tbuckley/cabot-search huggingface dataset:
OP0058 Low-dose radiation therapy as treatment for hand and knee osteoarthritis: two double-blinded rct’s
Authors: M. Minten, E. Mahler, M. Leseman-Hoogenboom, S. Boks, M. Kloppenburg, J.W. Leer, P. Poortmans, F. van den Hoogen, A. den Broeder, C. van den Ende
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Synovial inflammation plays an important role in osteoarthritis (OA) pathophysiology. In some countries, low-dose radiation therapy (LD-RT) is widely used as treatment for OA, while relatively unknown in others. Studies <i>in vitro</i> and in OA animal models have shown anti-inflammatory effects of LD-RT. However, systematic literature review has shown that high-level evidence for beneficial effects in clinical practice is lacking. <h3>Objectives</h3> To assess the effect of LD-RT on clinical outcomes and inflammation in patients with hand or knee OA, using two parallel prospective RCTs. <h3>Methods</h3> Patients with hand OA (n=56) or knee OA (n=55) according to ACR-criteria, with a pain score ≥5/10, not responding to analgesics and exercise therapy were included. They were randomly allocated 1:1 to the LD-RT (6 × 1 Gy LD-RT in two weeks) or sham (6 × 0 Gy in two weeks) intervention, stratified for pain score (&lt;8 vs≥8). The primary outcome was the number responders according to the OMERACT-OARSI responder criteria, 3 months post-intervention. Secondary outcomes were inflammatory aspects assessed by ultrasound (US; both knee and hand) and MRI (knee only). In hand OA, joints were scored semi-quantitatively (0–3) for US effusion, synovial thickening and power Doppler signal. In knee OA, we assessed the mean US effusion and synovial thickness (mm) at three locations, and the summed MRI effusion/synovitis (semi-quantitatively; 0–3) from four locations. Logistic and linear regression analyses were used to assess differences in dichotomous and continues outcomes, respectively. Analyses were adjusted for pain stratum. <h3>Results</h3> Baseline characteristics are shown in table 1. The proportion of responders over time is shown in figure 1. After 3 months, in hand OA, there were 8 (29%) responders in the LD-RT group and 10 (36%) in the sham group (OR 0.69; 95% CI: 0.22 to 2.17). In knee OA, there were 12 (44%) responders in the LD-RT group and 12 (43%) in the sham group (OR 1.09; 95% CI: 0.37 to 3.19). In both hand and knee OA, no significant changes in clinical outcomes and inflammatory aspects were observed in both groups. <h3>Conclusions</h3> We were unable to demonstrate a beneficial effect of LD-RT on pain and functioning, nor on inflammatory processes, in patients with hand or knee OA. In light of absence of other high-level evidence, we advise against the use LD-RT as treatment for hand and knee OA. Dutch Trial Register: NTR4574 <h3>Disclosure of Interest</h3> None declared
Discovery of Distinct Immune Phenotypes Using Machine Learning in Pulmonary Arterial Hypertension
Authors: Andrew J. Sweatt, Haley K. Hedlin, Vidhya Balasubramanian, Andrew Hsi, Lisa K. Blum, William H. Robinson, Francois Haddad, Peter M. Hickey, Robin Condliffe, Allan Lawrie, Mark R. Nicolls, Marlene Rabinovitch, Purvesh Khatri, Roham T. Zamanian
Journal: Circulation Research (2019)

