tbuckley/cabot-search huggingface dataset:
THU0436 Clinical significance of delta neutrophil index in the differential diagnosis between septic arthritis and acute gout attack within 24 hours after hospitalisation
Authors: JY Pyo, SM Jung, JJ Song, Y-B Park, S-W Lee
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> The most important differential diagnoses of acute monoarticular arthritis are septic arthritis and acute gout attack. Identifying infection is crucial in preventing the devastating outcome of septic arthritis. <h3>Objectives</h3> The delta neutrophil index (DNI) is a value that corresponds to the fraction of circulating immature granulocytes. As DNI reflects the burden of infection, we evaluated this index as a differentiating marker between septic arthritis and acute gout attack. <h3>Methods</h3> The medical records of 149 patients with septic arthritis and 194 patients with acute gout attack were reviewed. A specific cell analyser, ADVIA 2120, was used to measure DNI. Clinical and laboratory markers associated with predicting septic arthritis were assessed by using logistic regression. <h3>Results</h3> Patients with septic arthritis showed higher levels of DNI than those with acute gout attack (3.3 vs. 0.6%, <i>P</i>&lt;0.001). Similar results were observed in patients without monosodium urate (MSU) crystal confirmation or those with normouricemia (3.3 vs. 0.5 and 3.1 vs. 0.7%, respectively; <i>P</i> &lt;0.001 for both). A DNI level of 1.9% was determined as the cut-off value for predicting septic arthritis. In the multivariate analysis, DNI was the most powerful independent value for predicting septic arthritis (odds ratio 14.003). <h3>Conclusions</h3> This study showed the possibility of using DNI as a differentiating marker between septic arthritis and acute gout attack at the crucial early phase. DNI showed its relevance regardless of confirmation of MSU crystal deposition or serum level of uric acid. <h3>Disclosure of Interest</h3> None declared
Anti-Jagged Immunotherapy Inhibits MDSCs and Overcomes Tumor-Induced Tolerance
Authors: Rosa A. Sierra, Jimena Trillo-Tinoco, Eslam Mohamed, Lolie Yu, Bhagelu R. Achyut, Ali Arbab, Jennifer W. Bradford, Barbara A. Osborne, Lucio Miele, Paulo C. Rodriguez
Journal: Cancer Research (2017)

Abstract Myeloid-derived suppressor cells (MDSC) are a major obstacle to promising forms of cancer immunotherapy, but tools to broadly limit their immunoregulatory effects remain lacking. In this study, we assessed the therapeutic effect of the humanized anti–Jagged1/2-blocking antibody CTX014 on MDSC-mediated T-cell suppression in tumor-bearing mice. CTX014 decreased tumor growth, affected the accumulation and tolerogenic activity of MDSCs in tumors, and inhibited the expression of immunosuppressive factors arginase I and iNOS. Consequently, anti-Jagged therapy overcame tumor-induced T-cell tolerance, increased the infiltration of reactive CD8+ T cells into tumors, and enhanced the efficacy of T-cell–based immunotherapy. Depletion of MDSC-like cells restored tumor growth in mice treated with anti-Jagged, whereas coinjection of MDSC-like cells from anti–Jagged-treated mice with cancer cells delayed tumor growth. Jagged1/2 was induced in MDSCs by tumor-derived factors via NFkB-p65 signaling, and conditional deletion of NFkB-p65 blocked MDSC function. Collectively, our results offer a preclinical proof of concept for the use of anti-Jagged1/2 to reprogram MDSC-mediated T-cell suppression in tumors, with implications to broadly improve the efficacy of cancer therapy. Cancer Res; 77(20); 5628–38. ©2017 AACR.
