tbuckley/cabot-search huggingface dataset:
AB0649 Use of biological dmards in patients with primary vasculitis; results from turkbio registry
Authors: A. Yazici, A. Cefle, E. Dalkilic, Y. Pehlivan, G. Can, B. Goker, A. Tufan, S. Senel, S.S. Koca, S. Akar, N. Akkoç, F. Onen
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Untreated, The systemic vasculitides can be devastating, with high rates of morbidity and mortality. Recently, most of biological agents have evaluated in clinical trials, and management of systemic vasculitis has been revolutionised over the last decade.<sup>1 2</sup> <h3>Objectives</h3> Here, we report the frequency of using and switching rate of biological agents in different types of primary vasculitis patients. <h3>Methods</h3> TURKBIO registry is the Turkish version of Danish DANBIO rheumatological database which has been established in 2011. All patients with primary vasculitis who received biological agents registered in TURKBIO registry between dates of October 2011 and January 2018 were included in this study. The demographic data, the date of starting to use of biological drug, frequency of using and switching biological agents were collected. <h3>Results</h3> As of January 2018, 108 primary vasculitis patients were recruited (mean age: 38.4±10.9 [min-max: 19–67]; female 48%); 48 patients (44%) of them had Behcet's disease (BH), 35 (32%) had Takayasu arteritis (TA), 24 (22%) had granulomatosis polyangiitis, and one of them had microscopic polyangiitis. The most commonly used biological agents in current treatment were as follows: 75% of patients received infliximab (INF) and 15% received adalimumab (ADA) in BD patients; 48.6% received tocilizumab (TCZ), 23% received INF and 20% received ADA in TA patients; all patients with granulomatosis with polyangiitis (GPA) were treated with rituximab. The switching rate was 54% in TA patients, 27% in BD patients, and 4% in GPA patients. The most frequent switching was found at INF (28/78) and ADA (9/23) which was the most commonly used agent in TA and BD. The lowest switching rate was TCZ (2/17) in TA patients (table 1). <h3>Conclusions</h3> This is the first evaluation of primary vasculitis patients who used biological agents from TURKBIO registry. According our data, there was high switching rate with anti-TNF agents in TA patients. The limitation of this study was the low number of the patients with primary vasculitis who used biological agents. <h3>References</h3> [1] Jarrot PA, Kaplanski G. Anti-TNF-alpha therapy and systemic vasculitis. Mediators Inflamm. 2014;2014:493593. [2] Henderson CF, Seo P. Biologic agents in systemic vasculitis. Int J Clin Rheumtol. 2011; 6(4):453–462. <h3>Acknowledgements</h3> None <h3>Disclosure of Interest</h3> None declared
AB1115 Systemic lupus erythematosus in paediatric population- a single centre study from india
Authors: P.P. Giri, P. Pal
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> systemic lupus erythematosus is an autoimmune disease that can be manifest in paediatric polpulation in various ways. It is characterised by widespread inflammation of the blood vessels and connective tissues with positive autoantibodies. Though it is a chronic disease it can be fatal at times. <h3>Objectives</h3> 1. To study the diversity in clinical and laboratory profile in paediatric systemic lupus erythematosus patients at a tertiary care centre in Kolkata. 2. To identify the poor prognostic factors at the time of admission to the hospital. 3. To quantify the drug related adverse effects in follow up. <h3>Methods</h3> Both old known cases and newly diagnosed cases of paediatric SLE who presented to our rheumatology follow up clinic over last 18 months were retrospectively reviewed for their clinical and immunological presentation.SLICC diagnostic criteria has been applied to define a positive case. <h3>Results</h3> A total number of 64 patients were evaluated, among which 54 were girls and 10 were boys with a sex ratio of 5.4:1 favouring girls. Mean age on presentation was 9.9 years with a range of 2.5 to 16 years. Among the clinical presentation fever (72%) was the most common symptom, followed by skin manifestation (68.8%), musculoskeletal involvement (53.1%), haematological involvement (37.5%). Renal involvement