tbuckley/cabot-search huggingface dataset:
SP0152 Hypertension, bone marrow lesions and osteoarthritis (OA)
Authors: D. Felson
Journal: Annals of the Rheumatic Diseases (2018)

<h3></h3> Elements of the metabolic syndrome except for hypertension such as dyslipidemia and central adiposity are not consistently associated with knee osteoarthritis once obesity is adjusted for. However, after adjustment for obesity, hypertension is modestly associated with an increased risk of knee and even, in some studies, hand OA. A recent meta-analysis reported consistency across large cohort and case control studies; those with hypertension had a 1.49 fold increased odds of OA (p&lt;0.001). There a several possible explanations for this association especially if hypertension compromises the supply of nutrients to the joint. First, as OA develops, subchondral bone remodelling is accompanied by angiogenesis which could be inhibited by vascular insufficiency. In findings that are probably related, bone marrow lesions seen on MRI in OA represent lesions of bone trauma and, in these lesions, the number of vessels increases and the vessels have especially thick walls for their size. Bone marrow lesions have been linked to intraosseous hypertension that is probably not a consequence of arterial but rather of venous hypertension within bone. Further, NSAID use in persons with OA could raise blood pressure and create a spurious association of OA with hypertension. Given this range of potential explanations and the potential for identification of causal factors that may offer clues to OA treatment, further exploration of the biology of this relationship is needed. <h3>Disclosure of Interest</h3> None declared
AB0012 Allele and genotype frequency of some gene polymorphisms differs in various juvenile idiopathic arthritis subtypes
Authors: H.A. Yatskiu, N.V. Nikitchenko, N.V. Savina, T.D. Kuzhir, A.M. Tchitchko, I.D. Chyzheuskaya, N.L. Bilskaya, M.G. Myslivets, A.V. Sukalo, R.I. Goncharova
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> In spite of the fact that chronic arthritis has been the core of paediatric rheumatology, etiology and pathogenesis of juvenile idiopathic arthritis (JIA) are still unclear. It is important to ascertain genetic nature of such a heterogeneous disease. <h3>Objectives</h3> The aim of the study was to assess the role of some SNPs of six genes implicated in immune and inflammatory responses: <i>TNFα</i> (rs1800629, rs361525), <i>PTPN22</i> (rs2476601), <i>MIF</i> (rs755622, rs5844572), <i>TRAF/C5</i> (rs3761847), <i>CTLA4</i> (rs5742909, rs231775), <i>STAT4</i> (rs7574865); as well as homozygous deletions of xenobiotic biotransformation genes <i>GSTT1</i> and <i>GSTM1</i>. <h3>Methods</h3> 206 patients diagnosed with JIA (mean age 8.87±4.92), and 218 hospital controls with no signs of autoimmune or inflammatory diseases (mean age13.88±2.72) were recruited for the study. The JIA patients were divided into subgroups according to IIAR classification criteria; the majority of them (125 patients) had oligoarthritis, 42 children developed RF-negative polyarthritis and 27 patients were diagnosed with systemic arthritis. Genomic DNA was extracted from peripheral blood samples by means of the phenol-chloroform method. SNPs were genotyped using PCR-RFLP, Real-Time PCR or fragmental analysis. <h3>Results</h3> The allele frequencies for all SNPs in the hospital control group were similar to those in European populations. The allele and genotype frequency distribution for all SNPs was identical in patients and controls. However, when comparing distinct subtypes of JIA, <i>STAT4</i> polymorphism demonstrated higher frequencies of minor T allele (30.5% vs. 17.8%, p=0.01, OR=2.03, 95% CI [1.14–3.6] and G/T genotype (46.3% vs. 25.6%, p=0.03, OR=2.51, 95%[1.2–5.24]) in RF-negative polyarthritis than in oligoarthritis. On the contrary, Δ<i>GSTT1</i> appeared to prevail in oligoarthritis (23.7% vs. 7.9% in RF-negative polyarthritis, p=0.03, OR=3.6, 95% CI [1.03–12.7]). As to systemic arthritis, it was shown, that minor G allele of <i>TRAF/C5</i> was more frequent in comparison with oligoarthritis (p=0.037, OR=2.43, 95% CI [1.05–5.6]). <h3>Conclusions</h3> The results obtained can be considered as evidence for distinct genetic nature of the different JIA subtypes. <h3>Disclosure of Interest</h3> None declared
Exosome-Mediated miR-29 Transfer Reduces Muscle Atrophy and Kidney Fibrosis in Mice
Authors: Haidong Wang, Bin Wang, Aiqing Zhang, Faten Hassounah, Yiqi Seow, Matthew Wood, Fuying Ma, Janet D. Klein, S. Russ Price, Xiaonan H. Wang
Journal: Molecular Therapy (2019)

