tbuckley/cabot-search huggingface dataset:
THU0568 Prevalence and autoimmune rheumatic disease in patients with autoimmune/inflammatory syndrome induced by adjuvants associated to silicone breast implant
Authors: O Vera Lastra, NE Torres-Oliva, G Medrano-Rodriguez, MDP Cruz-Dominguez, J Sepulveda Delgado, LJ Jara, G Medina
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Autoimmune/inflammatory syndrome induced by adjuvants (ASIA) has been associated with previous exposure to various agents such as silicone implants, which elicit chronic stimulation of the immune system against the prosthetic material and clinical manifestation of autoimmune disease. This is particularly the case in genetically susceptible hosts. <h3>Objectives</h3> The aim is to describe de prevalence, family background and main autoimmune rheumatic disease (ARD) associated to silicone breast implant (SBI). <h3>Methods</h3> We study a cohort of 150 patients with diagnosis of ASIA associated injection of mineral oil and silicone breast implant (SBI) in a tertiary Hospital, from 2011 to 2016. All patients were evaluated for the fulfilment of ASIA criteria. We only included patients with ASIA criteria associated with SBI plus criteria for an autoimmune rheumatic disease according to The American College of Rheumatology or EULAR. We excluded patient with ASIA and without ARD. <h3>Results</h3> There were 17 women patients with mean age 42.4±15.3 years, mean disease duration of disease 8±3. The clinical manifestation post SBI appeared 8±2 years later. The ARD were systemic sclerosis (SSc) 5, systemic lupus erythematosus (SLE) 3, rheumatoid arthritis (AR) 3, overlap syndrome 2 (SSc plus SS and SLE plus SSc, Sjogren syndrome 1, Takayasu arteritis 1, Still disease 1, antiphospholipid syndrome 1, and 3 patients also had secondary fibromyalgia. Five Patients had more than 2 autoantibodies, 4 patients had relatives with an ARD. All patients are being treated according to the ARD (steroids plus immunosuppressive 8 patients, immunosuppressive 7, and only steroids 2), in 4 patients the prosthesis were withdrawn with improvement of clinical manifestations. <h3>Conclusions</h3> We found a prevalence of ASIA associated to SBI of 11%. The main ARD were SSc, SLE and RA. In these cases of ASIA associated with SBI some had genetic predisposition to ARD. The use of SBI is not recommended in women who have a family history of ARD. <h3>References</h3> Colaris MJ et al. Two hundred cases of ASIA syndrome following silicone implants: a comparative study of 30 years and rewiew of current literature. Immunol Res 2016 Jul 13. Jara LJ, et al. Severe manifestation of autoimmune syndrome induced by adjuvants (Shoenfeld9s syndrome) Immunol Res Jul 13. Watad et a. Autoimmune/Inflammatory induced by adjuvants (Shoenfeld9s syndrome) UN update. Lupus 2017 Jan 1. <h3>Disclosure of Interest</h3> None declared
AB0698 Complementary and alternative medicine usage and associated factors in ankylosing spondylitis: preliminary results of a cross-sectional study
Authors: FI Cinar, O Ozdemir, S Yilmaz, N Ozen, G Bagcivan, I Aydoğan, AG Yalcin, E Tekgoz, M Cinar
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Several surveys indicate that the complementary and alternative medicine (CAM) use is especially prevalent in patients with chronic painful conditions like ankylosing spondylitis (AS). Despite good treatment options such as tumor necrosis factor alpha (TNFα) inhibitors in AS, it is seen that patients have applied for CAM use for many reasons including local regulatory funding requirements, potential risks and accessibility of biological treatments. Few studies have examined the frequency of CAM use, and associations between demographic and disease-related factors of it in AS. <h3>Objectives</h3> To investigate the CAM usage of patients with AS and to determine the associated factors. <h3>Methods</h3> Total of 123 patients with AS, who were being followed in a tertiary rheumatology outpatient clinic, were included to the study. The demographic and clinical features along with the behaviors about the CAM usage of the patients agreeing to participate were recorded to the "Patient Assessment Form". The activity of the disease were determined with doctor global assessment (numeric visual analog scale (nVAS; 0–10), and Routine Assessment of Patient Index Data (RAPID)-3 score. The treatment adherence of the patients was assessed with the Morisky Green Levine Scale. <h3>Results</h3> One hundred eleven patients (%90.2) were male, and mean age was 36.5±8.8 years. The mean disease duration and mean delay in diagnosis were 10.9±6.4, and 3.7±3.9 years, respectively. The mean RAPID3 score, doctor and patient global assessment were; 9.9±5.3, 2.8±1.9, and 4.6±2.7, respectively. While 79 patients (%64.2) were on anti-TNF treatment, 76 patients were receiving NSAIDs, and 35 patients (%28.5) reported an adverse event related with the treatment. Forty-five patients (%36.6) reported to use any CAM (previous or current) (Table1). The reasons reported by the patients for the usage of CAM; media in %13, recommendations from family