tbuckley/cabot-search huggingface dataset:
THU0532 Paediatric uveitis in french referral ophthalmologic centers: a descriptive analysis of 74 children
Authors: L Moal, A Rousseau, C Titah, M Labetoulle, B Bodaghi, S Guillaume Czitrom
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Uveitis in children is rare. Intensive interactions between ophthalmologists and paediatric rheumatologists are needed in order to choose the best therapeutic strategies for severe uveitis attacks. <h3>Objectives</h3> Describe a cohort of 74 patients with paediatric uveitis. <h3>Methods</h3> Retrospective analysis of children followed for uveitis before 18, by one paediatric rheumatologist (SGC) for systemic treatments9 management and members of 3 ophthalmologic departments specialized in uveitis care in children (AR, CT, ML and BB) in Paris, during the 2006–16 period. <h3>Results</h3> There were 74 paediatric uveitis, 42 anterior (57%, group1), 16 intermediate (21%, gr2), 7 posterior (9%, gr3) and 9 pan-uveitis (12%, gr4). Gender was equal in gr2–4, but there were more females in gr1. At presentation, mean ages were 8.6±4.1, 9.8±3.9, 9.1±3.6 and 10±4.2 years old. Mean follow-up was 3.7±3.7 years. JIA was the leading cause of gr1 uveitis (45%); gr2–3 uveitis were idiopathic in 81% and 86%, respectively. In gr4, etiologies were found in 7 out of 9 patients (Behçet-3, JIA-2, BBS-1, TINU-1). <h3>Conclusions</h3> Paediatric uveitis induce a very high-level burden in children, even when anterior and sometimes despite optimal therapeutic management in tertiary care centers. Their early recognition and tight control in specialized units are absolutely required in order to decrease the level of definitive complications. <h3>Disclosure of Interest</h3> None declared
SAT0412 Association between smoking with spinal level of stiffness and functional limitation in patients with axial spondyloarthritis: results from the spanish atlas
Authors: M Garrido-Cumbrera, J Chacόn-García, J Gratacos-Masmitja, D Galvez-Ruiz, V Navarro-Compan, C Blanch-Mur, E Collantes-Estevez, P Zarco-Montejo, O Brace
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Smoking has been associated with greater disease activity and radiographic progression in patients with Axial Spondyloarthritis (ax-SpA). In addition, radiographic damage has been linked to greater functional limitation. However, clarification is still being sought as to whether or not this association exists. <h3>Objectives</h3> To investigate the association between smoking and both the area of spinal stiffness and functional limitation in patients with ax-SpA. <h3>Methods</h3> A sample of 680 patients diagnosed with ax-SpA was interviewed during 2016 as part of the Spanish Atlas, which aims to promote early referral and improve healthcare and the use of effective treatments in patients with ax-SpA. Tobacco consumption was recorded as: Smoker (62.4%), Occasional Smoker (8.9%) and Non-Smoker (28.7%). Spinal stiffness was assessed in the three different vertebral areas: cervical, dorsal and lumbar. To determine de degree of functional limitation we used a composed index which includes the sum of the degree of limitation in the 18 daily activities well established (dressing, grooming, bathing, tying shoelaces, moving around the home, stairs, getting to/out of bed, toilet, shopping, preparing meals, eating, cleaning, walking, using public transportation, going to the doctor, driving, physical exercise, sexual relations) using an ordinal variable (0=none, 1=little, 2=some and 3=moderate). A descriptive analysis was used to compare the level of stiffness (chi-squared test) and the mean degree of limitation (Kruskal-Wallis test) in the different groups of smokers consumptions. Regression analysis was also used to assess the relation between smoking and degree of limitation (0–54). <h3>Results</h3> 53% were females, mean age 46 years and 77.1% were HLA-B27+. The percentage of patients with stiffness in the lumbar region was significantly higher in habitual/occasional smokers than in non-smokers (89.0%, 93.8%, 83.5% respectively; p&lt;0.01) (Table). The mean degree of functional limitation increased with tobacco consumption, although this difference was not statistically significant (47.9±12.1 vs. 45.1±11.5 vs. 44.8±13.7 respectively; p=0.2). However, regression analysis showed a statistically significant correlation between smoking and functional limitation (r=0.096; p=0.02). <h3>Conclusions</h3> Smoking in patients with ax SpA is associated to greater stiffness in the lumbar region, but is not related to stiffness in the cervical or dorsal regions. Additionally, smoking is associated to the degree of functional limitation in these patients. <h3>Acknowledgements</h3> This project has been supported by Novartis <h3>Disclosure of Interest</h3> None declared
Physical Activity in Heart Failure With Preserved Ejection Fraction
Authors: Ambarish Pandey, Jarett D. Berry
Journal: Circulation (2017)