was seen in 35.9%, among which 59.1% had stage IV lupus nephritis, and central nervous system involvement was observed in 10.9%. Among immunological profile, ANA was positive in 95.3%, anti-double-stranded DNA was positive in 92.1% and low complement levels were seen in 92.1%. Antiphospholipid antibody was seen in 7 patients (n=21) and anti-Smith antibody in 3 (n=4). All the patients required therapy with steroids and hydroxychloroquine. Steroid sparing agents like azathioprine (54.7%), cyclophosphamide (28.1%), mycophenolate mofetil (23.4%), methotrexate (18.7%), and rituximab (10.9%) were also used. <h3>Conclusions</h3> Paediatric SLE has got a varied presentation, and a high index of suspicion is needed for early diagnosis and timely management with multiple drugs of this dreadful disease <h3>Disclosure of Interest</h3> None declared
AB0891 Disease activity predicts functional impairment and spinal mobility in axial spondyloarthritis
Authors: T. Williams, A. Wadeley, C. Cavill, M. Freeth, J. Hole, R. Sengupta
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Axial Spondyloarthritis (axSpA) is a chronic inflammatory disease, mainly affecting the spine and sacroiliac joints. This results in progressive spinal immobility and can result in a level of disability comparable to Rheumatoid Arthritis<sup>1</sup>. The natural history of axSpA and relationships between active inflammation, structural damage and functional impairment remain poorly understood. Previous studies have hypothesised that functional impairment and spinal mobility in axSpA are independently influenced by disease activity and radiographic damage<sup>1,2,3</sup>. <h3>Objectives</h3> To define the relationship between disease activity, spinal mobility and radiographic damage with other patient-reported outcome measures in axSpA. <h3>Methods</h3> We performed a cross-sectional analysis of axSpA patients attending the Royal National Hospital for Rheumatic Diseases, Bath. The most recent outcome measures for each patient were compared. Spinal mobility was assessed using the BASMI; structural radiographic damage by the mSASSS; disease activity by the BASDAI; functional impairment by the BASFI; fatigue by the FACIT score; work disability by the WPAI-overall; quality of life by the ASQoL; overall health by the EQ5D. We analysed the correlation between these variables, separately for patients with Ankylosing Spondylitis (AS) and non-radiographic axSpA (nr-axSpA). <h3>Results</h3> 721 axSpA patients were included for analysis (548 AS; 42 nrAxSpA; 39 inflammatory bowel disease-related SpA; 47 juvenile-onset SpA; 24 psoriatic SpA; 3 reactive SpA; 18 undifferentiated SpA). Results are summarised in table 1: <h3>Conclusions</h3> Spinal mobility and disease activity are both correlated with functional impairment, along with other measures of disability and poor health in axSpA, with BASDAI the strongest predictor of BASFI. Consistent with other studies, BASDAI was more predictive of spinal mobility in nrAxSpA than AS patients (p=0.002, 1-tailed). Structural radiographic damage is the strongest predictor of spinal mobility in AS. BASMI scores merit further investigation to ascertain their potential as a surrogate for radiographic disease burden in axSpA. <h3>References</h3> [1] Landewe R, et al. Physical function in ankylosing spondylitis is determined by both disease activity and radiographic damage of the spine. Ann Rheum Dis2009; 68: 863–7. [2] Calvo-Gutierrez J, et al. Is spinal mobility in patients with spondylitis determined by age, structural damage and inflammation?Arthritis Care Res2015; 67 (1): 74–9. [3] Machado P, et al. A stratified model for health outcomes in Ankylosing Spondylitis. Ann Rheum Dis2011; 70 (10): 1758–64. <h3>Disclosure of Interest</h3> None declared
Microbial network disturbances in relapsing refractory Crohn’s disease
Authors: Bahtiyar Yilmaz, Pascal Juillerat, Ove Øyås, Charlotte Ramon, Francisco Damian Bravo, Yannick Franc, Nicolas Fournier, Pierre Michetti, Christoph Mueller, Markus Geuking, Valerie E. H. Pittet, Michel H. Maillard, Gerhard Rogler, Reiner Wiest, Jörg Stelling, Andrew J. Macpherson
Journal: Nature Medicine (2019)
The anthracycline doxorubicin induces cathepsin B via activation of the transcription factor NFκB.
