normalized IF: 5

Vinciguerra P, Vinciguerra R, Romano MR.

Late-onset persistent epithelial ingrowth following uncomplicated clear corneal incision cataract surgery. Clin Experiment Ophthalmol. 2011 Jun 13. [Epub ahead of print]. Raw IF: 1.766 Normalized IF: 2 Zenoni S, Romano MR, Comi N, Fontana P, Bailo G.

Mussi C, Colombo P, Bertuzzi A, Coladonato M, Bagnoli P, Secondino S, Navarria P, Morenghi E, Santoro A, Quagliuolo V*.

Retroperitoneal Sarcoma: Is It Time to Change the Surgical Policy? Ann Surg Oncol. 2011 Aug;18(8):2136-42. Epub 2011 May 3. Raw IF: 4.182 Normalized IF: 6

Closed-globe intraocular lens fixation. J Cataract Refract Surg. 2011 Feb;37(2):419-20. Raw IF: 2.942 Normalized IF: 3 Zenoni S, Romano MR*, Palmieri S, Comi N, Fiorentini E, Fontana P.

Ocular tolerance and efficacy of short-term tamponade with double filling of polydimethyloxane and perfluoron-octane.

Taverna G*, Morandi G, Seveso M, Giusti G, Benetti A, Colombo P, Minuti F, Grizzi F, Graziotti P.

Colour Doppler and microbubble contrast agent ultrasonography do not improve cancer detection rate in transrectal systematic prostate biopsy sampling. BJU Int. 2011 Dec.; 108 (11): 1723-7. Epub 2011 Jul 16. Raw IF: 3.19 Normalized IF: 6

Clin Ophthalmol. 2011;5:443-9. Epub 2011 Apr 6. Raw IF: 0 Normalized IF: 0.1

PEDIATRIC SURGERY OTORHINOLARYNGOLOGY Alongi F*, Bignardi M, Garassino I, Pentimalli S, Cavina R, Mancosu P, Reggiori G, Poletti A, Ferrari D, Foa P, Bigoni A, Dragonetti A, Salvatori P, Spahiu O, Fogliata A, Cozzi L, Santoro A, Scorsetti M.

Prospective phase II trial of cetuximab plus VMATSIB in locally advanced head and neck squamous cell carcinoma : Feasibility and tolerability in elderly and chemotherapy-ineligible patients. Strahlenther Onkol. 2012 Jan;188(1):49-55. Epub 2011 Dec 24 Raw IF: 3.567 Normalized IF: 4

Cimolin V, Piccinini L, Portinaro N, Turconi AC, Albonico S, Crivellini M, Galli M.

The effects of femoral derotation osteotomy in cerebral palsy: a kinematic and kinetic study. Hip Int. 2011 Nov;21(6):657-64 [Epub 2011 Oct 28:0] Raw IF: 0.792 Normalized IF: 1 Portinaro NM*, Porteus A, Parafioriti A, Panou A, Benson MK.

Growth of the acetabular lateral cartilage in relation to congenital and developmental dysplasia of the hip. An histological study. Hip Int. 2011 Jan 28; 21(1) 9-13. Raw IF: 0.792

Normalized IF: 2

PATHOLOGY De Vincenzo F, Zucali PA, Ceresoli GL, Colombo P, Simonelli M, Lorenzi E, Perrino M. Gianoncelli L, De Sanctis R, Graziotti P, Santoro A.

Response to Sunitinib in an Adult Patient With Rhabdoid Renal Cell Carcinoma. 122

J Clin Oncol. 2011 Jun 20;29(18):e529-31. Epub 2011 Apr 11. Raw IF: 18.97 Normalized IF: 15

PLASTIC SURGERY II Caviggioli F, Maione L, Forcellini D, Klinger F, Klinger M*.

Autologous fat graft in postmastectomy pain syndrome. Plast Reconstr Surg. 2011 Aug;128(2):349-52. Raw IF: 2.647 Normalized IF: 6

Caviggioli F, Giannasi S, Vinci V, Cornegliani G, Levi D, Gaetani P.