Rationale: Accumulating evidence implicates inflammation in pulmonary arterial hypertension (PAH) and therapies targeting immunity are under investigation, although it remains unknown if distinct immune phenotypes exist. Objective: Identify PAH immune phenotypes based on unsupervised analysis of blood proteomic profiles. Methods and Results: In a prospective observational study of group 1 PAH patients evaluated at Stanford University (discovery cohort; n=281) and University of Sheffield (validation cohort; n=104) between 2008 and 2014, we measured a circulating proteomic panel of 48 cytokines, chemokines, and factors using multiplex immunoassay. Unsupervised machine learning (consensus clustering) was applied in both cohorts independently to classify patients into proteomic immune clusters, without guidance from clinical features. To identify central proteins in each cluster, we performed partial correlation network analysis. Clinical characteristics and outcomes were subsequently compared across clusters. Four PAH clusters with distinct proteomic immune profiles were identified in the discovery cohort. Cluster 2 (n=109) had low cytokine levels similar to controls. Other clusters had unique sets of upregulated proteins central to immune networks—cluster 1 (n=58; TRAIL [tumor necrosis factor-related apoptosis-inducing ligand], CCL5 [C-C motif chemokine ligand 5], CCL7, CCL4, MIF [macrophage migration inhibitory factor]), cluster 3 (n=77; IL [interleukin]-12, IL-17, IL-10, IL-7, VEGF [vascular endothelial growth factor]), and cluster 4 (n=37; IL-8, IL-4, PDGF-β [platelet-derived growth factor beta], IL-6, CCL11). Demographics, PAH clinical subtypes, comorbidities, and medications were similar across clusters. Noninvasive and hemodynamic surrogates of clinical risk identified cluster 1 as high-risk and cluster 3 as low-risk groups. Five-year transplant-free survival rates were unfavorable for cluster 1 (47.6%; 95% CI, 35.4%–64.1%) and favorable for cluster 3 (82.4%; 95% CI, 72.0%–94.3%; across-cluster P &lt;0.001). Findings were replicated in the validation cohort, where machine learning classified 4 immune clusters with comparable proteomic, clinical, and prognostic features. Conclusions: Blood cytokine profiles distinguish PAH immune phenotypes with differing clinical risk that are independent of World Health Organization group 1 subtypes. These phenotypes could inform mechanistic studies of disease pathobiology and provide a framework to examine patient responses to emerging therapies targeting immunity.
THU0498 Core endurance and postural stability impairments in osteoporotic women: a case-control study
Authors: S. Toprak Celenay, D. Ozer Kaya
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Crosstalk between bone and muscle has been focused, lately.<sup>1</sup> Any impairment in bone quality may affect core muscle endurance and whole postural control.<sup>2, 3</sup> <h3>Objectives</h3> This study aimed to compare core muscle endurance and postural stability in women with and without osteoporosis. <h3>Methods</h3> Women with (n: 40, age: 59.16±6.83 years, body mass index (BMI): 31.46±5.44 kg/m²) and without osteoporosis (Controls, n: 36, age: 56.10±7.17 years, BMI: 33.81±5.32 kg/m²) were recruited. Core endurance was assessed with McGill's trunk muscle endurance tests in seconds.<sup>4</sup> Postural stability were evaluated with Biodex Balance System SD in static-dynamic, eyes-open and closed conditions. Independent sample <i>t</i> and Mann Whitney U tests were used for analysis. <h3>Results</h3> The ages and BMI of the groups were similar (p&gt;0.05). The following scores were found respectively in osteoporotic women and controls: the endurance of trunk flexor [15.0 (20.0)/17.5 (15.2) s]; back extensor [9.0 (16.0)/12.5 (22.2) s], right lateral [0.0 (7.0)/6.5 (20.0) s] and left lateral muscles [0.0 (8.0)/5.0 (20.0) s], static eyes-open [1.93±0.80/1.44±0.86] and eyes-closed [2.46±1.71/1.68±0.73], dynamic eyes-open [3.08±1.95/2.86±1.39] and eyes-closed [6.31±2.31/5.40±1.24] postural stability. Lateral trunk muscle endurance decreased, static and dynamic eyes-closed instability increased in women with osteoporosis in comparison to women without