tbuckley/cabot-search huggingface dataset:
Overcoming Drug Resistance in Myeloma By Synchronized Delivery of Therapeutic and Bone Marrow Disrupting Agents By Nanoparticles Targeting Tumor-Associated Endothelium
Authors: Cinzia Federico, Barbara Muz, Jennifer Sun, Kinan Alhallak, Justin King, Daniel R. Kohnen, Mark A. Fiala, Aldo M. Roccaro, Ravi Vij, Abdel Kareem Azab
Journal: Blood (2018)
AB0376 Rapamycin induces remission in patients with newly diagnosed rheumatoid arthritis
Authors: M. Chen, Z. Li, H. Yao, F. Hu, J. Liang, N. Yan, H. Niu, C. Gao, X. Li, C. Wang
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Rheumatoid arthritis (RA) is an autoimmune disease characterised by chronic inflammation of the joints. We found that there was an imbalance between Th17 and Treg cells in the patients with active refractory RA, reduced absolute number of Treg cells was found in these patients. <h3>Objectives</h3> To observe the medium-term curative effect of rapamycin in the treatment of 25 cases newly diagnosed rheumatoid arthritis. <h3>Methods</h3> Collecting 25 patients of newly diagnosed rheumatiod arthritis, which accorded with RA diagnosis standard of ACR in 1987. The patients were treated with rapamycin at a dose of 0.5 mg every 2 days for 24 weeks, then we observed the change of clinical improvement and immunological assessments after 24 weeks. <h3>Results</h3> There was 25 patients enrolled. After rapamycin treatment for 24 weeks, the mean DAS28 of them was decreased from 5.36 [1.42] to 3.45 [1.29](p=0.001). The absolute number of Treg<sup>CD4+CD25+Foxp3+</sup>cells significantly higher than baseline (30.24 [14.44],46.64 [27.54],p=0.025). The absolute number of Th17 cells was not significantly different (6.40 [4.46],7.03 [5.60],p&gt;0.05), and the same as the ratio of Th17/Treg cells (0.25 [0.18],0.19 [0.16]),p&gt;0.05). Meanwhile, the mean dose of prednisone was decreased form 11.25 mg/d to 9.6 mg/d. <h3>Conclusions</h3> Rapamycin could induce the balance of Th17 cells and Treg cells, especially up-regulate the absolute number of Treg cells, thus induce remission in patients with newly diagnosed RA. <h3>Disclosure of Interest</h3> None declared
Abstract 34: Cardiorespiratory Fitness Response to Short Term Supervised Exercise Training Predicts Age Related Cardiorespiratory Fitness Decline Over Long Term Follow up
Authors: Ambarish Pandey, Cris A Slentz, Johanna L Johnson, Jarett D Berry, William E Kraus
Journal: Circulation (2017)

Introduction: Substantial heterogeneity exists in the cardiorespiratory fitness (CRF) change response to short-term supervised exercise training and its long-term prognostic implication is not well understood. Here, we evaluated the association between the short-term training related changes in CRF and CRF levels 10 years later. Methods: STRRIDE trial participants that were originally randomized to exercise training for 8 months and participated in the 10-year follow up visit were included. CRF levels were measured at baseline, post-training (8 months), and 10-year follow-up as peak oxygen uptake (VO 2 , ml/kg/min) using the maximal treadmill test. Participants were stratified into low, moderate, and high CRF response (CRF-R) groups according to the training-regimen specific tertiles of CRF change from baseline to post-training. Adjusted linear regression models were used to determine the association between short-term change in CRF with training and CRF levels at 10-year follow-up. Results: The study included 80 participants (age = 52 years, 35% women). There was no significant difference in the baseline characteristics of the CRF-R groups. At 10-year follow-up, high CRF-R group had the lowest decline in CRF compared with moderate or low CRF-R groups (-0.005 vs. -2.6. vs. -3.6 ml/kg/min, p = 0.009, Figure). This was largely related to the differential age-related changes in peak oxygen pulse across the three groups (0.58 vs. -0.23 vs. -0.86 ml/beat, p = 0.02) with no difference in the peak heart rate change. In adjusted analysis, high CRF-R was significantly associated with higher CRF levels at follow-up independent of the exercise intervention and other baseline characteristics [High vs. Low (ref) CRF-R: Std β = 0.25; p = 0.004] Conclusion: CRF change in response to short-term training is a significant predictor of age-related CRF decline over long-term follow-up. Thus, training responsiveness may identify individuals at risk for exaggerated CRF decline with aging and associated incidence of cardiovascular diseases.