Five-year outcome of surgical treatment of migraine headaches Plast Reconstr Surg. 2011 Nov;128(5):564e-5e. Raw IF: 2.635 Normalized IF: 6 Garcia-Etienne CA, Forcellini D, Sagona A, Caviggioli F, Barbieri E, Cornegliani G, Giannasi S, Tinterri C*.

Breast reconstruction: A quality measure for breast cancer care? Breast. 2011 Sep 2. [Epub ahead of print]. Raw IF: 2.089

Normalized IF: 4

Klinger ME*, Bandi V, Vinci V, Forcellini D, Maione L.

Innovations in the Treatment of Male Chest Deformity After Weight Loss: The Authors’ Technique.

certainties and still open issues. A review of recent literature. Tumori. 2011 Jan-Feb;97(1):1-8. Raw IF: 1.014

Normalized IF: 1

Alongi F*, Bignardi M, Garassino I, Pentimalli S, Cavina R, Mancosu P, Reggiori G, Poletti A, Ferrari D, Foa P, Bigoni A, Dragonetti A, Salvatori P, Spahiu O, Fogliata A, Cozzi L, Santoro A, Scorsetti M.

Aesthetic Plast Surg. 2011 Oct;35(5):856-8. Epub 2011 Apr 1. Raw IF: 1.252 Normalized IF: 2

Fogliata A, Nicolini G, Clivio A, Vanetti E, Mancosu P, Cozzi L.

Klinger M*, Caviggioli F, Forcellini D, Bandi V, Maione L, Vinci V, Pagliari AV, Klinger F, Mazzola RF.

Phys Med Biol. 2011 Mar 21;56(6):1879-904. Epub 2011 Mar 1. Erratum in Phys Med Biol. 2011 May 7; 56(9): 2885-6. Raw IF: 3.057 Normalized IF: 6

Primary Nasal Tip Surgery: A Conservative Approach Aesthetic Plast Surg. 2011 Nov 15. [Epub ahead of print] Raw IF: 1.252 Normalized IF: 2

Dosimetric validation of the Acuros XB Advanced Dose Calculation algorithm: fundamental characterization in water.

Scuderi N, Dessy LA, Buccheri EM, Marchetti F, Mazzocchi M, Chiummariello S, Klinger F, Onesti MG.

Fogliata A, Bergström S, Cafaro I, Clivio A, Cozzi L, Dipasquale G, Hållström P, Mancosu P, Navarria P, Nicolini G, Parietti E, Pesce GA, Richetti A, Scorsetti M, Vanetti E, Weber DC.

Phase 2 cross-over multicenter trial on the efficacy and safety of topical cyanoacrylates compared with

Cranio-spinal irradiation with volumetric modulated arc therapy: a multi-institutional treatment experience.

Aesthetic Plast Surg. 2011 Jun;35(3):373-81. Epub 2010 Nov 16. Raw IF: 1.252 Normalized IF: 1

Radiother Oncol. 2011 Apr;99(1):79-85. Epub 2011 Mar 21. Raw IF: 4.337 Normalized IF: 6

PNEUMOLOGY Gonnelli S, Caffarelli C, Maggi S, Guglielmi G, Siviero P, Rossi S, Crepaldi G, Nuti R; EOLO study group. Collaborators: (Ciccarelli M.)

Effect of inhaled glucocorticoids and beta(2) agonists on vertebral fracture risk in COPD patients: the EOLO study. Calcif Tissue Int. 2010 Aug;87(2):137-43. Epub 2010 Jun 22. Raw IF: 2.759 Normalized IF: 0.8

RADIOTHERAPY AND RADIOSURGERY Alongi F*, Cozzarini C, Di Muzio N, Scorsetti M.

Postoperative radiotherapy in prostate cancer: acquired

Fogliata A, Clivio A, Fenoglietto P, Hrbacek J, Kloeck S, Lattuada P, Mancosu P, Nicolini G, Parietti E, Urso G, Vanetti E, Cozzi L.