AB1191 Analysis of factors related to the learning of rheumatology by training doctors of other specialties
Authors: MA Belmonte-Serrano, P Tejόn-Menendez, JA Castellano-Cuesta, N Fernandez-Llanio, P Bernabeu, V Jovaní-Casado, J Gomez-Salazar Rosas, F Navarro-Blasco, A Ybañez-Garcia, A Lozano-Saez
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Many doctors in training of other specialities make a monthly rotation in the rheumatology unit, but usually no formal assessment of the skills and knowledge acquired is performed. <h3>Objectives</h3> To know which factors are related to learning of Rheumatology skills by training doctors (MIR) of other specialties rotating in spanish Rheumatology units. <h3>Methods</h3> An online platform for the evaluation of the knowledge of Rheumatology has been developed (REUMEVAL, see www.reumeval.com). It contains a set (DB) of 300 multiple-choice questions developed by staff rheumatologists on 10 topics of general interest. The set questions passed a Delphi round and 15% of them were replaced by more appropriate ones. Each MIR that goes to perform a rotation in a teaching Rheumatology Unit (REU) is offered to participate with two tests of 30 questions randomly extracted from the DB. The first test is done just arriving at REU, assessing the basic knowledge that was obtained in the university. At the end of the rotation in REU, usually 30 days, a second test is performed, assessing the increase of knowledge achieved. <h3>Results</h3> As of December 2016, 384 tests were carried out by 216 physicians training in 14 hospitals of the Valencian region in Spain Of these, 166 (77%) completed both tests. 74% were in training for family medicine (MFC). The mean score of the 1st test was 5.59 (out of 10 points), and the second test was 6.55 points, with an average increase of scorings of 22.4% (p&lt;0.001). Men showed higher scorings than women in their 1st test (5.92 vs 5.56), but the difference was lost in the 2nd test (6.79 vs 6.47). Younger residents (ages 20–30 years) had a 1st higher score than those aged 30–40 or&gt;40 years (5.8 vs 5.2 vs 5.1 respectively) but were similar in the 2nd test (6.6 Vs 6.3 vs. 6.8). By nationality, Spaniards had higher initial scores than foreigners (5.78 vs 4.91, p&lt;0.01) but there were no differences in the second test (6.55 vs 6.49). For specialties, dermatology, internal medicine and RHB had initial scores higher than MFC (7.3 - 6.1 - 6.3 vs. 5.4), but in the second test there were no significant differences. <h3>Conclusions</h3> The level of knowledge in Rheumatology of the residents who start a training rotation in this specialty is moderate, with an average of 5.59 points out of 10 possible. At the end of the rotation their scores increased an average of 22%, which shows a significant improvement but still not very high. Several factors were related to basic knowledge scores but lost significance in the final test, reflecting appropriate improvements in knowledge in all subgroups. <h3>Acknowledgements</h3> To Fundacion Valenciana de Reumatologia and to MSD laboratories for an unrestricted grant. <h3>Disclosure of Interest</h3> None declared
THU0131 Premature coronary heart disease frequency in rheumatoid arthritis who are receiving biologic agents: hur-bio real life results
Authors: B Armagan, A Sari, A Erden, L Kilic, EC Erdat, O Karadag, A Akdogan, S Apras Bilgen, U Kalyoncu, S Kiraz, I Ertenli
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Patients with rheumatoid arthritis (RA) are at increased risk of coronary heart disease (CHD) overall, as well as death from CHD. A direct impact of chronic inflamation on the vascular system, secondary effects of physical inactivity and some drugs used in the management of RA are shown as the reasons for the increase in this comorbidity (1). <h3>Objectives</h3> We aim to determine the frequency of CHD in the RA patients who receive biological agents. <h3>Methods</h3> Hacettepe University Biologic Registry (HUR-BIO) includes demographic and clinical data of patients treated with biological agent since 2005. By August 2016, 1235 