tbuckley/cabot-search huggingface dataset:
THU0433 The prevalence of spondyloarthropathy in patients with takayasu arteritis
Authors: S. Güzel, B. Arma&gbreve;an, Ö. Varan, A. Erden, H. Küçük, H. Babao&gbreve;lu, N. Atas, L. Kılıç, B. Göker, S. Haznerdaro&gbreve;lu, M. A. Öztürk, U. Kalyoncu, A. Akdo&gbreve;an, A. Tufan
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Takayasu arteritis (TA) is characterised by inflammation of large arteries causing stenosis, occlusion, dilatation and/or aneurysm of affected vessels. TA is most commonly seen in younger women between 20–30 ages. Etiopathogenesis of TA is largely unknown although evidence suggest complex interplay between environmental and genetic factors such as HLA (human leukocyte antigen) groups. The coexistence of TA with spondyloarthropathies (SPA) has been reported in limited case series, raising hypotheses about shared pathogenetic mechanisms. <h3>Objectives</h3> To determine prevalence of spondyloarthropathy in patients with TA. <h3>Methods</h3> Detailed clinical and demographic features of TA patients were recorded and all were screened for the presence of SPA following recommendations of (ASAS). Patients were questioned for inflammatory back pain, enthesitis, uveitis, inflammatory bowel disease, peripheral arthritis, and investigated accordingly with HLA-B27, plain X-rays of pelvis and sacroiliac magnetic resonance imaging. Radiographic spondyloarthritis was reported in case of bilateral grade ≥2 or unilateral grade ≥3 sacroiliitis. <h3>Results</h3> There were 65 patients (61 female, 4 male) in the cohort. Mean age was 43±13 years and age at the diagnosis of TA was 35±13 years. Inflammatory bowel disease, psoriasis and psoriatic arthritis were observed in four, three and one patients. Chronic axial pain was reported by 26 (40%) patients but inflammatory back pain was evident in 13 (20%) patients. Chronic arthritis was observed in 4 patients. HLA-B27 was positive in three patients. Six patients were diagnosed as radiographic SPA and 3 were diagnosed as non-radiographic SPA. In sum nine patients were diagnosed as SPA (14.2%). <h3>Conclusions</h3> Our study demonstrated that SPA is common in patients with Takayasu arteritis suggesting shared pathogenetic mechanisms. <h3>Disclosure of Interest</h3> None declared
AB1196 Role of capillaroscopy in the study of the raynaud phenomenon in conditions of clinical practice
Authors: J. Uceda, R. Hernandez, C. Almeida, J.L. Marenco
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> The Raynaud phenomenon (RP) is very common throughout the world, especially in cold climates, affecting approximately 3%–5% of the population. Most RPs are primary. The risk of the onset of autoimmune disease associated with RP (ADRP) is between 6% and 12%, and the diagnosis is usually made within 2 years of its onset. Capillaroscopy is a simple, innocuous and inexpensive technique that is very useful in the study of RP <h3>Objectives</h3> The primary goal was to evaluate the capillaroscopic findings in patients with RF as the only symptom and establish their relationship between the subsequent development of ADRF. <h3>Methods</h3> We conducted an observational, descriptive, cross-sectional study of a random sample of 98 patients with RP as the main manifestation, selected from within the capillaroscopy consult of our Unit. The capillaroscope used was a stereomicroscope (Stereoscope), with a triocular head, zoom range from 1x to 4x magnification, with cold light illuminator and high resolution ocular camcorder. Periungual capillaroscopy was performed in 3rd, 4th and 5thfinger of the right and left hands in each patient and always by the same rheumatologist. We described the sociodemographic variables of patients, and analytical results of the antinuclear antibodies (ANA). After an initial statistical exploration of the data, the same are described. The quantitative variables are expressed as means and standard deviations and if the distributions are asymmetric with medians and quartiles. The qualitative variables with percentages. To assess the validity of capillaroscopy as a diagnostic test, we determined the sensitivity, specificity, and positive and negative predictive value of the test. <h3>Results</h3> 73.5% were women, with an average age of 45.7 years. The median time of evolution of the RP until the capillaroscopy was 2.5 years. 76% of the patients were ANA negative. The evaluation of the predictive capacity of capillaroscopy for the development of EARP yields the following results: When analysing the relationship between the presence of ANA and the association with ADRF we found that it was independent (p=0.002) of the result of capillaroscopy, being the risk of developing the disease in a patient with positive ANA 8.5 times higher than in an ANA negative patient. <h3>Conclusions</h3> Capillaroscopy in patients with RP has a high predcitive negative value, which allows us to estimated, with high reliability, the association of this phenomenon with autoimmune disease in patients with normal capillaroscopic patterns. Given the results of our study, capillaroscopy should be protocol in the RP study <h3>Disclosure of Interest</h3> None declared
