tbuckley/cabot-search huggingface dataset:
SAT0036 Nicotine promotes mmp-3 and rankl secretion through overexpressed nicotinic acetylcholine receptor Α7 in rheumatoid arthritis fibroblast-like synoviocytes
Authors: J.-D. Ma, Y.-S. Mou, T. Yan, J. Jing, Y.-Q. Mo, Y.-L. Chen, L. Dai
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Smoking has been reported not only an established environmental risk factor for developing rheumatoid arthritis (RA), but also a predictor of radiographic progression. Nicotine, the major constituent of cigarette smoke, has been demonstrated inhibitory effect on proinflammatory cytokines through its receptor nicotinic acetylcholine receptor α7 (AChRα7) in RA fibroblast-like synoviocytes (FLS). However, its effects on other function of RA-FLS remain elusive. <h3>Objectives</h3> To explore the effect of nicotine on matrix metalloproteinases (MMPs) and RANKL expression from RA-FLS and its possible intracellular signalling mechanism. <h3>Methods</h3> Synovial tissues were obtained from 45 patients with active RA as well as 11 osteoarthritis (OA) and 11 noninflammatory orthopaedic arthropathies (Orth.A) patients for control. The expression of AChRα7 in synovial membrane and cultured FLS were detected by immunohistochemistry staining and Western blot. RA-FLS were treated <i>in vitro</i> with different concentration of nicotine and its effect on RA-FLS viability was evaluated by cell counting kit-8. After nicotine pretreatment on TNF-α stimulated RA-FLS, the expression of MMP-2, MMP-3, MMP-9, TIMP-1, TIMP-2, RANKL, and OPG in culture supernatant were measured by ELISA, while the change of AP-1 pathway including c-Fos and c-Jun were detected by quantitative real-time PCR and Western blot. <h3>Results</h3> Immunohistochemical analyses showed intense endochylema staining for AChRα7 mainly in lining layer. The percentage of both lining and sublining AChRα7 positive cells were significantly higher in RA than that in OA or Orth.A (figure 1A). Further western blot showed significantly higher expression of AChRα7 in RA-FLS than that in Orth.A-FLS (p<i>=</i>0.003, figure 1B). Nicotine (0.1 µM~50 µM) showed no cytotoxicity on RA-FLS proliferation. Pretreatment with 50 µM nicotine for 24 hours significantly promoted the secretion of MMP-3 and RANKL but inhibited TIMP-1 secretion in TNF-α stimulated RA-FLS (all p&lt;0.05, figure 1C). Furtherly, 25 µM and 50 µM nicotine treatment for 24 hours upregulated both mRNA and protein expression of c-Fos but not c-Jun which indicated that nicotine might activate AP-1 signalling pathway by c-Fos (all p&lt;0.05, figure 1D). <h3>Conclusions</h3> Nicotine can promote MMP-3 and RANKL expression through overexpressed AChRα7 in RA-FLS which might be involved in the pathogenesis of osteogenesis and bone destruction in RA. <h3>Acknowledgements</h3> This work was supported by National Natural Science Foundation of China (no. 81471597 and 81671612), Guangdong Natural Science Foundation (no. 2017A030313576 and 2017A030310236) and Fundamental Research Funds for the Central Universities (no. 17ykjc12). <h3>Disclosure of Interest</h3> None declared
AB1209 Usefulness of imagenology to differential diagnosis in patients with presumed seronegative rheumatoid arthritis and other arthropathies
Authors: P. Santos-Moreno, O. Valencia, E. Castillo, S. Farietta, L. Villareal, M. Cabrera
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> It is difficult to make a differential diagnosis between seronegative RA and other inflammatory arthropathies. Many patients could be wrong diagnosed followed of expensives treatments. <h3>Objectives</h3> To assess the usefulness of X-rays of hands and feet (X-rays), Ultrasound (US) and Magnetic Resonance Imaging (MRI) to discard false positive diagnosis of seronegative RA from real-world evidence. <h3>Methods</h3> An analysis from medical records of patients with presumptive seronegative RA diagnosis reportedly seronegative for both rheumatoid factor and anti-cyclic citrullinated peptide antibodies and clinical criteria of RA, in the period between July 2016 and ; June of 2017 who were assesed by imagenology (X-rays, US or MRI) in a centre of rheumatoid arthritis to confirm diagnosis or discard it. Laboratory, and imagenology data was retrospectively analysed and multivariate analysis was performed to determinate the usefulness of imagenology. <h3>Results</h3> 360 patients were received in the centre with presumptive diagnosis of RA in the period, mean of age was 58 years, 80,9% females and 19,1% males. X-rays shows only 3,59% of patients with erosions, 38,6% were positive for Ostheoarthritis (OA), and 58,6% of patients without erosions. From patients without erosions, 36% were confirmed for RA and 13,4% for OA by US; on the other hand 37% was confirmed for RA and 20% for OA by MRI. A total of 94 patients (26,1%) had a final diagnosis of seronegative RA, while (261) patients 72,5% were confirmed for Osteoarthrosis,<sup>5</sup> 1,4% were classified in other arthropaties. <h3>Conclusions</h3> According with our findings the screening by imagenology is a useful tool with low cost to make a differential diagnosis of seronegative RA and other arthropaties. In order to improves outcomes through well-defined treatments and to save high cost treatments for pathologies with more precise diagnoses. <h3>Disclosure of Interest</h3> None declared
Different levels of uroporphyrevogen decarboxylase (URO-D) activity in erythrocytes of porphyria cutanea tarda patients
Authors: M. D. Cappellini, D. Tavazzi, F. Martinez Di Montemuros, A. Comino, G. M. Danielli, S. Fargion, G. Fiorelli
Journal: Blood (2000)
<i>Paederus</i> beetle dermatitis
Authors: Yi Zhu, Yi-Ming Fan
Journal: BMJ (2019)

A 25 year old woman woke with erythema, oedema, and painless, non-pruritic pustules around her right eye (fig 1), accompanied by tingling, conjunctival hyperaemia, and lesions on her neck and right auricle. Allergic contact dermatitis was unlikely because the rash was …
THU0267 Gastrointestinal involvement in spondyloarthritis is not all ibd: increased risk of diverticulitis with longer disease duration in the asas-comospa cohort
Authors: M.H. Derakhshan, N. Goodson, J. Packham, R. Sengupta, A. Molto, H. Marzo-Ortega, S. Siebert
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Inflammatory bowel disease (IBD) is an established extra-articular manifestation of Spondyloarthritis (SpA). The association of SpA with other gastrointestinal and hepatic comorbidities is less well known. <h3>Objectives</h3> To examine the relationship between SpA disease duration and gastrointestinal comorbidities other than IBD. <h3>Methods</h3> ASAS-COMOSPA is a large global cross-sectional study comprising 3984 patients with SpA. We evaluated the association between “SpA disease duration” (defined in 5 year blocks) and upper gastrointestinal ulcers, hepatitis B (HBV), hepatitis C (HCV) and diverticulitis. Binary logistic regression models were created, adjusted for age, sex, BMI, smoking, alcohol, NSAIDs, DMARDs, biologics, steroids and IBD history. Subgroup analysis was performed, stratified by peripheral and/or axial joint involvement. <h3>Results</h3> The data of 3923 patients (64.9% male) were available for analysis, 5.3% of whom had a history of IBD. The self-reported prevalence of other gastrointestinal conditions was: upper gastrointestinal ulcers 10.7%; viral hepatitis 4.7% and diverticulitis 1.5%, with significant geographic variation. “SpA disease duration” was not associated with the occurrence of the upper gastrointestinal ulcers (OR=0.98, 95% CI: 0.92–1.05), HBV (OR=0.43, 95% CI: 0.28–0.67) or HCV (OR=0.27, 95% CI: 0.11–0.62). In contrast, the risk of diverticulitis was significantly increased by “SpA disease duration” (OR=1.14, 95% CI: 1.01–1.29); increased risk of 14% for every 5 years of disease duration) across the entire cohort, after adjustment for potential confounders, including age. Confounding variables showing significant association with diverticulitis were current age (OR=1.06, 95% CI: 1.04–1.08) and high alcohol (³3 units/day) intake (OR=3.84, 95% CI: 1.62–9.07) but not medication history (table 1). Subgroup analyses revealed stronger association of SpA disease duration with diverticulitis in those with axial (OR=1.24, 95% CI: 1.08–1.42) than those with peripheral (OR=1.12, 95% CI: 0.98–1.29) SpA disease. <h3>Conclusions</h3> Patients with SpA have a number of gastrointestinal comorbidities, including increased risk of diverticulitis with increased SpA disease duration, highest in those with axial disease. The reasons for this association are unclear and warrant further investigation. Diverticulitis should be considered, in addition to IBD, when patients with SpA present with lower gastrointestinal symptoms. <h3>Disclosure of Interest</h3> None declared
