tbuckley/cabot-search huggingface dataset:
THU0194 The role of enhanced liver fibrosis (ELF) score in patients with rheumatoid arthritis treated with methotrexate
Authors: J Swierkot, M Frankowski, M Skoczynska, A Starba, MS Gomulkiewicz, P Wojtala, M Bujak
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> MTX is still a basic medicament used in treatment of patients with RA. One of its adverse reaction is its hepatoxicity. Previous studies have established high diagnostic accuracy of the ELF score to assess hepatic fibrosis in chronic viral hepatitis and fatty liver disease. <h3>Objectives</h3> The aim of the research was the evaluation of the usefulness of ELF markings, by patients treated with MTX, as an indicator which shows potential liver damage. <h3>Methods</h3> In the research were analyzed results of 96 patients with RA treated with MTX. Average age of patients was 60 (19–85 years old), median of body mass was 70 kg (46–140), median of BMI was 26 (16–46). Average time of taking MTX were 4 years and median of the accumulated dose was 3140 mg (12,5–27400mg). Disease activity in the moment of evaluation, evaluated by DAS 28, was 4,3 (0,98–8,42). Achieved results ELF, PIIINP were correlated with body mass, BMI, dose of MTX, other illnesses (e.g. diabetes), taken nonsteroidal anti-inflammatory drugs and statins. In statistical analysis were used Pearson correlation and U Mann-Whitney test. <h3>Results</h3> The ELF values correlated with age, accumulated dose and DAS 28. Along with the increase of accumulated dose of MTX, disease activity and by older patients, were observed higher ELF values (the differences were statistically significant). The PIIINP values correlated with patients9 body mass, accumulated dose of MTX and disease activity, evaluated by DAS 28. The differences were statistically significant. Along with the increase of body mass, accumulated dose and DAS 28, were observed higher values of PIIINP. Patients with diabetes had statistically higher values of PIINP (average: 11.13, median: 11,38), than patients without diabetes (average: 8.06, median: 7.15). There was observed no relationship between ELF and PIIINP results with taken nonsteroidal anti-inflammatory drugs and statins. <h3>Conclusions</h3> The ELF test, and one of its elements, PIIINP, may be useful in the evaluation of patients with higher probability of hepatotoxic effect of MTX. Special attention should be paid to older, obese patients, with diabetes, patients who take higher accumulated dose of MTX and with higher disease activity. <h3>Disclosure of Interest</h3> None declared
Rates of hippocampal atrophy and presence of post-mortem TDP-43 in patients with Alzheimer's disease: a longitudinal retrospective study
Authors: Keith A Josephs, Dennis W Dickson, Nirubol Tosakulwong, Stephen D Weigand, Melissa E Murray, Leonard Petrucelli, Amanda M Liesinger, Matthew L Senjem, Anthony J Spychalla, David S Knopman, Joseph E Parisi, Ronald C Petersen, Clifford R Jack, Jennifer L Whitwell
Journal: The Lancet Neurology (2017)
Endocrine and clinical responses to steroid sulfatase inhibition: Results from the first phase I trial in women with breast cancer
Authors: S. Stanway, A. Purohit, L. W. Woo, R. H. Wilson, F. Z. Stanczyk, N. Dobbs, P. Delavault, B. V. Potter, M. J. Reed, R. C. Coombes
Journal: Journal of Clinical Oncology (2006)

580 Background: Steroid sulfatase (STS) inhibitors, such as STX64, were developed to block the sulfatase pathway of estrogen formation in postmenopausal (PM) women with ER+ breast cancer. They act by blocking the formation of estrone from estrone sulfate but also inhibit the synthesis of androstenediol (Adiol), a steroid with potent estrogenic properties, which is derived from dehydroepiandrosterone sulfate (DHEAS). Methods: Fourteen PM women with ER+ metastatic breast cancer were recruited for this Phase I trial. All patients had received at least two previous lines of endocrine therapy and all but one had received prior chemotherapy. STX64 was administered orally as an initial test dose (5mg, n=9; 20mg, n=5) followed one week later by 3 two weekly cycles with dosing for 5 days followed by 9 days off treatment for 12–145 days. Blood samples were collected for the assessment of STS activity in peripheral blood lymphocytes and steroid concentrations. For some patients core biopsies of tumor samples were obtained before and during therapy. Results: Almost complete inhibition of peripheral STS (median 98%) and tumor (median 99%) activity was achieved on dosing with STX64. This was associated with significant decreases in the concentrations of estradiol, androstenediol (up to 90%) and unexpectedly, androstenedione (up to 86%). Monitoring the ratios of DHEAS:DHEA (a marker of STS inhibition) in patients receiving extended dosing