Our previous study showed that miR-29 attenuates muscle wasting in chronic kidney disease. Other studies found that miR-29 has anti-fibrosis activity. We hypothesized that intramuscular injection of exosome-encapsulated miR-29 would counteract unilateral ureteral obstruction (UUO)-induced muscle wasting and renal fibrosis. We used an engineered exosome vector, which contains an exosomal membrane protein gene Lamp2b that was fused with the targeting peptide RVG (rabies viral glycoprotein peptide). RVG directs exosomes to organs that express the acetylcholine receptor, such as kidney. The intervention of Exo/miR29 increased muscle cross-sectional area and decreased UUO-induced upregulation of TRIM63/MuRF1 and FBXO32/atrogin-1. Interestingly, renal fibrosis was partially depressed in the UUO mice with intramuscular injection of Exo/miR29. This was confirmed by decreased TGF-β, alpha-smooth muscle actin, fibronectin, and collagen 1A1 in the kidney of UUO mice. When we used fluorescently labeled Exo/miR29 to trace the Exo/miR route in vivo and found that fluorescence was visible in un-injected muscle and in kidneys. We found that miR-29 directly inhibits YY1 and TGF-β3, which provided a possible mechanism for inhibition of muscle atrophy and renal fibrosis by Exo/miR29. We conclude that Exo/miR29 ameliorates skeletal muscle atrophy and attenuates kidney fibrosis by downregulating YY1 and TGF-β pathway proteins. Our previous study showed that miR-29 attenuates muscle wasting in chronic kidney disease. Other studies found that miR-29 has anti-fibrosis activity. We hypothesized that intramuscular injection of exosome-encapsulated miR-29 would counteract unilateral ureteral obstruction (UUO)-induced muscle wasting and renal fibrosis. We used an engineered exosome vector, which contains an exosomal membrane protein gene Lamp2b that was fused with the targeting peptide RVG (rabies viral glycoprotein peptide). RVG directs exosomes to organs that express the acetylcholine receptor, such as kidney. The intervention of Exo/miR29 increased muscle cross-sectional area and decreased UUO-induced upregulation of TRIM63/MuRF1 and FBXO32/atrogin-1. Interestingly, renal fibrosis was partially depressed in the UUO mice with intramuscular injection of Exo/miR29. This was confirmed by decreased TGF-β, alpha-smooth muscle actin, fibronectin, and collagen 1A1 in the kidney of UUO mice. When we used fluorescently labeled Exo/miR29 to trace the Exo/miR route in vivo and found that fluorescence was visible in un-injected muscle and in kidneys. We found that miR-29 directly inhibits YY1 and TGF-β3, which provided a possible mechanism for inhibition of muscle atrophy and renal fibrosis by Exo/miR29. We conclude that Exo/miR29 ameliorates skeletal muscle atrophy and attenuates kidney fibrosis by downregulating YY1 and TGF-β pathway proteins.
FRI0104 Predictors for the response to anti-tnf therapy and the impact of smoking in rheumatoid arthritis- results on a group of patients in romania
Authors: B.I. Gavrila, C.S. Ciofu, L. Macovei, A.M. Gheorghiu, M. Sasu, C. Mihai, V. Stoica, I. Ancuta, M. Bojinca
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> 20%–40% of the patients are declared nonresponders to at least one of the biologic agents. <h3>Objectives</h3> to test the possible predictive role of RF type IgM and IgA, anti-CCP, anti-MCV,14–3–3eta protein and COMP on a group of patients treated with anti-TNFα agents. We also followed the evolution of serum titres of these biomarkers under biologic therapy and the impact of smoking regarding response to treatment. <h3>Methods</h3> prospective and observational study including 64 patients followed 12 months with active RA, uncontrolled by csDMARDs. Clinical assessment was performed at 0,6 and 12 months according to ACR criteria and evaluation of treatment response according to EULAR criteria (good/moderate/nonresponder). <h3>Results</h3> Following baseline immunological parameters titres and the response at 6 months, tests for identifying differences between the groups showed that lower titres of both RF isotypes, anti-CCP,14–3–3eta protein and COMP had predictive value on achieving a good EULAR response at 6 months. Grouping patients in 2 categories (responders/nonresponders), just 14–3–3eta protein and anti-CCP maintained their predictive value for the response at 6 months. For the visit at 12 months, lower baseline titres for RF type IgM (92.93±120.22 U/ml,p=0.010) and IgA (49.96±98.08 U/ml,p=0.002) had predictive value for achieving a good response at 12 months. We didn't obtain other informations grouping patients in 2 categories. The status pretreatment influenced the good response for COMP at 6 months (p=0.001) and RF IgA at 12 months (p=0.004). Using multivariate logistic regression methods we obtained a statistical model for predicting the response at 6 months including normal values for 14–3–3eta protein, anti-CCP and COMP (Hosmer and Lemeshow according test λ²=5.795, p=0.670≥0.05 with a predictive response accuracy of 89.1%). Smoking had a negative impact on the EULAR response as well as on 2 groups respose at 6 months of treatment (p=0.017). Following the evolution of serum levels, we noticed a reduction for all biomarkers tested, statistically significant at 6 and/or 12 months from baseline. <h3>Conclusions</h3> in the future a version using multiple biomarkers could increase accuracy for identifying pretreatment patients who will respond to anti-TNF therapy. Smoking has a negative impact on the response to biologic treatment. <h3>Disclosure of Interest</h3> None declared
Generation of a Core Set of Items to Develop Classification Criteria for Scleroderma Renal Crisis Using Consensus Methodology
Authors: Emily‐Ann Butler, Murray Baron, Agnes B. Fogo, Tracy Frech, Cybele Ghossein, Eric Hachulla, Sabrina Hoa, Sindhu R. Johnson, Dinesh Khanna, Luc Mouthon, Mandana Nikpour, Susanna Proudman, Virginia Steen, Edward Stern, John Varga, Christopher Denton, Marie Hudson
Journal: Arthritis & Rheumatology (2019)

