tbuckley/cabot-search huggingface dataset:
FRI0044 Non-steroidal anti-inflammatory drugs are more beneficial than anti-tnfα drugs on the radiographic damage in arthritis: a study in adjuvant induced arthritis
Authors: F Verhoeven, C Prati, P Totoson, R Bordy, D Wendling, C Demougeot
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> The management of the chronic inflammatory rheumatisms has dramatically evolved in the last decade with a concept of "treat to target". The theory of a window of opportunity with more beneficial effects of an early intensive treatment is supported by several evidences. The positive impact of an early treatment with a TNFα blocker is expected but the place and the interest of non-steroidal anti-inflammatory treatments (NSAIDs) and glucocorticoids is not clear. <h3>Objectives</h3> The aim of this study was to evaluate the radiological outcomes after an early treatment during 21 days by Etanercept, or Naproxene, or Celecoxib, or Prednisone, or Diclofenac or Methotrexate in adjuvant induced arthritis in rats. <h3>Methods</h3> Adjuvant-induced arthritis (AIA) was induced in 6 weeks old male Lewis rats by injection of <i>Mycobacterium butyricum</i> in adjuvant at the basis of the tail. At the onset of arthritis, rats were daily treated with Naproxene (10 mg/kg/d i.p), or Diclofenac (5mg/kg i.p twice a day), or Celecoxib (3 mg/kg/d i.p) or Prednisone (10 mg/kg/d i.p), or Etanercept (10 mg/kg/3 days, s.c.), or Methotrexate (1mg/kg/3 days, s.c.), or saline solution (Vehicle), for 21 days. Arthritic score was daily monitored. At the end of treatment, paws9 radiological exam was performed with a BMA High Resolution Digital X Ray (40mV, 10mA). A score of 0 to 20 was determined for each paw using a grading scale modified from Ackerman <i>et al (1979)</i>. <h3>Results</h3> Compared to the Vehicle, all treatments significantly reduced (p&lt;0.001) arthritic score with a reduction of the arthritic score evaluated between 40% (for methotrexate) and 70% (for diclofenac) (figure 1. Compared to the vehicle, the radiographic score was improved by Naproxene, Diclofenac, Celecoxib, Glucocorticoids, Etanercept (p&lt;0.001) but not by methotrexate. Compared to Etanercept, Naproxene and diclofenac showed less radiological structural changes (p&lt;0.01) (figure 2). <h3>Conclusions</h3> Our study demonstrates for the first time that an early treatment with NSAIDs, excluding COX2 selective inhibitor, is more beneficial than Etanercept on the radiological damages in adjuvant induced arthritis. The close efficacy of all drugs on the arthritis score suggests that the beneficial impact of NSAID is not only driven by their impact on the systemic inflammation. NSAIDs should be used during the window of opportunity. <h3>Disclosure of Interest</h3> None declared
THU0567 Rapid improvement with tocilizumab in refractory and severe uveitic cystoid macular edema
Authors: N Vegas-Revenga, V Calvo-Río, N Palmou-Fontana, M Mesquida, A Adan, M Hernández, E Beltrán, E Valls, D Díaz-Valle, G Díaz-Soriano, M Hernández-Grafella, L Martínez-Costa, I Calvo, A Atanes, L Linares, C Modesto, E Aurrecoechea, M Cordero, L Domínguez-Casas, C Fernández-Díaz, J Hernández, M González-Gay, R Blanco
