tbuckley/cabot-search huggingface dataset:
SAT0525 The efficacy of peloid therapy in management of hand osteoarthritis
Authors: M Kasapoğlu Aksoy, L Altan, R Eröksüz, B ÖkmenMetin
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Hand osteoarthritis (OA) is associated with pain, reduced grip strength, loss of range of motion (ROM), and joint stiffness, leading to impaired hand function and difficulty in performance of daily living activities. Various randomized controlled clinical trials were conducted to assess the efficacy and tolerability of mud-pack therapy in patients with knee OA. Data from these clinical trials support the beneficial effect of mud-pack therapy on pain, function, and quality of life in knee OA. However, to the best of our knowledge, in spite of its significant impact of on the activities of daily life, there is a lack of adequate randomized controlled studies on peloid therapy in management of osteoarthritis of the hand <h3>Objectives</h3> To investigate the effects of peloid therapy in the patients with hand OA on pain, functional state, grip strength, and the quality of life <h3>Methods</h3> 63 patients aged between 35 and 75 years, who had been diagnosed with hand OA were included in the study. Patients were randomized into 2 groups with a random number table. Patients in Group 1 (n=33) underwent peloid therapy over 2 weeks, 5 sessions a week, for a total of 10 sessions and home exercise program. Patients in Group 2 (control, n=30) received only the same home exercise program as in Group 1. Patients were evaluated just before, and 2 and 6 weeks after the start of the study with Visual Analogue Scale (VAS), Australian/Canadian Osteoarthritis Hand Index (AUSCAN) Health Assessment Questionnaire (HAQ), Hand Grip Strength (HGS), Pinch strength (PS). <h3>Results</h3> Statistically significant improvements were observed in all parameters assessed at week 2 and week 6 in the Group 1 (p&lt;0.05). Statistically significant differences were observed in HGS scores in the Group 2 at week 2, and in AUSCAN scores at week 6 (p&lt;0.05). Intergroup comparisons of the scores revealed significant differences between the peloid therapy group and control group in VAS, HAQ, AUSCAN, HGS and PS scores at week 2 and week 6 (p&lt;0,05). <h3>Conclusions</h3> This study demonstrates that peloid therapy is an effective and confident treatment modality in the management of symptomatic osteoarthritis of the hand and provides effective pain control and improvements in the hand functions, quality of life and grip strength <h3>References</h3> Zhang Y, Niu J, Kelly-Hayes M, Chaisson CE, Aliabadi P, Felson DT. Prevalence of symptomatic hand osteoarthritis and its impact on functional status among the elderly. Am J Epidemiol 2002;156:1021–7. Bellometti S, Cecchettin M, Galzigna L (1997) Mud-pack therapy in osteoarthrosis. Changes in serum levels of chondrocyte markers. Clin Chim Acta 268:101–106. Odabaşı E, Turan M, Erdem H, Pay S, Güleç M, Karagülle MZ. The Effect of Mud Pack Treatment in Knee Osteoarthritis. Turk J Rheumatol 2009; 24: 72–6. <h3>Disclosure of Interest</h3> None declared
Genetic engineering of human NK cells to express CXCR2 improves migration to renal cell carcinoma
Authors: Veronika Kremer, Marteen A. Ligtenberg, Rosa Zendehdel, Christina Seitz, Annet Duivenvoorden, Erik Wennerberg, Eugenia Colón, Ann-Helén Scherman-Plogell, Andreas Lundqvist
Journal: Journal for ImmunoTherapy of Cancer (2017)

Adoptive natural killer (NK) cell transfer is being increasingly used as cancer treatment. However, clinical responses have so far been limited to patients with hematological malignancies. A potential limiting factor in patients with solid tumors is defective homing of the infused NK cells to the tumor site. Chemokines regulate the migration of leukocytes expressing corresponding chemokine receptors. Various solid tumors, including renal cell carcinoma (RCC), readily secrete ligands for the chemokine receptor CXCR2. We hypothesize that infusion of NK cells expressing high levels of the CXCR2 chemokine receptor will result in increased influx of the transferred NK cells into tumors, and improved clinical outcome in patients with cancer.Blood and tumor biopsies from 14 primary RCC patients were assessed by flow cytometry and chemokine analysis. Primary NK cells were transduced with human CXCR2 using a retroviral system. CXCR2 receptor functionality was determined by Calcium flux and NK cell migration was evaluated in transwell assays.We detected higher concentrations of CXCR2 ligands in tumors compared with plasma of RCC patients. In addition, CXCL5 levels correlated with the intratumoral infiltration of CXCR2-positive NK cells. However, tumor-infiltrating NK cells from RCC patients expressed lower CXCR2 compared with peripheral blood NK cells. Moreover, healthy donor NK cells rapidly lost their CXCR2 expression upon in vitro culture and expansion. Genetic modification of human primary NK cells to re-express CXCR2 improved their ability to specifically migrate along a chemokine gradient of recombinant CXCR2 ligands or RCC tumor supernatants compared with controls. The enhanced trafficking resulted in increased killing of target cells. In addition, while their functionality remained unchanged compared with control NK cells, CXCR2-transduced NK cells obtained increased adhesion properties and formed more conjugates with target cells.To increase the success of NK cell-based therapies of solid tumors, it is of great importance to promote their homing to the tumor site. In this study, we show that stable engineering of human primary NK cells to express a chemokine receptor thereby enhancing their migration is a promising strategy to improve anti-tumor responses following adoptive transfer of NK cells.