Objective To generate a core set of items to develop classification criteria for scleroderma renal crisis ( SRC ) using consensus methodology. Methods An international, multidisciplinary panel of experts was invited to participate in a 3‐round Delphi exercise developed using a survey based on items identified by a scoping review. In round 1, participants were asked to identify omissions and clarify ambiguities regarding the items in the survey. In round 2, participants were asked to rate the validity and feasibility of the items using Likert‐type scales ranging from 1 to 9 (where 1 = very invalid/unfeasible, 5 = uncertain, and 9 = very valid/feasible). In round 3, participants reviewed the results and comments from round 2 and were asked to provide final ratings. Items rated as highly valid and feasible (median scores ≥7 for each) in round 3 were selected as the provisional core set of items. A consensus meeting using a nominal group technique was conducted to further reduce the core set of items. Results Ninety‐nine experts from 16 countries participated in the Delphi exercise. Of the 31 items in the survey, consensus was achieved on 13, in the categories hypertension, renal insufficiency, proteinuria, and hemolysis. Eleven experts took part in the nominal group technique discussion, where consensus was achieved in 5 domains: blood pressure, acute kidney injury, microangiopathic hemolytic anemia, target organ dysfunction, and renal histopathology. Conclusion A core set of items that characterize SRC was identified using consensus methodology. This core set will be used in future data‐driven phases of this project to develop classification criteria for SRC .
Stephen I Katz: influential director of the National Institute of Arthritis and Musculoskeletal and Skin Diseases at the US National Institutes of Health
Authors: Bob Roehr
Journal: BMJ (2019)

