tbuckley/cabot-search huggingface dataset:
AB0273 Disease Characteristics and Change of Arthritis Activity According To Treatment in Hepatitis B Surface Antigen Positive Rheumatoid Arthritis Patients
Authors: H. Kim, Y. Eun, J.K. Ahn, J.-M. Oh, H. Jeong, J. Lee, E.-M. Koh, H.-S. Cha
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> Rheumatoid arthritis (RA) treatment may differ according to hepatitis B state and consequently bring about different outcome of arthritis. Only a small number of studies have addressed the differences in disease characteristics and treatment patterns of RA in relation to hepatitis B state. However, it has not yet been elucidated whether hepatitis B affects treatment outcome such as disease activity. <h3>Objectives</h3> We investigated possible differences in change of arthritis activity between RA patients according to concomitant hepatitis B virus (HBV) infection. <h3>Methods</h3> A retrospective analysis of 40 hepatitis B surface antigen (HBsAg)-positive RA patients and 112 HBsAg-negative RA patients was conducted. The longitudinal relationship between HBsAg-positivity and RA activity/medication use was analyzed using generalized estimating equations in regression models. <h3>Results</h3> There were no significant differences in group for baseline characteristics. In regression analysis, RA activity-related outcomes showed follow-up time-dependent improvement during study period. We observed significant interaction between time and HBsAg-positivity for disease activity score in 28 joints with 3 variables (DAS28–3; <i>P</i> =0.026), that means decreases in DAS28–3 with time influenced by HBsAg-positivity. But this interaction did not remain significant after adjustment. For tender joints, erythrocyte sedimentation rate, and C-reactive protein levels, there were no interaction between time and HBsAg-positivity, while swollen joints showed significant interaction (<i>P</i> =0.017). The time-association and group differences were not observed in alanine aminotransferase (ALT) level. Over all visits, HBsAg-positive patients were less likely to receive methotrexate (OR 0.09 [95% CI 0.04–0.19], <i>P</i> &lt;0.0001) and more likely to receive sulfasalazine (OR 3.67 [95% CI 1.94–6.95], <i>P</i> &lt;0.0001). In HBsAg-positive RA patients, initial hepatitis B state was related to use of DMARDs, especially methotrexate (<i>P</i> =0.040). Hepatitis reactivation occurred in 4 patients (10%) in HBsAg-positive RA patients. Among the patients who experienced HBV reactivation, only one patient had received previous antiviral treatment at baseline, but the patient exhibited lower adherence to drug. All patients who experienced HBV reactivation showed positive HBV DNA at baseline. There were no cases of hepatic failure or death. <h3>Conclusions</h3> There were no significant differences over time in DAS28–3, tender joints, inflammatory markers, according to HBsAg-positivity, while swollen joints showed significant difference over time. ALT level did not showed time-association and group differences. HBsAg-positive RA patients were less likely to receive methotrexate and more likely to receive sulfasalazine. <h3>Disclosure of Interest</h3> None declared
P0816 : Reduction in annual medical costs with early treatment of HCV using AbbVie 3D (ABT-450/ritonavir/ombitasvir and dasabuvir) +/− ribavirin in the United States
Authors: D.A. Misurski, S.J. Johnson, J.C. Samp, S.E. Marx, T.R. Juday, S. Virabhak, H. Parisé, S. Saab
Journal: Journal of Hepatology (2015)
Gender Differences during Long-Term Warfarin Anticoagulation in Patients with Atrial Fibrillation Monitored with Fiix-Prothrombin Time or Prothrombin Time. the Fiix Trial
Authors: Hulda M. Jensdottir, Brynjar Vidarsson, Brynja R. Gudmundsdottir, Alma R. Oskarsdottir, Olafur S. Indridason, David O. Arnar, Einar S. Bjornsson, Magnus K. Magnusson, Sigrun H. Lund, Charles W. Francis, Pall T. Onundarson
Journal: Blood (2015)
Hematopoietic Overexpression of the ETS Family Transcription Factor Erg, or the Oncogenic Fusion Protein TLS-ERG, Induces Erythro-Megakaryocytic Leukemia
Authors: Catherine L Carmichael, Donald Metcalf, Katya J. Henley, Elizabeth A Kruse, Ladina Di Rago, Sandra Mifsud, Jian Zhong Tang, Warren S. Alexander, Benjamin T. Kile
Journal: Blood (2012)
O114 : Serum HBV-RNA levels decline significantly in chronic hepatitis B patients dosed with the nucleic-acid polymer REP2139-CA
Authors: L. Jansen, A. Vaillant, F. Stelma, N.A. Kootstra, M. Bazinet, M. Al-Mahtab, H.W. Reesink
Journal: Journal of Hepatology (2015)
Children with TEL/AML1-Positive Acute Lymphoblastic Leukemia (ALL) and Favorable Presenting Features May Benefit from the Use of Vincristine-Dexamethasone (VCR-DXM) Pulses on Top of Antimetabolite-Based Continuation Therapy.
