tbuckley/cabot-search huggingface dataset:
THU0425 The first metatarsophalangeal joint (MTP1) is not the main localization of gout at diagnosis in sub-saharan africa
Authors: F Kemta Lekpa, MS Doualla, H Namme Luma
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Numerous data in sub-Saharan Africa suggest that MTP1 is not the hallmark of gout (1–5). <h3>Objectives</h3> We carried out this study with the aim to determine the joint most involved at the time of diagnosis of gout in Cameroon. <h3>Methods</h3> We performed a cross-sectional study in all outpatients seen at the Rheumatology unit of the Douala General Hospital, Cameroon, between 2004 and 2014. We included patients with diagnosis of gout according to ACR criteria 1977. The main characteristics of gout at diagnosis were collected, particularly the joints involved. A p&lt;0.05 was significant. <h3>Results</h3> At the end of this study, 511 patients (415 men and 96 women) with the diagnosis of gout were included. The mean age was 55.9±10.8 years. Joint pain (n=508, 99.4%) was the leading reason for consultation at the time of diagnosis. The knees (n=300, 62.6%)), ankles (n=187, 39.0%) and MTP1 (n=128, 26.7%) were the most affected joints. Table 1 presents the frequency of the joints affected, comparing our results with those of the other African series. There was no difference between MTP1 and others joints location (particularly knees and ankles) according to age, sex, place of residence, duration of disease, uric acid level, and associated comorbidities (p&gt;0.05). <h3>Conclusions</h3> MTP1 is not the joint most involved at the time of diagnosis of gout in sub-Saharan Africa. Diagnosis of gout should be considered before any inflammatory knee and ankle pain in patients from sub-Saharan Africa. Genetic studies would provide a better understanding of this feature. <h3>References</h3> Kodio B, et al. Afr J Rheumatol. 2015 3(1): 22–26. Adelewo OO, et al. Afr J Rheumatol. 2014 1(2): 23–28. Singwé-Ngandeu M, et al. Mali Medical. 2009 24:17–20. Mijiyawa M, et al. Joint Bone Spine. 2000;67(5):441–5. Cassim B, et al. Ann Rheum Dis. 1994 Nov;53(11):759–62. <h3>Disclosure of Interest</h3> None declared
OP0096 Interferon signature in systemic sclerosis lung microvascular endothelial cells
Authors: FA Mendoza, S Piera-Velazquez, P Wermuth, S Addya, C Feghali-Bostwick, SA Jimenez
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Systemic Sclerosis (SSc) is characterized by severe fibroproliferative vasculopathy, exaggerated deposition of extracellular matrix molecules (ECM) in skin and multiple internal organs, and alterations of humoral, cellular and innate immunity. Vascular changes are responsible for the earliest and most severe SSc clinical manifestations, however, the mechanisms responsible have not been elucidated. <h3>Objectives</h3> The goal of this study was to analyze the gene expression differences between normal and SSc lung microvascular endothelial cells (EC) to improve the understanding of SSc vasculopathy pathophysiology. <h3>Methods</h3> Pulmonary microvascular EC were isolated employing immunomagnetic procedures from lungs from patients with SSc undergoing lung transplantation. Control pulmonary microvascular EC were isolated from autopsies of individuals who died from non-pulmonary causes. Following isolation, microarrays were performed in EC from each group. Expression of genes with the highest differential expression was validated with RT-PCR and Western blots. <h3>Results</h3> Interferon-stimulated genes (ISGs) including IFI44L, IFI44, IFI6, IFIH1, IFIT1 displayed the highest differential expression; being overexpressed in EC obtained from the three SSc donors (Figure 1). Other genes such as those encoding ECM production related proteins, genes associated with post-translational methylation, and genes for numerous chemokines and cytokines were also differentially overexpressed in SSc EC. Increased gene expression and increased protein levels of selected ISGs were confirmed by Western blots. <h3>Conclusions</h3> Numerous ISGs are differentially overexpressed in SSc pulmonary microvascular EC in comparison with normal control EC. These results suggest that events leading to an interferon response in these cells may play a role in the pathogenesis of SSc lung vasculopathy. <h3>References</h3> Kahaleh B. Vascular Disease in Scleroderma: Mechanisms of Vascular Injury. Rheumatic Disease Clinics of North America 2008; 34(1):57–71. Trojanowska M. Cellular and molecular aspects of vascular dysfunction in systemic sclerosis. Nat Rev Rheumatol 2010; 6(8):453–60. Matucci-Cerinic M, Kahaleh B, Wigley FM. Review: evidence that systemic sclerosis is a vascular disease. Arthritis and rheumatism 2013; 65(8):1953–62. Pattanaik D, Brown M, Postlethwaite BC, Postlethwaite AE. Pathogenesis of Systemic Sclerosis. Frontiers in immunology 2015; 6:272. <h3>Disclosure of Interest</h3> None declared