osteoporosis (p&lt;0.05). No differences were found in trunk flexor and back extensor muscle endurance, and static and dynamic eyes open stability scores (p&gt;0.05). <h3>Conclusions</h3> Lateral core muscle endurance and static and dynamic eyes-closed postural stability impairments were observed in osteoporotic women. It might be appropriate to be aware of these deficits for prevention programs. <h3>References</h3> [1] Colaianni G, Mongelli T, Colucci S, Cinti S, Grano M. Crosstalk Between Muscle and Bone Via the Muscle-Myokine Irisin.CurrOsteoporos Rep. 2016;14(4):132–7. [2] Ma Y, Fu L, Jia L, Han P, Kang L, Yu H, Chen X, Yu X, Hou L, Wang L, Zhang W, Niu K, Guo Q. Muscle strength rather than muscle mass is associated with osteoporosis in older Chinese adults.J Formos Med Assoc2017Apr 13;S0929–6646(16)30402–8. [3] Burke TN, França FJ, Meneses SR, Cardoso VI, Pereira RM, Danilevicius CF, Marques AP. Postural control among elderly women with and without osteoporosis: is there a difference?Sao Paulo Med J2010;128(4):219–24. [4] McGill SM, Childs A, Liebenson C. Endurance time for low back stabilization exercises: clinical targets for testing and training from a normal database. Arch Phys Med Rehabil1999;80:941–44. <h3>Disclosure of Interest</h3> None declared
Abstract 18464: Different Modulation of MicroRNA by Ticagrelor and Clopidogrel in Non STEMI Patients (TIGER M Study NCT02071966)
Authors: Luigi M Biasucci, Claudia Mandolini, Giulio la Rosa, Maria Chiara Grimaldi, Filippo Crea
Journal: Circulation (2017)

Introduction: Ticagrelor (Ti) has been shown in the PLATO study to significantly reduce the rate of death from vascular causes, myocardial infarction or stroke, without a significant increase in the rate of major bleeding vs Clopidogrel (Cl). Hypothesis: As Ti has pleiotropic effects, we sought to assess whether the favourable effects of Ti vs. Cl in NSTEMI could be explained , at least in part, by different modulation of circulating MicroRNA (miRNA) and Microparticles (MP) Methods: we enrolled 56 pts ( 33 male, 23 female), randomized to Ti or Cl , blood samples were taken at first contact with the patients, before loading of Cl or Ti, and subsequently before PCI (at least 3 hours after drug administration), and at 24 and 48h , 1 and 3 months after PCI. Plasma samples and microparticles (MP) were separated by centrifugation steps of pts blood. Plasma RNA was extracted and pooled for microarrays PCR based panel of 90 microRNA analysis. Single plasma RNA of each patient was reverse transcribed for miRNA val...
FRI0568 Mr – enterography findings of intestinal inflammation in spondyloarthritis with high faecal calprotectin levels
Authors: I. Ergenç, E. Uner, R. Ergelen, G. Haklar, N. İmeryüz, Ö. Atuğ, P. Atagündüz
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Intestinal inflammation is seen in half of patients with spondyloarthropathy (SpA), and can be detected by faecal calprotectin(Fcal)<sup>1</sup>. Small bowel inflammation is detected by MR Enterography (MRE), accurately<sup>2</sup>. <h3>Objectives</h3> Definition of MRE changes in SpA patients with high Fcal levels. <h3>Methods</h3> A total of 231 SpA patients, 50 healthy subjects and 50 inflammatory bowel disease (IBD) patients were included. Stool specimens were obtained and data on BASDAI scores, abdominal pain, diarrhoea, NSAID and TNF inhibitor usage were noted. Fcal was measured by IDK ELISA 2 weeks after the cessation of NSAID. MREs were obtained in Fcal &gt;50 µg/g SpA patients. Contrast enhanced MRE was performed using 3 Tesla MRI device after 6 hours of fasting. <h3>Results</h3> Demographic and clinical characteristics are summarised in table 1 and flow diagram (figure 1). Median Fcal of SpA patients was