revealed an inverse relationship between this ratio and serum Adiol concentrations. Three patients with prior adjuvant tamoxifen and aromatase inhibitor therapy showed stable disease for &gt;6 months with a favorable safety profile. Full results will be presented at the meeting. Conclusions: STX64 is a potent, well tolerated STS inhibitor. The unexpected finding that androstenedione levels decreased indicates that peripheral formation, rather than secretion from the adrenal cortex, in the major source of this steroid which is the main substrate for the aromatase. The disease stabilization seen for 4 patients, all of whom had previously progressed on aromatase inhibitor therapy, suggests that STS inhibitors should have considerable therapeutic potential for the treatment of breast cancer. [Table: see text]
FRI0707 Drug levels and antidrug antibodies in the development of paradoxical psoriasis and palmoplantar pustulosis
Authors: J Ruwaard, E van der Vlugt, P Brevet, L Berkhout, T Rispens, M Nurmohamed, GJ Wolbink
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> The pathogenesis of psoriasis and palmoplantar pustulosis induced by Tumor Necrosis Factor inhibitors (TNFi) is largely unknown. Only one study, in 9 inflammatory bowel disease patients, investigated the relation with infliximab drug levels in the development of psoriasis or palmoplantar pustulosis and demonstrated no relation with of trough concentrations in these events (1). However, psoriasis and palmoplantar pustulosis were not studied separately. <h3>Objectives</h3> To study the differences in drug levels and antidrug antibodies (ADA) of TNFi in rheumatoid arthritis (RA) and ankylosing spondylitis (AS) patients who developed de novo psoriasis, palmoplantar pustulosis and those who did not develop skin adverse events. <h3>Methods</h3> In this retrospective study data was collected from the observational cohorts of Reade of consecutive RA and AS patients in whom TNFi was started. At every visit, serum samples were collected. We quantified the samples before/on time of event of the patients who developed psoriasis or palmoplantar pustulosis, for the patients with no skin adverse events (control group) at 24 or 28 weeks. Drug levels and ADA were measured with an Enzyme-linked immunosorbent assay and antibody binding test respectively. <h3>Results</h3> A total of 830 TNFi naive patients with RA and AS were included, of whom 21 developed psoriasis (n=11) or palmoplantar pustulosis (n=10). These patients were only observed in the adalimumab and etanercept cohorts. Sixteen patients with an event and 585 patients in the control group had serum samples available to quantify drug levels and ADA. No statistical significant differences were found in drug levels of adalimumab and etanercept for both RA and AS patients (table 1). Moreover, no statistical significant differences were observed in the detection of ADA between the three groups. However, no ADA were detected in patients who developed psoriasis or palmoplantar pustulosis compared to the overall 13.9% of the RA patients and 25.5% in AS patients. <h3>Conclusions</h3> Patients who develop paradoxical psoriasis and palmoplantar pustulosis have adequate drug levels and no ADA were detected. <h3>References</h3> J Crohns Colitis 2015 Nov;9(11):982–7. <h3>Disclosure of Interest</h3> None declared
OP0122 Venous thromboembolism in systemic sclerosis: prevalence, risk factors and impact on survival
Authors: SR Johnson, N Hakami, Z Ahmad, DN Wijeysundera
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Systemic sclerosis (SSc) is characterized endothelial dysfunction and vasculopathy, which may result in thrombosis. Venous thromboembolism (VTE) is a vascular phenomenon that includes deep vein thrombosis (DVT) and pulmonary embolism (PE). <h3>Objectives</h3> To evaluate the epidemiology of VTE in SSc, specifically cumulative incidence, risk factors and impact of VTE on survival. <h3>Methods</h3> We conducted a cohort study of patients who fulfilled the ACR–EULAR classification criteria for SSc attending the Toronto Scleroderma Program 1970–2017. DVT was defined as the presence of thrombus on doppler ultrasound of either upper or lower extremity. PE was defined as the presence of thrombus on CT angiogram of the thorax. Time to all-cause mortality was evaluated in Kaplan Meier and Cox models. <h3>Results</h3> 1181 subjects (971 (82%) female, 210 (18%) male) were included. There were 40 (3.4%) VTE events. The cumulative incidence of VTE was 2.7 (95% CI 1.9, 3.7) per 1000 patient years. The presence of ILD, PAH, ScL70 antibody, anticardiolipin antibody, coronary artery disease, diabetes mellitus and PVD occurred more frequently in subjects who developed VTE. On multivariate logistic regression PAH (OR 3.77 (96%CI 1.83, 8.17), ScL70 