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> In uveitis, remission-inducing therapy with even more vigor than does rheumatology is mandatory. Since the eye is so much less forgiving of chronic inflammation than is the joint, with profound life-altering consequences. Cystoid macular edema (CME) is the leading cause of blindness in uveitis. <h3>Objectives</h3> To evaluate the rapid efficacy of Tocilizumab (TCZ) in refractory CME. <h3>Methods</h3> Multicentre study of 25 patients with CME due to non-infectious uveitis who had inadequate response to traditional treatment with corticosteroids and at least one conventional immunosuppressive drug including in most cases biological therapy (n=22). CME was defined as OCT &gt;300 μm. The outcome variables were the degree of inflammation, visual acuity, macular thickness. The results are expressed as mean±SD for normally distributed variables, or as median [IQR] when are not. Comparison of continuous variables was performed using the Wilcoxon test. <h3>Results</h3> 25 patients (17 women/8 men), mean age 33.6±18.9 years were studied. The associated diseases were: juvenile idiopathic arthritis (9), Behçet9s (7), Birdshot (4), idiopathic (4), sarcoidosis (1). The ocular pattern was: panuveitis (9), anterior uveitis (7), posterior uveitis (5) and intermediate uveitis (4). Most patients had bilateral involvement (24). Prior to TCZ they received: intraocular corticosteroids (22), iv. methylprednisolone (7), methotrexate (MTX) (19), cyclosporine A (CSA) (17), mycophenolate (4), azathioprine (2), leflunomide (2), cyclophosphamide (1), sulfasalazine (1), acetazolamide (1) and thalidomide (1). The biological used before TCZ were infliximab (8), adalimumab (19), etanercept (2), golimumab (2), rituximab (2), abatacept (3), anakinra (1) and daclizumab (1). TCZ administration schedule was 8 mg/kg/4 weeks iv. (n=23), every 2 weeks (1) and subcutaneously 162 mg/2 weeks (1). TCZ was used in monotherapy (13) or combined with conventional immunosuppressive drugs (12). Most of intraocular inflammation parameters showed a rapid improvement after TCZ onset (Table), with corticosteroid-sparing effect (15.9±13.6 to 8.5±5.17 mg; p=0.001). Remission was achieved in 8 patients and improvement in 17. After one month of therapy, no side effects were observed. <h3>Conclusions</h3> TCZ seems a rapid effective treatment in refractory uveitic CME. <h3>Disclosure of Interest</h3> None declared
AB1043 Rheumatoid factor isotypes – still an useful tool in the diagnosis of rheumatoid arthritis?
Authors: M Guerra, R Vieira, AP Cruz, T Videira, P Pinto
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Rheumatoid factor (RF) and anti-citrullinated peptide antibodies (ACPA) are key serologic markers in the diagnosis of Rheumatoid Arthritis (RA) included in the 2010 ACR/EULAR diagnostic criteria. Determination by enzyme-linked immunosorbent assay (ELISA) allows RF isotypes9 quantification (IgG, IgA and IgM), improving diagnostic accuracy <sup>1,2</sup>. <h3>Objectives</h3> To assess the clinical value of RF-IgG/IgA/IgM (ELISA) in the diagnosis of RA, in comparison to RF-IgM (nephelometry). <h3>Methods</h3> A population of RA outpatients fulfilling the 2010 ACR/EULAR diagnostic criteria was cross-sectionally evaluated. Data on demographic and clinical characteristics was collected. RF-IgG / IgA / IgM (ELISA, Orgentec®), RF-IgM (nephelometry, Siemens®) and ACPA-IgG (ELiA, ThermoFisher®) were measured. Values three times or more above the upper limit of normal were considered high-positive (in agreement to 2010 ACR/EULAR diagnostic criteria). <h3>Results</h3> A total of 87 patients (70.1% female) were included, with a mean (SD) age of 57.3 (12.29) years. Median time of disease evolution was 6 years, ranging from 0 to 37 years. Erosions were present in 50.6% (N=44). RF-ELISA was positive (at least one isotype increased) in 85.1% (N=74); the most frequent isotype was IgM (70.1%;N=61) and the most frequent combination was IgG, IgA and IgM positivity (46.0%;N=40) (table1). FR-nephelometry and ACPA were positive in 58.6% (N=51) and 47.1% (N=41), respectively. Comparing the two RF methods, 56.3% (N=49) were both RF-nephelometry and RF-ELISA positive; 28.7% (N=25) were RF-ELISA positive and RF-nephelometry negative, and only 