AB1075 Relationship of serum cholecalciferol (VITAMIN D3) level with musculoskeletal symptoms
Authors: M.A. Razzaque, G. Dewan, R.S. biswas, M.N. karim, I. sultan
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Patients suffering from generalised aches and pains, not adequately responding to treatment are usually considered as fibromyalgia, depression, chronic fatigue syndrome etc. But those patients need further evaluation and low vitamin D is often the underlying cause. Both clinical and subclinical low level vitamin D is common.<sup>1</sup> <h3>Objectives</h3> To assess the relationship between musculoskeletal complaints and serum vitamin D<sub>3</sub>(cholecalciferol) level. <h3>Methods</h3> This prospective cross-sectional descriptive study was conducted during July 2017 to December 2017 in Chittagong, Bangladesh. Patients with common musculoskeletal complaints were enrolled. Each patient was screened to exclude common possibilities. Serum cholecalciferol was measured for each patient. Race, occupation, skin complexion, body mass index, sunlight exposure, covering of body with clothing’s and use of sunscreen were taken under consideration in final analysis. Visual analogue scale (VAS; 1–10) was used to quantify all complaints. Correlation of serum cholecalciferol level with VAS score of individual complaints was analysed. <h3>Results</h3> A total of 110 patients (79 Female and 31 Male) were enrolled after screening 165. All of them were Bangladeshi of multi-ethnic Asian origin. Mean age was 46.5±12.8 years. Their skin complexions were pale white to white skin 45.5%, light brown 30%, moderate brown 11.8% and dark brown 12.7%. Most had (90.9%; n=100) inadequate sunlight exposure and 77.2% (n=61) women used Burkah (full covered dress). Mean vitamin D<sub>3</sub> level was 25.2±7.3 ng/ml. Vitamin D deficiency was (mean 17.3±2.8 ng/ml) observed in 30 (27.3%), insufficiency (mean 25.1±2.7 ng/ml) in 62 (56.4%) and normal level (mean 34.8±4.4 ng/ml) in 18 (16.4%). After classifying Vitamin D level in relation to symptoms it was found that majority of patients (81.2% to 90.3%; depending on complaints) had insufficient or deficient cholecalciferol level (table 1). Significant negative correlation was found between the serum cholecalciferol level and VAS for difficulty in getting up from squatting position (r=−0.253, p=0.008) and positive correlation was found for muscle cramps (r=0.220, p=0.021). Correlations with remaining symptoms were not statistically significant. <h3>Conclusions</h3> Vitamin D status directly and indirectly influences musculoskeletal health. Hypovitaminosis D should consider in every patient with muscle cramp. <h3>Reference</h3> [1] Jones AN, Hansen KE. Recognizing the musculoskeletal manifestations of vitamin D deficiency. J Musculoskelet Med. 2009; 26(10): 389 – 96. <h3>Acknowledgements</h3> Hafsa habiba, Rayhana Begum <h3>Disclosure of Interest</h3> M. A. Razzaque Consultant for: research, G. Dewan Consultant for: research, R. biswas Consultant for: research, M. karim Consultant for: research, I. sultan Consultant for: research
FRI0063 Rapamycin induces remission in patients with refractory rheumatoid arthritis
Authors: H. Yao, H. Niu, N. Yan, X. Sun, Z. Li, M. Chen, C. Gao, X. Li, C. Wang