AB0168 Elevated serum levels of hmgb1 and srage in patients with antiphospholipid syndrome
Authors: S. Truglia, V. Manganelli, A. Capozzi, C. Alessandri, E. Lococo, T. Garofalo, M. Sorice, A. Longo, R. Misasi, F. Conti, G. Valesini
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Antiphospholipid syndrome (APS) is a systemic autoimmune disease characterised by the presence of at least one clinical event among vascular thrombosis and/or pregnancy morbidity, in the presence of circulating antiphospholipid antibodies (aPL). High-mobility group box-1 (HMGB1) is a non-histonic protein belonging to the family of alarmins. It is associated with chromatin and has a dual function depending on the cell state: in basal conditions it is located in the nucleus and promotes the interaction of some transcription factors with DNA, in inflammatory conditions it is secreted in the extracellular space and exerts the functions of a pro-inflammatory cytokine. One of the main receptor system responsible for the HMGB1 activity is the "receptor for advanced glycation end products" (RAGE). Increased serum HMGB1 levels have been reported in patients with Systemic Lupus Erythematosus and pre-eclampsia, as other alarmins are increased in patients with early abortions. <h3>Objectives</h3> To evaluate the serum levels of HMGB1 and soluble RAGE (sRAGE) in patients with obstetric and thrombotic APS. <h3>Methods</h3> 43 consecutive patients with APS, diagnosed according to the Sapporo criteria, were enrolled. The study cohort included both primary APS (=15) and APS associated with SLE (=28). In addition, 30 healthy subjects (HC) matched for age and sex were studied as controls. Serum levels of HMGB1 and sRAGE were analysed by Western blot. <h3>Results</h3> The clinical features of the enrolled patients (40 females and 3 males, mean age 40.98±13.48 years,) are reported in table 1. HMGB1 and sRAGE serum levels were significantly increased in APS patients in comparison with controls (p&lt;0.001) (figure 1). Furthermore, no difference in HMGB1serum leved were detected among patients with thrombotic or obstetric APS and patients with primary or secondary APS.APS patients with thrombosis showed higher levels of HMGB1 than APS patients without thrombosis; in addition, in APS patients there is a correlation between HMGB1 serum levels and thrombosis. <h3>Conclusions</h3> In this study, we investigated for the first time the serum levels of HMGB1 and sRAGE in patients with APS, showing increased levels in both primary and secondary APS compared to controls. Larger studies are needed to assess whether monitoring serum HMGB1/sRAGE levels could be a useful tool for risk stratification in patients with APS. <h3>Disclosure of Interest</h3> None declared
Epigenetic regulators of the revascularization response to chronic arterial occlusion
Authors: Joshua L Heuslein, Catherine M Gorick, Richard J Price
Journal: Cardiovascular Research (2019)

Peripheral arterial disease (PAD) is the leading cause of lower limb amputation and estimated to affect over 202 million people worldwide. PAD is caused by atherosclerotic lesions that occlude large arteries in the lower limbs, leading to insufficient blood perfusion of distal tissues. Given the severity of this clinical problem, there has been long-standing interest in both understanding how chronic arterial occlusions affect muscle tissue and vasculature and identifying therapeutic approaches capable of restoring tissue composition and vascular function to a healthy state. To date, the most widely utilized animal model for performing such studies has been the ischaemic mouse hindlimb. Despite not being a model of PAD per se, the ischaemic hindlimb model does recapitulate several key aspects of PAD. Further, it has served as a valuable platform upon which we have built much of our understanding of how chronic arterial occlusions affect muscle tissue composition, muscle regeneration and angiogenesis, and collateral arteriogenesis. Recently, there has been a global surge in research aimed at understanding how gene expression is regulated by epigenetic factors (i.e. non-coding RNAs, histone post-translational modifications, and DNA methylation). Thus, perhaps not unexpectedly, many recent studies have identified essential roles for epigenetic factors in regulating key responses to chronic arterial occlusion(s). In this review, we summarize the mechanisms of action of these epigenetic regulators and highlight several recent studies investigating the role of said regulators in the context of hindlimb ischaemia. In addition, we focus on how these recent advances in our understanding of the role of epigenetics in regulating responses to chronic arterial occlusion(s) can inform future therapeutic applications to promote revascularization and perfusion recovery in the setting of PAD.