Credit: NIAMS

Steve Katz’s selection to be director of the US National Institutes of Health (NIH) National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) in 1995 generated some apprehension among the arthritis community.

The institute had been separated from a larger body by law in 1985. Its first director was renowned rheumatologist Lawrence E Shulman. As its second director, Katz was an unknown figure, a dermatologist who had a laboratory at the National Cancer Institute.

“He quickly won over both the research and patient communities with his commitment to science, immunology, and the NIH,” Debra Lappin told The BMJ . She served on an advisory council to NIAMS and was a board member and later chair of the non-profit Arthritis Foundation when Katz was appointed.

“He was politically very astute. You don’t do all that he did without understanding how to manage, how to read the political tea leaves, and how to prioritise what was important for his time and leadership.” Lappin said, “I don’t think I ever sent him an email that he didn’t respond to within an …
Angiography Versus Hemodynamics to Predict the Natural History of Coronary Stenoses
Authors: Giovanni Ciccarelli, Emanuele Barbato, Gabor G. Toth, Brigitta Gahl, Panagiotis Xaplanteris, Stephane Fournier, Anastasios Milkas, Jozef Bartunek, Marc Vanderheyden, Nico Pijls, Pim Tonino, William F. Fearon, Peter Jüni, Bernard De Bruyne
Journal: Circulation (2017)

Among patients with documented stable coronary artery disease and in whom no revascularization was performed, we compared the respective values of angiographic diameter stenosis (DS) and fractional flow reserve (FFR) in predicting natural history.The present analysis included the 607 patients from the FAME 2 trial (Fractional Flow Reserve Versus Angiography in Multivessel Evaluation 2) in whom no revascularization was performed. FFR varied from 0.20 to 1.00 (average 0.74±0.16), and DS (by quantitative coronary analysis) varied from 8% to 98% (average 53±15). The primary end point, defined as vessel-oriented clinical end point (VOCE) at 2 years, was a composite of prospectively adjudicated cardiac death, vessel-related myocardial infarction, vessel-related urgent, and not urgent revascularization. The stenoses were divided into 4 groups according to FFR and %DS values: positive concordance (FFR≤0.80; DS≥50%), negative concordance (FFR>0.80; DS<50%), positive mismatch (FFR≤0.80; DS<50%), and negative mismatch (FFR>0.80; DS≥50%).The rate of VOCE was highest in the positive concordance group (log rank: X2=80.96; P=0.001) and lowest in the negative concordance group. The rate of VOCE was higher in the positive mismatch group than in the negative mismatch group (hazard ratio, 0.38; 95% confidence interval, 0.21-0.67; P=0.001). There was no significant difference in VOCE between the positive concordance and positive mismatch groups (FFR≤0.80; hazard ratio, 0.77; 95% confidence interval, 0.57-1.09; P=0.149) and no significant difference in rate of VOCE between the negative mismatch and negative concordance groups (FFR>0.80; hazard ratio, 1.89; 95% confidence interval, 0.96-3.74; P=0.067).In patients with stable coronary disease, physiology (FFR) is a more important determinant of the natural history of coronary stenoses than anatomy (DS).URL: https://clinicaltrials.gov. Unique identifier: NCT01132495.
Abstract 14990: The Current Landscape of Atrial Fibrillation and Atrial Flutter Clinical Trials: A Report of 348 Studies Registered With ClinicalTrials.gov
Authors: Ravi B Patel, Ramkumar V Venkateswaran, Abhayjit Singh, Deepak L Bhatt, Gregg C Fonarow, Rod Passman, Javed Butler, Clyde W Yancy, Muthiah Vaduganathan
Journal: Circulation (2017)