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Rheumatoid arthritis (RA) is a chronic inflammatory disease that results in destruction of joint cartilage and bone. However, many patients do not achieve satisfactory disease control by current therapy with high risk of adverse reactions. We have reported that absolute number of peripheral regulatory T (Treg) cells reduced in RA patients (EULAR Abstract). Moreover, rapamycin has been reported to inhibit differentiation of Th17 and promote growth of FoxP3 +Treg cells by inhibiting mTOR pathway<sup> [1]</sup>. <h3>Objectives</h3> To observe the therapeutic efficacy of rapamycin on the reduction of disease activity, increase in Tregs and decrease in Th17 to restore balance of Th17/Treg cells in RA patients with high disease activity (DAS28 ≥2.6). <h3>Methods</h3> Fifty RA patients who treated with two kinds of DMARDs for more than half a year did not achieve remission (DAS28 ≥2.6) were enrolled and were treated with rapamycin at a dose of 0.5 mg every 2 days for 24 weeks. The absolute number of CD4 +T cell subsets in peripheral blood from these patients were assessed by flow cytometry combined with internal standard beads before the treatment as baseline and at week 24 after treatment. Meantime, the DAS28, the dosage of corticosteroids and immunosuppressant were also recorded. <h3>Results</h3> Rapamycin treatment reduced the disease activity and induced remission (DAS28&lt;2.6) in 44.9% of active RA patients. Their DAS28 was reduced from a median 2.9 (at week 0) to 1.9 (at week 24) (P&lt;0.001) and the absolute number of peripheral Treg cells was increased from 27.14±15.11 cells/µl (at week 0) to 36.59±17.23 cells/µl (at week 24) (p=0.002). The ratios of Th17/Treg cells also had a significant decrease from 0.36±0.29 at baseline to 0.27±0.20 at week 24 (P&lt;0.041). In contrast, the decrease in the absolute number of Th17 cells was not statistically significant (p=0.846). After the treatment, the proportion of patients taking glucocorticoids decreased from 66.0% to 64.0% and the mean dosage of prednisone decreased from 9.89 mg/d to 7.70 mg/d. And the usages of DMARDs were also reduced (P&lt;0.001). <h3>Conclusions</h3> Rapamycin combined with low level of conventional therapy effectively reduced disease activity and induced remission among RA patients who received long-term conventional treatment without remission (DAS28 ≥2.6) by increasing the absolute number of Treg cells and restoring the balance of Th17 cells and Treg cells. As the research progresses, rapamycin is likely to become a promising therapeutic candidate. <h3>Reference</h3> [1] Shan J, Feng L, Sun G, et al. Interplay between mTOR and STAT5 signaling modulates the balance between regulatory and effective T cells. Immunobiology2015;220(4):510–517. <h3>Disclosure of Interest</h3> None declared
Abstract 19899: Insulin Treatment Induces Oxidative Stress in the Vascular Wall of Patients With Atherosclerosis Independently of Diabetes or Systemic Insulin Resistance: The Protective Role of DPP-IV Inhibition
Authors: Ioannis Akoumianakis, Laura Herdman, Marios Margaritis, Fabio Sanna, Rana Sayeed, George Krasopoulos, Norbert Tennagels, Paulus Wohlfart, Keith M Channon, Charalambos Antoniades
Journal: Circulation (2017)

Background: Insulin has protective roles in vascular cells, but its vascular effects in patients with atherosclerosis are unknown. We investigate the direct effects of insulin on human vascular redox signaling, and its' interaction with dipeptidyl peptidase IV inhibitors (DPPIV-i). Methods: Saphenous vein (SV) and internal mammary artery (IMA) segements obtained from 72 patients undergoing coronary bypass surgery, were incubated with insulin glargine active metabolite M1 (insulin), insulin degludec (DEG) and human insulin (HI) (1-100nM as stated), +/- pre-incubation with DPPIV-i KR62436 70μM. Vascular superoxide (O2.-) was quantified by lucigenin chemiluminescence, and nitric oxide bioavailability by acetylcholine vasorelaxations ex vivo. Results: Insulin increased NADPH-oxidases-derived O2.- in SV and IMA from diabetics and non-diabetics, effects reversed in vessels from patients treated with oral DPPIV-i (A). Pre-incubation of these vessels with DPPIV-i reversed this effect of insulin (B), improving eNO...