2.3% (N=2) verified the opposite (p=0.001). As for RF high-positivity, 4.6% (N=4) of the 87 patients were only RF-nephelometry high-positive, 9.2% (N=8) only RF-ELISA high-positive and 34.5% (N=30) both high-positive (p&lt;0.001). In the RF-nephelometry negative population (N=36), ACPA and RF-ELISA were both positive in 11.1% (N=4). Only 8.3% (N=3) were solely ACPA positive and 58.3% (N=21) solely RF-ELISA positive, however without statistical significance. Considering the ACPA negative population (N=46), 32.6% (N=15) were both RF positive; 45.7% (N=21) were RF-ELISA positive and RF-nephelometry negative and 4.3% (N=2) the opposite, without a statistical significance. <h3>Conclusions</h3> ELISA is superior to nephelometry detecting RF in patients with RA, as also in quantifying high-positive values. <h3>References</h3> Routine measurement of IgM, IgG, and IgA rheumatoid factors: high sensitivity, specificity, and predictive value for rheumatoid arthritis. Swedler W, Wallman J, Froelich CJ, Teodorescu M. J Rheumatol, 1997 Jun;24(6):1037–44. Is rheumatoid factor still a superior test for the diagnosis of rheumatoid arthritis? Singh U, Vishwanath A, Verma PK et al. Rheumatol int, 2010 June; 30(8):1115–9. <h3>Disclosure of Interest</h3> None declared
Induction of cancer cell stemness by depletion of macrohistone H2A1 in hepatocellular carcinoma
Authors: Oriana Lo Re, Caterina Fusilli, Francesca Rappa, Matthias Van Haele, Julien Douet, Jana Pindjakova, Sura Wanessa Rocha, Illar Pata, Barbora Valčíková, Stjepan Uldrijan, Raymond S. Yeung, Christina Alves Peixoto, Tania Roskams, Marcus Buschbeck, Tommaso Mazza, Manlio Vinciguerra
Journal: Hepatology (2017)

Hepatocellular carcinomas (HCC) contain a subpopulation of cancer stem cells (CSCs), which exhibit stem cell-like features and are responsible for tumor relapse, metastasis, and chemoresistance. The development of effective treatments for HCC will depend on a molecular-level understanding of the specific pathways driving CSC emergence and stemness. MacroH2A1 is a variant of the histone H2A and an epigenetic regulator of stem-cell function, where it promotes differentiation and, conversely, acts as a barrier to somatic-cell reprogramming. Here, we focused on the role played by the histone variant macroH2A1 as a potential epigenetic factor promoting CSC differentiation. In human HCC sections we uncovered a significant correlation between low frequencies of macroH2A1 staining and advanced, aggressive HCC subtypes with poorly differentiated tumor phenotypes. Using HCC cell lines, we found that short hairpin RNA-mediated macroH2A1 knockdown induces acquisition of CSC-like features, including the growth of significantly larger and less differentiated tumors when injected into nude mice. MacroH2A1-depleted HCC cells also exhibited reduced proliferation, resistance to chemotherapeutic agents, and stem-like metabolic changes consistent with enhanced hypoxic responses and increased glycolysis. The loss of macroH2A1 increased expression of a panel of stemness-associated genes and drove hyperactivation of the nuclear factor kappa B p65 pathway. Blocking phosphorylation of nuclear factor kappa B p65 on Ser536 inhibited the emergence of CSC-like features in HCC cells knocked down for macroH2A1. Conclusion: The absence of histone variant macroH2A1 confers a CSC-like phenotype to HCC cells in vitro and in vivo that depends on Ser536 phosphorylation of nuclear factor kappa B p65; this pathway may hold valuable targets for the development of CSC-focused treatments for HCC. (Hepatology 2018;67:636-650).
Sorafenib (SOR) plus docetaxel (DOC) as first-line therapy in patients with HER2-negative metastatic breast cancer (MBC): A randomized, placebo-controlled phase II trial.
