tbuckley/cabot-search huggingface dataset:
AB0213 High power doppler signals seems more important than synovitis scores in established rheumatoid arthritis
Authors: ED Keskin, FG Yurdakul, H Bodur, A Tan Akıncı, L Özçakar
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease characterized by synovial inflammation, potential cartilage and bone damages. Evaluation with ultrasound (US) has come into prominence due to conventional radiography is relatively insensitive on soft tissue inflammatory changes and early bone erosions (1,2). <h3>Objectives</h3> The value of US has been shown in early arthritis, but is not well known for established RA. The aim of this study is to determine the relation between US signal, disease activity, articular damage and disability in established RA patients. <h3>Methods</h3> Forty-four RA patients (21 women, 23 men) were enrolled to the study. Age and gender, duration of disease, morning stiffness, disease activity score 28 (DAS28), The Rheumatoid Arthritis Articular Damage (RAAD) score, Hand disability Index (HDI), DASH (Disabilities of the Arm, Shoulder and Hand) scale, and grip strength values were recorded. Wrist, I-II- III. metacarpophalangeal and proximal interphalangeal joints of dominant hand were examined by both B mode US (BMOD) and Power Doppler US (PDUS). <h3>Results</h3> All of the 44 patients were established RA. The median of disease duration was 156 (48–420) months. DAS 28 score was 2.86 (0.68–5.70) and 54.5% of the patients were in remission. BMOD synovitis, erosion and PDUS synovitis total scores were 20 (6–36); 6 (0–17); 1 (0–14) respectively. Although US findings were not correlated with DAS 28 and grip strength; there was poor correlation between US findings and DASH, RAAD and disease duration (Table 1). Signs of synovitis indicated with PDUS in 63.3% of the joints assessed. High-grade PDUS signal (grade 3) was found in 10 (22.7%) of the patients. Duration of morning stiffness, HDI and DASH scores were worse in the patients with high-grade PDUS signals (p=0.01, 0.04, 0.01 respectively) <h3>Conclusions</h3> US scores in established RA patients are usually high because of synovial hypertrophy. It is considered that the high grade PDUS signals are more appropriate for evaluation of long-standing RA patients. Furthermore in this study, grade 3 PDUS signals were found to be a good indicator of synovial inflammation, morning stiffness, and disability. <h3>References</h3> Concordance between Clinical and ultrasound findings in rheumatoid arthritis. Garrigues F, Jousse-Joulin S, Bouttier R et al. Joint Bone Spine 80 (2013) 597–603. Severity and Diurnal Improvement of Morning Stiffness Independently Associate with Tenosynovitis in Patients with Rheumatoid Arthritis. Kobayashi Y, Ikeda K, Nakamura T et al. Plos One (11) Doi: 10.1371/journal.pone.0166616. <h3>Disclosure of Interest</h3> None declared
PAOLA-1: An ENGOT/GCIG phase III trial of olaparib versus placebo combined with bevacizumab as maintenance treatment in patients with advanced ovarian cancer following first-line platinum-based chemotherapy plus bevacizumab.