antibodies (OR 2.45 95% CI 1.07, 5.30), anticardiolipin antibodies (OR 5.70 (95% CI 1.16, 21.2) and PVD (OR 5.31 (95% CI 1.99, 12.92) were independent predictors of VTE. Subjects with ILD more frequently experienced DVT (RR 2.85 95% CI (1.08, 7.54) but not PE (RR 1.82 (95% CI 0.89, 3.70). There were 440 deaths. There was no significant difference in survival between those with and without VTE (HR 1.6 (95% CI 0.70, 1.92). Only the presence of ILD (HR 1.54 (95% CI 1.27, 1.88) or PAH (HR 1.35 (95% CI 1.10, 1.65) remained independent predictors of mortality. <h3>Conclusions</h3> The risk of VTE in SSc is not increased, as the incidence of VTE in SSc is comparable to the general population. The presence of PAH, PVD, ScL70 and anticardiolipin antibodies are risk factors for VTE in SSc. VTE does not independently affect SSc survival. <h3>Acknowledgements</h3> Dr. Johnson is supported by the Canadian Institutes of Health Research. <h3>Disclosure of Interest</h3> None declared
SAT0349 Evaluation of standard swallowing function in assessing aspiration risk for patients with systemic sclerosis
Authors: L Yan, P Yunfeng, Y Mengru
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Swallowing dysfunction is a common symptom of systemic sclerosis, which usually induce aspiration pneumonia to aggravate lung progress. It is necessary to screen swallowing disorders effectively at an early stage. <h3>Objectives</h3> To investigate the value of standard swallowing function assessment (SSA) in aspiration screening for inpatients with Systemic sclerosis. <h3>Methods</h3> SSA and Video fluoroscopic swallowing study (VFSS) were performed in 120 inpatients with Systemic sclerosis from March 2014 to September 2016.The sensitivity, specificity, positive predictive value and negative predictive value of SSA in the diagnosis of aspiration in patients were calculated by taking VFSS examination as the gold standard. The incidence of pneumonia in SSA-positive and SSA-negative patients were compared. <h3>Results</h3> The diagnostic sensitivity of SSA was 81.2%, the specificity was 75%, the positive predictive value was 68.6% and the negative predictive value was 90.3%. The incidence of pneumonia in SSA positive patients was higher than that in SSA negative patients (54.1% vs 28.3%) (P&lt;0.01). <h3>Conclusions</h3> SSA is a valuable screening tool for the evaluation of aspiration risk in patients with Systemic sclerosis. <h3>References</h3> Systemic Sclerosis with Multiple Pulmonary Manifestations. Kotnur MR, Suresh P, Reddy VS, Sharma T, Salim NA. J Clin Diagn Res. 2016 Jun;10(6):OD16–7. doi: 10.7860/JCDR/2016/18781.8032. Progression of esophageal dysmotility in systemic sclerosis. Vischio J, Saeed F, Karimeddini M, Mubashir A, Feinn R, Caldito G, Striegel K, Rothfield N. J Rheumatol. 2012 May;39(5):986–91. doi: 10.3899/jrheum.110923. <h3>Disclosure of Interest</h3> None declared
SP0074 The future of epidemiological research in rheumatic and musculoskeletal disorders
Authors: L Gossec
Journal: Annals of the Rheumatic Diseases (2017)

Epidemiological research has gone through a very exciting time over the past years in rheumatic and musculoskeletal disorders (RMDs). The future is just as exciting. Although 9traditional9 epidemiology in terms of prevalence and incidence of diseases is quite well-known now, there are many gaps to our knowledge in particular in the field of outcomes research (what to assess, when and how?) but also in the field of predictive factors (e.g. predictive factors of severity and of treatment response). Better knowledge in outcomes assessment is key to feasibility of standardised assessments and is the basis of shared decision making. Better knowledge of predictive factors will open the door to truly personalised medicine. Some future directions will be discussed in this talk. <h3>Disclosure of Interest</h3> None declared
THU0027 Clusterin is elevated in serum and muscle tissue in idiopathic inflammatory myopathies and is associated with disease activity
Authors: T Lennerová, L Vernerová, M Klein, M Tomčík, H Mann, V Hrušková, K Pavelka, J Vencovský, L Šenolt