members or relatives in %10.6. It has been found that in married patients, the ones with lower the Morisky Green Levine Scale score (high adherence), CAM usage was statistically high (p&lt;0.05). Receiving NSAIDs or anti-TNF agents was not statistically associated with CAM usage. The underlying expectations for the usage of CAM were; considering it might be helpful in %27.6; considering it might heal in %17.9; to relieve the pain in %14.6; and preventing to deteriorate the disease status in %12.2. <h3>Conclusions</h3> In our study, we found that approximately one third of our AS patients were using CAM. When compared with the literature related with other diseases, CAM usage in AS patients was somewhat lower. Our results have demonstrated that treatment adherence was higher in those using concomitantly CAM in their therapy. <h3>Disclosure of Interest</h3> None declared
AB0417 Efficacy and safety of methotrexate and leflunomide as a combination therapy in rheumatoid arthritis patients with high disease activity presenting at a tertiary care setting in pakistan
Authors: B Salim, S Samreen, A Nasim, H Gul, A Masood
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> In the management of rheumatoid arthritis (RA), the goal is remission. However it is not easy to attain this goal in all patients. Its not only the high disease activity, but rather other factors like availability and cost of biologics in developing countries. Therefore various combination therapies of conventional DMARDs are in vogue in such scenarios. Methotrexate (MTX) and Leflunomide (LEF) in combination is an effective option which can be fairly utilized in resource constraint settings to induce remission. <h3>Objectives</h3> To study the efficacy and safety profile of MTX+LEF combination in patients with active RA at 24 weeks. <h3>Methods</h3> This is a quasi-experimental study conducted at Rheumatology department, Fauji Foundation Hospital, Rawalpindi. 95 patients with active RA despite optimal dose (20–25 mg/week) of MTX. Leflunomide 20mg/day was added. Patients underwent clinical and laboratory review at 0, 4, 12 and 24 weeks to note down primary efficacy end points and adverse effects. <h3>Results</h3> Ninety five patients were enrolled with a mean age (years) ± SD of 51.7±8.9 and a mean duration of disease (years) of 8.6±7.1.Patients had active disease at baseline with a mean disease activity score (DAS28) of 5.99±0.6. At 24 weeks the mean change in tender joint count (TJ), swollen joint count (SJ), patients pain score on visual analogue scale (VAS) and DAS 28 were all statistically significant (p-value 0.000).The mean change in m HAQ was also statistically significant (p-value 0.000). At 6 months the most frequent side effects (though mostly mild); were abdominal pain and nausea. 78 patients (79.1%) continued with the combination therapy. Only 3 patients stopped the treatment temporarily (due to raised ALT and vomiting).14 patients discontinued treatment mainly due to diarrhea, severe oral ulcers and markedly raised ALT. <h3>Conclusions</h3> MTX+LEF combination is an effective and safe option in RA patients failing MTX monotherapy provided regular clinical and laboratory monitoring is done. <h3>Disclosure of Interest</h3> None declared
Acute Inflammatory Response Following Increased Blood-Brain Barrier Permeability Induced by Focused Ultrasound is Dependent on Microbubble Dose
Authors: Dallan McMahon, Kullervo Hynynen
Journal: Theranostics (2017)

Rationale: Focused ultrasound (FUS), in conjunction with circulating microbubbles (MBs), can be used to transiently increase the permeability of the blood-brain barrier (BBB) in a targeted manner, allowing therapeutic agents to enter the brain from systemic circulation.While promising preclinical work has paved the way for the initiation of 3 human trials, there remains concern regarding neuroinflammation following treatment.The aim of this study was to assess the magnitude of this response following sonication and explore the influence of MB dose.Methods: Differential expression of NFκB signaling pathway genes was assessed in rats at 6 h and 4 days following a FUS-mediated increase in BBB permeability.Three sonication schemes were tested: (1) a clinical imaging dose of MBs + peak negative pressure (PNP) controlled by acoustic feedback, (2) 10x clinical imaging dose of MBs + constant PNP of 0.290 MPa, and (3) 10x clinical imaging dose of MBs + PNP controlled by acoustic feedback.Follow-up magnetic resonance imaging (MRI) was performed to assess edema and hemorrhage.Hematoxylin and eosin histology was used to evaluate general tissue health.Results: MB dose has a significant impact on the expression of several key genes involved in acute inflammation and immune activation, including Tnf, Birc3, and Ccl2.At a clinical imaging dose of MBs, there were no significant changes detected in the expression of any NFκB signaling pathway genes.Conversely, a high MB dose resulted in a clear activation of the NFκB signaling pathway, accompanied by edema, neuronal degeneration, neutrophil infiltration, and microhemorrhage.Results also suggest that post-FUS gadolinium enhancement may hold predictive value in assessing the magnitude of inflammatory response.Conclusion: While a significant and damaging inflammatory response was observed at high MB doses, it was demonstrated that FUS can be used to induce increased BBB permeability without an associated upregulation of NFκB signaling pathway gene expression.This emphasizes the importance of employing optimized FUS parameters to mitigate the chances of causing injury to the brain at the targeted locations.