Authors: Isabelle Ray-Coquard, Frédéric Selle, Philipp Harter, Claire Cropet, Christian Marth, Ignace Vergote, Keiichi Fujiwara, Antonio Gonzalez-Martin, Sandro Pignata, Nicoletta Colombo, Johanna Unelma Maenpaa, Eric Pujade-Lauraine
Journal: Journal of Clinical Oncology (2016)

TPS5607 Background: Olaparib (Lynparza) is an oral PARP inhibitor indicated in the EU for the maintenance treatment of patients (pts) with platinum-sensitive relapsed BRCA-mutated high grade serous ovarian cancer (HGSOC). Bevacizumab is an anti-VEGF monoclonal antibody indicated in the EU in first line or relapse for the treatment of OC in combination with specific chemotherapeutic agents. Bevacizumab treatment is associated with increasing hypoxia-induced homologous recombination repair deficiencies in tumor cells, and is hypothesized to increase ovarian tumor sensitivity to olaparib. Methods: PAOLA-1 (ENGOT-ov25) is a randomized, placebo-controlled trial evaluating the efficacy and safety of olaparib (tablet formulation) in pts with advanced HGSOC receiving bevacizumab maintenance therapy. Eligible pts must be in complete or partial response following first-line platinum chemotherapy plus bevacizumab, and for whom bevacizumab maintenance therapy is planned. All pts will undergo tumor BRCAtesting prior to randomization. Approximately 612 European and 24 Japanese pts will be randomized 2:1 to olaparib 300 mg twice daily or placebo for up to 24 months. All pts will receive standard maintenance care of bevacizumab (15 mg/kg every three weeks) for up to 15 months. PFS will be evaluated using a log-rank test stratified by response to first-line treatment and BRCA mutation status. Central BRCA testing (tumor) for all pts will be identified among five screening platforms in France. Tumor BRCA test results have to be available within two months of sample provision. Final analyses will be performed after 372 PFS events. The first pt from eight ENGOT groups plus Japan (10 participating countries) was randomized in July 2015. As of 31 December 2015, 44 pts have been randomized and the average period between the provision of a tumor sample and returned BRCA test result is 37 days (range). Last pt treatment completion is expected Q3 2018, with last pt follow up in Q3 2021. Clinical trial information: NCT02477644.Primary objective PFS1 according to RECIST 1.1 Secondary objectives PRO/QoL, PFS2, OS, Safety, TFST, TSST
The first wave of T lymphopoiesis in zebrafish arises from aorta endothelium independent of hematopoietic stem cells
Authors: Ye Tian, Jin Xu, Shachuan Feng, Sicong He, Shizheng Zhao, Lu Zhu, Wan Jin, Yimei Dai, Lingfei Luo, Jianan Y. Qu, Zilong Wen
Journal: The Journal of Experimental Medicine (2017)

T lymphocytes are key cellular components of the adaptive immune system and play a central role in cell-mediated immunity in vertebrates. Despite their heterogeneities, it is believed that all different types of T lymphocytes are generated exclusively via the differentiation of hematopoietic stem cells (HSCs). Using temporal-spatial resolved fate-mapping analysis and time-lapse imaging, here we show that the ventral endothelium in the zebrafish aorta-gonad-mesonephros and posterior blood island, the hematopoietic tissues previously known to generate HSCs and erythromyeloid progenitors, respectively, gives rise to a transient wave of T lymphopoiesis independent of HSCs. This HSC-independent T lymphopoiesis occurs early and generates predominantly CD4 Tαβ cells in the larval but not juvenile and adult stages, whereas HSC-dependent T lymphopoiesis emerges late and produces various subtypes of T lymphocytes continuously from the larval stage to adulthood. Our study unveils the existence, origin, and ontogeny of HSC-independent T lymphopoiesis in vivo and reveals the complexity of the endothelial-hematopoietic transition of the aorta.