Authors: Frederik Marme, Bernd Gerber, Marcus Schmidt, Volker Jochen Moebus, Frank Gerhard Foerster, Eva-Maria Grischke, Matthias W. Beckmann, Dirk Strumberg, Erich Solomayer, Peter Klare, Christiane Windemuth-Kieselbach, Andreas Schneeweiss
Journal: Journal of Clinical Oncology (2014)

1072 Background: Anti-angiogenic therapy with the monoclonal anti-VEGF antibody Bevacizumab (Bev) in combination with chemotherapy increases overall response rates (ORR) and progression free survival (PFS) but without impact on overall survival. SOR, an anti-angiogenic multi-tyrosine kinase inhibitor (TKI) also targeting tumor growth directly, is approved for advanced renal cell and hepatocellular carcinoma. Three phase IIb trials (SOLTI-0701, NU07B1, AC01B07) have reported efficacy of SOR in combination with chemotherapy in MBC, even after prior Bev (AC01B07). As TKIs might have superior activity we conducted this trial in first-line MBC. Methods: Pts were randomized to DOC (75mg/m2 q3w) + either SOR (400 p.o. twice daily (BID)) or placebo. Following an amendment after the inclusion of 63 pts, the SOR starting dose was reduced to 400 mg/d for cycle 1 and 600 mg/d for cycle 2 with the option to increase the dose to 800 mg/d after the second cycle in the absence of > grade 1 toxicities. The planned sample size was 288, but due to slow accrual the study was closed early after 102 patients. The primary end point was progression free survival (PFS). Important secondary endpoints were overall response rate (ORR), duration of response, time to progression (TTP), overall survival (OS) and safety/tolerability. Here we report the data after 78 PFS events in 95 evaluable patients. Results: Median age was 57 years with 71.6% of patients being post-menopausal. 74.5 of patients had a positive estrogen receptor (ER) status and 47.1% and 48.0% of patients had a tumor grading 2 and 3, respectively. Overall, as of December 13th2013, the median PFS was 7.4 months with a median TTP of 7.9 months, a median duration of response of 8.9 months and an ORR of 47.1%. The corresponding median OS was 21.2 months. Grade 3 to 4 toxicities (> 5% of pts) included neutropenia (31%), lymphopenia (25%), leukopenia (25%), HFSR (19%), diarrhea (11%), febrile neutropenia (9%), and fatigue (8%). Conclusions: Final efficacy data including overall survival and detailed safety data will be presented by treatment arm. Comparative efficacy and safety data will also be presented by SOR dosing schedule. Clinical trial information: EUDRACT-Nr. 2008-001090-15.
Immunogenetic Studies of a Histocompatibility Hemagglutinogen (R-1) in the Rat<xref ref-type="fn" rid="FN2">2</xref>
Authors: Arthur E. Bogden, Paul M. Aptekman
Journal: JNCI Journal of the National Cancer Institute (1961)

These immunogenetic studies in the rat establish the control of the R-1 factor hemagglutinogen B by a dominant gene following simple Mendelian laws and show its relationship to the inheritance of susceptibility to tumor-tissue implantation. Rats segregating as R-1 negative in the F2 and backcross generations were not only able to resist R-1 positive tumor implantation, but immunization induced the specific anti-R-1 (B) hemagglutinin and its associated cytotoxic antibody. In contrast to the H-2 system in the mouse, the R-1 factor hemagglutinogen B is found not only in embryonic tissues but in the erythrocytes of R-1 positive rats of all ages. In addition, 17 rat strains were screened for the B hemagglutinogen. Six inbred rat strains were positive and 9 were negative. The randombred Wistar strain (90% R-1 positive) and the penbred Chocolate strain (88% R-1 positive) illustrate the heterogeneity expected of noninbred systems. Eight transplantable rat tumors were tested; 5 tumors contained the R-1 factor hemagglutinogen B.
Comment on Bloomgarden et al. Is HbA1c &amp;lt;7% a Marker of Poor Performance in Individuals &amp;gt;65 Years Old? Diabetes Care 2017;40:526–528
Authors: Leonard M. Pogach, David C. Aron
Journal: Diabetes Care (2017)

Bloomgarden et al. (1) make four claims in their counterpoint to our proposal (2): 1 ) we confounded hypoglycemia with “good” glycemic control; 2 ) “good” glycemic control benefits all older adults, even those with serious comorbidities, making our measure harmful; 3 ) effects of anemia and kidney disease on HbA1c invalidate the measure; 4 ) newer drugs make this issue moot. We disagree.

