tbuckley/cabot-search huggingface dataset:
SP0150 Th17 cells drive and regulate tissue inflammation
Authors: V Kuchroo
Journal: Annals of the Rheumatic Diseases (2017)

Recently a subset of interleukin (IL)-17-producing T cells (T<sub>H</sub>17) distinct from T<sub>H</sub>1 or T<sub>H</sub>2 cells was described and shown to have a crucial role in the induction of autoimmune tissue injury. Accumulating data suggests that there are three distinct steps in Th17 differentiation: <i>Induction</i>, <i>Amplification</i> and <i>Stabilization</i> mediated by distinct cytokines. Whereas TGF-b + IL-6 or IL-1 + IL-6 induces them, IL-21 amplifies Th17 cells, IL-23 stabilizes the phenotype of Th17 cells. Loss of any of the cytokines (TGF-β, IL-1, IL-6, IL-21 or IL-23) in the pathway results in a defect in generation of Th17. However not all Th17 cells are pathogenic and induce autoimmunity, IL-23 is a key cytokine that induces pathogenicity in Th17 cells (Lee et al., 2012). Using expression profiling at very high temporal resolution, novel computational algorithms and innovative nano-wire based “knock-down” approaches, we have developed a regulatory network that governs the development of Th17 cells. In addition to high-density temporal microarray analysis, we have performed single-cell RNA-seq of Th17 cells in order to characterize cellular heterogeneity, identify subpopulations, functional states and learn how gene expression variation affects Th17 effector functions. We have identified novel regulators of Th17 cells both <i>in vivo</i> and <i>in vitro</i> that do not affect Th17 differentiation but affect pathogenic vs. non-pathogenic functional states of Th17 cells. Some of the regulators that make Th17 cells non-pathogenic are also utilized by CD8+ T cells to induce T cell “exhaustion” or “dysfunction”. These novel inhibitory molecules cooperate with other known “check-point” co-inhibitory receptors to suppress anti-tumor immunity. <h3>Disclosure of Interest</h3> None declared
OP0206 Performance of SLEDAI-2K to detect a clinically meaningful change in SLE disease activity: a 36-month prospective cohort study of 334 patients
Authors: D Jesus, M Rodrigues, A Matos, C Henriques, J da Silva, L Inês
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> The Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) is the core determinant of response in the SLE Responder Index (SRI), a primary efficacy outcome in SLE clinical trials. However, SLEDAI is unable to discriminate partial improvement/worsening, as it scores each item categorically. Furthermore, potentially severe lupus manifestations, such as hemolytic anemia are not scored in SLEDAI. <h3>Objectives</h3> To evaluate the performance of SLEDAI-2K to detect a clinically meaningful change in SLE disease activity. <h3>Methods</h3> Prospective cohort study of SLE patients followed at a tertiary care lupus clinic from January 2014 to December 2016. Consecutive patients fulfilling the ACR997 and/or the SLICC912 classification criteria were included. At each outpatient visit, disease activity from the last 30 days was scored in the Physician Global Assessment (PGA) (0–3 cm scale) and in SLEDAI-2k. The association between PGA and SLEDAI-2K at each visit was tested with Spearman9s Correlation. A clinically meaningful change in SLE disease activity was defined as difference in PGA ≥0.3 cm at follow-up compared to the baseline visit. Performance of change in SLEDAI-2K was tested in two models: against worsening and improvement in PGA ≥0.3 cm from baseline using Receiver Operating Characteristic (ROC) curve analysis. Sensitivity, specificity, positive and negative predictive values (PPV, NPV) of SLEDAI-2k to change in PGA was calculated. Statistical significance was set at 0.05. <h3>Results</h3> We included 334 patients (87.1% female, mean age at baseline - 44.8±14.5 years). At baseline, median PGA and SLEDAI-2k score was 0.2 points (range 0–2.5) and 2 points (range 0–19), respectively. Eighty-three patients (24.8%) had a PGA ≥0.4 points at baseline. During follow-up of 36 months, 2129 visits were performed. PGA and SLEDAI-2K scores presented a high correlation (rho=0.82, p&lt;0.0001) (fig. 1). Reductions in SLEDAI-2K presented in ROC analysis an area under curve (AUC) of 0.697 [95% CI (0.628–0.766), p&lt;0.0001] for an improvement in PGA≥0.3. For a worsening of PGA≥0.3 points, increase in SLEDAI-2K presented an AUC of 0.877 [95% CI (0.822–0.932), p&lt;0.0001]. Estimated sensitivities, specificities, PPV and NPV are presented in table 1. <h3>Conclusions</h3> SLEDAI-2K presents a limited performance in detecting a clinically meaningful change in SLE disease activity, failing to identify more than a quarter of cases with clinically meaningful improvement or worsening. There is a need to optimize SLE disease activity measures. <h3>Disclosure of Interest</h3> None declared