Authors: Christoph A. Ritter, Sandra Bien, Bernhard Sperker, Jürgen Sonnemann, Michael Hummel, James F. Beck, Heyo K. Kroemer
Journal: Cancer Research (2004)

2260  Anthracyclines like doxorubicin are widely used for the treatment of many human neoplasms. However, their therapeutic index is compromised by side effects like the irreversible cardiotoxicity leading to heart failure. Although antineoplastic action and cardiac toxicity seem to be closely related, the underlying mechanisms are not entirely understood. Therefore, cDNA microarray analysis of the cervical carcinoma cell line HeLa after treatment with doxorubicin was performed. Out of 22283 genes on the chip, 3979 genes were regulated by a 24 h-incubation with doxorubicin. Among the 2004 genes that were upregulated, one group of genes encoding for the lysosomal protein family of cathepsins was strongly induced by doxorubicin treatment. Cathepsin B is of particular interest since this cystein protease is highly expressed in tumor cells and involved in intracellular protein degradation, angiogenesis, metastasis and apoptosis. Incubation of HeLa cells with doxorubicin resulted in an induction of mRNA and protein expression as well as enzyme activity in a time and concentration dependent manner as determined by Real Time PCR, Western Blot Analysis and enzyme activity assay. Usage of NFκB inhibitors HNE, CAPE, and dexamethason, IκBα immunoblotting and electrophoretic mobility shift assay (EMSA) revealed that cathepsin B induction in response to doxorubicin treatment resulted from activation of the transcription factor NFκB. In addition, inhibition of PI3K and PKC with the specific inhibitors LY294002 and bisindolylmaleimide resulted in a significant reduction of doxorubicin-mediated cathepsin B induction. Since it is known that cathepsin B is involved in apoptosis we further investigated the effect of NFκB mediated cathepsin B induction by doxorubicin on apoptosis by measuring activities of caspases 3 and 9 as early markers of apoptosis. After preincubation of cells with the cathepsin B inhibitor CA-074Me, activities of caspases 3 and 9 were strongly reduced in HeLa cells. These data are relevant since cathepsin B can be used as activating enzyme for specific tumor targeted therapies. Moreover, induction of cathepsin B by doxorubicin could increase the therapeutic efficiency of tumor targeted drugs.
SP0090 Us for pulley lesions – clinical relevance
Authors: I. Möller
Journal: Annals of the Rheumatic Diseases (2018)

<h3></h3> In the human body the pulleys are represented as structures that change the path of a tendon as they pass over them. The pulleys are composed of fibrocartilage (finger pulleys), cartilage (trochlea of the eye), ligament (extensor retinaculum) or bone (lateral malleolus). The clinical relevance of the pulleys of the flexor digitorum tendons (FDT) of the hand is indisputable in that it affects the flexion and excursion efficiency of the FDT and can generate pain. This system is composed of the transverse carpal ligament, the palmar aponeurosis pulley, and the digital flexor pulley system. There is some controversy about the functional relevance of the injury of the different FDT pulleys including the palmar aponeurotic pulley. Pulleys can be affected by different conditions including chondroid metaplasia, tenosynovial ganglions, traumatic or inflammatory lesions of the FDT sheet, sport practice or work activities. Changes in thickness have recently been identified in flexor pulleys in patients with psoriasis arthropathy with a history of dactylitis and have been related to the so-called Koebner response. Musculoskeletal ultrasound allows the visualisation of these structures statically and dynamically while at the same time it is an instrument to increase the precision in steroid injection of the trigger finger when is needed <h3>Disclosure of Interest</h3> None declared
THU0462 Long term follow-up results of takayasu arteritis cohort: a tertiary-single centre study
Authors: S. Kaymaz Tahra, F. Alibaz-Oner, H. Direskeneli