RA patients were recorded in the database. Age, smoking status, comorbidities, current and previous treatments were analysed in 1000 patients. Disease activity was estimated by the 28-joint activity calculator (DAS28-ESR) and DAS28-CRP. Functional assesment was evaluated by the Health Assessment Questionnaire (HAQ). Premature CHD should be defined if clinical CHD or sudden death is documented in male younger than 55 years of age and in female younger than 65 years of age. <h3>Results</h3> Overall 1000 patients (79,8% female) were enrolled in this study. Mean age was 53,1±12,6 years old, mean disease duration was 12,3±9,3 years. CHD was detected 57 (5,7%) patients and female/male was 38/19. Premature CHD was observed in 38 (66,7%) patients. CHD patients had more frequently male, older, higher classical risk factors, higher baseline ESR level and higher functional disability (Table). HAQ score also remained high in CHD group at last visit. Classical cardiovascular risk factors, sex, seropositivity, disease activity score and HAQ score were similar in the premature and other CHD group. Coronary artery stenting, coronary artery bypass surgery and medical treatment was applied in 12 (21%), 20 (35,1%) and 25 (43,9%) CHD patients, respectively. There was no statistical difference in treatment of premature and other CHD. <h3>Conclusions</h3> As a results CHD were detected in 5,7 percents of RA patients who are receiving biological agents. Importantly, two third of these patients have premature CHD. Classical risk factors are observed more frequently in CHD patients as expected but interestingly, no additional risk factors other than age were detected between premature and other CHD patients. This suggests that the primary factor triggers premature CHD is the underlying inflammatory rheumatic disease. The presence of CHD was determined by patient history which the limitation of our study. We did not assess to subclinical CHD in this study. <h3>References</h3> Comorbidity in rheumatoid arthritis, Carl Turesson, Swiss Medical Weekly, 2016. <h3>Disclosure of Interest</h3> None declared
Intranasal administration of carbamazepine-loaded carboxymethyl chitosan nanoparticles for drug delivery to the brain
Authors: Shanshan Liu, Shili Yang, Paul C. Ho
Journal: Asian Journal of Pharmaceutical Sciences (2017)

Epilepsy is considered as a common and diverse set of chronic neurological disorders and its symptoms can be controlled by antiepileptic drugs (AEDs). The presence of p-glycoprotein and multi-drug resistance transporters in the blood-brain barrier could prevent the entry of AEDs into the brain, causing drug resistant epilepsy. To overcome this problem, we propose using carboxymethyl chitosan nanoparticles as a carrier to deliver carbamazepine (CBZ) intra-nasally with the purpose to bypass the blood-brain barrier thus to enhance the brain drug concentration and the treatment efficacy. Results so far indicate that the developed CBZ-NPs have small particle size (218.76 ± 2.41 nm) with high drug loading (around 35%) and high entrapment efficiency (around 80%). The in vitro release profiles of CBZ from the NPs are in accordance with the Korsmeyer-peppas model. The in vivo results show that both encapsulation of CBZ in nanoparticles and the nasal route determined the enhancement of the drug bioavailability and brain targeting characteristics.
THU0518 Biological therapy in non-systemic juvenile idiopathic arthritis patients followed in adult rheumatology department: hur-bio real life results
Authors: L Kilic, A Sari, B Armagan, A Erden, Ö Karadag, A Akdogan, S Apras Bilgen, S Kiraz, S Ozen, U Kalyoncu, AI Ertenli