SAT0286 Incidence and mortality of primary sjÖgren's syndrome: time trends over a 40-year period in a population-based cohort in the united states
Authors: G Maciel, C Crowson, E Matteson, D Cornec
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Few studies have reported the incidence of primary Sjögren9s syndrome (pSS) in well-defined populations worldwide, and none of them covered a period of time long-enough to analyze potential time trends in incidence rates. Whether pSS is associated with a higher mortality rate compared to the general population is also unclear from previously published studies. <h3>Objectives</h3> To estimate the incidence and mortality rates of pSS among residents of Olmsted County, Minnesota, and their evolution over time. <h3>Methods</h3> All medical records of patients with a diagnosis or suspicion of SS in Olmsted County, MN, from January 1, 2006 to December 31, 2015 were reviewed to identify incident cases of pSS (defined according to physician diagnosis). All patients with doubtful cases and all patients with an associated systemic autoimmune disease were excluded. These cases were combined with a previous 1976–2005 incident cohort from the same population (reference). Incidence rates were age and sex adjusted to the US white 2010 population. Survival rates were compared with the expected rates in the general population of Minnesota. <h3>Results</h3> With 61 incident cases of pSS diagnosed in Olmsted County in 2006–2015, the total cohort included 172 patients with incident pSS in 1976–2015. Of the 172 patients, 151 (88%) were women and 161 (94%) were white, with a mean (SD) age at diagnosis of 58.3 (16.7) years. The average age- and sex- adjusted annual incidence for 2006–2015 was 5.9 per 100,000 population (95% CI 4.4–7.4), and overall incidence for the entire period was 5.8 (95% CI: 4.9–6.6) per 100,000. Incidence was 2 to 7 times higher in females compared to males in the different age classes (5.9 times higher on average), and increased progressively with age, culminating at 19.6 per 100,000 in females aged 65–74 years, with a slight decline thereafter to 15.9 per 100,000 among females aged 75 years and older. The incidence increased with calendar time over the 40-year period (p=0.005, figure). There was no apparent seasonality in the incidence of pSS, with similar number of cases diagnosed during all four seasons. There was no difference in mortality in the pSS cohort compared to expected (standardized mortality ratio 1.15, 95% CI 0.86–1.50). <h3>Conclusions</h3> The average annual incidence of pSS in this population based-cohort was 5.8/100,000, with a progressive increase over the 40 years of the study. Overall survival of pSS patients was not different from the general population. <h3>References</h3> Nannini C et al. BMJ Open. 2013;3:e003569. <h3>Disclosure of Interest</h3> None declared
AB0557 Heart lesson in eosinophilic granulomatosis with polyangiitis
Authors: D Rednic, R Rancea, F Cozma, L Damian, L Muntean, MM Tamas, S-P Simon, I Felea, S Rednic
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Eosinophilic granulomatosis with polyangiitis (EGPA) is a disorder characterised by systemic small vessel vasculitis, that occurs typical in patients with a positive history of late-onset asthma and allergic rhinitis. Cardiac involvement is the major cause of mortality. There is required a standardised method to assess cardiac involvement in EGPA. <h3>Objectives</h3> To assess the clinical and imagistic caracteristics of EGPA patients with cardiac involvement in a tertiary referral hospital. <h3>Methods</h3> Fourteen patients (pts) with EGPA were retrospectively analysed between 2010–2016, in Rheumathology Departament in Cluj-Napoca. All patients were screened for cardiac involvement by electrocardiogram (ECG) and cardiac ultrasonography (CUS). Cardiac involvement was defined as follows: ventricular hypertrophy, kinetic abnormalities, valvulopathy, pericardial effusion or diastolic dysfunction. Cardiac magnetic resonance (CMR) and coronarographie was assessed in 4 pts with ECG or CUS abnormalities. <h3>Results</h3> Characteristics of EGPA patients is detailed in table 1. Six out of 14 pts had cardiac involvement (table 2). Only one patient was symptomatic. CMR abnormalities were: endocardial fibrosis in 2 pts, subepicardial