SAT0754-HPR ”a necessary investment in future health”. perceptions of physical activity maintenance among people with ra participating in an outsourced health-enhancing physical activity program
Authors: E Swärdh, B Nordgren, CH Opava, I Demmelmaier
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Health-enhancing physical activity (HEPA) is an active treatment in rheumatoid arthritis (RA) that may be difficult for patients to maintain over time. A two-year HEPA program including twice-weekly circuit training at public gyms and 150 weekly minutes of moderately intense aerobic exercise was conducted in Sweden between 2011 and 2013. Regular peer support sessions were held to guide adoption and maintenance of HEPA. Patient perceptions on maintained physical activity in RA have been minimally explored. <h3>Objectives</h3> To describe perceptions of physical activity maintenance during the second year of an outsourced 2-year HEPA-program among people with RA <h3>Methods</h3> A descriptive design with a qualitative inductive approach was used. Interviews were conducted with 18 participants with RA, including men and women differing in age, disease duration, activity limitation, perceived pain, levels of physical activity, training centers and peer support groups. Qualitative content analysis was used, and a pattern of theme, subthemes, categories, and subcategories was constructed based on the participants9 perceptions of the phenomenon. <h3>Results</h3> A main overarching theme and three subthemes were established, called `<i>A necessary investment in future health</i> through <i>dedication</i>, <i>affinity</i> and <i>awareness9</i>, which described participants9 experiences of maintenance during the second year of an outsourced 2-year HEPA-program. This was further described in eight categories with 16 subcategories. The categories described the participants9; `<i>mindsets, habits, commitments, social support, PA contexts, monitoring, insights in PA, and health gains9.</i> <h3>Conclusions</h3> The findings are partly in line with the theoretically derived explanations for maintenance of behavior change formulated to date, such as maintenance motives (self-determination and identity), self-regulation (skills and processes, lapse, relapse and coping) habits, resources (psychological and physical) as well as environmental and social influences. The results of this study could also be transferable to similar groups of people with RA in similar settings and useful in designing future HEPA interventions to facilitate maintenance of behavior change. <h3>Disclosure of Interest</h3> None declared
Connexins in Cardiovascular and Neurovascular Health and Disease: Pharmacological Implications
Authors: Luc Leybaert, Paul D. Lampe, Stefan Dhein, Brenda R. Kwak, Peter Ferdinandy, Eric C. Beyer, Dale W. Laird, Christian C. Naus, Colin R. Green, Rainer Schulz
Journal: Pharmacological Reviews (2017)

Connexins are ubiquitous channel forming proteins that assemble as plasma membrane hemichannels and as intercellular gap junction channels that directly connect cells. In the heart, gap junction channels electrically connect myocytes and specialized conductive tissues to coordinate the atrial and ventricular contraction/relaxation cycles and pump function. In blood vessels, these channels facilitate long-distance endothelial cell communication, synchronize smooth muscle cell contraction, and support endothelial-smooth muscle cell communication. In the central nervous system they form cellular syncytia and coordinate neural function. Gap junction channels are normally open and hemichannels are normally closed, but pathologic conditions may restrict gap junction communication and promote hemichannel opening, thereby disturbing a delicate cellular communication balance. Until recently, most connexin-targeting agents exhibited little specificity and several off-target effects. Recent work with peptide-based approaches has demonstrated improved specificity and opened avenues for a more rational approach toward independently modulating the function of gap junctions and hemichannels. We here review the role of connexins and their channels in cardiovascular and neurovascular health and disease, focusing on crucial regulatory aspects and identification of potential targets to modify their function. We conclude that peptide-based investigations have raised several new opportunities for interfering with connexins and their channels that may soon allow preservation of gap junction communication, inhibition of hemichannel opening, and mitigation of inflammatory signaling.