P2][3][4] Recent studies have demonstrated strong, dose-dependent inverse associations among physical activity, fitness, and risk of incident HF. 5 Physical activity has been shown to have a stronger and more graded association with risk of HF with preserved ejection fraction (HFpEF) than HF with reduced ejection fraction. 6However, the prognostic role of physical activity among patients with established HFpEF is less well established.This finding is particularly relevant given the near-universal presence of exercise intolerance among patients with HFpEF.In this issue of Circulation, Hegde et al 7 have addressed this knowledge gap by evaluating the association between physical activity levels and risk of adverse clinical outcomes among 1751 patients with HFpEF in the TOPCAT trial (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist).The authors observed several important findings.First, only 11% of the study participants engaged in guideline-recommended physical activity levels at baseline.Second, compared with individuals with ideal physical activity, those with poor and intermediate self-reported physical activity had a higher risk of HF hospitalization and mortality within the first 2 years of follow-up.Third, the authors observed a particularly interesting, dose-response relationship between physical activity levels and risk of adverse clinical outcomes, such that only physical activity levels at or above current guideline recommended doses were associated with a lower risk of HF hospitalization or mortality.Thus, these data suggest that some exercise may not be an improvement over no exercise among HFpEF patients and that a higher dose of exercise may be required to achieve clinical benefits.This is consistent with the dose-response association between physical activity levels and risk of incident HFpEF that was reported recently, with significant reductions in HFpEF risk only at physical activity levels above guideline recommendations. 6This is in stark contrast to prior reports of the dose-response relationship between exercise and other outcomes such as coronary artery disease where the majority of the benefit of physical activity was apparent at just modest doses of physical activity. 8Thus, the recommendation to get off the couch appears to be inadequate for the prevention and management of HFpEF-rather, we should be recommending doses of physical activity that are at or well-above the current recommendation of 30 minutes, 5 days per week of moderate intensity (ie, walking) exercise.What explains this unique, dose-response relationship between exercise and HFpEF?We suggest 2 potential explanations.First, higher levels of regular physical activity may have a direct effect on the underlying HFpEF substrate, reflecting higher levels of cardiorespiratory fitness in these individuals, which may have a Physical Activity in Heart Failure With Preserved Ejection FractionMoving Toward a Newer Treatment Paradigm
Mechanism of Action and Clinical Impact of Ribociclib—Letter
Authors: Steven Sorscher
Journal: Clinical Cancer Research (2017)

I read with great interest the very nice and recently published review “Ribociclib (LEE011): Mechanism of Action and Clinical Impact of This Selective Cyclin-Dependent Kinase 4/6 Inhibitor in Various Solid Tumors” (1). The authors state that the “active cyclin D-CDK4/6 complexes phosphorylate Rb, relieving its repression of E2 transcriptions factors” and that the released E2 activates transcription of genes “required for G1-S transition and cell cycle progression.” The result is that by inhibiting CDK4/6 activity, there would be less phosphorylation of Rb, and thereby less cancer cell-cycle progression.Although this is true, I believe it requires clarification. Rather than phosphorylating Rb, the active cyclin D–CDK4/6 actually hyperphosphorylates and thereby inhibits the Rb tumor suppressor gene (TSG) product function, leading to cancer cell-cycle progression (2). Ribociclib (like other CDK4/6 inhibitors) inhibits hyperphosphorylation, thereby activating Rb TSG product function, which results in inhibiting cell-cycle progression.Recognizing the distinction between inhibiting phosphorylation and inhibiting hyperphosphorylation is critical for two reasons. First, unlike nearly all of the targeted kinase inhibitors that have gained FDA approval for treating cancer in the past few years, CDK4/6 inhibitors basically activate TSG product function (i.e., Rb), as opposed to inhibiting oncogene function. Second, the implication from the mechanism of inhibition is that for large number of cancers lacking normal Rb gene product expression, CDK4/6 inhibition would be predicted to be ineffective.Targeted agents that replace lost TSG function may prove more efficacious than inhibiting oncogenes, and hopefully, the advent of CDK4/6 inhibitors will lead to more research of agents replacing lost TSG function.See the Response, p. 5658S. Sorscher has received speakers bureau honoraria from Celgene and Pfizer.