inflammation and fibrosis in 1 patient, ventricular hypoperfusion in 2 pts and hypertrophic cardiomyopathy (HCM) in 2 pts. The pts with subepicardial inflamation and HCM had a more severe outcome. Three out of the 6 pts with cardiac involvement were pANCA (+). Hypereosinophilia was singnificantly higher in the group with cardiac involvement (p&lt;0.012). None of the patients had positive coronarography. <h3>Conclusions</h3> Cardiac involvement is frecvent and is associated with hypereosinophilia. Absence of pANCA was not associated with the cardiac involvement, in contrast with other publications. CMR makes the difference between inflamatory and noninflamatory lesions, beeing useful in clinical assessment and in treatment decisions, therfore this examination could avoid a fatal outcome. Furthermore, in the future, CMR may replace cardiac byopsy. <h3>References</h3> Thomas Neumann Cardiac Involvement in Churg-Strauss Syndrome Impact of Endomyocarditis. Medicine (Baltimore). 2009 Jul;88(4):236–43. Nir Pillar, MD Hypereosinophilic Syndrome With Cardiac Involvement: Early Diagnosis by Cardiac Magnetic Resonance Imaging. Canadian Journal of Cardiology 28 (2012) 515.e11–515.e13. <h3>Disclosure of Interest</h3> None declared
Notice of Retraction and Replacement: Colla et al. Association between Medicare accountable care organization implementation and spending among clinically vulnerable beneficiaries. <i>JAMA Internal Medicine</i>. 2016;176(8):1167-1175
Authors: Carrie H. Colla, Valerie A. Lewis, Lee-Sien Kao, A. James O’Malley, Chiang-Hua Chang, Elliott S. Fisher
Journal: JAMA Internal Medicine (2017)

Notice of Retraction and Replacement. Colla et al. Association between Medicare accountable care organization implementation and spending among clinically vulnerable beneficiaries. JAMA Internal Medicine. 2016;176(8):1167-1175
Anticoagulation Timing for Atrial Fibrillation in Acute Ischemic Stroke
Authors: Kelvin K. H. Ng, William Whiteley
Journal: JAMA Neurology (2017)

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AB0839 The efficacy and safety of denosumab local experience)
Authors: J Al-Saleh, N Salah, AS Hasan, S Mohamad, FA ElBadawi, M Khamashta
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Denosumab was introduce to the United Arab Emirates Market in 2013.Given the limited experience in using Denosumab in the region we have explored it efficacy and safety in daily practice. <h3>Objectives</h3> To assess the efficacy and safety of Denosumab in our practice. <h3>Methods</h3> <i>Inclusion criteria:</i> All patients received Denosumab in a dose of 60mg every six months. Underwent DEXA scan in Dubai Health Authority. <i>Exclusion from analysis:</i> Other Doses of Denosumab, who received less than 3 doses, and those with no follow up DEXA scan. <i>Outcome measures:</i> 1) Efficacy: Proposed Criteria for Assessing Clinical Response [1,2]. a) "inadequate": incident fracture and significant BMD decrease. b) "possible inadequate": incident fracture or significant BMD decrease. c) "appropriate": no fracture and stability or increase in BMD. 2) Safety: Reviewing the medical records and conduct patients interview for occurrence of the following adverse events. <i>Statistical analysis:</i> Descriptive statistical analysis, Graphpad Prism 6 was used. <h3>Results</h3> 143 patient identified. Out 139 patients 86 were eligible for analysis (See table 1). At baseline 39% had normal vitamin D level, 57% had insufficiency and 4% had deficiency. 20 of 86 did not undergo repeated DEXA scan. 9% had osteopenia and 91% had osteoporosis before initiating Denosumab in comparison 8% had normal bone mineral density, 45% had osteopenia and 47% post four injections of Denosumab. Table 2 summarize the comparison between the responders and non-responders. There was a significant positive correlation in the increase in bone mineral density among the responders at the femoral neck and the lumbar spine, (r=0.56, 95% confidence interval: 0.31–0.74, P-value &lt;0.0001 No report of any of the adverse events 86 patients who completed 2 years or more on treatment. <h3>Conclusions</h3> Denosumab was effective and safe in our patients. Long-term follow up is required to verify these findings in our population. <h3>References</h3> Diez-Perez and Gonzalez-Macias. Inadequate responders to osteoporosis treatment: proposal for an operational definition. Osteoporos Int. 2008 Nov;19(11):1511–6. E. M. Lewiecki &amp; N. B. Watts. Assessing response to osteoporosis therapy Osteoporos Int (2008) 19:1363–1368. <h3>Disclosure of Interest</h3> None declared