higher than healthy controls and lower than IBD patients. Fcal levels were high in 15 (33.3%) of 45 healthy cases and all but two of them were NSAID users. The Fcal test was high in 45.9% (n=106) of SpA patients. There was no correlation between BASDAI index and Fcal results (r=0,08 p=0,42). Mean Fcal levels of active and in remission patients were 78.2±20 and 77.8±7.02 µg/g respectively (p=0.97). Fifty-two of the Fcal-high SpA patients were retested after cessation of NSAIDs for 14 days. In 15 patients Fcal levels remained elevated. MRE was performed 33 SpA patients with high Fcal levels. MRE findings were observed in 29 of 33 (87%) patients. Four out of 33 (%12,1) MRE imaging was totally normal. Patients with MRE findings had higher median Fcal levels than those with normal MRE imaging (98 vs. 52 µg/g p=0.002). All patients had increased mesenteric fat density and presence of mesenteric lymph nodes. Increased mesenteric vascularity (28/29), increased bowel wall enhancement (23/29) and thickness (18/29) were frequently detected. Approximately one-third of the patients had a luminal stricture (13/29) and loss of haustration (12/13). <h3>Conclusions</h3> In SpA patients with high Fcal levels MRE detected inflammation of mucosal as well as serosal surfaces, as in early CD. <h3>References</h3> [1] Cypers H. Elevated Calprotectin Levels Reveal Bowel Inflammation in Spondyloarthritis. ARD75:1357–62. [2] Toshimitsu Fujii. Current Progress of Endoscopy in Inflammatory Bowel Disease: Mr Enterography, Springer2018:57–70. <h3>Disclosure of Interest</h3> None declared
Chronic Graft Versus Host Disease Burden and Relapse Rates Are Lower with Comparable Overall Survival and Graft Versus Host Disease Free, Relapse Free Survival Following Adult Umbilical Cord Blood Compared to Matched Sibling Peripheral Blood Stem Cell Transplantation
Authors: Prashant Sharma, Enkhtsetseg Purev, Bradley M. Haverkos, Daniel A Pollyea, Clayton Smith, Manali Kamdar, Daniel W Sherbenou, Tomer M Mark, Peter A Forsberg, Jonathan A Gutman
Journal: Blood (2018)
AB1135 Cardiac magnetic resonancefindings in patients with biopsy-proven virus-negative lymphocytic myocarditis
Authors: C. Campochiaro, G. De Luca, S. Sartorelli, C. Candela, G. Cavalli, L. Dagna
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Cardiac magnetic resonance (CMR) is considered to be useful for non-invasive myocarditis diagnosis. Lake Louise Criteria(LLC) has been proved to have moderate accuracy in the diagnosis of acute or chronic myocarditis1. <h3>Objectives</h3> to describe the CMR findings in patients with virus-negative lymphocytic myocarditis(VNLM) from a large monocentric Italian cohort. <h3>Methods</h3> CMR findings in 40 patients(mean age 45.43±14.7 years; male:female ratio 1:1) diagnosed with endomyocardial biopsy-proven VNLM at our Centre from January 2015 to December 2017, were retrospectively evaluated. CMR was performed at time of clinical presentation and before EMB. At contrast-enhanced CMR we analysed: ventricular function, T2-weighted sequences, short inversion time inversion recovery sequences (STIR), early(EGE) and delayed gadolinium enhancement(LGE). Demographic, clinical and histological data were correlated with CRM findings. <h3>Results</h3> Mean left ventricular(LV) ejection fraction(EF) was 52.5%±10.8%. 50% of patients had reduced LVEF(&lt;55%). Mean right ventricle EF was 55.25%±7.2%. Akinetic or hypokinetic areas were detected in 3 (7.5%) and 17 (42.5%) patients, respectively. LLC were identified in 39 patients(92.5%). LGE was the most common CMR finding. 