tbuckley/cabot-search huggingface dataset:
SAT0563 Evaluation of role of sleep disturbance, depression, obesity, and physical inactivity in fatigue in chikungunya arthritis
Authors: M Bhama
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Chikungunya virus (CHIKV) is a mosquito-borne alphavirus that circulates predominantly in tropical and subtropical regions, potentially affecting over 1 billion people. <h3>Objectives</h3> Fatigue is a major concern in individuals where CHIKV results severe chronic arthralgia and/or arthritis lasting months to years. However, in order to treat fatigue adequately, its sources need to be identified. <h3>Methods</h3> All participants had physician-diagnosed CHIKV arthralgia. Data regarding self-reported sleep quality, depression, physical activity, disease activity, muscle strength, functional limitations, and body composition were collected during a single home visit (number of participants=117). Information on demographics, medications, alcohol intake and smoking was collected. The Fatigue Severity Inventory (FSI; measuring average fatigue over the past 7 days) was used as the primary outcome. Analyses were conducted to evaluate bivariate relationships with fatigue and correlations among risk factors. Multivariate analyses identified independent predictors of fatigue. <h3>Results</h3> The mean age was 48±16 years, the mean disease duration was 7±6 years, and 71% (M:33, F:84) of subjects were female. The mean FSI rating was 4.1±2.0 (range 0–10). In multivariate analyses, self-reported disease activity, poor sleep, depression, and obesity were independently associated with fatigue. Physical inactivity was correlated with poor sleep, depression, and obesity. Mediation analyses indicated that physical inactivity had an indirect association with fatigue, mediated by poor sleep, depression, and obesity. <h3>Conclusions</h3> This cross-sectional study suggests that fatigue may not be solely a result of CHIKV arthralgia, but may result from a constellation of factors that includes CHIKV arthralgia disease activity or pain, but also includes inactivity, depression, obesity, and poor sleep. The results suggest need of various interventions to improve fatigue in individuals with CHIKV arthritis, including increasing physical activity or addressing depression or obesity. <h3>References</h3> Thiberville S.D., Moyen N., Dupuis-Maguiraga L., Nougairede A., Gould E.A., Roques P., de Lamballerie X. Chikungunya fever: epidemiology, clinical syndrome, pathogenesis and therapy. Antiviral Res. 2013;99(3):345–370. Vijayan V, Sukumaran S. Chikungunya Virus Disease: An Emerging Challenge for the Rheumatologist. J Clin Rheumatol. 2016 Jun;22(4):203–11. Stebbings S, Herbison P, Doyle T, Treharne GJ, Highton J. A comparison of fatigue correlates in rheumatoid arthritis and osteoarthritis: disparity in associations with disability, anxiety, and sleep disturbance. Rheumatology (Oxford)2010;49:361–7. Whitehead L. The measurement of fatigue in chronic illness: a systematic review of unidimensional and multidimensional fatigue measures. J Pain Symptom Manage2009;37:107–28. <h3>Disclosure of Interest</h3> M. Bhama Consultant for: Orthopedics Consultant
SAT0223 Indirect comparative clinical effectiveness of intravenous and subcutaneous formulations of belimumab for the treatment of adult patients with active, autoantibody-positive systemic lupus erythematosus with high disease activity
Authors: D Parks, S Ramachandran, M Kurtinecz, Y Asukai, R Alfonso-Cristancho
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> The efficacy of belimumab (BEL) vs placebo (PBO), in adult patients with active, autoantibody-positive systemic lupus erythematosus (SLE) who are receiving standard SLE therapy has been demonstrated. To date, no direct comparison of intravenous (IV) BEL vs subcutaneous (SC) BEL has been performed, hence the importance of an indirect treatment comparison (ITC). <h3>Objectives</h3> To indirectly compare the clinical effectiveness of BEL IV and SC formulations in patients with SLE high disease activity (HDA) via an ITC. <h3>Methods</h3> Three BEL IV Phase lll randomised controlled trials (RCTs; HDA/BLISS-52, 327/577; HDA/BLISS-76, 265/548; HDA/North East Asia study [BEL113750], 427/677) and one BEL SC RCT (HDA/BEL112341; 356/836) were compared via a Bayesian ITC (BEL207255). We evaluated the relative efficacy of the formulations in patients meeting three measures of HDA at baseline (1. BLISS-52 and BLISS-76, C3 &lt;0.9 g/L or C4 &lt;0.16 g/L; BEL112341 and BEL113750, C3 &lt;0.9 g/L or C4 &lt;0.10 g/L; and 2. anti-dsDNA positive [≥30 IU/mL] or 3. Safety of Estrogen in Lupus