ABIM/ACC Competency-Based Education Pilot in Internal Medicine and Cardiovascular Disease
Authors: Julie B. Damp, Lisa A. Mendes, Mitchell Goldman, Eric H. Stern, Shouvik Chakrabarty, Deepak Bhakta, Salvatore Cilmi, John McPherson, Eric S. Williams, Chittur A. Sivaram
Journal: Journal of the American College of Cardiology (2017)
Survival End Points for Huntington Disease Trials Prior to a Motor Diagnosis
Authors: Jeffrey D. Long, James A. Mills, Blair R. Leavitt, Alexandra Durr, Raymund A. Roos, Julie C. Stout, Ralf Reilmann, Bernhard Landwehrmeyer, Sarah Gregory, Rachael I. Scahill, Douglas R. Langbehn, Sarah J. Tabrizi
Journal: JAMA Neurology (2017)

<h3>Importance</h3> Predictive genetic testing in Huntington disease (HD) enables therapeutic trials in<i>HTT</i>gene expansion mutation carriers prior to a motor diagnosis. Progression-free survival (PFS) is the composite of a motor diagnosis or a progression event, whichever comes first. <h3>Objective</h3> To determine if PFS provides feasible sample sizes for trials with mutation carriers who have not yet received a motor diagnosis. <h3>Design, Setting, and Participants</h3> This study uses data from the 2-phase, longitudinal cohort studies called Track and from a longitudinal cohort study called the Cooperative Huntington Observational Research Trial (COHORT). Track had 167 prediagnosis mutation carriers and 156 noncarriers, whereas COHORT had 366 prediagnosis mutation carriers and noncarriers. Track studies were conducted at 4 sites in 4 countries (Canada, France, England, and the Netherlands) from which data were collected from January 17, 2008, through November 17, 2014. The COHORT was conducted at 38 sites in 3 countries (Australia, Canada, and the United States) from which data were collected from February 14, 2006, through December 31, 2009. Results from the Track data were externally validated with data from the COHORT. The required sample size was estimated for a 2-arm prediagnosis clinical trial. Data analysis took place from May 1, 2016, to June 10, 2017. <h3>Main Outcomes and Measures</h3> The primary end point is PFS. Huntington disease progression events are defined for the Unified Huntington's Disease Rating Scale total motor score, total functional capacity, symbol digit modalities test, and Stroop word test. <h3>Results</h3> Of Track's 167 prediagnosis mutation carriers, 93 (55.6%) were women, and the mean (SD) age was 40.06 (8.92) years; of the 156 noncarriers, 87 (55.7%) were women, and the mean (SD) age was 45.58 (10.30) years. Of the 366 COHORT participants, 229 (62.5%) were women and the mean (SD) age was 42.21 (12.48) years. The PFS curves of the Track mutation carriers showed good external validity with the COHORT mutation carriers after adjusting for initial progression. For required sample size, PFS with a motor diagnosis or total motor score progression required about 4 times fewer participants than a motor diagnosis alone. Including additional cognitive progression events further reduced the number. For example, a 3-year trial with 10% attrition and a treatment effect of 50% requires a total of 661 with motor diagnosis as the survival end point but only 177 with a total motor score PFS. <h3>Conclusions and Relevance</h3> Reasonably sized prediagnosis Huntington disease trials can be planned with PFS, and there is evidence of generalizability of this approach.
AB1121 Trabecular bone score combined with clinical risk factors can predict incident fracture in rheumatoid arthritis patients
Authors: D Kim, S-K Cho, H-R Park, YY Choi, Y-K Sung
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Fracture is one of the most common and important comorbidities in rheumatoid arthritis (RA) patients, especially patients who use glucocorticoids (GC). However, bone mineral density (BMD) by dual-energy x-ray absorptiometry (DXA) which is the gold standard of diagnosing and monitoring osteoporosis is not a useful tool for predicting new fracture in RA patients. Previous studies suggested the possibility of trabecular bone score (TBS) as a useful predictor for incident fracture. <h3>Objectives</h3> We aimed to evaluate the accuracy of TBS combined with clinical risk factors or BMD for prediction of new fracture in patients with RA. <h3>Methods</h3> A total of 100 female RA patients were enrolled with assessment of TBS, BMD, and clinical risk factors for fracture. During follow-up period, we calculated the incident rate of all fractures. After dividing the patients according to the use of GCs, we compared baseline characteristics and fracture-free survival between two groups. We