AB0287 Mutual assent towards comprehensive disease control: the relationship between us measures and patient reported outcomes in early rheumatoid arthritis
Authors: Y El Miedany, M El Gaafary, N El Arousi, SS Youssef, A Nasr
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Objectives</h3> Assessment of the relationship between US measures of joint inflammation/damage and patient reported outcomes (PROs): HAQ, pain and patient global assessment in early rheumatoid arthritis (early RA) patients over 5-years follow up period. <h3>Methods</h3> This longitudinal cohort of 261 patients with early RA was derived from the US monitoring study [1]. Adopting OMERACT definitions; correlations between total US scores (synovial hypertrophy, synovial fluid, Power Doppler, bone erosion and tenosynovitis) and PROs [2] namely functional disability (HAQ), pain and patient global scores were determined at 0, 1, and 5years. Radiological damage was assessed using modified Total Sharp score (mTSS). Univariate correlations as well as correlations between interval changes were assessed. Multivariable regression models were used to evaluate the associations over all time-points and their relationship to clinical disease activity measures. <h3>Results</h3> There were significant correlations (p&lt;0.01) between total US score and HAQ (r=0.71), pain (r=0.69) and patient global scores (r=0.66) at all timepoints. The association tends to be stronger with increase disease duration (Spearman correlation 0.12 at baseline, 0.22 at 1-year and 0.41 at 5-years). Change in mTSS score at 5-years was not associated with changes in PROs. Improvements in US scores were also associated with improvements in PROs. Multivariate models revealed that synovial hypertrophy and Power Doppler scores were associated (p&lt;0.01) with functional disability, pain and patient global assessment, controlling for clinical disease activity measures. Studying the pattern of joint involvement, it was associated significantly (p&lt;0.01) with the US score of the affected joints. US total score at 1-year predicted subsequent 5-year HAQ score (R2=0.17). At 0, 1- and 5-years, total US scores were higher in patients whose HAQ score was &gt;1 (9.26) compared to those below 1 (4.16, p&lt;0.01). <h3>Conclusions</h3> the link between joint inflammation/structural damage and PROs is of critical importance to the care of patients with inflammatory arthritis. US measures of inflammation and structural damage correlated independently with physical function, pain and patient global assessments. A clear relationship between radiographic structure damage and the patient9s perceived remission/flare provide the basis for comprehensive disease assessment and management. <h3>References</h3> El Miedany et al. Current Rheumatology Reviews 2015; 11, 18–27. El Miedany et al. Clin Exp Rheumatol 2010; 28(5):734–44. <h3>Disclosure of Interest</h3> None declared
Macrophage dysfunction in the pathogenesis and treatment of asthma
Authors: Michael Fricker, Peter G. Gibson
Journal: European Respiratory Journal (2017)

Asthma is a chronic respiratory condition frequently associated with aberrant airway and systemic inflammation. Various inflammatory phenotypes in asthmatic airways have been described that relate to clinical phenotypes and impact on responses to conventional and novel asthma therapies. Macrophages are abundant immunocytes in the lung, capable of mounting diverse responses required for homeostasis and defence against pathogens. Here, we summarise the clinical evidence regarding macrophage dysfunction in asthma. We also describe evidence supporting the role of macrophages as therapeutic targets in asthma. We conclude that macrophage dysfunction in asthma is highly prevalent and heterogeneous, and hypothesise that macrophages may play roles in promoting the discrete inflammatory phenotypes of asthma. These clinical findings, along with recent ground-breaking insights into the ontogeny, behavioural complexity and longevity of pulmonary macrophages, support continued research into the role of macrophages as disease modifiers, biomarkers and therapeutic targets in asthma.