Authors: Carmelo Rizzari, Giovanni Cazzaniga, Maria Grazia Valsecchi, Daniela Silvestri, Valentino Conter, Maurizio Aricò, Elena Barisone, Fiorina Casale, Giulio De Rossi, Franco Locatelli, Luca Lo Nigro, Chiara Messina, Concetta Micalizzi, Andrea Pession, Rosanna Parasole, Roberto Rondelli, Nicola Santoro, Anna Maria Testi, Giuseppe Basso, Giuseppe Masera, Andrea Biondi
Journal: Blood (2005)
AB0133 Increased Expression of Activated Ly6g+Cd11b+Cd62l- Neutrophils in Balb/c Mice with Pristane Induced Lupus-like Disease
Authors: N. Ugriumov, C. Goldenstein-Schainberg, S. Carrasco, I. Begalli Mendes, T.M. Lima, T. Vasconcelos Peixoto, S.B. Veríssimo de Mello, F.G. Soriano
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> Neutrophils are important cells of innate immunity9s first line of defense and IL-8 cytokine contributes to its activation. In patients with lupus there is an increase of activated neutrophils in plasma, however data about the contribution of IL-8 on disease development are conflicting. <h3>Objectives</h3> To analyze and quantify activated Ly6G+CD11b+CD62L- neutrophils in peripheral blood (PB) and spleen as well to evaluate the production of IL-8 in Balb/c mice with pristane induced lupus-like disease. <h3>Methods</h3> We studied 37 mice (13 healthy controls; 24 pristane-induced mice). Pristane-induced mice (PIM) received a single intraperitoneal 0.5ml dose of pristane, while healthy controls received the same dose of saline. Samples of blood and spleen were collected after euthanasia 90 and 120 days after injections; red blood cells were lysed and remaining cells stained with monoclonal antibodies: anti-Ly6G (total neutrophils), anti-CD11b (activated neutrophils) and anti-CD62L (anergic neutrophils) (BDPharmingen™). All cell samples were evaluated by flow cytometry (Guava EasyCyte™ HT, Millipore). Plasmatic IL-8 levels were assessed by ELISA (MyBioSource™). Mann-Whitney9s non-parametric test was used for statistical analysis, and P&lt;0.05 considered significant. <h3>Results</h3> Compared to control, PIM had higher percentage of total neutrophils 90 and 120 days after injection in PB (26.9±2.46 vs. 46.75±5.41%, P=0.002 and 26.9±2.46 vs. 38.52±4.03%, P=0.004) and spleen (15.94±1.86 vs. 33.7±6.48%, P=0.01 and 15.94±1.86 vs. 35.98±3%, P&lt;0.0001) respectively. In PB, the percentage of activated neutrophils was similar in PIM compared to controls (P&gt;0.05), while in the spleen, PIM had increased activated neutrophils 120 days after induction (41.83±3.63 vs. 58.73±3.94%, P=0.004). PIM and controls expressed similar percentages of anergic neutrophils in both PB and spleen (P&gt;0.05). Controls and PIM produced similar plasmatic IL-8 levels 90 and 120 days after injection (0.65±0.18 vs. 0.2±0.05pg/ml, P≥0.05 and 0.65±0.18 vs. 1.2±0.51pg/ml, P&gt;0.05), respectively though PIM had higher plasmatic IL8 levels 120 days compared to 90 days after induction (1.2±0.51 vs 0.2±0.05pg/ml, P=0.01). <h3>Conclusions</h3> Increased percentage of activated neutrophils in PIM indicates innate immunity involvement. Delayed IL8 levels increments over time might suggests that this cytokine may be involved in neutrophil activation in this animal model. Therefore, additional studies are needed in order to clarify IL8 role and further pathways involved in neutrophil activation and disease development in PIM. <h3>References</h3> Abbas, A.K.; et al. 2008. Baggiolini, M.; et al. 1992. Coquery, C.M.; et al. 2014. Rönnerfarth, V.M.; et al. 2006. Hrycek, E.; et al. 2013. <h3>Disclosure of Interest</h3> None declared
AB0096 Presence of ACPA and RF Autoantibodies in Ulcerative Colitis and Crohn's Disease
Authors: K.M.J. Janssen, H. Hop, A. Vissink, G. Dijkstra, E. Brouwer, J. Westra