compared accuracies of TBS, BMD, clinical risk factors for fracture and their combinations for predicting new fractures using areas under the receiver operator characteristic (ROC) curve (AUC). <h3>Results</h3> A total of 14 fractures in 12 patients were occurred among 100 patients during follow-up (428.8 person-years): 9 among the 44 in GC users and 5 in 56 GC non-users. Incidence of fracture was not different between two groups (log-rank test, p=0.27). AUC for incident fracture prediction of TBS alone [AUC 0.54, 95% confidence interval (CI) 0.35–0.72] was comparable with TBS combined with L-spine BMD (AUC 0.54, 95% CI 0.36–0.71) or with hip BMD (AUC 0.55, 95% CI 0.37–0.73). Accuracy for prediction of new fracture is increased when TBS was combined with age and history of previous fracture (AUC 0.74, 95% CI 0.62–0.85). In GC users, history of previous fracture alone (AUC 0.79, 95% CI 0.62–0.97) showed the best accuracy for predicting new fracture among TBS, BMD, clinical risk factors for fracture and their combinations. <h3>Conclusions</h3> TBS combined with age and previous history of fracture showed the highest accuracy for predicting new fracture compared to TBS or BMD alone or their combinations in RA patients. In GC users, history of previous fracture alone showed the highest accuracy for predicting new fracture. <h3>References</h3> Briot K, Paternotte S, Kolta S, Eastell R, Reid DM, Felsenberg D, et al. Added value of trabecular bone score to bone mineral density for prediction of osteoporotic fractures in postmenopausal women: the OPUS study. Bone 2013;57:232–6. McCloskey EV, Oden A, Harvey NC, Leslie WD, Hans D, Johansson H, et al. A Meta-Analysis of Trabecular Bone Score in Fracture Risk Prediction and Its Relationship to FRAX. J Bone Miner Res 2016;31:940–8. <h3>Disclosure of Interest</h3> None declared
AB0499 Total body water and its correlation with sicca symptoms in primary sjÖgren's syndrome
Authors: G Hernandez-Molina, P Almeda-Valdés, G Lόpez-Carrasco, M Astudillo-Angel, M González-Acevedo, V Zamora-Legoff, P Sánchez-Fernández, C Aguilar-Salinas, I Cruz Bautista
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Patients with primary Sjögrens9 syndrome (PSS) suffer from severe alterations in both the quality and quantity of saliva and tears. Body water represents around 50–55% of the body weight. Tears contain 98% of water and saliva 99.5%. <h3>Objectives</h3> To evaluate the percentage of total body water (TBW) among patients with PSS and to assess its correlation with sicca symptoms. <h3>Methods</h3> We included 85 patients with PSS and 85 historical non diabetic controls matched by gender, age (±3 years) and body mass index (±1kg/m<sup>2</sup>) (BMI). We assessed the presence of sicca symptoms, Schirmer-I test, non-stimulated whole salivary flow (NSWSF) and ocular staining. We also evaluated the ocular and oral domains of the ESSPRI, a validated scale for symptoms (a higher score implies worst symptoms). We obtained the TBW percentage with a bioelectric impedance analysis (BIA-SECA-514, Hamburgo). <h3>Results</h3> 80% were women, mean age 54.8±13.7 years and mean disease duration 11.5±7.52 years. The percentage of TBW was similar among patients and controls (PSS 46.85±4.6 vs. 46.9±4.5, p=0.88). Among the patients, the TBW negatively correlated with age (ρ=-0.25, p=0.02), disease duration (ρ=-0.30, p=0.005), BMI (ρ=-0.78, p=0.001) and the ocular component of the ESSPRI (ρ=-0.28, p=0.01), but not with the NSWSF or the ESSPRI oral component. When we compared the patients in the 25% percentile (group with the lowest % of water) vs. the remaining patients, the former group was older (56.6±8.1 vs. 54±14.2, p=0.02), with longer disease duration (12.4±5.9 vs. 10.8±7.12, p=0.03), lower scores at the Schirmer test (1 (range 0–8) vs. 2 (range 0–9), p=0.01), higher BMI (31.1±5.1 vs. 23.7±2.9, p=0.001) as well as with higher ESSPRI ocular domain scores (8.3±1.4 vs. 6.7±2.5, p=0.007). With the linear regression analysis, the variables that remained associated with the TBW were disease duration (β -0.22, p=0.001), BMI (β-0.76, p&lt;0.001) and the ocular domain of the ESSPRI (β-0.15, p&lt;0.001). <h3>Conclusions</h3> Patients with PSS had similar TBW percentage than controls. However among patients with PSS, the TBW had a negative correlation with the intensity of ocular symptoms independently of disease duration, age and BMI. <h3>References</h3> Guyton, Arthur C. (2006). Textbook of Medical Physiology (11th ed.). Philadelphia: W.B. Elsevier Saunders. p. 295. ISBN 0–7216–0240–1. <h3>Disclosure of Interest</h3> None declared