20 patients(50%) met one LLC, 16 patients(40%) 2 LLCs. 1 patient met all 3 LLCs. STIR abnormalities were identified in the LV lateral wall in 8 (19%), septal wall in 9 (21.4%), LV inferior wall in 9 (21.4%), in the apex in 3 (7.1%), LV posterior wall in 3 (7.1%) and LV anterior wall in 2 (4.8%) patients. Myocardial oedema on T2 images was detectable in 21 (52.5%), EGE in 1 (2.5%) and LGE in 36 (90%) patients. LGE was intramural in 22 (55%), subepicardial in 23 (57.5%) and subendocardial in 4 (10%) patients. Multiple LGE patterns were disclosed in 10 (25%) patients. Pericardial effusion was detected in 9 patients(22.5%). 2 patients did not meet any LLC at CMR. When comparing CMR findings with Holter-ECG tape, clinical presentation, histology, biochemistry and autoimmunity results we found CRM oedema positively correlated with the detection of active myocarditis on EMB(11 vs 4,p=0.027). Serum anti-heart antibodies positively correlated with the detection of pericarditis at CMR (3 vs 1,p=0.050). Patchy/intramural LGE positively correlated with rhythm abnormalities at Holter-ECG tape(12 vs 6,p=0.037). <h3>Conclusions</h3> VNLM is an overlooked disease defined by EMB established histological, immunological and immune-histochemical criteria. Although the diagnostic power of CMR needs to be further investigated, it seems to correlate with EMB results and arrhythmic burden. <h3>Reference</h3> [1] Friedrich MG, et al. Cardiovascular magnetic resonance in myocarditis: A JACC White Paper. J Am Coll Cardiol. 2009 <h3>Disclosure of Interest</h3> None declared
Increased STAT5/STAT3 Intracellular Signaling in Circulating CD34+ Cells of Patients with PMF Correlates with Disease Severity
Authors: Carlotta Abbà, Rita Campanelli, Paolo Catarsi, Laura Villani, Vittorio Abbonante, Christian Andrea Di Buduo, Melania Antonietta Sesta, Vittorio Rosti, Giovanni Barosi, Margherita Massa
Journal: Blood (2018)
FRI0701 French specialists and immune-related adverse events of cancer immunotherapy: a state of the art from several national expert networks.
Authors: M. Kostine, C. Richez, J.-E. Gottenberg, O. Lambotte
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background:</h3> Immunotherapeutic strategies with immune checkpoint inhibitors (ICI) are now commonly used in treating patients with advanced-stage cancer. An important proportion of patients experiences inflammatory or autoimmune side effects, also known as immune-related adverse events (irAEs), as a consequence of dysregulated immunity which can affect any organ system (1). A recent survey conducted by our colleagues from United States highlighted that rheumatologists had limited experience and lacked confidence in the management of rheumatic irAEs (2). <h3>Objectives:</h3> To evaluate the knowledge of French specialists regarding ICI and irAEs through an online survey. <h3>Methods:</h3> The online survey has been sent in January 2018 to several French national expert networks: Société Française de Rhumatologie (SFR), Club Rhumatismes et Inflammations (CRI), Société Nationale de Médecine Interne (SNFMI), Groupe d'Etude Thérapeutique des Affections Inflammatoires du Tube Digestif (GETAID) and Société Française d'Endocrinologie (SFE). <h3>Results:</h3> 349 French specialists participated to this study: rheumatologists (n=159), internists (n=112), endocrinologists (n=55), gastroenterologists (n=22) and one respiratory physician. As detailed in table <b>1</b>, participants were mainly working in academic or hospital with various levels of experience in clinical practice. Overall, half of the specialists reported some basic knowledge of ICI and irAEs. Around 25% either have never heard about these therapies and their side effects or were not knowledgeable. The majority of the participants has never or rarely managed irAEs (31% and 40% respectively), and only 11% declared being very confident in treating