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> Presence of arthritis autoantibodies is specific for rheumatoid arthritis (RA). Anti-citrullinated peptide antibodies (ACPA) and rheumatoid factor (RF) can be detected several years before the onset of arthritis and are thought to have a pathogenic role. However, where and when autoantibody production starts is unclear. A potential trigger could be chronic mucosal inflammation as in inflammatory bowel disease (IBD) since the gut microbiome is thought to be involved in induction of (auto) immunity. This assumption is supported by the demonstration of citrullinated proteins in intestinal tissue of IBD patients. <h3>Objectives</h3> To assess the prevalence of ACPA and RF in IBD patients as well as to assess the prevalence of joint complaints in autoantibody positive versus autoantibody negative IBD patients. <h3>Methods</h3> Serum was collected from 227 patients with ulcerative colitis (UC) and 164 with Crohn9s disease (CD) participating in the Dutch IBD pearl chain institute biobank initiative. Baseline disease characteristics including enthesitis, arthralgia, arthritis and comorbid conditions like spondylarthropathy were obtained from medical electronic records. IgG and IgA ACPA levels were measured by anti-CCP2 ELISA from EuroDiagnostica (ED) and IgM and IgA-RF levels were measured by in-house ELISA. The cut-off value for IgG ACPA positivity was 2 U/mL and for IgA ACPA 1.04 aU/ml based on the mean +2SD of a group of healthy reference samples. Seropositivity for IgM and IgA-RF was defined at ≥10 IU/ml and ≥25 IU/ml, respectively. <h3>Results</h3> Thirty-two (14.1%) UC and 33 (20.1%) CD patients had an IgG ACPA level &gt;2 U/ml. However, all IgG ACPA levels were below the diagnostic cut off level for RA which is set at ≥25 U/ml. IgA ACPA levels were increased in 83 (36.5%) UC and 48 (29.3%) CD patients. IgM-RF seropositivity was observed in 11 (4.8%) UC and 6 (3.7%) CD patients. IgA-RF seropositivity was observed in 6 (2.6%) UC and 8 (4.9%) CD patients. A total of 101 (44.5%) UC and 76 (46.3%) CD were seropositive for at least 1 arthritis autoantibody. Arthralgias were reported in 19.1% of UC and 33.3% of CD, respectively. Among patients with arthralgias, the percentage of individuals being seropositive for 1 or more autoantibodies was comparable to patients without arthralgias. <h3>Conclusions</h3> The results of our study support the hypothesis that inflammation of intestinal mucosa induces low systemic levels of ACPA, which eventually may play a role in induction of RA. However, the development of arthralgias in IBD patients is independent on the presence of low systemic presence of arthritis autoantibodies. <h3>Disclosure of Interest</h3> None declared
Inhibition of the GAS6/AXL pathway augments the efficacy of chemotherapies
Authors: Mihalis S. Kariolis, Yu Rebecca Miao, Anh Diep, Shannon E. Nash, Monica M. Olcina, Dadi Jiang, Douglas S. Jones, Shiven Kapur, Irimpan I. Mathews, Albert C. Koong, Erinn B. Rankin, Jennifer R. Cochran, Amato J. Giaccia
Journal: Journal of Clinical Investigation (2016)

The AXL receptor and its activating ligand, growth arrest–specific 6 (GAS6), are important drivers of metastasis and therapeutic resistance in human cancers. Given the critical roles that GAS6 and AXL play in refractory disease, this signaling axis represents an attractive target for therapeutic intervention. However, the strong picomolar binding affinity between GAS6 and AXL and the promiscuity of small molecule inhibitors represent important challenges faced by current anti-AXL therapeutics. Here, we have addressed these obstacles by engineering a second-generation, high-affinity AXL decoy receptor with an apparent affinity of 93 femtomolar to GAS6. Our decoy receptor, MYD1-72, profoundly inhibited disease progression in aggressive preclinical models of human cancers and induced cell killing in leukemia cells. When directly compared with the most advanced anti-AXL small molecules in the clinic, MYD1-72 achieved superior antitumor efficacy while displaying no toxicity. Moreover, we uncovered a relationship between AXL and the cellular response to DNA damage whereby abrogation of AXL signaling leads to accumulation of the DNA-damage markers γH2AX, 53BP1, and RAD51. MYD1-72 exploited this relationship, leading to improvements upon the therapeutic index of current standard-of-care chemotherapies in preclinical models of advanced pancreatic and ovarian cancer.