Prognostic impact of local therapy of the primary tumor in metastatic breast cancer.
Authors: Isabelle Katrin Himsl, Nina Ditsch, Miriam Susanne Lenhard, Jutta Engel, Michael Untch, Ingo Bauerfeind, Klaus Friese, Nadia Harbeck, Steffen Kahlert
Journal: Journal of Clinical Oncology (2012)

1114 Background: MBC is an incurable disease and the treatment aims are palliative. It is not known whether the difference in OS is the result of a selection bias or caused by dissemination of tumor stem cells in pat. without surgery. Methods: To identify the impact of surgical therapy of the primary tumor, a mono-institutional retrospective review from 1990-2006 was done in primary MBC pts. Results: We identified 269 pts. with primary MBC, 63 of whom had received no surgical local treatment. Mean follow up is 65 m for pts., observed mortality 87%. Location of metastases were bone only (36%), visceral or soft tissue (one organ only, 19%), multiple organs (40%) and including CNS metastases (5%). 50% had G3 tumors, 25% negative receptor status, 7% non-resectable local disease and 57% symptomatic metastases. In univariate analysis, pat. without local treatment had a median OS of 14.4m, pts. with local therapy 28.1m (p&lt;0.001). Pts. not receiving local treatment were significantly more likely to have multiorgan or CNS involvement (p&lt; 0.001), symptoms at diagnosis (p=0.009), non-resectable tumor (p&lt;0.001) and were more likely to die within the first 30d after diagnosis (p&lt; 0.001). In multivariate analysis, local treatment had no significant impact on OS. The only significant variables were: number of involved organs, symptoms at diagnosis, receptor status, grading, and size of the local tumor. The effect of local treatment on OS was not homogenous across subgroups. Local treatment was a significant factor in tumors with only one involved organ or asymptomatic disease. In all other groups, local treatment did not result in an OS benefit. Conclusions: Our cohort showed significantly improved OS in univariate analysis if the breast primary tumor had been removed in metastatic disease. Yet, the decision for local treatment was biased by the extent and presentation of metastatic disease. Pts. with more advanced MBC seem not to benefit from removal of the primary tumor. However, we see significant influence in pts. with limited and asymptomatic MBC. The potential dissemination of tumor stem cells from the breast primary in metastatic but locally untreated disease may only influence prognosis in pts. with limited disease.