THU0018 Angiotensinogen as a marker of injury in lupus nephritis
Authors: LA Mas, S Retamozo, MJ Haye Salinas, V Saurit, EV Palomino, JL De la Fuente, M Angelina, JP Pirola, A Alvarellos, T Alvarellos
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Lupus Nephritis (LN) is one of the most severe forms of systemic lupus erythematosus (SLE) (1). Angiotensinogen (AGT) gene encodes the only glycoprotein known to be a precursor of the vasopresor angiotensin II (Ang II). Ang II is also a growth factor and a profibrogenic cytokine (2). In kidney transplantation AGT has been founded down expressed in biopsies with chronic allograft dysfunction (3). In LN, AGT deserves evaluation. <h3>Objectives</h3> To investigate AGT expression in biopsies and urines from LN patients. <h3>Methods</h3> 32 biopsies/urines paired from 32 LN patients was included. Kidney biopsies were evaluated according to the ISN/RPS classification system. Levels of AGT were evaluated using Quantitative Real Time PCR. Threshold cycle (C<sub>t</sub>) scores were averaged for calculations of relative expression values. The C<sub>t</sub> scores were normalized against C<sub>t</sub> scores by subtracting β2Microglobuline control, or ΔCt=C<sub>t,gene</sub>- C<sub>t,B2M</sub>. Data expressed as ΔCt are inversely proportional to gene expression level. Nonparametric Mann Whitney test analysis and Anova with Bonferroni test were performed. <h3>Results</h3> 26 (81.3%) patients were female with a mean age at biopsy time of 31.9±29 years. The SLEDAI at the time of biopsy was 10.5 (IQR 0–15.7) and SLICC ≥1 in 13 (32.5%), hypocomplementemia 13/31 (41.9%) and positive DNA in 11/29 (37.9%) patients. Biopsies from patients with proteinuria ≥0.5 and renal failure (n=23), proteinuria isolated (n=14), LN remission (n=9), renal failure (n=7) and nephrotic syndrome (n=2) were performed. The mean value of ΔCt AGT gene expression in renal biopsy was 4.50 (IQR 3.51 – 5.67) and AGT in urine samples was 13.94 (IQR 11.66 – 17.89). <h3>Conclusions</h3> In the present study we found a potential utility of AGT mRNA levels in samples of active vs remission LN patients. Prospective studies are needed for confirming these results. <h3>References</h3> Yajuan Li et al. Biomarkers Profiling for Lupus Nephritis. Genomics Proteomics Bioinformatics 11; 158–165, 2013. Eriguchi M et al. Assessment of urinary angiotensinogen as a marker of podocyte injury in proteinuric nephropathies. Am J Physiol Renal Physiol 310: F322–F333, 2016. Mas V et al. Establishing the molecular pathways involved in chronic allograft nephropathy for testing new non-invasive diagnostic markers. Transplantation. 83:448–57, 2007. <h3>Disclosure of Interest</h3> None declared
SAT0124 Higher bmi and shorter disease duration are associated with “fibromyalgic” rheumatoid arthritis – evaluation using power doppler ultrasonography
Authors: P Cheung, M Lahiri
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Power Doppler ultrasonography (PDUS) can differentiate RA patients who truly have active disease. Patients with persistent joint tenderness may not necessarily have true inflammation; yet composite disease activity indices remain high, leading to treatment escalation. These patients are often referred to having "fibromyalgic RA" where tender joints far exceed that of swollen joints. <h3>Objectives</h3> We evaluated the predictors of "fibromyalgic RA (FMRA)," defined as patient-reported tender joint count (TJC) at least 7 greater than PDUS joint count. <h3>Methods</h3> Consecutive RA patients were recruited in a tertiary rheumatology centre in Singapore. Patients self-assessed 28 joints for tenderness, followed by blinded PDUS assessment of the corresponding joints. Patients were grouped into either, (i) PDUS joint count &gt; patient-reported TJC, (ii) PDUS joint count = patient-reported TJC (iii) patient-reported TJC &gt; PDUS joint count, (difference &lt;7) (iv) patient-reported TJC &gt; PDUS joint count, (difference ≥7). Group (iv) is defined as FMRA. Predictors of FMRA were evaluated by multinomial logistic regression. <h3>Results</h3> Of the 101 patients, 81% were female, 72% Chinese, median age of 53.8 (IQR 48.1;62.4) and disease duration of 6.2 (1.9;8.8) years. Median BMI was 23.6 (20.8;27.0) and DAS28 was 3.2 (2.5;4.2). FMRA patients (15%) had a high median patient-reported TJC of 13 (10;18) but low median PDUS joint count of 1 (0;4). Compared to the other groups, they had higher median DAS28 of 4.6 (3.3;5.2), shorter mean disease duration of 2.3 (0.4;6.8) years, and higher median BMI of 26.9 (23.7;32.2). No differences in mean ESR or proportion of patients with seropositive disease were observed. Using Group (i) as the reference, patients with FMRA were more likely to have a higher BMI (adjusted OR=1.6, 95% CI 1.2; 2.1,p=0.001 for every unit increase) and shorter disease duration (adjusted OR=0.8, 95% CI 0.7;0.98,p=0.03 for every additional year). Age, gender, ethnicity, disease activity (PDUS score) and seropositivity were not significant predictors of FMRA. <h3>Conclusions</h3> Higher BMI and shorter disease duration were independent predictors of FMRA. Use of PDUS would be useful in this group, rather than basing treatment decisions on composite disease activity indices alone. <h3>Disclosure of Interest</h3> None declared
SAT0614 Ultrasound and urate crystal deposition: how many joints to screen?