OP0127 Low Frequency of Us Determined Erosions in Early Psoriatic Arthritis: Results from The Leeds Sparro Cohort: Table 1.
Authors: M. Merashli, G. De Marco, P. Helliwell, L. Horton, M.A. D'agostino, D. Mcgonagle, R. Wakefield, J. Freeston, H. Marzo-Ortega
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> Ultrasound (US) is playing an increasingly important role in the early evaluation of psoriatic arthritis (PsA) being capable of detecting inflammatory changes at the enthesis, synovium and extra capsular tissues. Peri-articular radiographic erosions in PsA and rheumatoid arthritis are associated with a worse outcome. Further, US is shown to be a more sensitive imaging technique than conventional radiography (CR) to identify erosions in early RA. By contrast, there is a paucity of data in the literature on the prevalence of erosions and/or the capability of US to detect erosions in early PsA. <h3>Objectives</h3> To assess the prevalence of erosions in early PsA using CR and high resolution US. <h3>Methods</h3> We studied 860 joints of 43 patients (Table 1) with early PsA, all fulfilling CASPAR criteria from the Leeds Spondyloarthropathy Register for Research and Observation study (SpARRO) which is a prospective longitudinal observational cohort of patients with early spondyloarthritis. Radiographic and sonographic erosions of the wrists, MCPs (2, 3), PIPs (2, 3), and MTPs (1–5) bilaterally were independently evaluated. We looked at the frequency of erosions using both imaging methodologies. CR and US scoring systems used for defining erosions were the van der Heijde version of the Sharp and OMERACT respectively. <h3>Results</h3> Erosions were identified in a total of 8 patients, all negative for RF and CCP antibodies; 40% (3/8) of whom were ex-smokers. Four patients had six erosions at MTP4, MTP5, and PIP3 by CR whilst six patients had six erosions on US. The exact agreement between the 2 methods was 99%. Agreement on absence of erosions in both CR and US was 99% while agreement on their presence was 17%. The proportions of joints where the CR and US disagreed in either direction (US&gt;XR, US <h3>Conclusions</h3> In keeping with the emerging data in PsA, these results show a low frequency of erosions at clinical presentation on CR. Unlike studies in early RA, in this preliminary study of early PsA the burden of erosive disease detected using US was not measurably different. <h3>References</h3> Weiner, S M,Jurenz, S,Uhl, M,Lange-Nolde, A,Warnatz, K,Peter, H H,Walker, U A.Ultrasonography in the assessment of peripheral joint involvement in psoriatic arthritis: a comparison with radiography, MRI and scintigraphy. Clinical rheumatology, vol. 27, no. 8, p. 983–989, 0770–3198 (August 2008) <h3>Acknowledgement</h3> Dr Richard Fawcett who works as a radiology fellow at Chapel Allerton Hospital <h3>Disclosure of Interest</h3> None declared
FRI0601 Role of Group Learning To Improve Reproducibilty of DAS-28 amongst Healthcare Professionals:
Authors: S.S. Majeed, E.M. Clark
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> Interprofessional group learning is a valuable educational tool in multidisciplinary settings as it helps improve clinical care and encourages professionals to learn with, from and about each other (CAIPE, 2006). Disease activity in rheumatoid arthritis is assessed using the DAS28 scoring system; and changes in treatment are influenced by the result of the DAS28 score. In our Rheumatology Department DAS28 assessment is carried out by many members of our multidisciplinary team including doctors, nurses and pharmacists. This necessitates checking of, and ensuring reproducibility of DAS28 scoring amongst our team, to enable appropriate management of patients. <h3>Objectives</h3> We utilised educational theory to organise a group learning exercise to assess reproducibility of DAS-28 score and identify areas for improvement amongst multidisciplinary rheumatology healthcare professionals, based at a large general hospital in South West England. <h3>Methods</h3> Four patients with rheumatoid arthritis were selected for the exercise based on availability. All members of the multidisciplinary team assessed the patients using the DAS28. 