Introduction: Atrial fibrillation/atrial flutter (AF/AFL) is a global cardiovascular epidemic. Despite an abundance of clinical trials in this field, there is a relative lack of high-level evidence guiding AF/AFL management. We aimed to systematically characterize trial-level patterns in AF/AFL using the ClinicalTrials.gov database. Methods: We included closed, phase II-IV interventional trials registered with ClinicalTrials.gov enrolling adult patients (≥18 years) with known AF/AFL. The PubMed and MEDLINE databases were queried for full-text publications. Published trials were evaluated for methodologic quality using the 3-item Jadad scale (range: 0-5; 5 being of highest quality). Results: The initial search yielded 465 uniquely-registered studies, of which 348 directly studied AF/AFL patients. Of this final sample, 173 were published (49.7%); 28.8% of completed trials remain unpublished. Industry sources accounted for most funding (54.3%), while government agencies funded <10%. The mean Jadad score of p...
CCGs and trusts are complacent over deficits, says watchdog
Authors: Matthew Limb
Journal: BMJ (2019)

Auditors’ “red flag” warnings about financial instability in NHS and other public bodies are being met with “inadequate or complacent responses,” the financial watchdog has said.

The National Audit Office (NAO) said the number of organisations in England with “significant weaknesses” in their arrangements for delivering value for money was “unacceptably high and increasing.”

Aymas Morse, who heads the NAO, said, “I am shocked by the persistent high level of qualified audit reports at local public bodies. A qualification is a judgment that something is seriously wrong.”

He said local and national bodies must take seriously, and act appropriately, when local auditors highlight weaknesses or concerns to maintain public confidence.

A NAO report on …
Continued Endocrine Therapy Is Associated with Improved Survival in Patients with Breast Cancer Brain Metastases
Authors: Elisabeth S. Bergen, Anna S. Berghoff, Mela Medjedovic, Margaretha Rudas, Florian Fitzal, Zsuzsanna Bago-Horvath, Karin Dieckmann, Robert M. Mader, Ruth Exner, Michael Gnant, Christoph C. Zielinski, Guenther G. Steger, Matthias Preusser, Rupert Bartsch
Journal: Clinical Cancer Research (2019)