Erythematosus National Assessment-SLE Disease Activity Index [SELENA-SLEDAI] scores ≥10). Analyses were conducted in patients meeting Criteria 1: low C3/C4 and high anti-dsDNA; and Criteria 2: low C3/C4 and high anti-dsDNA or SELENA-SLEDAI ≥10 or low C3/C4. The primary endpoint was SLE Responder Index (SRI) response (≥4-point reduction in SELENA-SLEDAI, no worsening in Physician9s Global Assessment, no new 1A/2B British Isles Lupus Assessment Group domain scores) at Week 52. Secondary endpoints included ≥4-point reduction in SELENA-SLEDAI and SLE Flare Index rate. Safety endpoints were not assessed. <h3>Results</h3> Baseline characteristics were relatively similar between RCTs and a fixed effects model binomial distribution with logit link was used for all efficacy endpoints (Table). In this indirect comparison, no differences were identified between BEL IV and BEL SC for the efficacy endpoints. <h3>Conclusions</h3> In this indirect comparison, BEL IV and BEL SC were similar for SRI response, ≥4-point reduction in SELENA-SLEDAI, or rate of severe flare at Week 52 in patients with SLE. Outcomes were consistent irrespective of the criteria applied. <h3>Acknowledgements</h3> Study funded by GSK. Katie White, PhD, Fishawack Indicia Ltd, UK, provided editorial assistance funded by GSK. <h3>Disclosure of Interest</h3> D. Parks Shareholder of: GSK, Employee of: GSK, S. Ramachandran Shareholder of: GSK, Employee of: GSK, M. Kurtinecz Employee of: GSK, Y. Asukai Shareholder of: GSK, Employee of: GSK, R. Alfonso-Cristancho Shareholder of: GSK, Employee of: GSK
SAT0542 Subclinical crystal arthropathy might influence functional disability in patients with knee osteoarthritis? an egyptian cross sectional study
Authors: RHA Mohammed
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Osteoarthritis is a complex slowly progressive degenerative disease that affects joint components.Concomittant articular crystal deposits are able to stimulate an inflammatory response in OA through stimulation of the innate immune system. <h3>Objectives</h3> Assess the contribution of sonographically detected crystal deposits to pain severity and functional disability in patients with knee OA (WOMAC score) <h3>Methods</h3> Single-center cross sectional study. Adult patients diagnosed with knee OA diagnosed in accordance with ACR criteria from the Department of Rheumatology and Rehabilitation, Kasr Alainy School of Medicine, Cairo University were recruited. Clinical assessment of pain and functional status in patients with knee osteoarthritis was measured using: Western Ontario and McMaster Universities Arthritis Index score. The Logic p5 ultrasound machine (GE) with linear array probe (8–13 MHz). Examination of the articular and periarticular structures was performed by a trained rheumatologist according to the standard EULAR guidelines for exam of the knee. Serum uric acid was investigated. Plain radiography was done for comparison. <h3>Results</h3> 53 patients (44 females 83% &amp; 9 males 17%) were included, mean age 53.5 years ± 8.3 SD, disease duration 42.5 months ± 49.5 SD, body mass index mean 34.9±6.3 SD. Crystal deposits were sono-graphically diagnosed in 73 knees (68.9%), Monosodium urate deposits found in 33 knees (31.1%) and Calcium Pyrophosphate Dihydrate deposits were diagnosed in 67 knees (63.2%). Pain, stiffness and disability scores were significantly higher in OA knees with crystal deposition as compared to those without (p&lt;0.05) that was in fact resistant to conventional analgesics, chondro-protectives and physiotherapy demanding the ongoing use of NSAIDs. <h3>Conclusions</h3> Crystal deposition was associated with significantly increased pain intensity, knee joint stiffness and functional disability as measured by WOMAC in patients with knee OA. <h3>References</h3> Altman R, Asch E, Bloch D, Bole G, Borenstein D, Brandt K, et al., Development of criteria for the classification and reporting of osteoarthritis. Classification of osteoarthritis of the knee. Diagnostic and Therapeutic Criteria Committee of the American Rheumatism Association. Arthritis Rheum. 1986; 29(8):1039–49. Naredo E, Cabero F, Palop MJ, Collado P, Cruz A, Crespo M. Ultrasonographic findings in knee osteoarthritis: A comparative study with clinical and radiographic assessment. Osteoarthr Cartil. 2005; 13(7):568–74. <h3>Disclosure of Interest</h3> None declared
Organic solute transporter‐β (SLC51B) deficiency in two brothers with congenital diarrhea and features of cholestasis
Authors: Mutaz Sultan, Anuradha Rao, Orly Elpeleg, Frédéric M. Vaz, Bassam Abu‐Libdeh, Saul J. Karpen, Paul A. Dawson
Journal: Hepatology (2017)