SAT0133 Sudomotor dysfunction in rheumatoid arthritis patients in the absence of traditional cardiovascular risk
Authors: T Syngle, S Kaur, I Verma, A Syngle
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Rheumatoid arthritis (RA) is an autoimmune chronic inflammatory disease associated with cardiovascular autonomic neuropathy. Cardiovascular autonomic neuropathy is a significant risk predictor for sudden cardiac death in rheumatoid arthritis.<sup>1</sup> Sudomotor dysfunction reflects small fibre neuropathy, cardiovascular autonomic neuropathy and peripheral sympathetic autonomic neuropathy.<sup>2</sup> However, sudomotor dysfunction and its relationship with inflammatory measures remain unexplored in RA patients in the absence of traditional cardiovascular (CV) risk factors. <h3>Objectives</h3> The aim of present study was to assess the sudomotor function and its association with disease specific measures: ESR, CRP and DAS-28 in RA patients with no apparent conventional cardiovascular risk factor. <h3>Methods</h3> In this cross-sectional study, 60 RA patients fulfilling 2010 Rheumatoid Arthritis Classification Criteria<sup>3</sup> and 40 age and sex-matched healthy controls were recruited. Sudomotor function was assessed using Sudoscan (Impeto Medical, Paris, France) through measurement of electrochemical skin conductance of hands and feet.<sup>2</sup> Sudoscan investigates the sweat gland activity and used as a surrogate to study the damage of sympathetic sudomotor nerves in neuropathy. It is an indirect assessment tool of sudomotor function. Inflammatory measures such as ESR and CRP and DAS-28 (disease activity score in 28 joints) were determined. <h3>Results</h3> Rheumatoid arthritis patients had significantly impaired sudomotor function (56.90±12.95 vs. 76.15±8.45 μs, p&lt;0.00, Figure 1A), elevated ESR (31.30±12.34 vs. 16.72±4.46, p&lt;0.001) and CRP (10.55±3.81 vs. 3.81±1.03, p=0.002) as compared to healthy controls, respectively. The mean disease duration of RA patients was 9.15±5.76 and they had high disease activity (mean DAS-28, 4.60±1.72). Sudomotor function was found to be inversely correlated with ESR (r =0.42, p=0.001, Figure 1B), CRP (r =0.60, p&lt;0.001, Figure 1C) and DAS-28 (r =0.38, p=0.003, Figure 1D). <h3>Conclusions</h3> Cardiovascular autonomic neuropathy occurs in RA in the absence of traditional CV risk factors. Sudomotor dysfunction is significantly associated with increased level of ESR, CRP and disease activity suggesting that increased inflammation may cause sudomotor dysfunction. <h3>References</h3> Milovanovic B et al. Srp Arh Celok Lek 138:26–32. Mayaudon H et al. Diabetes Metab. 2010;36:450–54. Aletaha D et al. Arthritis Rheum. 2010;62:2569–81. <h3>Acknowledgements</h3> None. <h3>Disclosure of Interest</h3> None declared
AB0920 Tuberculosis osteomyelitis of the pubic symphysis: report of two cases
Authors: R Sonia, S Boussaid, I Abdelkafi, S Hela, C Ilhem, E Mohamed
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Infection of the symphysis pubis is a rare complication for less than 1% of cases of osteomyelitis. The predisposing causes reported are pelvic surgery, trauma and intravenous drug abuse. We report cases of osteomyelitis of the pubic symphysisdue to mycobacterium tuberculosis which is extremely <h3>Results</h3> The two patients were 47 and 75 year-old women. They were admitted because of three month9s history of progressive perineal pain and a hypogastric mass without fever in the first case, and bilateral inguinal pain with limited flexion and rotation of the right hip in the second one. Blood tests showed an elevated erythrocyte sedimentation rate (ESR) of 27 mm and 75 mm. The leucocytes rates were at 5580/mm<sup>3</sup> and 6000/mm<sup>3</sup>. Plain X-ray revealed irregularity and widening of the symphysis pubis. Tuberculin skin test was positivein one case and negative in the other. Chest radiograph was normal. The bacteriological cultures for tubercule bacillus in sputum and urines negative. The typhic and brucellian serological diagnosis as well as blood cultures were negative. CT scan showed irregular destruction and erosion of the pubic bone with a soft tissue mass. A biopsy of the symphysis was performed. Histologic examination of the bone material revealed a granulomatous inflammation with caseous necrosis confirming the diagnosis of tuberculosis. Anti-tuberculous treatment was prescribed and led to full recovery. <h3>Conclusions</h3> Tuberculosis is a major health problem in mediterranean countries,including Tunisia. These two cases present a timely reminder that tuberculosis should always be considered as part of the differential diagnosis of treatment of tuberculosis osteomyelitis of the pubic symphysis. Radiological investigations with plain X-rays, CT, MRI and bone scan are hepful. Treatment of tuberculous osteomyelitis of the pubic symphysis is based mainly on anti-tuberculous drugs. <h3>Disclosure of Interest</h3> None declared