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Objectives</h3> To assess the clinical characteristics and long term follow-up outcomes of patients with Takayasu's arteritis (TAK) in a tertiary referral centre. <h3>Methods</h3> In this retrospective study, 107 (F/M: 96/11) patients fullfilling <sup>ACR 1990</sup> criteria for Takayasu Arteritis and referred to our centre between 2004 and 2017 were investigated. All clinical and demographic data during first diagnosis and longitudinal follow-up were abstracted from medical records. Relapse was defined according to the physician's global assessment (PGA). <h3>Results</h3> The median age was 30<sup>14–67</sup> years at symptom onset and 33<sup>14–68</sup> years at diagnosis. Median follow-up duration was 72 (6–264) months. According to Hata Angiographic Classification, Type 5 (51.8%) and Type 1 (38.8%) were the most common patterns with the most frequently affected vessel subclavian artery (82.2%). At diagnosis 0.5–1 mg/kg/day corticosteroid treatment was started in 94.6% patients and a steroid-sparing immunsuppressive (IS) agent in 96.3% of the patients. An initial pulse steroid (1 g/day) therapy was chosen for 8 patients. Before diagnosis 24% patients had a history of a revascularisation procedure. After IS treatments, 24% of the patients were undergone a new revascularisation procedure. During follow-up, biologic agents were chosen for 13.8% of the patients (5 infliximab and certolizumab each, 2 adalimumab and 2 tociluzumab). Remission was observed in 84% of the patients. At least one relapse was occured in 43% and &gt;1 relapse in%14 patients. At the last visit 26% were determined to have an active disease. A&gt;4 mg of methylprednisolone dose was required in only 8.4%. Mortality rate was 3.7% (4 patients). Table 1 Clinical characteristics and outcomes of patients <h3>Conclusions</h3> We have defined the long-term follow-up results of our Takayasu's arteritis cohort. Comparing with European and Asia series published recently, requirement for a surgical intervention was lower under immunosuppressive treatments in our series. However, disease activity and relapse rate were still high under conventional ISs, suggesting a need for better therapeutic options. <h3>Disclosure of Interest</h3> None declared
Vitamin D to prevent exacerbations of COPD: systematic review and meta-analysis of individual participant data from randomised controlled trials
Authors: David A Jolliffe, Lauren Greenberg, Richard L Hooper, Carolien Mathyssen, Rachida Rafiq, Renate T de Jongh, Carlos A Camargo, Christopher J Griffiths, Wim Janssens, Adrian R Martineau
Journal: Thorax (2019)

Randomised controlled trials (RCTs) of vitamin D to prevent COPD exacerbations have yielded conflicting results.Individual participant data meta-analysis could identify factors that explain this variation.PubMed, Embase, the Cochrane Central Register of Controlled Trials and Web of Science were searched from inception up to and including 5 October 2017 to identify RCTs of vitamin D supplementation in patients with COPD that reported incidence of acute exacerbations. Individual participant data meta-analysis was performed using fixed effects models adjusting for age, sex, Global Initiative for Chronic Obstructive Lung Disease spirometric grade and trial.Four eligible RCTs (total 560 participants) were identified; individual participant data were obtained for 469/472 (99.4%) participants in three RCTs. Supplementation did not influence overall rate of moderate/severe COPD exacerbations (adjusted incidence rate ratio (aIRR) 0.94, 95% CI 0.78 to 1.13). Prespecified subgroup analysis revealed that protective effects were seen in participants with baseline 25-hydroxyvitamin D levels <25 nmol/L (aIRR 0.55, 95% CI 0.36 to 0.84) but not in those with baseline 25-hydroxyvitamin D levels ≥25 nmol/L (aIRR 1.04, 95% CI 0.85 to 1.27; p for interaction=0.015). Vitamin D did not influence the proportion of participants experiencing at least one serious adverse event (adjusted OR 1.16, 95% CI 0.76 to 1.75).Vitamin D supplementation safely and substantially reduced the rate of moderate/severe COPD exacerbations in patients with baseline 25-hydroxyvitamin D levels <25 nmol/L but not in those with higher levels.CRD42014013953.
Abstract 17650: Myocardial Fibrosis in Systemic Sclerosis, Progression and Response to Therapy Measured by Cardiovascular Magnetic Resonance
Authors: Daniel C Lee, Sanjiv J Shah, Brandon C Benefield, James C Carr, Benjamin H Freed, Carol Ann Burns, Richard K Burt
Journal: Circulation (2017)

Introduction: Myocardial fibrosis is seen in half of Systemic Sclerosis (SSc) patients, and is associated with an increased risk of cardiac death. Extracellular volume fraction (ECV), an index of m...