AB0790 Frequency of osteoporosis in postmenopausal women with systemic sclerosis
Authors: O. Dobrovolskaya, N. Demin, A. Smirnov, O. Koneva, N. Toroptsova
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> The prevalence of low bone mass or osteoporosis in patients with systemic sclerosis (SSc) varies significantly between studies performed in different countries and vary from 3% to 51% (Omair MA et al. 2013). <h3>Objectives</h3> To determine the frequency of osteoporosis (OP) in postmenopausal women with SSc in comparison with healthy control. <h3>Methods</h3> 163 postmenopausal women were enrolled in the study: 83 with SSc (mean age 58.5±8.1 years, mean disease duration 9.7±6.8 years) and 80 healthy control (mean age 59.2±6.6 years). Demographic characteristics and risk factors for OP in study groups are summarised in table 1. BMD was measured at lumbar spine, femoral neck and total hip by dual energy X-ray absorptiometry (DXA, Hologic 4500A). BMD decreasing grade was determined in according to WHO criteria. <h3>Results</h3> BMD in women with SSc was significantly lower than in control group at any site: lumbar spine – 0.832±0119 vs 0.867±0,098 g/sm<sup>2</sup> (p=0.031); femoral neck – 0.633±0.098 vs 0.739±0.114 g/sm<sup>2</sup> (p&lt;0.0001), and total hip – 0.752±0116 vs 0.839±0,119 g/sm<sup>2</sup> (p&lt;0.0001). Frequency of OP in SSc group was 32%, in control group – 13% (p&lt;0.002). Mean age at menopause was less in SSc women than in control (p&lt;0.05). OP was significantly more often in SSc patients taking oral glucocorticoids compared to those without glucocorticoid therapy (39% and 20%, respectively, p&lt;0.05). Low BMD was associated with age and interstitial lung disease in SSc women (p&lt;0.05). At the same time no associations were found out among low BMD and disease duration, daily and cumulative doses of glucocorticoids. 23 (28%) of patients had osteoporotic fracture, among them 8 (10%) of women had two or more fractures in the anamnesis. The most frequent localizations of the fractures were distal forearm and vertebrae: 7 (32%) and 5 (23%) patients, respectively. <h3>Conclusions</h3> OP in postmenopausal women with SSc were detected among 1/3 of cases, significantly exceeded its frequency in healthy control. Risk factors for OP were age, oral glucocorticoids and interstitial lung disease. <h3>Reference</h3> [1] Omair MA, Pagnoux C, McDonald-Blumer H, Johnson SR. Low bone density in systemic sclerosis. A systematic review. J Rheumatol.2013;40(11):1881–90. doi:10.3899/jrheum.130032 <h3>Disclosure of Interest</h3> None declared
THU0585 Personalised treatment in juvenile idiopathic arthritis – future or fiction? preliminary results of using s100a8a9, s100a12 and vascular endothelial cadherin as diagnostic and prognostic biomarkers
Authors: K. Orczyk, E. Smolewska
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Serological biomarkers with ability to predict outcome and therapeutic response of patients might be helpful in introducing the concept of treat-to-target into management of juvenile idiopathic arthritis (JIA). Among others, calprotectin (S100A8A9) and calgranulin C (S100A12) are considered to be valuable markers of disease activity and risk factors for flare after withdrawal of treatment. Vascular endothelial cadherin (VE-cadherin) is a marker of endothelial permeability which has been postulated to predict response to methotrexate therapy in rheumatoid arthritis (RA) patients. <h3>Objectives</h3> The aim of the study was to assess the clinical significance of measuring serum concentrations