tbuckley/cabot-search huggingface dataset:
AB0602 Antiphospholipid syndrome components in patients with coronary heart disease
Authors: M. Nazarova, M. Stanislavchuk, L. Burdeina
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Antiphospholipid antibodies (aPL), such as anticardiolipin antibodies (aCL), are the immunological markers of the antiphospholipid syndrome (APS).<sup>1</sup> The aPL are found in association with venous and/or arterial thrombosis. Myocardial infarction (MI) is usually related to atherosclerosis and thrombosis of coronary arteries.<sup>2</sup> The clinical significance of aPL in MI, however, has not yet been well established. <h3>Objectives</h3> To evaluate the presence and levels of aPL in patients with history MI. <h3>Methods</h3> 50 patients (100% male) with average age 49.5±6.09 (M±SD) years with history of MI were examined. Serum IgG aPL (anti-cardiolipin, -phosphatidylserine, phosphatidylinositol, -phosphatidylacetate) were determined by enzyme-linked immunosorbent assay (ELSSA). <h3>Results</h3> IgG isotype aPL were detected in 26 (52%) patients with the history of MI and 24 patients were negative. The average age (M±SD) of aPL positive patients was 44.1±5.00 years and of aPL negative patients was 47.7±4.83 years (p&lt;0.01). The difference comprises more than 3,5 years. Patients with recurrent MI (two and more) had higher level of IgG aPL, then patients with one MI (18,0±7,53 v.s. 11,5±4,21 GPL-U/ml). The difference is significant (p&lt;0.05). <h3>Conclusions</h3> Determined younger age of the first MI in aPL positive patients and higher level of IgG aPL in patients with recurrent MI indicate the possible involvement of the autoimmune factor in the pathogenesis of MI. This proves the necessity for further research in this direction. <h3>References</h3> [1] Miyakis S, Lockshin MD, Atsumi T, et al. International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J Thromb Haemost. 2006;4:295–306. [2] Anand SS, Islam S, Rosengren A, Franzosi MG, Steyn K, Yusufali AH, et al. Patterns of alcohol consumption and myocardial infarction risk: observations from 52 countries in the INTERHEART case-control study. Eur Heart J2008;29;932–940. <h3>Disclosure of Interest</h3> None declared
AB0059 Fetuin-a: clinical and laboratory associations in women with rheumatoid arthritis
Authors: E. Papichev, L. Sivordova, J. Polyakova, Y. Akhverdyan, B. Zavodovsky, T. Rogatkina
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> <i>Fetuin-A</i> is an acute-phase protein with contradictory effects. It is well kno<i>wn that fetuin-A</i> low levels are associated with calcification and higher risk of cardiovascular diseases and its level is downregulated by pro-inflammatory cytokines.<sup>1</sup> Nevertheles, it was shown, that fetuin-A induces synthesis of pro-inflammatory cytokines in adipocites and macrophages.<sup>2</sup> <h3>Objectives</h3> To investigate the level of fetuin-A in women with rheumatoid arthritis (RA). <h3>Methods</h3> At baseline we measured fetuin-A level, femoral neck, total hip and L<sub>I</sub>-L<sub>IV</sub> BMD by DXA in 110 women with RA (mean age 54,5±12,6; hereinafter M±Std.dev.) and 30 healthy controls. Serum CRP and ESR were measured to assess inflammation. DAS28 was calculated to determine RA activity. The diagnosis of osteoporosis was set according to the recommendations of world health organisation – T-score≤−2,5 for patients without glucocorticoid therapy in anamnesis, T-score≤−1,5 for patients treated with glucocorticoid for 3 months in anamnesis or with an osteoporotic fracture in anamnesis. Fetuin-A in serum was determined by enzyme-linked immunosorbent assay. <h3>Results</h3> Mean concentration of fetuin-A in group with RA was 765,69±120,64 ug/ml, which was lower than of healthy controls – 812,95 ug/ml (p=0,0438). Secondary osteoporosis was revealed in 52 patients (47%) with RA with mean level of fetuin-A at 733,7±18,83 ug/ml vs. 794,36±12,83 ug/ml (p=0,0078) of 58 (53%) non-osteoporotic patients. Moderate negative correlations were observed between fetuin-A and DAS28 (r=-0,4334; p&lt;0,001), fetuin-A and CRP (r=-0,3148; p&lt;0,001), fetuin-A and ESR (p=-0,344; p&lt;0,001). Mean concentrations of fetuin-A were significantly different between the subgroups with moderate (3,2≤DAS28&lt;5,1) and high disease activity (5,1≤DAS28) of RA patients and healthy controls: 742,41±12,07 ug/ml vs. 812,95 ug/ml (p=0,0021) and 663,9±39,14 ug/ml vs. 812,95 ug/ml (p&lt;0,001). <h3>Conclusions</h3> Our study confirm<i>s</i> that lower levels of fetuin-<i>A</i> are associated with higher activity of RA and with the loss of bone mineral density. <h3>References</h3> [1] Brylka L, et al. Calcif Tissue Int2012;93(4):355–364. [2] Stefan N, et al. Diabetes2008;57(10):2762–2767. <h3>Disclosure of Interest</h3> None declared
P117 Visfatin down-regulates growth promoting lncrna H19 during osteogenic differentiation of mesenchymal stromal cells
Authors: DM Küppers, L Tsiklauri, M-L Hülser, K Frommer, S Rehart, U Müller-Ladner, E Neumann
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Career situation of first and presenting author</h3> Student for a master or a PhD. <h3>Introduction</h3> Osteoarthritis (OA) and osteoporosis are destructive bone diseases causing chronic pain and leading to disability. Mesenchymal stromal cells (MSC) are essential to bone health and tissue repair. Adipokines such as visfatin alter the osteogenic potential of MSCs and contribute to the loss of bone homeostasis. Long non-coding RNA H19 is one of the first lncRNAs discovered and relevant for distinct processes, e.g. during embryonic growth and tumor formation. lncRNAs interact directly with DNA, RNA as well as proteins, modulating transcription, protein expression and protein function. H19 upregulation was shown in osteogenic differentiation of MSCs.<sup>1</sup> H19 increases the osteogenic potential via TGFβ1 and Wnt/β-catenin pathways.<sup>2 3</sup> <h3>Objectives</h3> To investigate the influence of visfatin on H19 expression during osteogenesis. <h3>Methods</h3> Human MSCs from healthy donors (hMSC) and primary human MSCs from osteoarthritis patients (phMSC) after knee replacement surgery were treated with differentiation medium to induce osteogenic differentiation (OD). Matrix mineralization (MM) was quantified after 21 days by Alizarin Red. H19 expression by realtime PCR and IL-6 production by ELISA were measured. <h3>Results</h3> lncRNA H19 was up-regulated during OD. Although the H19 upregulation was not altered by co-stimulation with resistin, leptin or TNFα, visfatin co-stimulation during OD down-regulated H19 expression up to 10-fold as compared to unstimulated MSCs. The effect was significant in phMSCs at two of three measured time points (day 7 p=0.03; day 14 p=0.002, n=3) and in hMSCs at day 14 (p=0.0003, n=4). Visfatin co-stimulation of MSCs in OD increased MM, as well as IL-6 levels. However, TNF did not alter H19 expression or increase MM. <h3>Conclusions</h3> Visfatin co-stimulation during osteogenesis down-regulated lncRNA H19 expression, indicating a loss of the growthpromoting effects of lncRNA H19 in affected areas of destructive bone disease. This regulatory effect was specific to visfatin and did not occur upon co-stimulation with other adipokines or inflammatory stimuli such as TNF supporting a TNF-independent effect of visfatin. <h3>References</h3> Wang, L. Differential expression of long noncoding ribonucleic acids during osteogenic differentiation of human bone marrow mesenchymal stem cells. <i>Int. Orthop.</i> 2015;39:1013–1019. Huang, Y. Long Noncoding RNA H19 Promotes Osteoblast Differentiation Via TGF-?1/Smad3/HDAC Signaling Pathway by Deriving miR-675. <i>Stem Cells</i> 2015;33:3481–3492. Liang, W.-C. H19 activates Wnt signaling and promotes osteoblast differentiation by functioning as a competing endogenous RNA. <i>Sci. Rep.</i> 2012;6:20121. <h3>Disclosure of Interest</h3> None declared.