FRI0181 Twelve years follow-up of patients with spondyloarthritis in an endemic city demonstrates high risk of active tuberculosis infection
Authors: A. Morsch, D. Silva, G. Garziera, M. Ferreira, C. Kohem, R. Xavier, A. Gasparin, C. Brenol, R. Bohn, N. de Andrade, D. Viecceli, F. Menegat, P. Palominos
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Anti-tumour necrosis factor (anti-TNF) agents can induce progression from latent tuberculosis infection (LTBI) to active tuberculosis (TB) in patient with rheumatic diseases<sup>1,2</sup>. In a high tuberculosis incidence setting, TB cases developed despite the screening and treatment for LTBI. <h3>Objectives</h3> To identify, in a high TB incidence setting, the TB incidence rate in patients with spondyloarthritis (SpA) during twelve years of follow-up. <h3>Methods</h3> Electronic medical records from patients attending the SpA Clinic between 2004 and 2016 in a public university hospital were reviewed. Patients were grouped in those exposed to anti-TNF therapy and those non-exposed. The tuberculosis incidence rate (IR) was calculated for both groups and expressed as number of events per 1 00 000 patients/year; the incidence rate ratio (IRR) associated to the anti-TNF therapy was calculated. <h3>Results</h3> A total of 274 patients were evaluated, 102 exposed to anti-TNF drugs and 172 non-exposed. All the 102 patients underwent screening for LTBI before anti-TNF therapy: 38.2% (n=39) were diagnosed with LTBI and underwent 6 months of isoniazid preventive therapy (IPT). The total follow up time (in patients/year) was 729 in the group exposed to anti-TNF and 1243 in the group non-exposed. Ten patients were diagnosed with TB: 4 exposed to anti-TNF therapy and 6 non-exposed. Among the 4 patients exposed to anti-TNF therapy who developed TB, three had negative screening for LTBI. The TB IR (per 1 00 000 patients/year) among those exposed to anti-TNF was 548, compared to 321 in non-exposed; the IRR associated with the use of anti-TNF drugs was 1.7. <h3>Conclusions</h3> In a region with high TB prevalence, patients with SpA exposed to anti-TNF drugs had a higher incidence of TB compared to those who have never been exposed to these drugs. Our data reinforces the American College of Rheumatology's recommendation that patients who live in endemic TB settings should be tested annually for LTBI. <h3>References</h3> [1] Keane J, Gershon S, Wise RP, Mirabile-Levens E, Kasznica J, Schwieterman WD, et al. Tuberculosis associated with infliximab, a tumor necrosis factor alpha-neutralizing agent. N Engl J Med2001;345(15):1098–1104. [2] De Vries MK, et al. Tuberculosis risk in ankylosing spondylitis, other spondyloarthritis and psoriatic arthritis on Sweden: a population-based cohort study. Arthritis Care Res (Hoboken)2017Dec 1. doi:10.1002/acr.23487. [Epub ahead of print] <h3>Disclosure of Interest</h3> None declared
THU0017 Dna methylation of regulatory sites of hand osteoarthritis susceptibility genes in finnish women
Authors: S. Hämäläinen, S. Solovieva, T. Vehmas, A. Hirvonen, P. Leino-Arjas
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Despite the hard effort in OA genetic studies only a small part of the estimated effect has been found so far and thus the focus has been changing from genetic to epigenetic studies. The most widely studied epigenetic control mechanism is DNA methylation. There are only few studies on hand OA concerning DNA methylation but their results are promising. <h3>Objectives</h3> Our aim was to study methylation of the regulatory sites of our previously found hand OA susceptibility genes and to replicate some previously reported methylation sites associated with hand OA, in our Finnish women hand OA material. <h3>Methods</h3> The study design was cross-sectional. Bilateral hand radiographs of 542 occupationally active Finnish female dentists and teachers aged 45 to 63 and classified them according to the presence of OA by using reference images. Radiographic hand OA at least mild, in at least three joints (ROA2_3), and radiographic findings summary score (OASUM) were used to define hand OA status. The methylation percentages were determined by bi-sulfite converted DNA pyrosequencing