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Clusterin (also known as apolipoprotein J) is a molecular chaperone that participates in inflammatory and apoptotic processes. Recent data indicate its possible protective role in the development of chronic autoimmune disorders. <h3>Objectives</h3> The aim of this study was to analyse the skeletal muscle expression of clusterin and its serum levels in patients with idiopathic inflammatory myopathies (IIM) and in healthy donors, and to examine the association of clusterin with disease activity. <h3>Methods</h3> Clusterin mRNA expression in skeletal muscle specimens, obtained by muscle biopsy (mini-invasive Bergstrom technique), was determined using qPCR in 10 patients with IIM and 10 healthy subjects. Serum concentrations of clusterin were measured by ELISA (Biovendor) in 65 patients with IIM (27 dermatomyositis (DM), 28 polymyositis (PM), 10 immune-mediated necrotizing myopathy (IMNM)) and in 54 healthy individuals. Disease activity was assessed using myositis intention to treat index (MITAX), myositis disease activity assessment visual analogue scales (MYOACT), health assessment questionnaire (HAQ) and global disease assessment evaluated by doctor and patient. Data are presented as mean ± SD. <h3>Results</h3> Clusterin mRNA expression in skeletal muscles was increased in patients with IIM compared to healthy donors (p=0.029). In addition, serum clusterin levels were significantly higher in all IIM patients than in healthy subjects (87.1±22.8 vs 68.4±12.4, p&lt;0.0001) and also in individual subsets of patients in comparison to the control group (DM: 87.7±24.7, PM: 86.1±23.2, IMNM: 88.15±18.0, p&lt;0.0001 for all). Clusterin levels in all patients with IIM positively correlated with MYOACT (r=0.337, p=0.008), MITAX (r=0.357, p=0.004) and global disease assessment evaluated by doctor (r=0.309, p=0.015). In patients with DM, positive correlations with MYOACT (r=0.499, p=0.009), MITAX (r=0.491, p=0.009), HAQ (r=0.470, p=0.014), global disease assessment evaluated by doctor (r=0.559, p=0.004), γ-glutamyl transpeptidase and asparate aminotransferase were found (r=0.504, p=0.007; r=0.429, p=0.025, respectively). PM and IMNM subsets showed no significant association. <h3>Conclusions</h3> We demonstrate increased local and systemic expression of clusterin in IIM patients compared to healthy individuals and its association with disease activity, especially in dermatomyositis. <h3>Acknowledgements</h3> Supported by the project of MHCR for conceptual development of research organization 00023728 and project NV16–33746A. <h3>Disclosure of Interest</h3> None declared
FRI0380 Patient preferences and difficulties concerning the home treatment options in systemic sclerosis (SSC)
Authors: B Pagnotelli, C Bruni, S Bellando Randone, S Guiducci, G Lepri, J Blagojevic, L Rasero, M Matucci Cerinic, DE Furst
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> SSc patients suffer from Raynaud9s phenomenon, hand skin hardening and scarring, digital ulcers, esophagus/gastric dysmotility, dysphagia and mucosal dryness. These symptoms significantly reduce patient9s life autonomy and impair the capacity to handle their therapy usually made by different modalities of administration: oral, topical, inhalation, intramuscular, subcutaneous, intravenous, and rectal. <h3>Objectives</h3> to investigate the methods of administration used by SSc patients, their preferred methods, their compliance to pharmacological therapy, and the difficulties that are encountered by the patients during pharmacotherapy. <h3>Methods</h3> 2 questionnaires were prepared on an ad hoc basis. The first given to patients, the second to be filled out by the patient9s physician. The first questionnaire comprised 25 questions to investigate the problems encountered by patients when taking their medications by correlating these with two validated activities indices: SHAQ-DI (activities of daily living) and the COCHIN scale (hand activities). The second questionnaire collected demographic and important SSc-related clinical information (eg.age, sex, disease duration, symptoms). 80 Ssc patients completed the questionnaires, maintaining anonymity. A "difficulty index" was also filled out, where: 0 = no difficulty to 4 = impossible to use or too difficult to use. <h3>Results</h3> In particular, the dimension of the pills is problematic, and has identified a paradoxical situation because large pills are difficult to swallow (41,25% patients who use pills) but at the same time small pills are difficult to pinch with the fingers (62,25% patients who use pills). <h3>Conclusions</h3> SSc patients experience significant problems in maintaining adherence to treatments due to difficulties in the use of blisters and bottles with children proof stoppers. Pills still remain the most preferred method of treatment. In conclusion, patients unanimously wished to avoid the use of blisters, defintively preferring bottles without the children proof stopper to make the treatment easier and provide a more independent life. <h3>Disclosure of Interest</h3> None declared
SAT0091 Is clinical arthritis always preceded by subclinical inflammation? a longitudinal study at joint level in patients with arthralgia that developed arthritis
Authors: RM Ten Brinck, HW van Steenbergen, AH van der Helm-van Mil