FRI0054 A novel pharmacological action of MTX through circadian clock genes in RA fibroblast-like synovial cells
Authors: K Suzuki, K Yoshida, T Hashimoto, K Kaneshiro, A Nakai, N Hashimoto, Y Kawasaki, N Shibanuma, N Nakagawa, Y Sakai, A Hashiramoto
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Methotrexate inhibits the proliferation of RA fibroblast-like synovial cells (RA-FLS) by folate anti-metabolism. We previously reported that disruptions of circadian clock genes were involved in the pathogenesis of inflammatory arthritis (1,2). <h3>Objectives</h3> To explore pharmacological effects of MTX on circadian clock genes of RA-FLS. <h3>Methods</h3> Under treatments of MTX on RA-FLS, cell viabilities were determined by WST-8 assay, expressions of circadian clock genes (<i>Clock, Bmal1, Cry1</i> and <i>Per2</i>), circadian transcriptional factor PAR bZip (<i>Dbp, Tef</i> and <i>Hlf</i>), and pro-apoptotic Bcl-2 interacting killer (<i>BIK</i>) were examined by real time PCR, and expressions of PER2 and CYTOCHROME C were examined by western blotting. The expressions of PER2, BIK, CYTOCHROME C and morphological changes of the nucleus were observed by fluorescent immunostaining. RA-FLS were transfected with <i>Per2</i> and <i>BIK</i> siRNAs and successively treated with MTX to determine cell viabilities by WST-8 assay. <h3>Results</h3> MTX (1,10 nM) treatment significantly decreased the cell viabilities. MTX (10nM) have increased mRNA expression of <i>Per2, Dbp, Tef, Hlf</i>, and <i>BIK</i>, and protein expressions of PER2 and CYTOCHROME C, as well. In fluorescent observations, PER2, BIK, and CYTOCHROME C were increased in apoptotic cells. Cytotoxicity of MTX was attenuated by knockdowns of <i>Per2</i> or <i>BIK</i> in RA-FLS. <h3>Conclusions</h3> The transcriptional factor PAR bZip binds to the D-box elements of <i>Per2</i> and <i>BIK</i> promoters (3,4). Here, we propose a novel action of MTX that up-regulates the expressions of <i>Per2</i> and <i>BIK</i> via PAR bZip to induce apoptosis in RA-FLS. <h3>References</h3> Hashiramoto A, J Immunol. 2010 Feb 1;184(3):1560–5. Hand LE, FASEB J. 2016 Nov;30(11):3759–3770. Yoshida K, Scand J Rheumatol. 2013;42(4):276–80. Ritchie A, Cell Death Differ. 2009 Jun;16(6):838–46. <h3>Disclosure of Interest</h3> None declared
EGFR-mutation detection in VTX-1-enriched CTCs, ctDNA, and comparison to tumor in patients with non-small cell lung cancer (NSCLC).