such patients. The type of content requested for education was mainly about treatment algorithms (80%) followed by clinical description of irAEs (59%) then general information on ICI (mechanism of action, administration, efficacy). <h3>Conclusions:</h3> Since there has been an increasing emphasis on irAEs within the last three years, we confirmed the need of a dedicated medical education regarding this new clinical entity. <h3>References</h3> (1) Postow MA, Sidlow R, Hellmann MD. Immune-Related Adverse Events Associated with Immune Checkpoint Blockade. N Engl J Med. 2018Jan 11;378(2):158–168. (2) Cappelli L, Calabrese C, Calabrese LH, Bingham III CO. Immunotherapy-Induced Rheumatic Disease: How Prepared Are Rheumatologists to Address This Emerging Condition? [Abstract]. Arthritis Rheumatol2017;69(suppl 10). <h3>Acknowledgements:</h3> We thank all respondents for their active participation. <h3>Disclosure of Interest:</h3> None declared
Mendelian Randomization Analysis of Hemoglobin A1c as a Risk Factor for Coronary Artery Disease
Authors: Aaron Leong, Ji Chen, Eleanor Wheeler, Marie-France Hivert, Ching-Ti Liu, Jordi Merino, Josée Dupuis, E Shyong Tai, Jerome I. Rotter, Jose C. Florez, Inês Barroso, James B. Meigs
Journal: Diabetes Care (2019)

OBJECTIVE Observational studies show that higher hemoglobin A1c (A1C) predicts coronary artery disease (CAD). It remains unclear whether this association is driven entirely by glycemia. We used Mendelian randomization (MR) to test whether A1C is causally associated with CAD through glycemic and/or nonglycemic factors. RESEARCH DESIGN AND METHODS To examine the association of A1C with CAD, we selected 50 A1C-associated variants (log10 Bayes factor ≥6) from an A1C genome-wide association study (GWAS; n = 159,940) and performed an inverse-variance weighted average of variant-specific causal estimates from CAD GWAS data (CARDIoGRAMplusC4D; 60,801 CAD case subjects/123,504 control subjects). We then replicated results in UK Biobank (18,915 CAD case subjects/455,971 control subjects) and meta-analyzed all results. Next, we conducted analyses using two subsets of variants, 16 variants associated with glycemic measures (fasting or 2-h glucose) and 20 variants associated with erythrocyte indices (e.g., hemoglobin [Hb]) but not glycemic measures. In additional MR analyses, we tested the association of Hb with A1C and CAD. RESULTS Genetically increased A1C was associated with higher CAD risk (odds ratio [OR] 1.61 [95% CI 1.40, 1.84] per %-unit, P = 6.9 × 10−12). Higher A1C was associated with increased CAD risk when using only glycemic variants (OR 2.23 [1.73, 2.89], P = 1.0 × 10−9) and when using only erythrocytic variants (OR 1.30 [1.08, 1.57], P = 0.006). Genetically decreased Hb, with concomitantly decreased mean corpuscular volume, was associated with higher A1C (0.30 [0.27, 0.33] %-unit, P = 2.9 × 10−6) per g/dL and higher CAD risk (OR 1.19 [1.04, 1.37], P = 0.02). CONCLUSIONS Genetic evidence supports a causal link between higher A1C and higher CAD risk. This relationship is driven not only by glycemic but also by erythrocytic, glycemia-independent factors.
An engineered <i>E. coli</i> Nissle improves hyperammonemia and survival in mice and shows dose-dependent exposure in healthy humans
Authors: Caroline B. Kurtz, Yves A. Millet, Marja K. Puurunen, Mylène Perreault, Mark R. Charbonneau, Vincent M. Isabella, Jonathan W. Kotula, Eugene Antipov, Yossi Dagon, William S. Denney, David A. Wagner, Kip A. West, Andrew J. Degar, Aoife M. Brennan, Paul F. Miller
Journal: Science Translational Medicine (2019)

An engineered E. coli strain lowers blood ammonia, improves survival in models of hyperammonemia, and demonstrates safety in healthy volunteers.