AB0705 Continued effectiveness of a biosimilar adalimumab after stoppage of initial treatment in patients with ankylosing spondylitis
Authors: S Bandyopadhyay, A Ray, RN Sarkar, S Dash, S Mondal
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Adalimumab, an anti TNF-α agent, has been proven to be safe and effective in treatment of ankylosing spondylitis (AS). A biosimilar adalimumab was approved for use by Indian regulators in 2014. It is a "fingerprint match" of the reference adalimumab in terms of purity, potency, safety and clinical efficacy.<sup>1,2</sup> ln the absence of availability of adalimumab in India, this biosimilar adalimumab currently serves as an accessible, cost-effective option for treatment of AS patients. <h3>Objectives</h3> This retrospective analysis evaluates effectiveness of biosimilar adalimumab (bADA), in terms of disease activity, safety and outcomes in real-life Indian AS patients treated for initial 24 weeks and then followed for next 24 weeks off biologic treatment. <h3>Methods</h3> Medical records of AS patients with Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Bath Ankylosing Spondylitis Functional Index (BASFI) &gt;4, who were prescribed bADA therapy between January to December 2015 were analysed. For patients, who stopped bADA treatment after 24 weeks, standard AS outcome-measurement scores including ESR, CRP, BASDAI, BASFI, and Health Assessment Questionnaire (HAQ) at baseline, week 24 and at week 48 were measured to evaluate ongoing efficacy, were compared using paired Student9s T-test. Patients were allowed to continue methotrexate and salazopyrin as part of routine medical care. <h3>Results</h3> During the study period, 52 AS patients were prescribed bADA 40 mg s/c; 24 of these patients, who had stopped treatment after 6 months, were considered for this analysis. Mean age for this group was 36.57±10.81 years; 10 females. At the end of 24 weeks9 treatment, there were significant reductions in levels of inflammatory markers ESR, CRP, as well as in BASDAI, BASFI and HAQ scores. Eight patients continued to receive methotrexate and 8 patients sulfasalazine as concomitant medications. After week 48 (24 weeks post stoppage), BASDAI and BASFI scores did not deteriorate despite discontinuation of bADA treatment. The patients9 HAQ scores were also indicative of similar trends of continuing improved health status post the therapy. <h3>Conclusions</h3> Biosimilar adalimumab therapy was effective in treating AS patients. The disease activity and health assessment scores continued to remain stable with no worsening after the stoppage of treatment for 6 months, indicating a post-therapy effectiveness in these patients with no reported adverse event. <h3>References</h3> Bandyopadhyay S, et al. Biosimilars. 2015;5:1–18. Jani RH et al. int J Rheum Dis. 2015 Jul 14. <h3>Disclosure of Interest</h3> None declared
FRI0396 Levels pentraxin 3 and c1q in systemic sclerosis: association with pulmonary arterial hypertension and clinical findings
Authors: R Cevik, K Nas, T Bozan, A Ekinci, A Kamanlı, I Tekeoglu, MO Ayyildiz
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Systemic sclerosis (SSc) is an autoimmune rheumatic disease with unknown etiology that characterized fibrosis and vascular endotelial damage with obliteration of the microvasculature caused from exaggerated syntesis of collagen and extracellular matrix deposition in skin and internal organs. Pentraxin 3 (PTX3) accepted as a vascular inflammatory marker which secreted in early stage of endothelial dysfunction. <h3>Objectives</h3> In this study, we aimed to investigate plasma PTX3 and serum complement C1q levels and their relations with cytokines and pulmonary arterial pressure in SSc. <h3>Methods</h3> Fifty nine patients diagnosed SSc and 28 subjects without inflammatory rheumatic disease recruited to the study. Plasma PTX3, and serum TNF-α, IL-1β, IL-4, IL-10, INF-γ, TGF-β and complement C1q measured in both groups. Clinical findings and pulmonary arterial pressure of the SSc patients assessed. <h3>Results</h3> Ages of fifty nine with SSc (54 female and 5 male) and 28 