Primary bile acid malabsorption is associated with congenital diarrhea, steatorrhea, and a block in the intestinal return of bile acids in the enterohepatic circulation. Mutations in the ileal apical sodium‐dependent bile acid transporter (ASBT; SLC10A2 ) can cause primary bile acid malabsorption but do not appear to account for most familial cases. Another major transporter involved in the intestinal reclamation of bile acids is the heteromeric organic solute transporter alpha‐beta (OSTα‐OSTβ; SLC51A ‐ SLC51B ), which exports bile acid across the basolateral membrane. Here we report the first patients with OSTβ deficiency, clinically characterized by chronic diarrhea, severe fat soluble vitamin deficiency, and features of cholestatic liver disease including elevated serum gamma‐glutamyltransferase activity. Whole exome sequencing revealed a homozygous single nucleotide deletion in codon 27 of SLC51B , resulting in a frameshift and premature termination at codon 50. Functional studies in transfected cells showed that the SLC51B mutation resulted in markedly reduced taurocholic acid uptake activity and reduced expression of the OSTα partner protein. Conclusion : The findings identify OSTβ deficiency as a cause of congenital chronic diarrhea with features of cholestatic liver disease. These studies underscore OSTα‐OSTβ's key role in the enterohepatic circulation of bile acids in humans. (H epatology 2017).
AB0573 Autologous stem cell transplantation in the management of refractory behÇet's syndrome: a case series from a single centre of excellence
Authors: L Chadwick, D Thong, J Nair, N Goodson, R Moots
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Evidence regarding haematopoietic stem cell transplantation (HSCT) in refractory Behçet9s Syndrome (BS) is limited. A systematic review in 2014 identified 20 patients with BS who had undergone HSCT, from which 9 patients underwent HSCT with refractory BS as the primary indication. Of these 20 patients: 15 achieved complete remission, 1 patient achieved partial remission, 2 patients relapsed, 1 patient died and 1 had no outcome reported. Nine patients had reported complications, 5 patients had no complications and 6 patients were missing data. All data was sourced from single case studies (1). <h3>Objectives</h3> Outline the indications, outcomes and complications of HSCT in a case series of 4 patients with BS managed at a single centre of excellence. <h3>Methods</h3> Case notes were reviewed for 4 patients from the Liverpool Behçet9s Centre of Excellence (LBCE) who have undergone HSCT. <h3>Results</h3> The primary indication for 3 of the 4 patients who have undergone autologous HSCT at LBCE was refractory BS. Patient 1 underwent HSCT for multiple myeloma, but suffered from severe BS with neurological and venous involvement and is now in partial remission with occasional mild muco-cutaneous ulceration, not requiring systemic immunosuppression. Patient 2 underwent HSCT for severe refractory neuro-Behçet9s. This patient is now in complete remission after commencing azathioprine for oral ulceration. The indications for HSCT in patients 3 and 4 were severe muco-cutaneous ulceration and dermatological involvement refractory to numerous biologic agents with high ongoing steroid dependency. Patient 3 also had previous thrombophlebitis and patient 4 had previous gastro-intestinal ulceration. They are both currently in complete remission but follow up time is limited. Patient 3 had a post-HSCT complication of pneumonia and mucositis which resolved without persistent morbidity, patient 4 had an upper limb deep vein thrombosis (DVT) as an inpatient. <h3>Conclusions</h3> HSCT is an effective treatment modality for severe refractory BS and can result in medication free remission. However, the associated risks should be considered and alternative treatment options deliberated or exhausted before opting for this treatment modality. <h3>References</h3> Soysal T, Salihoğlu A, Esatoğlu SN, Gültürk E, Eşkazan AE, Hatemi G, et al. Bone marrow transplantation for Behçet9s disease: a case report and systematic review of the literature. Rheumatology. 2014; 53(6):1136–41. <h3>Disclosure of Interest</h3> None declared
OP0195 What is the impact of juvenile idiopathic arthritis in adulthood? the monocentric experience of 240 patients followed in a transition tertiary clinic of rheumatology
Authors: I Pontikaki, LM Argolini, C Artusi, PL Meroni