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic disorder in childhood and more than one-third of patients have active inflammation during adult years that can cause disability. <h3>Objectives</h3> To define the demographic and clinical characteristics of non-systemic JIA (ns-JIA) patients under biological therapy followed in adult rheumatology department. <h3>Methods</h3> Hacettepe University Biologic Registry (HUR-BIO) is a single center biological registry since 2005. HUR-BIO database includes demographic and clinical characteristics of patients, disease activity parameters, history of articular prosthesis. The use of biological agents in routine rheumatology practice has been approved by the Ministry of Health since 2003. <h3>Results</h3> In this study, 95 (72.6% women) ns-JIA patients were included. The demographic and clinical characteristics of the patients were shown in the table. The first biological agents were; Etanercept (63.2%), adalimumab (16.8%), infliximab (12.6%) and the others 7 (7.4%). After a mean follow-up of 60 (48) months, 42 (44.2%) patients required biologic switch. The last visit HAQ scores of 75 patients were known and 16 (21.3%) patients had HAQ score ≥1.0 (female 15/54 vs. male 1/21, p=0.029). The last visit DAS-28 score of 72 patients was known and 46 (63.9%) patients had remission or low disease activity. 14 patients (14.7%) had history of articular prosthesis and were all female. Patients with history of articular prosthesis were older [39.1±10.1 vs. 29.6±10.3 years, p&lt;0.0001], had longer disease duration [25.7±6.6 vs. 17.2±11.9 years, p=0.001] and had longer time until the biological therapy [19.6±8.4 vs. 11.5±11.6 years, p=0.002]. The time until the biological therapy of 38 ns-JIA patients diagnosed after 2003 was shorter [3.2±2.9 vs. 19.4±10.6 years, p&lt;0.001]. <h3>Conclusions</h3> Structural damage and history of articular prosthesis was more common in female ns-JIA patients receiving biological therapy. Functional disability and disease activity were also higher in female patients. On the other hand, the follow-up ns-JIA patients had a good level of remission and low disease activity.The shorter duration until the time of biological treatment in patients diagnosed after 2003 indicates that both pediatric and adult rheumatologists have begun to treat these patients more effectively. <h3>Disclosure of Interest</h3> None declared
Small Cell Transformation and T790M Mutation as Coresistance Mechanisms for First-line Epidermal Growth Factor Receptor (EGFR) Tyrosine Kinase Inhibitor (TKI) Therapy Failure
Authors: Chee Shee-Chai, Chong-Kin Liam, Kein-Seong Mun
Journal: Journal of Thoracic Oncology (2017)
THU0200 Risk for developing adverse effects caused by salazosulfapyridine in rheumatic diseases
Authors: K Nakanishi, M Kinjo
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Salazosulfapyridine is non-antimicrobial sulfonamides, which is used as a synthetic disease modified anti-rheumatic-drug (DMARD) for rheumatoid arthritis and psoriatic arthritis. Prior study suggested sulfa allergy may be more commonly seen in patients with positive anti- Ro/SS-A antibody (anti-Ro). <h3>Objectives</h3> To identify the risk factor for adverse effects (AEs) caused by salazosulfapyridine in patients with rheumatic diseases. <h3>Methods</h3> We retrospectively identified patients ≥18 years old who received salazosulfapyridine at a tertiary medical center in Japan between 2010–2015. Data were collected on the incidence of AEs, clinical features and autoantibodies. <h3>Results</h3> We identified 313 patients with rheumatic diseases who received salazosulfapyridine. Median age was 61 (range, 20–95); 215 of 313 (67%) were female (Table). The incidence of AEs was 15% (48/313); Median duration until developing AEs was 14 days (range, 2–50). AEs included rash (28), fever (19), elevated liver function tests (13), gastrointestinal symptoms (9), lymphadenitis (3), neutropenia and eosinophilia (1). Factors associated with AEs are female gender, positive anti-Ro or psoriatic arthritis. Multivariate logistic controlling for age, gender and anti-Ro showed that positive anti-Ro has 2.33 odds (P=0.03; 95% CI: 1.07–5.08) of having AE of salazosulfapyridine. Among patients without anti-Ro, subjects with psoriasis showed 9.95 odds (P&lt;0.001; 95% CI: 3.51–28.2) of developing AEs than non-psoriatic patients. <h3>Conclusions</h3> AEs caused by salazosulfapyridine are common in patients with rheumatic diseases. Presence of anti- Ro or psoriasis may be a risk factor for AEs caused by salazosulfapyridine. <h3>References</h3> Suyama Y, Okada M, Rokutanda R, et al: Safety and efficacy of upfront graded administration of trimethoprim-sulfamethoxazole in systemic lupus erythematosus: A retrospective cohort study. Mod Rheumatol. 2016;26:557–61. Maezawa R, Kurasawa K, Arai S, et al: Positivity for anti-RNP antibody is a risk factor for adverse effectscaused by trimethoprim-sulfamethoxazole, a prophylactic agent for P. jiroveci pneumonia, in patients with connective tissue diseases. Mod Rheumatol. 2013;23:62–70. <h3>Disclosure of Interest</h3> None declared