13 professionals participated in this activity: six rheumatology consultants (two academics), three rheumatology specialist registrars, three rheumatology specialist nurses and one rheumatology specialist pharmacist. Median scores and coefficient of variation expressed as a percentage (CV, calculated by standard deviation/mean x 100) were calculated for each patients overall DAS28 score and the constituent parts. CRP levels were fixed for each patient. <h3>Results</h3> <h3>Conclusions</h3> Reproducibility of overall DAS28 scores and its constituent parts were generally poor according to the CV. No differences in reproducibility were seen when stratifying by professional group. All subcomponents of the DAS28 showed equally poor reproducibility. This may have important clinical implications for patient care, particularly when deciding on treatment escalation. This interprofessional learning exercise, deliberately bringing together all members of the rheumatology multidisciplinary team, has enhanced learning for all by identifying the following points: (1) no professional group is "better" than another when assessing DAS28; (2) standardisation of how we ask about the VAS subcomponent will be introduced immediately; (3) tender joints are to be classed as ones with any tenderness from reasonable palpation; and (4) clinical judgement should be used when assessing rheumatoid disease activity. <h3>References</h3> CAIPE (2006) UK Centre for the Advancement of Interprofessional Education (CAIPE) re-issues its statement on the definition and principles of interprofessional education. CAIPE Bulletin. 26:3 <h3>Disclosure of Interest</h3> None declared
Quantitative Analysis of Minimal Residual Disease at the Completion of Induction Therapy Predicts Relapse in Children with B-Lineage Acute Lymphoblastic Leukemia in DFCI ALL Consortium Protocol 95-01.
Authors: Jianbiao Zhou, Aihong Li, Meredith A. Goldwasser, Hongjun Wang, Virginia Dalton, Cheryl Lyons, Kathryn D. McBride, Stephen E. Sallan, Lewis B. Silverman, John G. Gribben
Journal: Blood (2004)
Hepatitis B Virus Reactivation in Chronic Myeloid Leukemia Treated with Various Tyrosine Kinase Inhibitors: Multicenter, Retrospective Study
Authors: Sung-Hyun Kim, Hyeoung Joon Kim, Jae-Yong Kwak, Jin Seok Kim, Yeung-Chul Mun, Joon Seong Park, Sang Kyun Sohn, Dong-Wook Kim
Journal: Blood (2012)
Osteotropic peptide-mediated bone targeting for photothermal treatment of bone tumors
Authors: Yitong Wang, Jian Yang, Hongmei Liu, Xinyu Wang, Zhengjie Zhou, Quan Huang, Dianwen Song, Xiaopan Cai, Lin Li, Kaili Lin, Jianru Xiao, Peifeng Liu, Qiang Zhang, Yiyun Cheng
Journal: Biomaterials (2016)
Efficacy and Safety of Fludarabine/Cyclophosphamide (FC) as Front-Line Treatment of CLL. Final Results of a Phase II Clinical Trial in a Single Center.
Authors: Ana Marin-Niebla, Eduardo Rios-Herranz, Juan M. Rodriguez, Ramiro Nunez, Ascension Herrera, Ricardo Parody, Ildefonso Espigado
Journal: Blood (2004)
Impact of eplerenone on cardiovascular outcomes in heart failure patients with hypokalaemia
Authors: Patrick Rossignol, Nicolas Girerd, George Bakris, Orly Vardeny, Brian Claggett, John J.V. McMurray, Karl Swedberg, Henry Krum, Dirk J. van Veldhuisen, Harry Shi, Sean Spanyers, John Vincent, Renaud Fay, Zohra Lamiral, Scott D. Solomon, Faiez Zannad, Bertram Pitt
Journal: European Journal of Heart Failure (2016)
Lymphoma-Associated Macrophage (LAM) Content Is an Independent Predictor of Survival in Patients with Follicular Lymphoma (FL).