Authors: D Bhadu, SK Das, A Wakhlu, U Dhakad
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Gout is one of the most common inflammatory joint disease in males. The new ACR/EULAR 2015 gout classification criteria has included imaging as a scoring item [1]. Naredo et al [2], found that in intercritical gout, assessment of one joint (ie, radiocarpal) and two tendons (ie, patellar and triceps) for HAGs, and three articular cartilages (ie, first metatarsal, talar and second metacarpal/femoral) for double contour sign (DCS) showed the best balance between sensitivity and specificity (84.6% and 83.3%, respectively). Ultrasound screening at these 6 sites is time consuming and not feasible in a busy outpatient service. So we aimed to compare the two sites (knee and 1st MTP joints) with these 6 sites for the ultrasound detected abnormalities namely DCS and HAGs in patients of gout particularly with the idea to find the best possible minimum joint combination without compromising the sensitivity and specificity. <h3>Objectives</h3> To compare the ultrasound-detected abnormalities namely double contour sign (DCS) and hyperechoic aggregates (HAGs) at knee and first metatarsophalangeal (1st MTP) joint (two sites) verses six sites (knee joint, 1st MTP joint, radiolcarpal joint, patellar tendon and triceps tendon) in patients of gout. <h3>Methods</h3> Forty seven gout and fifty controls (serum uric acid &lt;7mg/dl) with age more than 18 years were included in this study. DCS was looked for at three articular cartilage sites (first metatarsal, tibiotalar and femoral condyle) whereas HAGs were looked for at one joint site (radiocarpal joint) and two tendon sites (patellar tendon and triceps tendon). Ultrasound findings of all three groups were compared. <h3>Results</h3> We found sensitivity, specificity, positive predictive value, negative predictive value and positive likelihood ratio of two joint areas (knee and 1st MTP) ultrasound findings for gout were 87.2%, 84%, 83.7%, 85.6% and 5.5 respectively. Similar sensitivity, specificity, positive predictive value, negative predictive value and positive likelihood ratio were observed with 6 sites ultrasound findings. Amongst controls 17.5% were found to have these abnormal ultrasound findings by both two joint area and 6 sites exams. <h3>Conclusions</h3> Screening of two joint areas (knee and 1st MTP) has similar sensitivity, specificity and positive likelihood ratio as compared to six sites in diagnosing gout. While utilizing lesser time in examination. <h3>References</h3> Neogi T, Tim L, Dalbeth N, Fransen J, Schumacher HR, Berendsen D, et al. 2015 Gout classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Annals of the Rheumatic Diseases. 2015;74:1789. Naredo E, Uson J, Jiménez-Palop M, Martínez A, Vicente E, Brito E, et al. Ultrasound-detected musculoskeletal urate crystal deposition: which joints and what findings should be assessed for diagnosing gout? Ann Rheum Dis 2014;73: 1522–1528. <h3>Disclosure of Interest</h3> None declared
Proteinase‐activated receptor‐2 blockade inhibits changes seen in a chronic murine asthma model
Authors: M. Asaduzzaman, C. Davidson, D. Nahirney, Y. Fiteih, L. Puttagunta, H. Vliagoftis
Journal: Allergy (2017)

Abstract Background Proteinase‐Activated Receptor‐2 ( PAR 2 ) is a G protein‐coupled receptor activated by serine proteinases. We have shown that PAR 2 activation in the airways is involved in the development of allergic inflammation and airway hyperresponsiveness ( AHR ) in acute murine models. We hypothesized that functional inhibition of PAR 2 prevents allergic inflammation, AHR and airway remodeling in chronic allergic airway inflammation models. Material and Methods We developed and used a 12 week model of cockroach extract ( CE )‐mediated AHR , airway inflammation and remodeling in BALB /c mice. Results Mice sensitized and challenged with CE for 12 weeks exhibit AHR , increased numbers of eosinophils in bronchoalveolar lavage ( BAL ) and increased collagen content in the lung tissue compared to saline controls. Administration of an anti‐ PAR 2 antibody, SAM ‐11, after the initial development of airway inflammation significantly inhibited all these parameters. Conclusions Our data demonstrate that PAR 2 signaling plays a key role in CE ‐induced AHR and airway inflammation/remodeling in long term models of allergic airway inflammation. Targeting PAR 2 activation may be a successful therapeutic strategy for allergic asthma.