with commercial CpG Assays. Statistical analyses were performed using hierarchical multiple linear regression. <h3>Results</h3> Of the studied methylation sites the <i>COL2A1_1</i> methylation site was associated with ROA2_3 (p=0.04). Also <i>ALDH1A2_01</i> methylation site was associated with OASUM (p=0.02). When the data was stratified by occupation the association was only significant, and stronger, in teachers but not in dentists (<i>COL2A1_1</i> p=0.02 vs. p=0.36 for ROA2_3, and <i>ALDH1A2_1</i> p=0.01 vs. p=0.36 for OASUM, respectively). The studied methylation sites in <i>TGFB1, RRP9</i> and <i>TRAPP5</i> genes had methylation percentages under the detection limit and they were excluded from the analysis. <h3>Conclusions</h3> Our results lend further support to <i>COL2A1</i> and <i>ALDH1A2</i> being hand OA susceptibility genes at the epigenetic level. <h3>Acknowledgements</h3> The study was financially supported by a grant from the Finnish Work Environment Fund (113369). <h3>Disclosure of Interest</h3> None declared
AB1146 The association of common mefv gene mutations with axial spondylarthritis in fmf patients: a retrospective study
Authors: K. Ayar, E.K. Ozturk, O. Yesiloz
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Familial Mediterranean fever (FMF) is an autoinflammatory disease seen with autosomal recessive inheritance and is characterised by recurrent and self-limiting attacks with peritonitis, pleuritis, arthritis or fever alone. The association of spondylarthritis and FMF is reported in some studies. There are few studies evaluating the association of MEFV gene mutations with axial spondylarthritis in FMF patients. <h3>Objectives</h3> The aim of this study is to identify patients with FMF associated spondylarthritis retrospectively and to compare the frequency of common MEFV gene mutations in FMF patients with and without axial spondylarthritis. <h3>Methods</h3> We have reviewed 138 charts of FMF patients. The data of 116 patients (70 female, 46 male) who met the diagnosis of FMF with Tel Hashomer classification criteria and have the results of MEFV gene mutation were examined. Patients' age, sex, MEFV gene mutations were recorded. The presence of inflammatory back pain (IBP) obtained from rheumatological system questionnaire in the patients' charts were recorded. The x-ray and MR images of sacroiliac joint registered in the PACS system were evaluated by a Rheumatologist. Patients with inflammatory low back pain and sacroiliitis detected by X-ray or MR were included in the FMF with axial spondylarthritis (FMF-SPA) group and others to FMF group. The frequency of MEFV gene mutations were compared between two groups. <h3>Results</h3> The frequency of M694V, M680I, V726A, E148Q and R202Qare 82.4%, 19.6%, 16.7,%10.8% and 16.7% respectively in FMF group and 78.6%, 21.4%, 14.3%, 21.4% and 28.6% respectively in FMF-AS group. There was no significant difference between groups (p=0.716, p=1.000, p=1.000, p=0.373 and p=0.279 respectively). The frequency of M694V homozygotes and heterozygotes mutations were 27.5% and 21.6% respectively in FMF group and 35.7% and 7.1% respectively in FMF-SPA group and difference between groups was not significant (p=0.537, p=0.296 respectively). <h3>Conclusions</h3> The frequency of common MEFV gene mutations in this study is not different between FMF patients with and without axial spondylarthritis. Increased frequency of axial spondylarthritis in FMF patients may not be associated with MEFV gene mutations. <h3>References</h3> [1-] Akar S, Soysal O, Balci A, Solmaz D, Gerdan V, Onen F, Tunca M, Akkoc N. High prevalence of spondyloarthritis and ankylosing spondylitis among familial Mediterranean fever patients and their first-degree relatives: further evidence for the connection. Arthritis Res Ther. 2013 Jan 28;15(1):R21. doi: 10.1186/ar4154. [2] - Livneh A, Langevitz P, Zemer D, Zaks N, Kees S, Lidar T, Migdal A, Padeh S, Pras M. Criteria for the diagnosis of familial Mediterranean fever. Arthritis Rheum. 1997Oct;40(10):1879–85. <h3>Disclosure of Interest</h3> None declared
SAT0197 Adherence to biologic therapy of rheumatoid arthritis patients – is there any relation with disease activity?