Quality assurance of RapidArc in clinical practice using portal dosimetry. Br J Radiol. 2011 Jun;84(1002):534-45. Raw IF: 2.062

Normalized IF: 2

Fogliata A, Cozzi L, Clivio A, Ibatici A, Mancosu P, Navarria P, Nicolini G, Santoro A, Vanetti E, Scorsetti M.

Preclinical Assessment of Volumetric Modulated Arc Therapy for Total Marrow Irradiation. Int J Radiat Oncol Biol Phys. 2011 Jun 1;80(2):628-36. Epub 2011 Jan 27. Raw IF: 4.503 Normalized IF: 6

123

Papers published 2011

Fogliata A, Clivio A, Cozzi L, Nicolini G, Pesce GA, Richetti A, Vanetti E, Bergstrรถm S, Hรฅllstrรถm P, Cafaro I, Parietti E, Dipasquale G, Weber DC, Mancosu P, Navarria P, Scorsetti M.

Reply to the Letter to the editor on Cranio-spinal irradiation with volumetric modulated arc therapy by G. Saini. Radiother Oncol. 2011 Sep 19. [Epub ahead of print]. Raw IF: 4.337 Normalized IF: 3 Mancosu P, Danna M, Bettinardi V, Aquilina MA, Lobefalo F, Cozzi L, Fogliata A, Scorsetti M.

Semiautomatic method to identify the best phase for gated RT in lung region by 4D-PET/CT acquisitions. Med Phys. 2011 Jan;38(1):354-62. Raw IF: 3.075

Normalized IF: 6

Mussi C, Colombo P, Bertuzzi A, Coladonato M, Bagnoli P, Secondino S, Navarria P, Morenghi E, Santoro A, Quagliuolo V*.

Retroperitoneal Sarcoma: Is It Time to Change the Surgical Policy? Ann Surg Oncol. 2011 Aug;18(8):2136-42. Epub 2011 May 3. Raw IF: 4.182 Normalized IF: 6 Navarria P*, Mancosu P, Alongi F, Pentimalli S, Tozzi A, Reggiori G, Ascolese AM, Arcangeli S, Lobefalo F, Rodriguez YnBaena RR, Castiglioni S, Pessina F, Tancioni F, Santoro A, Fogliata A, Cozzi L, Scorsetti M.

Clerici E, Reggiori G, Lobefalo F, Fogliata A, Cozzi L.

Stereotactic body radiation therapy (SBRT) for adrenal metastases : a feasibility study of advanced techniques with modulated photons and protons. Strahlenther Onkol. 2011 Apr;187(4):238-44. Raw IF: 3.567 Normalized IF: 6 Scorsetti M, Bignardi M, Alongi F, Fogliata A, Mancosu P*, Navarria P, Castiglioni S, Pentimalli S, Tozzi A, Cozzi L.

Stereotactic body radiation therapy for abdominal targets using volumetric intensity modulated arc therapy with RapidArc: Feasibility and clinical preliminary results. Acta Oncol. 2011 May;50(4):528-38. Epub 2011 Feb 21 Raw IF: 3.137 Normalized IF: 4 Scorsetti M, Alongi F*, Castiglioni S, Clivio A, Fogliata A, Lobefalo F, Mancosu P, Navarria P, Palumbo V, Pellegrini C, Pentimalli S, Reggiori G, Ascolese AM, Roggio A, Arcangeli S, Tozzi A, Vanetti E, Cozzi L.

Feasibility and early clinical assessment of flattening filter free (FFF) based stereotactic body radiotherapy (SBRT) treatments. Radiat Oncol. 2011 Sep 12;6:113. Raw IF: 2.409

Normalized IF: 4

Vertebral metastases reirradiation with volumetricmodulated arc radiotherapy.

Tancioni F, Lorenzetti MA*, Navarria P, Pessina F, Draghi R, Pedrazzoli P, Scorsetti M, Alloisio M, Santoro A, Rodriguez y Baena R.

Radiother Oncol. 2011 Dec 20. [Epub ahead of print] Raw IF: 4.337 Normalized IF: 6

Percutaneous vertebral augmentation in metastatic disease: state of the art.