SAT0413 The trend of incidence rate, frequency, outcomes and hla phenotype of reactive arthritis and uveitis in japanese patients with bladder cancer following intravesical bcg therapy: a 20-year, two-centre retrospective study
Authors: Y. Nakatani, Y. Taniguchi, S. Inotani, H. Nishikawa, T. Karashima, Y. Yoshinaga, Y. Terada
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Intravesical instillation of Bacillus Calmette-Guerin (iBCG) is used as an effective immunotherapy of bladder cancer. However it may have, as adverse event, a reactive arthritis (ReA) and the frequencies are known as about 0.5% to 1% in Western countries. <h3>Objectives</h3> To evaluate the trend of incidence rate, frequency and HLA phenotype of reactive arthritis (ReA), uveitis and other adverse events in Japanese patients with bladder cancer following iBCG therapy. <h3>Methods</h3> The clinical findings of Japanese patients who received iBCG (n=555 [250 and 305 in Kochi Medical School Hospital and Kurashiki Medical Centre, respectively]) for bladder cancer from March 1997 to February 2017 were retrospectively assessed, with specific attention to patients with ReA and uveitis. HLA phenotypes of patients with ReA were also looked. Moreover, iBCG-induced ReA diagnosed from 1997 to 2007 were compared with that from 2007 to 2017. Finally, outcomes of ReA patients were also evaluated. <h3>Results</h3> Patients' mean age was 72±10 years and male/female ratio was 438/117. Fever, haematuria, and dysuria were presented in 91/555 (16.4%), 121/555 (21.8%), and 196/555 (35.3%), respectively of all enrolled patients. Of the 555 cases, ReA and uveitis were revealed in 11/555 (2.0%) and 4/555 (0.7%). The protocol of iBCG therapy was stable over the 20 years. Notably, HLA-B27, -B35, -B39 and -B51 positivity was more frequent in ReA patients (9.1%, 36.3%, 36.3% and 63.6%, respectively) (p&lt;0.05) than in healthy subjects without ReA (0.3%, 8.3%, 4.0% and 9.1%, respectively). All 4 cases with uveitis had ReA, and showed positive HLA-B27 (25%), -B39 (50%) and -B51 (25%). Moreover, the overall incidence of iBCG-ReA was not different between from 1997 to 2007 and 2007 to 2017. Finally, all ReA patients did not progress to chronic type and spondyloarthritis (SpA) as outcomes. <h3>Conclusions</h3> The 2.0% iBCG-induced ReA frequency in Japanese patients exceeds that in Western countries, and its incidence has been stable and all ReA did not progress chronic type and SpA over the last 20 years. HLA phenotype, especially HLA-B51 and -B39 alleles in addition to -B27, may be a risk factor in iBCG-induced ReA in Japanese patients. <h3>Disclosure of Interest</h3> None declared
AB0249 Influence of autoantibodies profile on disease activity measurement in a colombian cohort of rheumatoid arthritis patients
Authors: J.B. Florez, G. Quintana, P. Mendez, P. Coral
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Traditionally, the role of Rheumatoid Factor (RF) and/or Anti-citrullinated antibodies (ACCP) presence have characterised for diagnosis and prognosis of Rheumatoid Arthritis (RA). However, Anti-nuclear antibodies (ANA) are not routinely measured for the diagnosis of the disease or RA prognosis establishment during first appointment. Recently, evidence showed that positive ANA titles could be considered as poor prognosis factor for RA, and also a higher probability of developing immunogenicity against biologic therapies. <h3>Objectives</h3> To compare the disease activity measurement from a Colombian cohort of patients with RA, based on their auto-antibodies profile. <h3>Methods</h3> The study used a cohort of Colombian patients with RA. A database was developed using the information from the clinical records. The data included were: RF, ACCP, ANA, and