of S100A8A9, S100A12 and VE-cadherin in patients with freshly diagnosed JIA and those with exacerbated course of the disease. <h3>Methods</h3> Serum levels of the listed biomarkers were determined in 30 patients diagnosed with JIA and 21 age- and sex-matched healthy controls. In the study group blood samples were obtained in two time points in order to evaluate dynamics of concentrations of markers. <h3>Results</h3> S100A8A9 and S100A12 serum concentrations at baseline were positively correlated with ESR at second time point (r=0.378 and 0.425, p=0.0397 and 0.0193, respectively). S100A12 had equal correlation with CRP at second time point (r=0.391, p=0.0329). Patients freshly diagnosed with JIA had higher levels of S100A12 (8.49±4.92 ng/ml vs. 5.49±2.21 ng/ml, p=0.007) and VE-cadherin (5.31±1.13 ng/ml vs. 3.50±0.58 ng/ml, p&lt;0.001) when compared to healthy controls. VE-cadherin level was elevated in JIA patients at second time point as well (4.10±0.93 ng/ml, p=0.0194). Patients who underwent arthrocentesis at baseline had higher concentrations of S100A12 at second time point (6.69±3.56 ng/ml vs. 3.84±2.58 ng/ml, p=0.0168). Levels of markers were independent of sex and age. <h3>Conclusions</h3> Presented study group needs to be expanded with more patients, especially with minimal disease activity, in order to validate demonstrated preliminary results. VE-cadherin may be considered as a future diagnostic biomarker, however its specificity requires detailed assessment. S100A8A9 and S100A12 merit further evaluation as potential prognostic biomarkers for more aggressive course of the disease. <h3>Disclosure of Interest</h3> None declared
Feasibility, Acceptability, and Behavioral Outcomes from a Technology-enhanced Behavioral Change Intervention (Prostate 8): A Pilot Randomized Controlled Trial in Men with Prostate Cancer
Authors: Stacey A. Kenfield, Erin L. Van Blarigan, Niloufar Ameli, Emil Lavaki, Benjamin Cedars, Alan T. Paciorek, Cynthia Monroy, Lucy K. Tantum, Robert U. Newton, Coralie Signorell, Jung H. Suh, Li Zhang, Matthew R. Cooperberg, Peter R. Carroll, June M. Chan
Journal: European Urology (2019)
Constant Degradation of the Androgen Receptor by MDM2 Conserves Prostate Cancer Stem Cell Integrity
Authors: Premkumar Vummidi Giridhar, Karin Williams, Andrew P. VonHandorf, Paul L. Deford, Susan Kasper
Journal: Cancer Research (2019)

Abstract Prostate cancer stem cells (CSC) are implicated in tumor initiation, cancer progression, metastasis, and the development of therapeutic-resistant disease. It is well known that the bulk of prostate cancer cells express androgen receptor (AR) and that androgens are required for prostate cancer growth, progression, and emergence of castration-resistant disease. In contrast, the small subpopulation of self-renewing CSCs exhibits an AR-negative (AR−) signature. The mechanisms underlying the absence of AR are unknown. Using CSC-like cell models isolated from clinical biopsy tissues, we identify the E3 ligase MDM2 as a key regulator of prostate CSC integrity. First, unlike what has been reported for the bulk of AR+ tumor cells where MDM2 regulates the temporal expression of AR during transcriptional activity, MDM2 in CSCs promoted the constant ubiquitination and degradation of AR, resulting in sustained loss of total AR protein. Second, MDM2 promoted CSC self-renewal, the expression of stem cell factors, and CSC proliferation. Loss of MDM2 reversed these processes and induced expression of full-length AR (and not AR variants), terminal differentiation into luminal cells, and cell death. Selectively blocking MDM2-mediated activity in combination with androgen/AR-targeted therapy may offer a novel strategy for eliminating AR− CSCs in addition to the bulk of AR+ prostate cancer cells, decreasing metastatic tumor burden and inhibiting the emergence of therapeutic resistance. Significance: These findings provide a novel mechanistic aspect of prostate cancer cell stemness that advances our understanding of the diverse transcriptional activity that bypasses AR in contributing to therapeutic resistance, tumor progression, and metastasis.