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> There are many differences in clinical manifestations, assessment and management of Juvenile Idiopathic Arthritis (JIA) between childhood and adults9 arthritis onset. The transition from pediatric to the adult care emphasizes a lot of aspects that need to be addressed. <h3>Objectives</h3> To describe the long-term outcome of JIA. <h3>Methods</h3> Two-hundred and forty patients affected by JIA and referred to a transition care rheumatology tertiary centre were considered between 1999 and 2016. The outcome assessment included disease activity, medications, number of prosthesis implantation, pregnancy, mortality, social integration (mobility, employment status and educational level). <h3>Results</h3> Seventy-four (30.8%) males and 166 (69.2%) females were included; 53 (22.1%) patients were lost in follow up. Subtypes of JIA at disease onset included 101 oligoarthirtis (42.1%), 67 polyarthritis (27.9%), 43 systemic arthritis (17.9%), 7 psoriatic arthritis (2.9%), 22 enthesitis related arthritis (9.2%). Forty-eight (20%) patients had persistent uveitis. Ninety-three implant prosthesis and 14 arthodesis were recordered. The average disease duration was 20 years, the median age of the patients was 27 (18–57) years. Five deaths (2.1%) occurred in this cohort. At follow up 117 (48.7%) had low active disease activity, 70 (29.2%) had moderate disease activity, 14 (5.8%) had a high disease activity, 24 (10%) were on remission ON medication and 15 (6.3%) OFF medication. Among patients still on medication, 59 (24.6%) were treated with oral steroids, 18 (7.5%) with csDMARDs and 169 (70.4%) with bDMARDs. Seventy-five (31.3%) patients had a higher educational level (university), 195 (81.3%) had an employment, 128 (53.3%) had a driving license. Twenty-one (8.8%) pregnancies were registered. The transition age was considered after age of sixteen years old. In this contest, it was important the multidisciplinary approach of each patient that was realized with the collaboration of other specialists (ophthalmologist, orthopedic, dermatologist, obstetric, psychologist). <h3>Conclusions</h3> In the era of biologic therapy there was an important improvement in a lot variables of the long-term outcome of JIA. One-hundred-eighty-seven (77.9%) patients were still in tight control, not only because of the continuation of the biological therapy but also because of the multidisciplinary care carried out even during remission. JIA often persists over the adulthood. The long term follow up and care of these patients has to be conducted by a rheumatologist expertized in JIA in collaboration with other specialists. <h3>Disclosure of Interest</h3> None declared
Abstract #4478: Proteomic Profiling of Human Colorectal Adenocarcinoma Tissues and Characterization of Down-regulated Heat Shock Protein 20 (Hsp20)
Authors: Kee Kang, Young-Tae Ju, Eun-Jung Jung, Bok Cho, Sang-Kyung Choi
Journal: Cancer Research (2009)

Cancer development and progression are multistep processes in which control of cell growth is progressively perturbed resulting from either a loss of tumor suppressor genes or activation of oncogenes. Colorectal cancer is a 4 th  common malignancy with an annual incidence of over 945,000 cases worldwide and an annual mortality of 492,000. In contrast to the genome, the proteome is dynamic and is in constant flux because of a combination of factors. It has predicted post-translational modification that most proteins undergo and new disease markers and/or drug targets can be identified through it. Based on the assumptions, two-dimensional gel electrophoresis was performed with proteins from twenty-paired colorectal cancer (CRC) and the corresponding normal tissues, and analyzed a number of proteins to isolate and identify tumor-specific proteins in CRC. In current study, six proteins were dominantly expressed and four proteins were largely repressed in CRC by the analysis of 2-DE, tryptic digestion, and MALDI-TOF/mass spectrometry. Of these, we focused heat shock protein 20 (Hsp20) down-regulated in CRC with no less than 3-fold. To investigate whether Hsp20 could act as a novel tumor-associated marker protein in CRC, we set out to verify the presence of altered expression of human Hsp20 in CRC using Western blot analysis. Diminished expression of protein level for Hsp20 in CRC tissues compared with normal tissues was clearly demonstrated. Immunohistochemistry (IHC) confirms largely down-regulation of Hsp20 in CRC in 94 colorectal cancer patients. Especially, CRC tissues concerned with lymph node metastasis, progressive lesion, and/or recurred cancer after surgery shows significantly reduced level of Hsp20 in IHC, and these findings strongly suggest that Hsp20 protein might be involved in the suppression of tumor progression.   Citation Information:  In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 4478.