the disease activity measured using DAS-28 ESR. Disease activity results were obtained in the following periods of time: 0, 3, 12, 24 and 36 months. Patients were classified based on the different autoantibody profiles (RF/ACCP/ANA:—, +–, -+-, –+, ++-, +-+, -++, +++). Mean DAS-28 ESR results from each period of time were calculated. Also mean weekly Methotrexate (MTX) dose was calculated for each profile. Mean differences between initial, and the follow-up period were calculated using Kruskal-Wallis test. Statistical analysis was made using STATA 12.0 software. <h3>Results</h3> 635 patients with RA were included. 32% of them were men, and 68% were women. Mean age was 54.3 years. The most prevalent profile was +++with 118 patients, and the less frequent was +–. Patients with +++profile had the best response to treatment over time, but also they required more MTX dose. Less response during time was observed with +– profile, however the amount of patients from these group was relatively low. As it was expected,—profile patients required less weekly MTX dose (9.26 mg). It was interesting that patients with –+profile present a worst outcome based on DAS-28 activity, and less response to the treatment. <h3>Conclusions</h3> Results from the study suggest the importance of including the measurement of ANA titles in the initial categorization and follow-up of patients with RA. The presence of ANA seems to have a worst prognosis. ANA co-existence with ACCP appear to have a worst outcome, compared to ++- or +-+profile. Auto-antibody profile in RA could direct the best therapeutic strategy for each patient. Validation of these results are required based on other cohorts. <h3>Reference</h3> [1] Sanmarti R, Gomez-Puerta JA. Biomarcadores en la artritis reumatoide. Reumatol Clin. 2011;6(S3):S25–S28. <h3>Disclosure of Interest</h3> None declared
Aberrant FGFR Tyrosine Kinase Signaling Enhances the Warburg Effect by Reprogramming LDH Isoform Expression and Activity in Prostate Cancer
Authors: Junchen Liu, Guo Chen, Zezhen Liu, Shaoyou Liu, Zhiduan Cai, Pan You, Yuepeng Ke, Li Lai, Yun Huang, Hongchang Gao, Liangcai Zhao, Helene Pelicano, Peng Huang, Wallace L. McKeehan, Chin-Lee Wu, Cong Wang, Weide Zhong, Fen Wang
Journal: Cancer Research (2018)

The acquisition of ectopic fibroblast growthfactor receptor 1 (FGFR1) expression is well documented in prostate cancer progression. How it contributes to prostate cancer progression is not fully understood, although it is known to confer a growth advantage and promote cell survival. Here, we report that FGFR1 tyrosine kinase reprograms the energy metabolism of prostate cancer cells by regulating the expression of lactate dehydrogenase (LDH) isozymes. FGFR1 increased LDHA stability through tyrosine phosphorylation and reduced LDHB expression by promoting its promoter methylation, thereby shifting cell metabolism from oxidative phosphorylation to aerobic glycolysis. LDHA depletion compromised, whereas LDHB depletion enhanced the tumorigenicity of prostate cancer cells. Furthermore, FGFR1 overexpression and aberrant LDH isozyme expression were associated with short overall survival and biochemical recurrence times in patients with prostate cancer. Our results indicate that ectopic FGFR1 expression reprograms the energy metabolism of prostate cancer cells, representing a hallmark change in prostate cancer progression.Significance: FGF signaling drives the Warburg effect through differential regulation of LDHA and LDHB, thereby promoting the progression of prostate cancer.Graphical Abstract: http://cancerres.aacrjournals.org/content/canres/78/16/4459/F1.large.jpg Cancer Res; 78(16); 4459-70. ©2018 AACR.
THU0212 Reinvestment of biosimilar savings: what are the best options?