Abstract 11503: Circadian Timing of Food Intake is Associated With Cardiometabolic Risk in US Hispanics/Latinos: Results From the Hispanic Community Health Study/Study of Latinos
Authors: Nour Makarem, Brooke Aggarwal, Dorothy D Sears, Marie-Pierre St-Onge, Sheila F Castañeda, Gregory A Talavera, Catherine R Marinac, Ruth Patterson, Daniela Sotres-Alvarez, Melawhy L Garcia, Linda C Gallo
Journal: Circulation (2018)

Introduction: Emerging evidence suggests that eating at unconventional circadian times is associated with adverse metabolic effects. Recently, the American Heart Association released a statement hi...
AB0809 A new score to predict digital ulcers combining clinical data, imaging and patient history in systemic sclerosis
Authors: S. Friedrich, S. Lüders, G.-R. Burmester, G. Riemekasten, S. Ohrndorf
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Ischaemic complications such as digital ulcers (DU) are a common complication in systemic sclerosis (SSc) patients. <h3>Objectives</h3> The aim of this study was to combine clinical characteristics and imaging methods to a composite predictive score. <h3>Methods</h3> Seventy-nine SSc patients received clinical examination and their patient history was taken. Furthermore, we performed nailfold capillaroscopy (NC), colour Doppler ultrasonography (CDUS) and fluorescence optical imaging (FOI) of the hands at baseline. Newly developed digital ulcers over a period of approximately 12 months were registered. We used criteria with significant (p&lt;0.5) OR values above 3.5 in regard to the development of these new DU to create the score (<b>CIP-DUS</b>, <b>c</b>linical features, <b>i</b>maging, <b>p</b>atient history – <b>d</b>igital <b>u</b>lcer <b>s</b>core) <h3>Results</h3> Twenty-nine percent of the patients developed new DU during follow-up (48.1% diffuse SSc, 18.4% limited SSc). The following criteria were used: SSc diffuse subtype (OR 4.127, p=0.0087), modified Rodnan skin score &gt;8 (OR 9.429 [95%CI: 3.0–29.2], p&lt;0.0001), pulmonary arterial hypertension (OR 6.854 [95%CI: 1.6–9.7], p=0.0088), present digital ulcers or pitting scars at baseline (OR 15.71 [95%CI: 3.3–74.3], p&lt;0.0001), history of digital ulcer or pitting scars (OR 36.15 [95%CI: 2.1–626.9], p&lt;0.0001), NC pattern (OR 18.6 [95%CI: 1.1–326.4], p=0.0035), reduced capillary density (n&lt;7/mm) in digit III of the right hand in NC (OR 9.0 [95%CI: 1.1–73.6], p=0.0266), missing initial enhancement in FOI in digit III of the right hand (OR 3.857 [95%CI: 1.2–12.8], p=0.0323), percentage of pathologic (i. e. narrowed or occluded) vessels&gt;35% in CDUS (OR 4.286 [95%CI: 1.5–12.4], p=0.0099). Criteria with greater OR should impact the score to a higher degree so we appointed three points to dichotomous criteria with OR &gt;10, two points for criteria with OR between 5–10, and one point for criteria with OR &lt;5. Regarding the NC pattern, 3 points were given to patients with late pattern, 2 points for active and 1 point for early pattern. Best results were found for a cut-off of &gt;10 points with obtained sensitivity levels of 95% and specificity levels of 74% in regard to new DU (AUC=0.8687, p&lt;0.0001). In the absence of CDUS and FOI data, specificity levels dropped slightly to 72% with unchanged sensitivity values of 95%. <h3>Conclusions</h3> A new score was introduced with the aim to predict digital ulcers. If applied correctly and with the new imaging techniques proposed, 95% of patients at risk of digital ulcers throughout 12 months could be identified. <h3>Disclosure of Interest</h3> None declared