SP0118 Recent advances in the treatment of rheumatoid arthritis
Authors: M.H. Buch
Journal: Annals of the Rheumatic Diseases (2018)

<h3></h3> Modern management of rheumatoid arthritis (RA) is underpinned by the principle of establishing a clear treatment goal through the efficient strategic use of DMARDs in order to minimise adverse outcomes. With evolving ambitions and new targeted therapies, ongoing advances in the management of RA continue to be made: this HOT session will summarise our progress in the understanding and management across the RA disease continuum; including the state of at risk of RA status to early and later RA disease. In particular, the session will focus on studies that inform on (i) the ability to potentially abrogate progression from autoimmunity to development of RA disease (ii) currently identified strategies that offer the optimal opportunity for remission induction in ERA (iii) ability to drug taper and (iv) use of recently introduced synthetic and biologic targeted therapies. Finally, with co-morbidity outcomes including cardiovascular disease, another key focus in the contemporary management of RA, developments in improving this area of health concern will also be presented. <h3>Disclosure of Interest</h3> None declared
Effect of cap-assisted esophagogastroduodenoscopy on examination of the major duodenal papilla: a noninferior, randomized controlled trial
Authors: Xin Shi, Hui Luo, Bo Ning, Xiangping Wang, Qin Tao, Shuhui Liang, Rongchun Zhang, Jie Chen, Bing Luo, Shaowei Yao, Yanglin Pan, Xuegang Guo, Daiming Fan
Journal: Endoscopy (2019)

Abstract Background Cap-assisted esophagogastroduodenoscopy (CA-EGD) using a transparent cap fitted to the tip of the scope has emerged as an alternative method for examination of the major duodenal papilla (MDP). However, it remains unclear whether CA-EGD is noninferior to standard duodenoscopy for MDP examination. The aim of this study was to compare the efficacies of the two methods for complete examination of the MDP. Methods This prospective, noninferior, randomized controlled study was conducted at two endoscopy centers. Consecutive patients who underwent endoscopic retrograde cholangiopancreatography were randomized (1:1) to undergo CA-EGD or standard duodenoscopy for MDP examination. The primary outcome was complete examination of the MDP, defined as visualization of the upper end, opening, and lower end of the papilla. Secondary outcomes included endoscopic findings and the time taken for the MDP examination. Results The study was terminated for futility after the interim analysis. A total of 171 patients were randomly allocated to CA-EGD (n = 85) or standard duodenoscopy (n = 86). The baseline characteristics were comparable between the two groups. Complete examination of the MDP was achieved in 58/85 patients (68.2 %) in the CA-EGD group and in 74/86 (86.0 %) in standard duodenoscopy group. The difference in proportions was – 17.81 percentage points (95 % confidence interval [CI] –28.14 to –7.48) by intention-to-treat analysis and – 18.22 percentage points (95 %CI –28.34 to –8.10) by per-protocol analysis, both of which were significantly lower than the noninferiority margin of –5 %, and therefore the noninferiority of CA-EGD could not be confirmed. Examination time was significantly longer with CA-EGD (69.5 [SD 46.4] vs. 33.0 [SD 28.9] seconds; P &lt; 0.001). Conclusions Although complete examination of the MDP can be achieved by CA-EGD in most patients, it could not replace duodenoscopy as the standard method for examination of the MDP.
Abstract 20290: Inhibition of Neuronal Sodium Channel Isoforms Highly Contributes to the Suppression of Torsades De Pointes Arrhythmias in the Chronic Av Block Dog
Authors: Alexandre Bossu, Marien J Houtman, Jet D Beekman, Sridharan Rajamani, Marcel A van der Heyden, Marc A Vos
Journal: Circulation (2017)

Introduction: Enhancement of late sodium current (INaL) is proarrhythmic in heart failure. While the NaV1.5 isoform is believed to be the main carrier, the exact molecular origin of this current and the role of neuronal (NaV1.1 and NaV1.2) and peripheral (NaV1.8) isoforms to cardiac electrophysiology remain unclear. Eleclazine (E) is a NaV1.5 INaL inhibitor (1.1 μM IC50), A-803467 (A-8) a specific NaV1.8 blocker (10 nM) and GS-458967 (GS) a NaV1.5 INaL inhibitor (200 nM) with significant effects on NaV1.8 and neuronal isoforms NaV1.1 and NaV1.2. Hypothesis: To determine whether inhibition of neuronal and/or peripheral sodium channel isoforms provides additional antiarrhythmic effect in a sensitive canine arrhythmic model. Methods: The suppression of dofetilide-induced EADs and TdPs by E, GS and A-8 were respectively determined in single ventricular cardiomyocytes and chronic AV block (CAVB) dogs. Results: In isolated ventricular cardiomyocytes, E (3 μM) and GS (1 μM) similarly reduced dofetilide-induced E...