THU0009 In vitro studies using cybrids, show that mtdna from healthy and oa patients have different mitochondrial activity
Authors: M Fernández-Moreno, A Dalmao-Fernandez, T Hermida-Gomez, MJ Sanchez-Dopico, ME Vazquez-Mosquera, E Cortes-Pereira, S Relaño-Fernandez, I Rego-Perez, FJ Blanco
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Mitochondrial dysfunction is well documented in OA and has the capacity to promote abnormalities in chondrocyte function and viability contributing to cartilage degeneration. Previous studies have showed the mtDNA haplogroup J are associated with incidence and progression of OA. Cybrids are optimal cellular models to study the real mitochondrial biology and function implications in the cellular behaviour, since they carry different mitochondrial variants with the same nuclear background, therefore, excluding the variations because of nuclear genome. <h3>Objectives</h3> The aim of this work is to test the real role of mtDNA in cellular activity, using cybrids with mtDNA from healthy donors (without OA) and from patients with knee OA. <h3>Methods</h3> Cybrids were developed using 143B.TK<sup>-</sup> Rho-0 cell line (nuclear donor) and platelets (mitochondrial donors) from healthy (without AO-N-) and knee OA donors. The OXPHOS function was evaluated by SeaHorse XFp after addition of oligomycin, FCCP and Rotenone/Antimycin A. The metabolic status was evaluated by glucose consumption and lactic acid production. The glycolytic activity was measure after addition of glucose, oligomycin and 2-dioxyglucose using Seahorse XFp. Appropriate statistical analyses were performed with GraphPad Prism v6. <h3>Results</h3> OA cybrids had lower basal respiration (92.07±39.9 and 155.5±54.08, p&lt;0.0005), and maximal respiratory capacity (114.7±50.1 and 160.6±44.7, p&lt;0.05) than N. The analysis of ATP production was lower in OA than in N cybrids (66.69±28.69 versus 101.5±42.04 p≤0.05). The % spare respiratory capacity value for the N was significantly lower than in OA cybrids (107±16.21 versus 124.7±5.97, p≤0.0005). Cybrids carrying the mtDNA from OA patients showed higher glucose consumption than N cybrids (43.77±8.87 mg/ml and 31.91±13.69 mg/ml; p&lt;0.05) however in the lactic acid production did not exit differences. The glycolytic activity was evaluated and showed that OA cybrids had lower glycolysis (71.05±4.83 versus 85.43±11.18, p&lt;0.05) but higher glycolytic reserve than N cybrids (56.60±7.5 versus 39.73±19.13, p≤0.05). <h3>Conclusions</h3> Cybrids have different metabolic behaviour, being N more efficient using glucose via glycolysis. We found differences statistical significate in the parameters that describe the mitochondrial respiration capacity, in this line OA cybrids had lower mitochondrial respiration and produce less ATP than the cybrids obtained from healthy patients. These results showed that the mitochondria obtained from healthy and OA donors had a different behaviour. These data also offer a real rationale for why mitochondria alterations play an important role in the incidence of OA. <h3>Disclosure of Interest</h3> None declared