FRI0029 Clinical significance of 14–3–3eta protein levels in patients with rheumatoid arthritis
Authors: O. Shovman, B. Gilburd, A. Watad, H. Amital, P. Langevitz, N.L. Bragazzi, M. Adawi, D. Pérez, G. Bornstein, M. Lidar, M. Blank, Y. Azuri, N.K. Biln, A. Marotta, Y. Shoenfeld
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> 14–3–3η is a protein that is overexpressed in serum and joint fluid of patients with rheumatoid arthritis (RA) and may represent a diagnostic biomarker for RA. <h3>Objectives</h3> We assessed the prevalence and serum levels of 14–3–3η in patients with RA and with other rheumatic diseases. <h3>Methods</h3> Serum levels of 14–3–3η were measured in 96 patients with RA, in 101 patients with other rheumatic diseases and in 66 healthy subjects. The RA group consisted of 51 patients with well-established RA who were treated with different DMARDs, and 45 patients with early untreated disease (onset of less than 1 year). The disease control group included 33 patients with systemic lupus erythematosus (SLE), 44 patients with ankylosing spondylitis (AS) and 24 psoriatic arthritis (PsA) patients. All of the sera samples were evaluated by JOINT stat 14–3–3η ELISA test kits (Augurex Life Sciences Corp.). The cut-off was defined as 0.19 ng/ml. <h3>Results</h3> Median (IQR) 14–3–3η levels were significantly higher in the early RA group [0.25 ng/ml (0.075–3.11)] and in established RA patients [0.15 ng/ml (0.08–1.26)] in comparison with healthy subjects [0 ng/ml (0–0)] and disease controls: SLE [0.01 ng/ml (0–0.055)], AS [0.05 ng/ml (0–0.255)] and PsA [0.01 ng/ml (0–0.065)]. The prevalence of 14–3–3η positivity in early RA patients was 58%, significantly higher than in the disease control group (SLE: 9%, p&lt;0.001; AS: 27%, p&lt;0.002, PsA: 12.5%, p&lt;0.001) and in the healthy subjects group (5%, p&lt;0.001). In established-RA patients, this prevalence was 43%, and it was significantly higher than in disease control and healthy subjects groups (p&lt;0.05), excluding the AS group (p=0.054). <h3>Conclusions</h3> The concentration of 14–3–3η protein may be used to distinguish between patients with early RA and patients with other rheumatic diseases and serve as an additional biomarker in the diagnosis of RA. <h3>Disclosure of Interest</h3> O. Shovman: None declared, B. Gilburd: None declared, A. Watad: None declared, H. Amital: None declared, P. Langevitz: None declared, N. L. Bragazzi: None declared, M. Adawi: None declared, D. Pérez: None declared, G. Bornstein : None declared, M. Lidar : None declared, M. Blank: None declared, Y. Azuri: None declared, N. K. Biln Employee of: Augurex Life Sciences Corp, A. Marotta Employee of: Augurex Life Sciences Corp, Y. Shoenfeld: None declared
Single-Agent Ibrutinib Vs Chemoimmunotherapy Regimens for Treatment-Naïve Patients with Chronic Lymphocytic Leukemia (CLL): A Cross-Trial Comparison
Authors: Tadeusz Robak, Jan A. Burger, Alessandra Tedeschi, Paul M. Barr, Carolyn Jane Owen, Osnat Bairey, Peter Hillmen, David Simpson, Sebastian Grosicki, Stephen Devereux, Helen McCarthy, Steven Coutre, Hang Quach, Gianluca Gaidano, Zvenyslava Maslyak, Don A Stevens, Carol Moreno, Devinder Gill, Ian W. Flinn, John Gribben, Ahmad Mokatrin, Mei Cheng, Lori Styles, Danelle F. James, Thomas J. Kipps, Paolo Ghia
Journal: Blood (2017)