FRI0119 A proposal for a SDAI, CDAI, and RAPID3-based definition of minimal disease activity for use in routine care of rheumatoid arthritis: results from a japanese national database
Authors: N Yokogawa, A Komiya, K Shimada, S Sugii, J Nishino, S Tohma
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> The OMERACT group proposed minimal disease activity (MDA) as a treatment target, given the current treatment possibilities and limitations. Whereas a Disease Activity Score 28 (DAS28)-based definition of MDA has been proposed<sup>1</sup>, definitions based on the Simplified Disease Activity Index (SDAI), Clinical Disease Activity Index (CDAI), and Routine Assessment of Patient Index Data 3 (RAPID3) have not, despite the increasing use of these indices. <h3>Objectives</h3> To define SDAI, CDAI, and RAPID3-based definition of MDA for use in routine care. <h3>Methods</h3> We analyzed 15,101 patients registered in the Japanese National Database (NinJa 2015). As the OMERACT group proposed, patients with tender joint count (TJC) of 0, swollen joint count (SJC) of 0, and erythrocyte sedimentation rate (ESR) ≤10 mm/hour or patients with five of the following seven criteria, namely, pain ≤2, SJC ≤1, TJC ≤1, HAQ ≤0.5, physician9s global ≤1.5, patient9s global ≤2, and ESR ≤20, were considered to be in MDA.<sup>1</sup> The ROC curve was used to obtain the best cut-off points for the SDAI, CDAI, and RAPID3-based definitions of MDA, which emerged as good predictors of MDA as defined by the core dataset. To compare the usefulness of the indices, the interclass correlation of MDA in DAS28, SDAI/CDAI, and RAPID3 was compared to that of low disease activity (LDA). <h3>Results</h3> 57.6% of patients (5,629/9,767) were categorized as having MDA, and 29% of patients (4,003/13,781) were categorized as Boolean remissions. In the ROC analysis, the area under the curve for DAS28, SDAI, CDAI, and RAPID3 was 0.911, 0.955, 0.953, and 0.930, respectively. Based on the Youden index, SDAI ≤5.3, CDAI ≤4.8, and RAPID3 ≤5 were defined as SDAI, CDAI, and RAPID3-based MDA, respectively. The sensitivity and specificity of the DAS28, SDAI, CDAI, and RAPID3-based definitions were higher than those of the DAS28-based definition, with a sensitivity of 81.5%, 89.2%, 88.8%, and 90.0%, respectively, and a specificity of 83.5%, 89.4%, 89.9%, and 88.4%, respectively. Each index-based definition of MDA showed better interclass correlation than that of LDA; DAS28 vs CDAI/SDAI: MDA of 0.643/0.662 and LDA of 0.540/0.540; DAS28 vs RAPID3: MDA of 0.541 and LDA of 0.482; CDAI/SDAI vs RAPID3: MDA of 0.677/0.671 and LDA of 0.433/0.425. <h3>Conclusions</h3> SDAI ≤5.3, CDAI ≤4.8, and RAPID3 ≤5, values two points higher than each remission criterion, may provide a more stringent therapeutic goal than LDA in clinical practice. <h3>References</h3> Wells GA, et al. Minimal disease activity for rheumatoid arthritis: a preliminary definition. J Rheumatol 2005;32:2016–24. <h3>Acknowledgements</h3> Supported in part by a Health and Labor Sciences Research Grant from the Ministry of Health, Labor, and Welfare of Japan. <h3>Disclosure of Interest</h3> None declared
LRIG1 negatively regulates Met Receptor and suppresses changes associated with HGF stimulation in breast cancer lines
Authors: David Shattuck, Jamie Miller, Kermit Carraway, Colleen Sweeney
Journal: Cancer Research (2007)