Reggiori G, Mancosu P, Tozzi A, Cantone MC, Castiglioni S, Lattuada P, Lobefalo F, Cozzi L, Fogliata A, Navarria P, Scorsetti M.

Cone beam CT pre- and post-daily treatment for assessing geometrical and dosimetric intrafraction variability during radiotherapy of prostate cancer. J Appl Clin Med Phys. 2010 Dec 2;12(1):3371. Raw IF: 1.008 Normalized IF: 1 Scorsetti M, Ceresoli GL, Navarria P, Alongi F, Mancosu P, Santoro A, Fogliata A, Cozzi L.

J Support Oncol. 2011 Jan-Feb;9(1):4-10. Raw IF: 0 Normalized IF: 0.1 Tancioni F, Navarria P, Pessina F, Marcheselli S, Rognone E, Mancosu P, Santoro A, Rodriguez y Baena R.

In response to dr. Russi and colleagues. Int J Radiat Oncol Biol Phys. 2011 Mar 15;79(4):1279-80 Raw IF: 4.503 Normalized IF: 3

REHABILITATION Bellelli G, Bernardini B, Trabucchi M.

124

Scorsetti M, Mancosu P, Navarria P, Tozzi A, Castiglioni S,

The specificity of Geriatric Rehabilitation: Myth or

Reality? A Debate from an Italian Perspective. J Am Med Dir Assoc. 2012 Feb;13(2):94-95.e1. Raw IF: 4.492 Normalized IF: 6 Belloli L, Cugno M, D’Agostino MC, Ughi N, Tedeschi A, Respizzi S, Marasini B.

Shock wave therapy for systemic sclerosis. Rheumatol Int. 2011 Dec 25. [Epub ahead of print] Raw IF: 1.431 Normalized IF: 1 D’Agostino C, Romeo P, Amelio E, Sansone V.

Effectiveness of ESWT in the Treatment of Kienböck’s Disease. Ultrasound Med Biol 2001 Sep; 37(9):1452-6 Epub 2011 Jul 20 Raw IF: 2.493 Normalized IF: 6

REPRODUCTIVE MEDICINE Lodigiani C, Di Micco P, Ferrazzi P, Libré L, Arfuso V, Polatti F, Benigna M, Rossini R, Morenghi E, Rota L, Brenner B, Levi Setti PE.

Low-molecular-weight heparin in women with repeated implantation failure. Womens Health (Lond Engl). 2011 Jul;7(4):425-31. Raw IF: 0 Normalized IF: 0.1 Vitobello D*, Siesto G, Bulletti C, Accardi A, Levi Setti PE.

Gynecological fertility-sparing surgery. Placenta. 2011 Sep;32 Suppl 3:S224-31. Epub 2011 Jul 18. Raw IF: 2.985 Normalized IF: 6

RESEARCH LABORATORIES OF SCIENTIFIC SUPERINTENDENCE Taverna G*, Morandi G, Seveso M, Giusti G, Benetti A, Colombo P, Minuti F, Grizzi F, Graziotti P.

RHEUMATOLOGY Adami S, Maugeri G, Toscano V, Topa G, Carminiti M, Brancati A, Massarotti M, Osella G, Malavolta N, Iolascon G, Cagnoni C, Camozzi V, Corradini C, Nardi A, Migliaccio S, Ulivieri F, Resmini G, Valle D, Tauchmanovà L, Silvestri S.

Baseline characteristics of the population enrolled in the Italian observational Study on Severe Osteoporosis (ISSO). Clin Exp Rheumatol. 2011 May-Jun;29(3):477-84. Epub 2011 Jun 29. Raw IF: 2,358 Normalized IF: 2 Belloli L, Cugno M, D’Agostino MC, Ughi N, Tedeschi A, Respizzi S, Marasini B.