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> The clinical phase of Rheumatoid arthritis (RA) is preceded by a phase with subclinical inflammation. MRI can detect subclinical inflammation and, at patient level, this is predictive for the development of clinical arthritis. However, at joint level it is unknown how arthritis develops. It is unknown how frequently joints with subclinical inflammation progress to clinical arthritis, and vice versa, how often joints that developed clinical arthritis had local subclinical inflammation during the preceding phase of arthralgia. A longitudinal MRI study in patients that developed arthritis can unravel if arthritis development is restricted to some locations in which the severity of inflammation increases over time or, alternatively, if the process is more generalized with a weak association between the locations of subclinical inflammation and subsequent clinical arthritis. <h3>Objectives</h3> This longitudinal study at joint level during progression from pre-RA to RA determined the relation between the location of subclinical inflammation and clinical arthritis over time. <h3>Methods</h3> 290 small joints (4 MCPs, 1 wrist, 5 MTPs per person) of 29 patients that presented with arthralgia and developed clinical arthritis were studied with 1.5T MRI at both time-points. MRIs were evaluated for BME, synovitis and tenosynovitis by three readers (ICCs 0.98, 0.96 and 0.97) that were blind to clinical data and the order in time. Subclinical inflammations was defined as presence of BME, synovitis and/or tenosynovitis. <h3>Results</h3> The median time between presentation with arthralgia and clinical arthritis development was 17 weeks. At presentation with arthralgia 68 joints had subclinical inflammation and no significant association was found between joint tenderness and the presence of local MRI-detected subclinical inflammation (OR 0.98; 95% CI 0.48–1.9). Over time, 21% of 68 joints had resolution of subclinical inflammation, 60% had persistent subclinical inflammation and 19% developed clinical arthritis. At arthritis development 37 joints were swollen. Of these, 24 (65%) had no prior subclinical inflammation at the time of presentation with arthralgia (Figure). <h3>Conclusions</h3> This first longitudinal MRI-study on joint level in pre-RA suggested that the majority of joints that developed clinical arthritis had no (long-lasting) preceding phase with subclinical inflammation. <h3>Disclosure of Interest</h3> None declared
AB0006 MICRORNA-499 in behcet disease and possible association with disease activity
Authors: M Eissa, M Al Kaffas, S Abdel Wahab, L Rashed
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Behçet Disease (BD) is a relapsing inflammatory autoimmune disease. Although the etiology of BD is not yet known, genetic predisposition and immune dysregulation are thought to be critical factors in the pathogenesis of the disease. MicroRNAs (miRNAs) are small RNA fragments that can regulate the gene expression. miRNAs play a critical role in the pathogenesis of autoimmune or auto inflammatory diseases. Sinngle nucleotide polymorphisms (SNPs) may change the property of miRNAs through altering miRNA expression and/or maturation. <h3>Objectives</h3> The aim of this work was to detect miRNA-499 (rs3746444) genotyping and relative expression in BD patients in order to find out the possible association between them and disease activity and severity. <h3>Methods</h3> Relative expression of miRNA-499 was measured by Real-Time PCR and miRNA-499 gene (rs 3746444) genotyping was performed by TaqMan SNP Genotyping Assay in blood samples obtained from 47 patients BD diagnosed according to 1990 international criteria for behcet disease and 50 matched healthy controls. Disease activity was done using BD current activity form (BDCAF). <h3>Results</h3> Study of miRNA-499 polymorphism, showed that the genotype frequencies of TT, CT, and CC were 21.3%, 63.8%, and 14.9% in BD patients and 18.0%, 52.0%, and 30.0% in the control group respectively. A significant increase in the relative expression of miRNA-499 was found in BD patients compared to control (P&lt;0.05). There was no significant relation between relative expression of miRNA-499 and activity of BD patients assessed by BDCAF (P&gt;0.05). In addition there was association between genotypes of miRNA-499 and posterior uveitis (P&lt;0.05). There was association of the relative expression of miRNA-499 with miRNA-499 (rs3746444) polymorphism and vascular manifestations (P&lt;0.05). <h3>Conclusions</h3> Genotyping of miRNA-499 showed higher percentage of TT genotype in BD patients than control and also miRNA relative expession, they may be implicated in pathogenesis of the disease. Genotype TT for miRNA-499 is associated with posterior uveitis. miRNA relative expression is associated with vascular manifestations and aneurysm. <h3>Disclosure of Interest</h3> None declared