Authors: Pedro Farinha, Hamid Masoudi, Brian Skinnider, Karey Shumansky, John Spinelli, Karamjit Gill, Richard Klasa, Joseph M. Connors, Randy D. Gascoyne
Journal: Blood (2004)
Inhibition of Class I PI3K Isoforms Restores the Sensitivity of Acute Myelogenous Leukemia Cells to Multi-Tyrosine Kinase Inhibitors in the Bone Marrow Microenvironment.
Authors: Akira Shimada, Hongmei Niu, Shelley Orwick, Hiroto Inaba, Jeffrey E Rubnitz, Dario Campana, Sharyn D Baker
Journal: Blood (2009)
FRI0033 TNFalpha Production In Cultured Human Macrophages after CTLA4-IG (abatacept) In Vitro Treatment
Authors: R. Brizzolara, P. Montagna, S. Soldano, A.C. Trombetta, S. Paolino, C. Pizzorni, A. Sulli, B. Ruaro, D. Camellino, V. Tomatis, M. Cutolo
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> Proinflammatory cytokines and particularly tumor necrosis factor alpha (TNFalpha) are abundantly expressed in rheumatoid arthritis (RA) synovitis. Our recent data showed that CTLA4-Ig (abatacept), by interacting with the CD86 molecule on RA synovial macrophages, may induce reverse signaling with anti-inflammatory effects, involving NFkB intracellular pathway [1–4]. <h3>Objectives</h3> We investigated the expression and production of TNFalpha on cultured human activated macrophages before and after <i>in vitro</i> CTLA4-Ig treatment. <h3>Methods</h3> THP-1 human monocytes, differentiated with phorbol myristate acetate (0.05 μg/ml for 24 hrs) into activated macrophages, were cultured in multiwells bottoms or flexiperm slides for 3, 24 and 48 hrs, in the absence (cells untreated) and in the presence of CTLA4-Ig (500 μg/ml). TNFalpha gene expression was investigated by quantitative real time polymerase chain reaction (qRTPCR), after 3 and 24 hrs from CTLA4-Ig treatment. Intracytoplasmatic TNFalpha protein expression was investigated by immunocytochemistry (ICC) analysis after 24 and 48 hrs from treatment. Extracellular TNFalpha production was evaluated in the culture surnatants, by immunoassay (ELISA) analysis, after 24 hrs from treatment. Experiments were done in triplicate. <h3>Results</h3> Interestingly, at gene level, qRTPCR showed already after 3 hrs (and 24 hrs) from CTLA4-Ig treatment a significant downregulation of TNFalpha gene expression (p&lt;0.05 for both 3 and 24 hrs), compared to the untreated cells. ICC analysis showed that TNFalpha production resulted decreased (not significant) both after 24 hrs and 48 hrs from CTLA4-Ig (500 mg/ml) treatment, compared to the untreated cells. Extracellular evaluation by ELISA at 24 hrs, also demonstrated a reduction (not significant) of TNFalpha levels, compared to the untreated condition. <h3>Conclusions</h3> In cultured activated macrophages TNFalpha production was significantly reduced by CTLA4-Ig <i>in vitro</i> treatment at gene level, already after 3 hrs and still evident at 24 hrs. Regarding the protein synthesis, as expected, a trend for their reduction was observed on longer time (24–48 hrs). <h3>References</h3> Cutolo M et al. Arthritis Res Ther 2009, 11:176–85. Brizzolara R et al. Reumatismo 2011, 63:80–5. Brizzolara R et al. J Rheumatol 2013;40(5):738–40. Cutolo M et al. Clin Exp Rheumatol 2013;31(6):943–6. <h3>Disclosure of Interest</h3> R. Brizzolara: None declared, P. Montagna: None declared, S. Soldano: None declared, A. C. Trombetta: None declared, S. Paolino: None declared, C. Pizzorni: None declared, A. Sulli: None declared, B. Ruaro: None declared, D. Camellino: None declared, V. Tomatis: None declared, M. Cutolo Grant/research support from: Research grant by Bristol Myers Squibb