OP0297 Disease activity in rheumatoid arthritispatients is influenced by countries’ socioeconomics: results from the meteor registry
Authors: S.A. Bergstra, J. Tavares-Costa, M. Garzo-Elizondo, K. Salomon-Escoto, N. Govind, C. Allaart, R. Landewé
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> The treatment and prognosis of rheumatoid arthritis (RA) patients have improved tremendously, but patients across the world may not benefit similarly. One of the potentially critical factors may be poorer access to expensive biologic (b)DMARDs. <h3>Objectives</h3> To investigate daily practice data regarding bDMARD-use in different countries worldwide and assess if a lower country's socioeconomic status (SES) is associated with worse clinical outcomes and lower usage of bDMARDs. <h3>Methods</h3> Data on disease activity and drug use from countries that contributed ≥100 RA patients after 1–1–2000 were extracted from the daily practice, observational METEOR database. Missing data were imputed using multivariate normal imputation (30 cycles). Gross domestic product (GDP) per capita in international dollar (Intl$) was used as indicator of SES. Per country average DAS28 and the proportion of patients in DA28-remission (DAS28 &lt;2.6) were calculated by taking the average of all patients at the last available visit. Univariable logistic regression analyses were performed to assess associations between GDP, bDMARD use and disease outcomes at a country level. <h3>Results</h3> In total, 20.379 patients were included from 12 countries: United States, Mexico, South-Africa, Japan, Brazil, United Kingdom, Spain, Ireland, Portugal, France, India and the Netherlands. The number of patients ever using a bDMARD varied between 0.9% (South-Africa) and 75% (Ireland). The proportion of patients in remission at the final visit varied between 2% (India) and 39% (Netherlands). Patients in countries with a higher GDP per capita had a lower average DAS28 and consequently, a higher proportion of them were in DAS28-remission: β (95% CI) −0.32 (-0.41; −0.021) lower DAS28 and an additional 4.2% (0.14; 8.26) of patients in DAS28-remission for every 10.000 Intl$ additional GDP. To underscore the assumption that the association between SES and DAS28 is mediated by bDMARD use, we assessed whether SES was associated with bDMARD use per country. Indeed, a higher GDP per capita was associated with a higher proportion of patients using a bDMARD: β (95% CI) 11.2 (4.82; 17.5), indicating an additional 11% of patients using a bDMARD per 10.000 Intl$ increase in GDP per capita. Furthermore, DAS28 was β (95% CI) −0.14 (-0.28; −0.0054) lower and 2.8% (-0.13; 5.8) more patients achieved DAS28-remission per 10% increase in proportion of patients using a bDMARD, figure 1. <h3>Conclusions</h3> RA patients in countries with a lower SES had worse disease activity. Although patients in countries with a lower SES less often used bDMARDs, the effect of bDMARD use on disease activity was smaller than expected, indicating that other factors than access to bDMARDs may contribute to the effectiveness of RA treatment. <h3>Disclosure of Interest</h3> None declared
SAT0643 Ultrasound abnormalities in wrist, mcp2 and mtp5 are most discriminative in predicting arthritis development in seropositive arthralgia patients
Authors: A. Blanken, M. van Beers-Tas, M. Nielen, M. Meursinge Reynders, F. Turkstra, C. van der Laken, D. van Schaardenburg
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Seropositive arthralgia patients are at risk of developing rheumatoid arthritis (RA). Ultrasound (US) might be used to further predict which seropositive individuals will progress to RA. However, the value of US in the prediction of RA is still a point of debate, mainly due to the use of different scoring systems and compositions of joints in US protocols in literature. <h3>Objectives</h3> To investigate which joints are most discriminative in predicting arthritis development in seropositive arthralgia patients. <h3>Methods</h3> We included 174 seropositive patients with arthralgia, but without clinical arthritis. US was performed at baseline in 16 joints: bilateral metacarpal phalangeal (MCP) 2 and 3, proximal interphalangeal (PIP) 2 and 3, wrist and metatarsal phalangeal (MTP) joints 2, 3 and 5. Images were scored for grey-scale (GS) synovitis and Power Doppler (PD) on a scale of 0–3. Grades≥2 for GS synovitis and grades≥1 for PD were regarded as abnormal. Clinical arthritis development was assessed in