First, serious hypoglycemia is a limiting factor in diabetes treatment, especially with insulin. Its prevention has been identified as a public health issue by the Department of Health and Human Services (3). It has been recommended that the current HbA1c <8% performance measure applicable to older adults be “revisited” to stratify by medication, include comorbid conditions, and incorporate a balancing measure of <7%. Our measure is …
SAT0427 Asas health index: validity and reliability in argentinean patients with spondyloarthritis
Authors: VM Duarte, U Kiltz, V Navarro-Compán, N Lloves, G Crespo Amaya, L Ferreyra, C Orozco, EE Schneeberger, H Maldonado Ficco, D Baenas, F Colombres, M Mamani, JA Maldonado Cocco, E Soriano
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Objectives</h3> The aim of the study was to translate and validate the ASAS Health Index (ASAS-HI) for Argentinean patients with spondyloarthritis. <h3>Methods</h3> Translation was done using a forward-backward procedure and qualitative interview were done with the translation. Patients fulfilling ASAS classification criteria for either axial (axSpA) or periphereal SpA (pSpA) were included to test psychometric properties. Test-retest reliability was assessed by intraclass correlation coefficient (ICC) in patients without treatment changes (stable disease state). In patients who required therapeutic modifications due to changes of disease activity, responsiveness was evaluated using a standardized response mean (SRM). Construct validity against other health outcomes was evaluated by Spearman correlation. Internal consistency (Cronbach-alfa) and discriminative ability between ASAS-HI and ASDAS were assessed. <h3>Results</h3> Translation into Argentinean Spanish was accepted with minor changes. Fifty two patients were recruited [65% male, mean (SD) age 39. 5 (12.5) years and median (IQR) disease duration 72 (45–138) months]. Most of the patients had axSpA diagnosis (AS: 26, nr-axSpA: 18) while the rest had pSpA (8). The total score of the ASAS-HI was 7.4 (SD: 4.4), BASDAI: 4.4 (SD: 2.7), BASFI: 4.0 (SD: 3.1), ASDAS-CRP: 2.4 (SD: 0.9). Test-retest reliability (n: 20) was good ICC: 0.88 (95%IC 0.76 to 0.98). Sensitivity to change was tested in 13 patients and SMR was -0.61 for those patients receiving TNF inhibitors (n: 11). Convergent validity ranged as hypothesized with Spearman correlations from low (age: 0.27) to good (pain: 0.65), (table 1). The ASAS-HI discriminated well between patients with different stages of disease activity and function irrespective of the measure applied (ASDAS, BASDAI and BASFI) (table 2). The internal consistency according to Cronbach9s alfa was 0.81. <h3>Conclusions</h3> The Argentinean version of the ASAS-HI was comprehensive and reliable by patients with SpA. The ASAS-HI is a valid tool for assessing overall functioning and health in spondyloarthritis. <h3>References</h3> The ASAS Health Index (ASAS HI)a new tool to assess the health status of patients with spondyloarthritis, Clin Exp Rheumatol 2014;32:S105-S108. <h3>Disclosure of Interest</h3> V. Duarte Employee of: Novartis Argentina, U. Kiltz: None declared, V. Navarro-Compán: None declared, N. Lloves: None declared, G. Crespo Amaya: None declared, L. Ferreyra: None declared, C. Orozco: None declared, E. Schneeberger: None declared, H. Maldonado Ficco: None declared, D. Baenas: None declared, F. Colombres: None declared, M. Mamani: None declared, J. Maldonado Cocco: None declared, E. Soriano: None declared
THU0066 Osteoclast differentiation gene expression profiling reveals ccl4 mediates rankl-induced osteoclast migration
Authors: W Xuan, X Feng, Y Shi, F Wang, M Zhang, W Tan