Authors: Jonathan Wade Goldman, Haiyan Liu, Meghah Vuppalapaty, Charles Wilkerson, Clementine Lemaire, Steve Crouse, Elodie Sollier-Christen
Journal: Journal of Clinical Oncology (2017)

e20525 Background: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI's) have shown dramatic clinical benefits when EGFR mutations are detected. These assays are mainly performed on tumor biopsies, which carry risks, are expensive and are not always successful. Moreover, secondary mutations, causing resistance to 1 st &amp; 2 nd generation TKI’s develop during treatment and therefore mutations require ongoing monitoring. Circulating tumor cells (CTCs) or circulating tumor DNA (ctDNA) are promising for monitoring the patient over time and show enhanced sensitivity when combined 1 . The VTX-1 Liquid Biopsy System enables label-free capture of CTCs from blood and genomic assays downstream 2 . In this study, we demonstrate the sensitivity of a combined EGFR assay on VTX-1-enriched CTCs and ctDNA, using blood spiked with cancer cells &amp; DNA and then with NSCLC patients. Methods: NSCLC cells (A549: wt, H1975: L858R+ &amp; T790M+, HCC827: 19del+) were used to validate the assay. H1975 cells and HCC827 DNA were spiked in blood. Plasma was extracted and the plasma depleted blood was processed through VTX-1. The collected plasma and enriched cells were subjected to the detection of 19del, L858R and T790M EGFR mutations using the EntroGen ctEGFR kit. Later, blood and tumor were collected from NSCLC patients and analyzed for EGFR mutations on biopsies, ctDNA and CTCs. Results: Mutant DNA was detected for an input as low as 0.5 ng (~83 cells), with a sensitivity from 0.1% to 2% for a total DNA of 25ng (~4 cancer cells &amp; 4000 WBCs) to 1ng (~4 cancer cells &amp; 200 WBCs). Processing of plasma-depleted-blood with Vortex showed the same efficiency compared to whole blood. Mutations were detected from enriched cells and plasma respectively for 100 H1975 cells and 0.5ng of HCC827 DNA spiked in 2mL blood. NSCLC patients are being enrolled and results will be presented at the conference. Conclusions: The ctEGFR assay performed well on VTX-1 enriched cells and ctDNA, enabling a low cost approach to analyze EGFR mutations from a single blood tube with high sensitivity, potentially being a useful tool for guiding treatment of NSCLC patients. 1.Sundaresan, et al. Clin Cancer Res 2016. 2. Kidess-Sigal, et al. Oncotarget 2016.
Effects of Chemotherapy on Extracellular Vesicles and Coagulation Activation in Colorectal Cancer Patients: A Pilot Study
Authors: Ludwig Traby, Hannah C. Puhr, Marietta Kollars, Kammer Michael, Gerald Prager, Werner Scheithauer, Gabriela Kornek, Paul Alexander Kyrle, Sabine Eichinger
Journal: Blood (2016)
AB1154 Characterization of chilean patients with pulmonary disease associated to a rheumatologic diagnosis in an integrated polyclinic. hospital padre hurtado experience
Authors: O Valenzuela, V Agar, JP Leiva, I Allende, G Bozzano, G Miranda, SE Ibáñez Vodnizza
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Pulmonary diseases associated to a rheumatologic condition constitute a heterogeneous group of pathologies that are grouped according to their clinical and radiological similarity. There is a perception that the incidence of these diseases has been increasing, however, in Chile, there are no up-to-date publications regarding the characteristics of this group of patients. <h3>Objectives</h3> To describe and characterize patients with pulmonary disease associated to a rheumatologic diagnosis at Hospital Padre Hurtado, Chile, between the years 2014 and 2016. <h3>Methods</h3> Patients with suspected lung involvement associated to a connective tissue disease were evaluated by a bronchopulmonar specialist and a rheumatologist in a joint polyclinic. If the diagnosis was confirmed by the specialist the patient was included in the database. Data collected included age, gender, rheumatologic diagnosis and radiological pattern. <h3>Results</h3> 76 patients were included. 85.5% were female. The mean age was 58 years. Eighty-nine percent of the patients came from the Rheumatology department. These patients developed respiratory symptoms during the course of their disease. The remaining 11% were patients controlled in the Pulmonary diseases department, and the respiratory symptoms were the first manifestation of their conective tissue disease.The rheumatologic diagnoses that were concluded in this multidisciplinary polyclinic were distributed as described in Table 1. 69.7% of the patients have completed the radiological evaluation (Table 2). <h3>Conclusions</h3> Having a multidisciplinary clinical unit allowed us to order and protocolize the study, follow-up and treatment of the patients with lung involvement associated with a connective tissue disease. Currently, the multidisciplinary management of these patients is indispensable, as described in the literature. <h3>Disclosure of Interest</h3> None declared