Authors: M. Martin, R. Campbell, J. Jacob
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Biosimilars are becoming available for many of the biologic compounds in rheumatoid arthritis (RA). Biosimilars provide similar benefit at a reduced cost, therefore generating potential savings to the health care system. <h3>Objectives</h3> To investigate whether it is most beneficial to reinvest biosimilar savings to treat additional RA patients or whether this same budget would be more beneficially spent on alternative treatments from a UK payer perspective. <h3>Methods</h3> We developed a model to first estimate the savings obtained from using biosimilars from a UK National Health Service (NHS) perspective. Then we identified five treatment alternatives, in addition to RA: melanoma, hepatitis C (HepC), multiple sclerosis (MS), Duchenne's disease (MD), and non-small cell lung cancer (NSCLC). These indications were considered because of their burden of illness, high cost but high efficacy treatments being available which are associated with investment pressures. The treatments selected were: ataluren (MD), natalizumab (MS), pembrolizumab (melanoma), crizotinib (NSCLC), sofosbuvir +ribavirin (HepC), and etanercept biosimilar. We estimated the health gain (expressed as QALYs) that could be obtained from treating the patients in the four indications of interest using the available savings to identify the most cost-effective way to spend the savings. Data on QALY gains were obtained from published sources, mostly HTA assessments. <h3>Results</h3> Based on a biologics expenditure of ~£430 million, we estimated that ~£5 million in savings would be generated over a 5 year period. Based on the outcome of QALY maximisation, over a 5 year period, biosimilar savings in the UK are best spent on treatments in hepatitis C, followed by NSCLC and melanoma. Re-investment in an RA biosimilar only came in 5th place, before cystic fibrosis. <h3>Conclusions</h3> In a country like the UK, where patients have ready access to biologicals, the savings from prescribing biosimilars can be better spent, if QALY maximisation is desired, on non-RA therapies where over a 5 year period more QALYs are generated. On the basis of the research, payers should consider the potential to reinvest biosimilar savings in disease areas with higher QALY yields. <h3>Disclosure of Interest</h3> None declared
Brain Metastasis of Medullary Thyroid Carcinoma Without Macroscopic Calcification Detected First on 68Ga-Dotatate and Then on 18F-Fluoride PET/CT
Authors: Paulo Schiavom Duarte, José Flávio Gomes Marin, José Willegaignon De Amorim De Carvalho, Marcelo Tatit Sapienza, Carlos Alberto Buchpiguel
Journal: Clinical Nuclear Medicine (2018)

We report a case of a medullary thyroid carcinoma noncalcified brain metastasis characterized on Ga-dotatate PET/CT but not on an F-fluoride PET/CT performed 1 month later. Subsequent F-fluoride PET/CT studies performed 7 and 19 months after the Ga-dotatate PET/CT study demonstrated focal uptake in the metastasis. The CT images of the last PET/CT study also depicted a small focus of calcification beginning in the metastatic site.
Contributions by<i>MC1R</i>Variants to Melanoma Risk in Males and Females
Authors: Judith Wendt, Christoph Mueller, Sabine Rauscher, Ingrid Fae, Gottfried Fischer, Ichiro Okamoto
Journal: JAMA Dermatology (2018)

<h3>Importance</h3> Recently, the red hair variants of<i>MC1R</i>were found to contribute differently to pigmentation phenotype in males and females. <h3>Objective</h3> To investigate the role of these variants in melanoma risk in males and females separately because carriers of the red hair variants of<i>MC1R</i>are at increased risk of melanoma. <h3>Design, Setting, and Participants</h3> In this hospital-based, case-control study, we evaluated the effect of<i>MC1R</i>and melanoma risk for males and females separately by performing multivariate logistic regression analyses. <h3>Main Outcomes and Measures</h3> Association of<i>MC1R</i>variants and melanoma risk in males and females. <h3>Results</h3> A total of 905 females (473 melanoma cases, 432 controls) and 886 males (518 melanoma cases, 368 controls) were included in the analyses. The mean (SD) age of the study population was 59.2 (15.6). In females, carrying any<i>MC1R</i>red hair variants remained an independent risk factor of melanoma in a multivariable analysis (adjusted odds ratio [OR], 2.19 [95% CI, 1.60-2.99]), whereas in males, only signs of actinic skin damage (lentigines on the back [OR, 2.56; 95% CI, 1.47-4.45;<i>P</i> = .001] and the hands [OR, 2.31; 95% CI, 1.24-4.29;<i>P</i> = .008] and wrinkling on the neck [OR, 2.17; 95% CI, 1.23-3.82;<i>P</i> = .007]) and sunburns (OR, 1.65; 95% CI, 1.12-2.42;<i>P</i> = .01) remained significant risk factors. <h3>Conclusions and Relevance</h3> <i>MC1R</i>variants contribute differently to melanoma risk in males and females. This could be helpful to better classify melanoma risk factors between the sexes.