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> The migration of osteoclast from circulation and bone marrow into bone surface has suggested as a novel therapeutic point for bone erosion in RA. <h3>Objectives</h3> We explored the mechanisms involved in osteoclast migration. <h3>Methods</h3> Gene expression profiling was identified by microarray analysis and validated by Real-time PCR during differentiation of bone marrow-derived macrophages (BMMs) into osteoclast (OCs). RANKL induced osteoclast precursor cell line RAW264.7 migration and invasion in the presence and absence of anti-CCL4 antibody was measured in vitro. Intracellular signaling pathway was assessed by Western blotting. Osteoclast formation was identified by TRAP staining. <h3>Results</h3> A panel of 11 chemokines signal was significant increase in osteoclastic differentiation of BMMs by Microarray. High expression of CCL4 was validated in primary BMMs and RAW264.7 cell line during differentiated into OCs. RANKL induced osteoclast precursor cell migration and invasion was decreased upon addition of anti-CCL4 antibody. OCs formation and OCs related genes expression were not affected by CCL4 inhibition. Neutralization of CCL4 promoted the PI13K phosphorylation at 45 to 60min after RANKL stimulation in RAW264.7. <h3>Conclusions</h3> CCL4 regulates RANKL-induced OCs migration, suggesting that CCL4 inhibition could be bone protective in RA <h3>References</h3> Boyce BF: Advances in the regulation of osteoclasts and osteoclast functions. Journal of dental research 2013, 92(10):860–867. Crotti TN, Dharmapatni AA, Alias E, Haynes DR: Osteoimmunology: Major and Costimulatory Pathway Expression Associated with Chronic Inflammatory Induced Bone Loss. Journal of immunology research 2015, 2015:281287. Boyle WJ, Simonet WS, Lacey DL: Osteoclast differentiation and activation. Nature 2003, 423(6937):337–342. <h3>Acknowledgements</h3> Support for this work was obtained from the National Natural Science Foundation of China (NSFC): 30701129 (WT), 30901332 (FW), 81172845 (WT), 81273294 (MZ), National Natural Science Foundation of Jiangsu province: BK2011851 (WT), BK2012875 (MZ), the special project of clinical medicine from Jiangsu province: BL2013034 (MZ), A Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD), and scholarship from Asia Pacific League of Associations for Rheumatology (APLAR) and International League of Associations for Rheumatology (ILAR) (WT). <h3>Disclosure of Interest</h3> None declared
Checkpoint blockade for metastatic melanoma and Merkel cell carcinoma in HIV-positive patients
Authors: M.V. Heppt, M. Schlaak, T.K. Eigentler, K.C. Kähler, F. Kiecker, C. Loquai, F. Meier, D. Tomsitz, N. Brenner, A.C. Niesert, R. Thonke, A. Hauschild, C. Berking
Journal: Annals of Oncology (2017)
SP0181 Failure of natural regulatory autoantibody network as cause of autoimunity
Authors: OC Marques
Journal: Annals of the Rheumatic Diseases (2017)

The role of autoantibodies in normal physiology is under debate. In investigating autoantibody (aab) concentrations against G protein-coupled receptors (GPCR) in different autoimmune diseases, we found both increased and decreased aab concentrations, which suggests physiological anti-GPCR aab levels may be dysregulated in autoimmune diseases. During our analysis of healthy donor antibodies to 16 GPCR and 15 growth factors and related signaling molecules, we discovered several clusters of correlations in these antibody concentrations. Possible functional interactions of these 31 autoantibody target molecules were studied by STRING, DAVID, and enriched Gene Ontology analyses. Through these analyses, a network of GPCR, growth factors, and signaling molecules with endothelin receptor type A (ETAR) in the center was revealed. Migration and locomotion were suggested to be the most significant functions regulated by the antibody network. Accordingly, IgG from healthy donors induced both IL-8 expression by peripheral blood mononuclear cells (PBMCs) as well as migration of neutrophils and tumor cells, which was specifically diminished by the ETAR inhibition. These data supports a change of paradigm from the notion that autoantibodies are an exclusive autoimmune phenomenon to the concept that they are part of the normal human physiology, which become dysregulated under the influence of different factors and subsequently cause autoimmune diseases. <h3>Disclosure of Interest</h3> None declared