Authors: N. Madeira, A. Cardoso, R. Trinca, C. Silva, H. Santos, C. Miguel, F. Barcelos, D. Medeiros, R. Campanilho Marques, L. Cunha Miranda
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background:</h3> In the last years, there has been an increase interest in using Patient Reported Outcomes (PROs) in clinical trials and daily clinical practice in Rheumatology to provide patient-centered care. The most frequently reported PROs are patient's pain, patient's global assessment (PGA) of disease activity and reports of functional capacity, fatigue, anxiety and depression. To date, studies that explore patient adherence to rheumatic medications are scarce. <h3>Objectives:</h3> To study the level of adherence to biologic therapy of Rheumatoid Arthritis (RA) patients, followed at a day care hospital of Rheumatology. <h3>Methods:</h3> Observational and cross-sectional study which took place in two months of consultation of day care hospital (5 periods per week). Patients with a diagnosis of RA according to 1987 American College of Rheumatology (ACR) and/or 2010 ACR/European League Against Rheumatism criteria, on biologic therapy, able to complete a questionnaire autonomously and who agreed to participate were included. Demographic and clinical data (DAS28, CDAI and SDAI to assess RA disease activity, HADS-A for anxiety, HADS-D for depression, FACIT-F for fatigue) were collected. To assess adherence, a Portuguese version of the Morisky Medication Adherence Scale (MMAS-8) was used and the patients were asked to apply it only to biologic therapy. Three levels of adherence were considered based on the following scores: 0 to &lt;6 (low); 6 to &lt;8 (medium); 8 (high). Statistics: Kruskal-Wallis and Mann-Whitney tests, p&lt;0.05, SPSS® v.23. <h3>Results:</h3> In total, 61 patients were included, 91.8% female, 82.0% on anti-Tumor Necrosis Factor (anti-TNF), the others on Tocilizumab (16.4%) or Abatacept (1.6%). Table 1 reports the means and medians of demographic and clinical variables included. The mean MMAS-8 score was 7.0±1.2, the median 7.0 (6.8–8.0), with a minimum of 2.5 and a maximum of 8. The adherence was medium in 50.8%, high in 36.1% and low in 13.1% patients. The median of current age was significantly higher for patients with high and medium levels of adherence compared to those with low levels (p=0.030). The time on treatment with the current biologic therapy was significantly different between the levels of adherence (p=0.028); the median of time on treatment for patients with medium levels of adherence was significantly higher comparatively to the other patients (p=0.009). No other significant difference was found among the levels of adherence for the studied variables. <h3>Conclusions:</h3> The adherence to biologic therapy was at least medium for 86.9% of patients. Differences between levels of adherence were found only for current age and time on treatment. Disease activity of RA does not seem to influence the levels of adherence. <h3>Disclosure of Interest:</h3> None declared