SP0094 The swedish experience - how a patient organisation could reach out to immigrants and develop through integration
Authors: T Diao
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Bakground</h3> in the early years of the new millennium many European countries faced an increased number of immigrants due to the second Iraqi war that affected the whole sub region. Some of these immigrants reached the Swedish shores and many of them have RMDs. In an attempt to help integrate them to the Swedish society, the SRA reached out to these immigrants with RMDs to give them the tools and the knowledge of how to live a decent life with RMDs and also to inform them about how the Swedish healthcare system works. By informing them and giving them the tools to live their lives to the fullest in Sweden the SRA participated indirectly to reduce the burden of the welfare system and also increased the number of our members and embraced the diversity in the organisation. <h3>Objectives</h3> By running some tests with our local chapters the SRA noticed that the lack of knowledge about the RMDs was immense among these minorities. So the SRA decided to act together with other actors to facilitate the inclusiveness of these minorities into the society. <h3>Methods</h3> To achieve this giant task the SRA applied and received financial support from the Swedish General inheritance fund and collaborated with several health providers, the employment office, some Folk High Schools, ABF (Adult Liberal Education Association) and our local chapters and joinders in 5 of the biggest cities: Stockholm, Örebro, Gothenburg, Norrköping and Umeå. <h3>Results</h3> This experience was a breakthrough for the SRA. The SRA was the firth patient organisation that walked this new path. The iconoclastic experience enriched the SRA and gave it a great knowledge of how to reach out to minority groups and giving them the tools to be a fully part of the society despite the burden of the RMDs. <h3>Conclusion</h3> The SRA increased it9s knowledge, capacity and flexibility during this experience. Today the SRA is cited as a reference in Sweden when it comes to reaching out to different minorities suffering of RMDs. Many organisations are now lining up to work with the SRA in these matters. In 2007 the SRA received the price for best project from the Swedish General Inheritance Fund. <h3>Disclosure of Interest</h3> None declared
Clinical and analytical evaluation of the new Aptima Mycoplasma genitalium assay, with data on M. genitalium prevalence and antimicrobial resistance in M. genitalium in Denmark, Norway and Sweden in 2016
Authors: M. Unemo, K. Salado-Rasmussen, M. Hansen, A.O. Olsen, M. Falk, D. Golparian, M. Aasterød, J. Ringlander, C. Stezckó Nilsson, M. Sundqvist, K. Schønning, H. Moi, H. Westh, J.S. Jensen
Journal: Clinical Microbiology and Infection (2017)

Mycoplasma genitalium (MG) causes urethritis and cervicitis, potentially causing reproductive complications. Resistance in MG to first-line (azithromycin) and second-line (moxifloxacin) treatment has increased. We examined the clinical and analytical performance of the new Conformité Européene (CE)/in vitro diagnostics (IVD) Aptima Mycoplasma genitalium assay (CE/IVD AMG; Hologic); the prevalence of MG, Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG); and MG resistance to azithromycin and moxifloxacin in Denmark, Norway and Sweden in 2016.From February 2016 to February 2017, urogenital and extragenital (only in Denmark) specimens from consecutive attendees at three sexually transmitted disease clinics were tested with the CE/IVD AMG, the research-use-only MG Alt TMA-1 