any of 44 joints during yearly follow-up or during an unscheduled visit in case of progression of symptoms. Patients were followed until clinical arthritis development or for a maximum of 5 years. <h3>Results</h3> In a total of 2784 joints that were imaged, 112 showed GS synovitis and 14 PD. The majority of GS synovitis was present in MTP2 and MTP3 joints (56 (50%) and 32 (29%), respectively), followed by wrists (15 (13%)), MCP3 (4 (4%)), MTP5 (3 (3%)), MCP2 (2 (2%)) and none in PIPs. Out of 14 joints with PD, 7 were wrists, 3 MTP5, 2 MCP2 and 2 PIP3. Fifty-one (29%) of the patients developed clinical arthritis in at least one joint after a median follow-up of 12 (interquartile range 6–23) months. For GS synovitis, the wrist, MCP2 and MTP5 were most discriminative in predicting clinical arthritis development (12/15 (80%) of patients with GS synovitis in wrist developed clinical arthritis, 3/3 (100%) in MTP5 and 2/2 (100%) in MCP2). MTP2 and 3 were least discriminative (&lt;27%). No substantial differences were found between left and right joints. No clear association with clinical arthritis development was found in the limited number of joints that had positive PD. <h3>Conclusions</h3> Wrist, MCP2 and MTP5 joints (although numbers were small) showed the highest predictive value for development of clinical arthritis in any of 44 joints. Although most GS synovitis was observed in MTP2 and 3, predictive value of MTP2 and 3 joints for development of clinical arthritis was low. These results indicate that the choice of joints in the US protocol may influence the predictive value of ultrasound in predicting clinical arthritis development in seropositive arthralgia patients. <h3>Disclosure of Interest</h3> None declared
AB0194 Sparc is elevated in the affected skin of systemic sclerosis patients and induces the expression of fibrotic genes in dermal fibroblasts and macrophages
Authors: S. García Pérez, B. Malvar Fernández, M. Bergin, T. Johnson, W. Marut, K.A. Reedquist, T.R. Radstake
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Systemic sclerosis (SSc) is an autoimmune disease characterised by inflammation, vascular injury and excessive fibrosis in multiple organs. SPARC is a matricellular glycoprotein that can bind to extracellular matrix (ECM) components, as well as cellular receptors and secreted growth factors. In doing so, SPARC regulates biological activities dependent upon cellular interactions with the ECM as well as processes dependent upon cell adhesion, including tissue remodelling, wound healing, angiogenesis and immune responses. Several studies have implicated SPARC in the pathology of SSc but the specific role of SPARC in fibrosis is still unknown. <h3>Objectives</h3> The aim of this study was to analyse the potential role of SPARC as a regulator of fibrosis in SSc. <h3>Methods</h3> Expression of SPARC in the skin of healthy donors (HD) and SSc patients was measured by immunohistochemistry. Peripheral blood-derived monocytes from HD and SSc patients were differentiated into macrophages with M-CSF (25 ng/ml). Dermal fibroblasts and M-CSF macrophages from both HD and SSc patients were stimulated with SPARC (0.1 and 1 µg/ml) for 6 hour and 24 hour. mRNA and protein expression of SPARC and other fibrosis-related genes were measured by qPCR and western blot. <h3>Results</h3> We found increased expression of SPARC in the affected skin of SSc patients compared to HD. We also observed a higher expression of SPARC and ECM components (colagen(Col)−1 and fibronectin-1 (FN1) in dermal fibroblasts derived from SSc patients. SPARC stimulation induced mRNA expression of important fibrosis-related genes such as <i>TGFB1</i>, <i>PDGFB</i>, <i>SERPINE1</i> and <i>CTGF</i>, and ECM components including <i>COL1A1</i>, <i>COL3A1</i>, <i>COL4A1</i> and <i>FN1</i> in dermal fibroblasts from SSc patients, but not healthy donors. In M-CSF macrophages from SSc patients, SPARC also up-regulated mRNA expression of <i>TGFB1</i>, <i>PDGFB</i>, <i>STAB1</i>,<i>COL1A1</i> and <i>FN1</i>. <h3>Conclusions</h3> These results suggest that SPARC is an important pro-fibrotic mediator contributing to the pathology driving SSc. Therefore, SPARC could be a promising therapeutic target for reducing fibrosis in SSc. <h3>Disclosure of Interest</h3> S. García Pérez: None declared, B. Malvar Fernández: None declared, M. Bergin Employee of: UCB, T. Johnson Employee of: UCB, W. Marut: None declared, K. A. Reedquist: None declared, T. R. Radstake: None declared