Brain metastases (BMs) are a rare but devastating condition in estrogen receptor (ER)-positive metastatic breast cancer (MBC). Although endocrine therapy (ET) is the mainstay of treatment in this disease subtype, only case reports have been published concerning the activity of ET in BMs henceforth. Therefore, we aimed to systematically investigate the impact of ET after diagnosis of BM on outcome and clinical course of disease in patients with ER-positive MBC.Patient characteristics, detailed information about BMs including diagnosis-specific graded prognostic assessment class (DS-GPA), and clinical outcome were obtained by retrospective chart review for all patients treated for ER-positive breast cancer BMs between 1990 and 2017 at an academic care center. Overall survival (OS) was measured as the interval from diagnosis of BM until death or last date of follow-up.Overall, 198 patients [female: 195/198 (98.5%); male: 3/198 (1.5%)] with ER-positive breast cancer BMs were available for this analysis. Eighty-eight of 198 patients (44.4%) received ET after diagnosis of BM including aromatase inhibitors (AIs; letrozole, anastrozole, exemestane), tamoxifen, and fulvestrant. Median OS was significantly longer in patients receiving ET after diagnosis of BM compared with patients who did not (15 vs. 4 months, P < 0.001; log-rank test). No significant difference in terms of OS was observed between patients receiving AIs, tamoxifen, or fulvestrant. In patients with concomitant leptomeningeal carcinomatosis (LC), ET prolonged median OS significantly as well (7 vs. 3 months, P = 0.012; log-rank test). In a multivariate analysis including DS-GPA and ET, only treatment with ET after diagnosis of BM (HR, 0.69; 95% confidence interval, 0.48-0.99; P = 0.046) was associated with prognosis (Cox regression model).Continuing ET after BM diagnosis was associated with a significantly prolonged OS in this large single-center cohort. No substantial differences between substances were observed. These findings should be validated in a prospective cohort.
Biomarkers of Overall Survival and Response to Glasdegib and Intensive or Non-Intensive Chemotherapy in Patients with Acute Myeloid Leukemia
Authors: Jorge E. Cortes, Akil Merchant, Catriona Jamieson, Daniel A Pollyea, Michael Heuser, Geoffrey Chan, Panpan Wang, Keith A Ching, Jillian Johnson, Thomas O'Brien
Journal: Blood (2018)
SP0060 Eular recommendations for the use of imaging in mechanical low back pain
Authors: Bjarke B Hansen, Lene Terslev, Francis Berenbaum, Ingrid Möller, Mikael Boesen, Jean Denis Laredo, Francois Rannou, Stefan Lohmander, Martin Englund, Xenofon Baraliakos, Philip Conaghan, Stéphane Genevay, Clémence Palazzo, David John Wilson, Ross Wilkie, Daniel Prieto-Alhambra, Alison Kent, Souzi Makri, Victoria Navarro Compán, Christelle Nguyen, Maria Else Marie Bartels, Cecilie Nordberg, Antonietta D’Agostino, Gilles Fournier, G.L. Fournier
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Low back pain is common and relates to a variety of overlapping pathologies. Imaging of the spine has a high priority in the assessment of patients with low back pain. However, studies have shown that clinicians vary widely in how frequently they obtain imaging tests for assessment of low back pain. Technical advances in the field of lumbar spine imaging are made at an increasingly high rate, and it seems likely that improved imaging procedures can indeed increase the understanding of low back pain and aid the diagnostic precision to the diagnostics of mechanical low back pain. The EULAR Task Force consists of radiologists, orthopaedic surgeons, rheumatologists, doctors in physical medicine and general medicine, physiotherapist and patients and the aim of the group was to develop evidence-based recommendations for the use of imaging modalities in low back pain with or without radiculopathy Based on PICOs established at the first meeting and using European League Against Rheumatism (EULAR) standardised operating procedures a systematic literature review was conducted to retrieve data on the role of imaging modalities including both conventional, contrast enhanced and dynamic approaches in radiography, ultrasound, MRI and CT. The recommendations will be based on the results of the systematic literature review and expert opinion and will be relevant for to all health care professionals who treat mechanical low back patients due to its multifactorial nature. <h3>Reference</h3> [1] Hansen BB, Hansen P, Carrino JA, Fournier G, Rasti Z, Boesen M. Imaging in mechanical back pain: Anything new? Best Pract Res Clin Rheumatol [Internet]. <i>Elsevier Ltd</i>2016Aug;30(4):766–85. [2] Chou R, Fu R, Carrino JA, Deyo RA. Imaging strategies for low-back pain: Systematic review and meta-analysis. Lancet<i>. Elsevier Ltd</i>2009;373(9662):463–72. [3] Stochkendahl MJ, Kjaer P, Hartvigsen J, Kongsted A, Aaboe J, Andersen M, et al. National Clinical Guidelines for non-surgical treatment of patients with recent onset low back pain or lumbar radiculopathy. Eur Spine J2017;1–16. <h3>Disclosure of Interest</h3> None declared
Hypoxia enhances CD8+ TC2 cell–dependent airway hyperresponsiveness and inflammation through hypoxia-inducible factor 1α
Authors: Fangkun Ning, Katsuyuki Takeda, Michaela Schedel, Joanne Domenico, Anthony Joetham, Erwin W. Gelfand
Journal: Journal of Allergy and Clinical Immunology (2019)