control subjects (23 female and 5 male) were 49,47±12.74 and 43,07±13,71 respectively. PTX3, IL-1β and IL-4 levels found decreased in SSc patients. There were no differentiations between limited and diffuse cutaneous SSc subgroups in terms of PTX3, cytikines and C1q levels. Plasma PTX3 and serum IL-1β concentrations found decreased only limited cutaneous SSc subgroup comparing controls. According to the immunosupressive drugs use; PTX3 levels found decreased in using group and TNF-α ve IL-1β levels found decreased in not using group comparing controls. Significant positive association found between PTX3 and C1q and all cytokines except TGF- β. <h3>Conclusions</h3> PTX3 suggested to be used in the pathogenesis and assessment of disease treatment efficacy of SSc, because of found decreased in SSc patients especially in limited cutaneous and immunosupressive drugs using subgroups. Associations between C1q, and PTX3 and pulmonary artey pressure highlighted possible roles of both parameters in development of pulmonary hypertension. It is possible to develop preventive treatment strategies with better understanding of these associations. Advanced studies should be carried out for clarifying this condition. <h3>Disclosure of Interest</h3> None declared
SIDT2 Transports Extracellular dsRNA into the Cytoplasm for Innate Immune Recognition
Authors: Tan A. Nguyen, Blake R.C. Smith, Michelle D. Tate, Gabrielle T. Belz, Marilou H. Barrios, Kirstin D. Elgass, Alexandra S. Weisman, Paul J. Baker, Simon P. Preston, Lachlan Whitehead, Alexandra Garnham, Rachel J. Lundie, Gordon K. Smyth, Marc Pellegrini, Meredith O’Keeffe, Ian P. Wicks, Seth L. Masters, Craig P. Hunter, Ken C. Pang
Journal: Immunity (2017)
MicroRNA‐506 promotes primary biliary cholangitis–like features in cholangiocytes and immune activation
Authors: Oihane Erice, Patricia Munoz‐Garrido, Javier Vaquero, Maria J. Perugorria, Maite G. Fernandez‐Barrena, Elena Saez, Alvaro Santos‐Laso, Ander Arbelaiz, Raul Jimenez‐Agüero, Joaquin Fernandez‐Irigoyen, Enrique Santamaria, Verónica Torrano, Arkaitz Carracedo, Meenakshisundaram Ananthanarayanan, Marco Marzioni, Jesus Prieto, Ulrich Beuers, Ronald P. Oude Elferink, Nicholas F. LaRusso, Luis Bujanda, Jose J.G. Marin, Jesus M. Banales
Journal: Hepatology (2017)

Primary biliary cholangitis (PBC) is a chronic cholestatic liver disease associated with autoimmune phenomena targeting intrahepatic bile duct cells (cholangiocytes). Although its etiopathogenesis remains obscure, development of antimitochondrial autoantibodies against pyruvate dehydrogenase complex E2 is a common feature. MicroRNA (miR) dysregulation occurs in liver and immune cells of PBC patients, but its functional relevance is largely unknown. We previously reported that miR‐506 is overexpressed in PBC cholangiocytes and directly targets both Cl–/ HCO3− anion exchanger 2 and type III inositol 1,4,5‐trisphosphate receptor, leading to cholestasis. Here, the regulation of miR‐506 gene expression and its role in cholangiocyte pathophysiology and immune activation was studied. Several proinflammatory cytokines overexpressed in PBC livers (such as interleukin‐8 [IL8], IL12, IL17, IL18, and tumor necrosis factor alpha) stimulated miR‐506 promoter activity in human cholangiocytes, as revealed by luciferase reporter assays. Experimental overexpression of miR‐506 in cholangiocytes dysregulated the cell proteomic profile (by mass spectrometry), affecting proteins involved in different biological processes including mitochondrial metabolism. In cholangiocytes, miR‐506 (1) induced dedifferentiation with down‐regulation of biliary and epithelial markers together with up‐regulation of mesenchymal, proinflammatory, and profibrotic markers; (2) impaired cell proliferation and adhesion; (3) increased oxidative and endoplasmic reticulum stress; (4) caused DNA damage; and (5) sensitized to caspase‐3‐dependent apoptosis induced by cytotoxic bile acids. These events were also associated with impaired energy metabolism in mitochondria (proton leak and less adenosine triphosphate production) and pyruvate dehydrogenase complex E2 overexpression. Coculture of miR‐506 overexpressing cholangiocytes with PBC immunocytes induced activation and proliferation of PBC immunocytes. Conclusion: Different proinflammatory cytokines enhance the expression of miR‐506 in biliary epithelial cells; miR‐506 induces PBC‐like features in cholangiocytes and promotes immune activation, representing a potential therapeutic target for PBC patients. (Hepatology 2018;67:1420‐1440)