Integrated Genomic Classification of Melanocytic Tumors of the Central Nervous System Using Mutation Analysis, Copy Number Alterations, and DNA Methylation Profiling
Authors: Klaus G. Griewank, Christian Koelsche, Johannes A.P. van de Nes, Daniel Schrimpf, Marco Gessi, Inga Möller, Antje Sucker, Richard A. Scolyer, Michael E. Buckland, Rajmohan Murali, Torsten Pietsch, Andreas von Deimling, Dirk Schadendorf
Journal: Clinical Cancer Research (2018)

Purpose: In the central nervous system, distinguishing primary leptomeningeal melanocytic tumors from melanoma metastases and predicting their biological behavior solely using histopathologic criteria may be challenging. We aimed to assess the diagnostic and prognostic value of integrated molecular analysis.Experimental Design: Targeted next-generation sequencing, array-based genome-wide methylation analysis, and BAP1 IHC were performed on the largest cohort of central nervous system melanocytic tumors analyzed to date, including 47 primary tumors of the central nervous system, 16 uveal melanomas, 13 cutaneous melanoma metastases, and 2 blue nevus-like melanomas. Gene mutation, DNA-methylation, and copy-number profiles were correlated with clinicopathologic features.Results: Combining mutation, copy-number, and DNA-methylation profiles clearly distinguished cutaneous melanoma metastases from other melanocytic tumors. Primary leptomeningeal melanocytic tumors, uveal melanomas, and blue nevus-like melanoma showed common DNA-methylation, copy-number alteration, and gene mutation signatures. Notably, tumors demonstrating chromosome 3 monosomy and BAP1 alterations formed a homogeneous subset within this group.Conclusions: Integrated molecular profiling aids in distinguishing primary from metastatic melanocytic tumors of the central nervous system. Primary leptomeningeal melanocytic tumors, uveal melanoma, and blue nevus-like melanoma share molecular similarity with chromosome 3 and BAP1 alterations, markers of poor prognosis. Clin Cancer Res; 24(18); 4494-504. ©2018 AACR.
A harmonised European training syllabus for thoracic surgery: report from the ESTS/ERS task force group
Authors: Gilbert Massard, Nathalie Tabin, Sharon Mitchell, Hasan Batirel, Alessandro Brunelli, Stefano Elia, Anna Frick, Martin Huertgen, Antoon Lerut, Laureano Molins, Kostas Papagiannopoulos, Dragan Subotic, Paul van Schil, Gonzalo Varela, Dirk van Raemdonck
Journal: European Respiratory Journal (2018)

As has been reported for respiratory medicine, a high variance exists among European countries in the content and modes of delivery for specialty training in thoracic surgery. According to a survey by the Union Européenne des Médecins Spécialistes (UEMS; European Union of Medical Specialists) section of thoracic surgery conducted in 2013, disparities begin at the certifying body level: the specialist diploma is delivered by the ministry of health in half of the countries, and by various other authorities in the remaining countries [1]. Additionally, the designation of the specialty differs considerably: in 13 countries, thoracic surgery is practised as a monospecialty; in eight countries, it is combined with cardiac surgery; and in two countries (Belgium and Luxembourg), the designation does not exist. A harmonised European training syllabus for thoracic surgery is now available <http://ow.ly/xQMP30iZ50E>