THU0151 Acpa are associated with low bone mineral density in rheumatoid arthritis
Authors: L Bautista Aguilar, A Salmoral Chamizo, R Jimenez Gasco, I Gomez Gracia, P Font Ugalde, ML Ladehesa Pineda, EC Lopez Medina, L Perez Sanchez, A Escudero Contreras, E Collantes Estevez
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Several studies have related ACPA with the presence of bone erosion in rheumatoid arthtitis patients as they induce the differentiation and activation of osteoclasts <h3>Objectives</h3> Our main aim is to evaluate the association of ACPA with bone mineral density (BMD) in RA <h3>Methods</h3> Case-control study of 73 RA patients (2010 EULAR criteria) and a long standing disease of 5 years. Demographic and clinical variables were collected. BMD values using densitometry at the lumbar (CL), hip (CT) and femoral neck (CF) were collected. The presence of low bone mineral density (osteopenia: tscore≤-1) and ACPA levels were compared using logistic regression analysis, adjusting variables related to BMD: age, sex, menopause, body mass index (BMI), habit Smoking, disease duration, daily corticoid doses, methotrexate treatment and inflammatory disease activity (DAS28) <h3>Results</h3> A group of 73 patients were included (14 men) with a mean age of 66,45±10,41 years, mean body mass index 28,48±5,22 kg/m<sup>2</sup>, mean long standing disease of 2,28±1,75 years and mean DAS 28 of 3,17±1,18. A total of 29 patients were negative for ACPA compared to 44 patients that were positive for ACPA. Osteopenia in lumbar spine was found in 82.2% of patients 65.8% hip and 75.3% in femoral neck. Logistic regression was performed without finding statistically significant association between osteopenia and inflammatory activity (DAS 28), vitamin D levels and positive rheumatoid factor, adjusted for variables that can modify BMD. ACPA Positive (any titer) were associated with the presence of lumbar spine osteopenia (OR 7.19, 95% CI 1.77–29.17) (p=0.006), hip (OR 15.17, 95% CI 3.96–58.18) (p=0.001) and femoral neck (OR 3.76; 95% CI 1.20–11.82) (p=0.023). In addition, a simple variance analysis (ANOVA) was performed to compare T scores and ACPA levels divided into three categories: ≤25U/mL, 25–300U/mL and&gt;300U/mL. ACPA group ≤25U/mL differed in mean T score values in lumbar spine, hip and femoral neck. No differences were found between ACPA positive patients with low and high levels for T score values. <h3>Conclusions</h3> ACPA positivity in RA is associated with an increased risk of osteopenia in lumbar spine, hip and femoral neck independently of other variables that may modify bone mineral density. These data suggest that ACPA may play a role in bone remodeling <h3>References</h3> Referencias: Harre et al.J Clin Invest (2012), 122(5):1791–1802. Bugatti et al. Arthritis Research &amp; Therapy (2016), 18:226. Geusens and Lem. Arthritis Research &amp; Therapy (2011), 13:242. <h3>Disclosure of Interest</h3> None declared
AB0586 Evaluation of asssociation between antiphospholipid antibodies or lupus anticoagulant positivity and severity of vascular involvement in takayasu arteritis patients
Authors: E Fırat, A Erden, A Sari, B Armagan, L Kilic, O Karadag, A Akdogan
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Takayasu Arteritis is a rare large-vessel vasculitis variant that affects the aorta and its main branches and the pulmonary arteries. Antiphospholipid syndrome is characterized by obstetric and thrombotic complications in the presence of antiphospholipid antibodies, which consist of anticardiolipin antibody, lupus anticoagulant and anti -β2 glycoprotein I. The association of antiphospholipid antibodies and Takayasu arteritis is very rare and few cases decumented it, while others argued aganist such association. <h3>Objectives</h3> This study was planned to find out the prevelance of immunoglobulinIgM/G anti-cardiolipinantibodies, anti beta 2 glycoprotein- 1antibodies and lupus anticogulant and evaluate the relationship between these antibodies and disease severity/complications in Takayasu arteritis patients. <h3>Methods</h3> 53 patients with Takayasu arteritis patients were enrolled in this study. We obtained blood samples to detectIgM/G anti-cardiolipin antibodies, anti beta 2 glycoprotein 1 antibodies and lupus anticogulant (LA) levels from all patients during their routine control. ImmunoglobulinIgM/G anti-cardiolipin antibody, anti beta 2 glycoprotein 1 antibodies were measured by using a standardized enzyme-linked immunosorbent assay (ELISA) and lupus anticogulant was measured using the diluteRussell9s viper venom time (dRVVT). <h3>Results</h3> No patients was positive forIgM/G anti-cardiolipin antibody. Seven were positive immunoglobulin IgM anti beta 2 glycoprotein 1 antibodies, three were positive immunoglobulin IgG anti beta 2 glycoprotein 1 antibodies, one waspositive LA. All of the antibody titters were low. TA patients who had antibody positivity had longer disease duration (p&lt;0.05). Antibody and LA positive patients had superior mesenteric artery and celiac artery involvement more frequently then the antibody negative patients (p&lt;0.05). <h3>Conclusions</h3> In this study that there were no association between the antibodies positivity and vascular involvement or disease complications and severity in TA patients. In conclusion we can not suggest the routine evaluation of antiphospholipid antibodies or lupus anticoagulant test during the follow-upTakayasu arteritis patients. These antibodies may only be measured in the presence of clinical suspicion. <h3>Disclosure of Interest</h3> None declared
FRI0296 Single center experience with 300 systemic lupus erythematosus patients
Authors: S Tekeoglu, D Temiz Karadag, O Ozdemir Isik, A Yazici, A Cefle
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Systemic lupus erythematosus (SLE) is an autoimmune disease with diverse clinical manifestations. <h3>Objectives</h3> Here, we present 300 patients with SLE attending our clinic between 2001 and 2017. <h3>Methods</h3> Demographics, clinics, laboratory findings, Systemic Lupus International Clinics (SLICC)/American College of Rheumatology (ACR) damage index scores and treatments were analyzed. Diagnosis was confirmed with 1997 ACR (1) or 2012 SLICC (2) classifications. Descriptive statistical tests were used for analysis. <h3>Results</h3> Demographics and clinical characteristics are presented in Table 1. Anti-dsDNA was positive in 185 (61.6%), anti-Sm was positive in 35 (11.6%), anti-phospholipid antibodies was positive in 67 (22.3%), direct Coombs test was positive in 69 (23%) patients. Complement levels were low in 171 (57%) patients. In patients with renal disease, class IV lupus nephritis was the most common form (37 patients [12%]) followed by class II nephritis (34 patients [11%]). Forty-six patients had antiphospholipid syndrome. Treatments patients ever received are presented in Table 2. Cyclophosphamide treatment was given mostly for renal disease. Within 22 patients receiving rituximab, 2 had thrombocytopenia and 1 had hemolytic anemia unresponsive to other treatments, 1 had protein-losing enteropathy and 1 had lupus enteritis; the rest had lupus nephritis. One patient received intravenous immune globulin (IVIG) for severe neutropenia and 2 patients for severe thrombocytopenia. One patient received plasmapheresis for vasculitis. One patient received IVIG, plasmapheresis, rituximab for severe renal failure, alveolar hemorrhage requiring intensive care unit admission and 1 patient received same treatment for severe unresponsive hemolytic anemia. <h3>Conclusions</h3> In long term, SLICC/ACR damage index was highest in patients received pulse steroid for renal disease (min:0, max:5). Four (1.3%) patients had pulmonary hypertension, 31 (10.3%) had avascular necrosis, 24 (8%) had viral infections requiring treatment or bacterial infections requiring admission due to immunosuppression, 12 (4%) had malignancy. SLE is an autoimmune disease requiring multi-faceted approach. <h3>References</h3> ) Hochberg MC: Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum. 40:1725 1997. ) Petri M, Orbai AM, Alarcon GS, et al.: Derivation and validation of the Systemic Lupus International Collaborating Clinics classification criteria for systemic lupus erythematosus. Arthritis Rheum. 64:2677–2686 2012. <h3>Disclosure of Interest</h3> None declared
In knee OA, intraarticular triamcinolone increased cartilage loss and did not differ from saline for knee pain
Authors: Lawrence E. Hart
Journal: Annals of Internal Medicine (2017)

Source Citation McAlindon TE, LaValley MP, Harvey WF, et al. Effect of intra-articular triamcinolone vs saline on knee cartilage volume and pain in patients with knee osteoarthritis: a randomized clinical trial. JAMA. 2017;317:1967-75. 28510679
Sequential Vacc-4x and romidepsin during combination antiretroviral therapy (cART): Immune responses to Vacc-4x regions on p24 and changes in HIV reservoirs
Authors: G. Tapia, J.F. Højen, M. Ökvist, R. Olesen, S. Leth, S.K. Nissen, D.J. VanBelzen, U. O'Doherty, A. Mørk, K. Krogsgaard, O.S. Søgaard, L. Østergaard, M. Tolstrup, G. Pantaleo, M.A. Sommerfelt
Journal: Journal of Infection (2017)