419   The Met receptor, a member of the receptor tyrosine kinase (RTK) family that is ubiquitously expressed in epithelial cells, regulates a complex program of cellular behavior collectively known as “invasive growth”. Aberrant activation and overexpression of the Met receptor in human breast cancer has been linked with aggressive tumor behavior and correlates with disease relapse, distant metastases, and decreased survival. Loss of molecules that regulate the Met receptor may cooperate to increase Met signaling. Hence, identification of negative regulators is crucial to understanding Met’s role in human cancer. The leucine-rich repeat protein, LRIG1, has previously been shown to oppose signaling by the Her/ErbB family of receptor tyrosine kinases through enhanced receptor degradation. Her2, a frequently overexpressed RTK in breast tumors, has been shown to synergize with the Met receptor and promote enhanced invasiveness. Here, we demonstrate that LRIG1 is a negative regulator of the Met receptor. We show that endogenous Met receptor and LRIG1 form a complex in cells and that the functional outcome of this interaction is a destabilization of the Met receptor. The loss of LRIG1 expression, through siRNA knockdown, increases the half-life of endogenous Met by two-fold. LRIG1 overexpression can suppress synergistic increases in motility and growth associated with Met/Her2 synergy. Our results indicate that LRIG1 may be a potent negative regulator of the Met receptor and can regulate multiple RTK’s simultaneously. Consequently, LRIG1 may present an opportunity for therapeutic intervention in tumors driven by Met and LRIG1 loss may have prognostic value.
SAT0099 Polypharmacy is associated with an increased risk of adverse outcomes in patients with rheumatoid arthritis
Authors: AD Amarilla Vallejo, A Rutherford, M Filkova, M Molokhia, E Nikiphorou, S Norton, K Hyrich, J Galloway
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> In the general population, polypharmacy (PP) is associated with increased risk of adverse events. The relationship between adverse outcomes and PP in Rheumatoid Arthritis (RA) has not been studied in depth. The mantra of treatment in RA encourages PP through combination Disease Modifying Anti-Rheumatic Drugs (DMARD). <h3>Objectives</h3> To study the relationship between PP and serious adverse events in RA, including the influence of DMARDs within the PP count. <h3>Methods</h3> Data from the British Society for Rheumatology Biologics Register were analysed. PP was defined as number of drugs co-prescribed at baseline, with two models: (1) including DMARDs (2) excluding DMARDs from the medication count. PP was stratified by 0–5, 6–9 and &gt;10. Patients were studied from initiation of 1st biologic until 1st serious adverse event (SAE), 3 years of follow up, or last available visit, whichever came first. A Cox-proportional hazard model was used, with adjustment for a priori selected cofounders. <h3>Results</h3> This study included 15,004 patients commencing biologics. The demographics are shown in table 1. Excluding DMARDs from the PP cohort, 7,115 (47%) of the patients were taking up to 5 drugs; 6,010 (40%) were taking 6 to 9 drugs; 1,870 (12%) were taking 10 or more medications. Higher levels of PP associated with older age, more severe disease, and longer disease duration. PP predictably associated with comorbidities; the relationship was not linear: comorbidity count appeared to show a ceiling effect. The overall incidence of SAEs was 25.5/100 person years (95% CI 24.7–26.3). The rate of SAEs increased across the PP counts (See Table 1). The relationship remained significant after adjusting for comorbidities. Including DMARDs within the PP count attenuated the association. <h3>Conclusions</h3> PP is common in patients with RA and is associated with adverse outcomes especially when patients are on &gt;10 drugs. Including or excluding DMARDs from the PP model had negligible impact on findings. The relationship between PP and comorbidity is worthy of further research, as PP represents a potentially simple but valuable predictor of adverse outcomes, and a suitable surrogate for comorbidity in epidemiological analyses. <h3>Disclosure of Interest</h3> None declared