assay (Hologic), Aptima Combo 2 (CT/NG) assay and a laboratory-developed TaqMan real-time mgpB quantitative real-time PCR (qPCR). Resistance-associated mutations were determined by sequencing. Strains of MG and other mycoplasma species in different concentrations were also tested.In total 5269 patients were included. The prevalence of MG was 7.2% (382/5269; 4.9-9.8% in the countries). The sensitivity of the CE/IVD AMG, MG Alt TMA-1 and mgpB qPCR ranged 99.13-100%, 99.13-100% and 73.24-81.60%, respectively, in the countries. The specificity ranged 99.57-99.96%, 100% and 99.69-100%, respectively. The prevalence of resistance-associated mutations for azithromycin and moxifloxacin was 41.4% (120/290; 17.7-56.6%) and 6.6% (18/274; 4.1-10.2%), respectively. Multidrug resistance was found in all countries (2.7%; 1.1-4.2%).Both transcription-mediated amplification (TMA)-based MG assays had a highly superior sensitivity compared to the mgpB qPCR. The prevalence of MG and azithromycin resistance was high. Validated and quality-assured molecular tests for MG, routine resistance testing of MG-positive samples and antimicrobial resistance surveillance are crucial.
The Incidence and Prevalence of Systemic Lupus Erythematosus in New York County (Manhattan), New York: The Manhattan Lupus Surveillance Program
Authors: Peter M. Izmirly, Isabella Wan, Sara Sahl, Jill P. Buyon, H. Michael Belmont, Jane E. Salmon, Anca Askanase, Joan M. Bathon, Laura Geraldino‐Pardilla, Yousaf Ali, Ellen M. Ginzler, Chaim Putterman, Caroline Gordon, Charles G. Helmick, Hilary Parton
Journal: Arthritis & Rheumatology (2017)

Objective The Manhattan Lupus Surveillance Program (MLSP) is a population‐based registry designed to determine the prevalence of systemic lupus erythematosus (SLE) in 2007 and the incidence from 2007 to 2009 among residents of New York County (Manhattan), New York, and to characterize cases by race/ethnicity, including Asians and Hispanics, for whom data are lacking. Methods We identified possible SLE cases from hospital records, rheumatologist records, and administrative databases. Cases were defined according to the American College of Rheumatology (ACR) classification criteria, the Systemic Lupus International Collaborating Clinics (SLICC) classification criteria, or the treating rheumatologist's diagnosis. Rates among Manhattan residents were age‐standardized, and capture–recapture analyses were conducted to assess case underascertainment. Results By the ACR definition, the age‐standardized prevalence and incidence rates of SLE were 62.2 and 4.6 per 100,000 person‐years, respectively. Rates were ∼9 times higher in women than in men for prevalence (107.4 versus 12.5) and incidence (7.9 versus 1.0). Compared with non‐Hispanic white women (64.3), prevalence was higher among non‐Hispanic black (210.9), Hispanic (138.3), and non‐Hispanic Asian (91.2) women. Incidence rates were higher among non‐Hispanic black women (15.7) compared with non‐Hispanic Asian (6.6), Hispanic (6.5), and non‐Hispanic white (6.5) women. Capture–recapture adjustment increased the prevalence and incidence rates (75.9 and 6.0, respectively). Alternate SLE definitions without capture–recapture adjustment revealed higher age‐standardized prevalence and incidence rates (73.8 and 6.2, respectively, by the SLICC definition and 72.6 and 5.0 by the rheumatologist definition) than the ACR definition, with similar patterns by sex and race/ethnicity. Conclusion The MLSP confirms findings from other registries on disparities by sex and race/ethnicity, provides new estimates among Asians and Hispanics, and provides estimates using the SLICC criteria.