Shock wave therapy for systemic sclerosis Rheumatol Int. 2011 Dec 25. [Epub ahead of print] Raw IF: 1.431 Normalized IF: 1 Distler JH, Jordan S, Airo P, Alegre-Sancho JJ, Allanore Y, Balbir Gurman A, Caporali R, Caramaschi P, Carreira PE, Chizzolini C, Cutolo M, Tuncay Duruöz M, Farge-Bancel D, Hesselstrand R, Iannone F, De Keyser F, Kucharz EJ, Launay D, García de la Peña Lefebvre P, Lukacova O, Marasini B, Martinovic D, Marques Neto JF, Radic M, Rednic S, Riemekasten G, Rovensky J, Seidel MF, Senel S, Smith V, Sunderkötter C, Ton E, van Laar JM, Matucci-Cerinic M, Müller Ladner U, Distler O.

Is there a role for TNFα antagonists in the treatment of SSc? EUSTAR expert consensus development using the Delphi technique. Clin Exp Rheumatol. 2011 Mar-Apr;29(2 Suppl 65):S40-5. Epub 2011 May 12. Raw IF: 2.358 Normalized IF: 2 Eller-Vainicher C, Chiodini I, Santi I, Massarotti M, Pietrogrande L, Cairoli E, Beck-Peccoz P, Longhi M, Galmarini V, Gandolini G, Bevilacqua M, Grossi E.

Recognition of Morphometric Vertebral Fractures by Artificial Neural Networks: Analysis from GISMO Lombardia Database. PLoS One. 2011;6(11):e27277. Epub 2011 Nov 4. Raw IF: 4.441 Normalized IF: 3 Fabbriciani G, De Socio GV, Massarotti M.

Antiretroviral therapy and adverse skeletal effects. Mayo Clin Proc. 2011 Sep;86(9):916-7. Raw IF: 5.712

Normalized IF: 3

125

Papers published 2011

Fabbriciani G, de Socio GV, Massarotti M, Ceriani R, Marasini B.

Metastatic melanoma in a young woman treated with TNF-alpha inhibitor for psoriatic arthritis: a case report. Curr Drug Saf. 2011 Sep 1;6(4):275-6. Raw IF: 0

Normalized IF: 0.1

Salaffi F, Ciapetti A, Gasparini S, Migliore A, Scarpellini M, Corsaro SM, LaganĂ B, Mozzani F, Varcasia G, Pusceddu M, Castriotta M, Serale F, Maier A, Foti R, Scarpa R, Bombardieri S; NEW INDICES Study Group (Marasini B).

Comparison of the Recent-Onset Arthritis Disability questionnaire with the Health Assessment Questionnaire disability index in patients with rheumatoid arthritis. Clin Exp Rheumatol. 2010 Nov-Dec;28(6):855-65. Epub 2011 Jan 3. Raw IF: 2.358 Normalized IF: 0.4

THORACIC SURGERY Tancioni F, Lorenzetti MA*, Navarria P, Pessina F, Draghi R, Pedrazzoli P, Scorsetti M, Alloisio M, Santoro A, Rodriguez y Baena R.

Percutaneous vertebral augmentation in metastatic disease: state of the art. J Support Oncol. 2011 Jan-Feb;9(1):4-10. Raw IF: 0 Normalized IF: 0.1

UROLOGY De Vincenzo F, Zucali PA, Ceresoli GL, Colombo P, Simonelli M, Lorenzi E, Perrino M, Gianoncelli L, De Sanctis R, Graziotti P, Santoro A.

Response to Sunitinib in an Adult Patient With Rhabdoid Renal Cell Carcinoma. J Clin Oncol. 2011 Jun 20;29(18):e529-31. Epub 2011 Apr 11. Raw IF: 18.97 Normalized IF: 15 Taverna G*, Morandi G, Seveso M, Giusti G, Benetti A, Colombo P, Minuti F, Grizzi F, Graziotti P.

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Scientific Report ÂŠ Istituto Clinico Humanitas May 2012 Scientific Direction: Alberto Mantovani Communication Manager: Walter Bruno Editorial Coordination: Humanitas: Monica Florianello in collaboration with: Michele Tedeschi (Clinical Trials Office) Annalisa Franceschetti and Elena Pisano (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 May 2012 by Tipografia F.lli Verderio, Milano