Differential NOVA2-Mediated Splicing in Excitatory and Inhibitory Neurons Regulates Cortical Development and Cerebellar Function
Authors: Yuhki Saito, Yuan Yuan, Ilana Zucker-Scharff, John J. Fak, Saša Jereb, Yoko Tajima, Donny D. Licatalosi, Robert B. Darnell
Journal: Neuron (2019)
SAT0160 Effect of periodontal treatment on e-selectin level in rheumatoid arthritis patients
Authors: S. A. Kusumo, H. Isbagio, S. Marhamah, C. Intan, D. Antono, K. Harimurti
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background:</h3> Cardiovascular (CV) disease is the main cause of mortality in rheumatoid arthritis (RA).<sup>1</sup> Studies showed that periodontitis is associated with RA and CV diseases.<sup>2–4</sup> Endothelial dysfunction is the first step in the pathogenesis of atherosclerosis. E-selectin is a marker of endothelial dysfunction and was expressed specifically in endothelial cells. To date, there is no study on the effect of periodontal treatment on endothelial dysfunction in RA patients. <h3>Objectives:</h3> To determine the effect of periodontal treatment on E-selectin level in RA patients. <h3>Methods:</h3> This was a clinical trial in RA patients visiting Rheumatology Clinic in our hospital between March-May 2017. Inclusion criteria: adult RA patients, has periodontitis, low-high RA disease activity, RA duration of 10 years or less, has received DMARD. Exclusion criteria: subjects who smoke, have diabetes, underwent dental treatment for the past 3 months, have other autoimmune diseases, and patients who refused to join the study. Subjects was randomized into intervention group (periodontal scaling for 1 month) and control group. Study flow is visualized in figure 1. E-selectin level was measured at the start and at the end of the study. T-test was used to measure the difference of E-selectin level changes before-after study between groups. <h3>Results:</h3> There were 31 subjects who completed the study. The prevalence of periodontitis was 64.5%. There was no statistically significant difference on delta E-selectin before-after treatment between both groups (table 1). We further divided the subjects based on disease activity and lipid profile at the end of the study. Subjects on the treatment group who was on remission and has normal lipid profile (normal LDL and decreased total cholesterol/HDL ratio) has decreased E-selectin level compared to other subjects. <h3>Conclusions:</h3> Periodontal treatment for a month has no effect on E-selectin level in RA patients. Further studies on the effect of periodontal treatment on endothelial dysfunction in RA patient needs to be done on patients on remission, without dyslipidemia, and with longer treatment period. <h3>References</h3> [1]Zochling J, Braun J. Clin Exp Rheumatol2009;27(Suppl.55):S127–30. [2]Chou YY, Lai KL, Chen DY, et al. PLoS ONE2015;10(10):e0139693. [3]Leng WD, Zeng XT, Kwong JSW, et al. Int J Cardiol2015;201:469–72. [4]Abou-Raya S, Abou-Raya A, Naim A, et al. Clin Rheumatol2008;27(4):421–7. <h3>Disclosure of Interest:</h3> None declared
Selective BMP-9 Inhibition Partially Protects Against Experimental Pulmonary Hypertension
Authors: Ly Tu, Agnès Desroches-Castan, Christine Mallet, Laurent Guyon, Amélie Cumont, Carole Phan, Florian Robert, Raphaël Thuillet, Jennifer Bordenave, Ayumi Sekine, Alice Huertas, Olli Ritvos, Laurent Savale, Jean-Jacques Feige, Marc Humbert, Sabine Bailly, Christophe Guignabert
Journal: Circulation Research (2019)

Rationale: Although many familial cases of pulmonary arterial hypertension exhibit an autosomal dominant mode of inheritance with the majority having mutations in essential constituents of the BMP (bone morphogenetic protein) signaling, the specific contribution of the long-term loss of signal transduction triggered by the BMPR2 (type 2 BMP receptor) remains poorly characterized. Objective: To investigate the role of BMP9, the main ligand of ALK1 (Activin receptor-like kinase 1)/BMPR2 heterocomplexes, in pulmonary hypertension. Method and Results: The absence of BMP9 in Bmp9 −/− mice and its inhibition in C57BL/6 mice using neutralizing anti-BMP9 antibodies substantially prevent against chronic hypoxia-induced pulmonary hypertension judged by right ventricular systolic pressure measurement, right ventricular hypertrophy, and pulmonary distal arterial muscularization. In agreement with these observations, we found that the BMP9/BMP10 ligand trap ALK1 ECD administered in monocrotaline or Sugen/hypoxia (SuHx) rats substantially attenuate proliferation of pulmonary vascular cells, inflammatory cell infiltration, and regresses established pulmonary hypertension in rats. Our data obtained in human pulmonary endothelial cells derived from controls and pulmonary arterial hypertension patients indicate that BMP9 can affect the balance between endothelin-1, apelin, and adrenomedullin. We reproduced these in vitro observations in mice chronically exposed to hypoxia, with Bmp9 −/− mice exhibiting lower mRNA levels of the vasoconstrictor peptide ET-1 (endothelin-1) and higher levels of the 2 potent vasodilator factors apelin and ADM (adrenomedullin) compared with Bmp9 +/+ littermates. Conclusions: Taken together, our data indicate that the loss of BMP9, by deletion or inhibition, has beneficial effects against pulmonary hypertension onset and progression.