THU0081 Differences in patient-reported outcomes between baricitinib and comparators among patients with rheumatoid arthritis who achieved low disease activity or remission
Authors: B Fautrel, M van de Laar, B Kirkham, R Alten, R Cseuz, S Van der Geest, B Zhu, F De Leonardis, P Taylor
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Achieving remission is the ideal goal in treating rheumatoid arthritis (RA). In a randomised phase 3 trial, high remission and low disease activity (LDA) rates were achieved with baricitinib (BARI). However, little is known about the differences in patient reported outcomes (PROs) among patients (pts) who have already achieved these targets. <h3>Objectives</h3> To compare PROs between BARI, adalimumab (ADA), and placebo (PBO) in pts with RA who achieved LDA or remission in the Phase 3 RA-BEAM study. <h3>Methods</h3> 1305 pts with RA and background treatment with methotrexate were randomised to receive PBO (n=488), ADA (n=330), or BARI 4 mg (n=487) for 52 wks (24 wks for PBO). In each treatment group, pts in remission (DAS28-ESR&lt;2.6) and with LDA (DAS28-ESR≤3.2) at wk 24 were assessed from baseline for the following PROs: Pain VAS, HAQ-DI, WPAI, Morning Joint Stiffness (MJS), and FACIT-F. Sensitivity analyses were conducted for pts in remission or LDA by DAS28-CRP, SDAI, or CDAI. The assessment of response at wk 24 was determined by using the observed data, and the missing values for PRO measures were imputed by using mLOCF. <h3>Results</h3> Among pts in LDA, significantly greater improvements in Pain VAS and HAQ-DI scores were observed with BARI than ADA and PBO, and significantly greater improvements in MJS were observed with BARI and ADA than PBO. Significantly greater residual pain and HAQ-DI scores were observed with PBO. Among pts in remission, significantly greater improvements in pain and HAQ-DI scores were also observed with BARI than PBO. Patients in remission or LDA showed greater numerical improvement and less residual impairment in other PROs with BARI and ADA than PBO (Table 1). Consistent results were observed using other composite measures to define LDA and remission. <h3>Conclusions</h3> The preliminary findings from this study suggest that BARI showed greater improvements in pain and HAQ-DI compared to ADA for pts in LDA, and greater improvements in pain and HAQ-DI scores as well as less physical impairment compared to PBO for pts in LDA and remission. <h3>Acknowledgements</h3> The authors acknowledge the contribution of Inmaculada de la Torre MD, PhD, Senior Medical Advisor. <h3>Disclosure of Interest</h3> B. Fautrel: None declared, M. van de Laar: None declared, B. Kirkham: None declared, R. Alten Consultant for: Eli Lilly and Company, R. Cseuz Consultant for: Eli Lilly and Company, S. Van der Geest Employee of: Eli Lilly and Company, B. Zhu Employee of: Eli Lilly and Company, F. De Leonardis Employee of: Eli Lilly and Company, P. Taylor Consultant for: Eli Lilly and Company; Abvie
AB1011 Reliability of sonographic peritenon extensor tendon inflammation pattern in psoriatic arthritis
Authors: C Macía, HB Hammer, S Falcao, J Medina, M Gutierrez, E De Miguel
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Preliminary results demonstrate that the peritenon inflammation of the extensor digitorum tendon (PTI) is a specific ultrasound (US) pattern of Psoriatic Arthritis (PsA) at metacarpophalangeal joint (MCPj) level. It was suggested as a pattern playing a key role in the differential diagnosis between Rheumatoid Arthritis and PsA <sup>(1,2)</sup>. <h3>Objectives</h3> In spite of PTI9s clinical impact, there are no data regarding the reliability of US PTI evaluation. The present study addressed this topic by testing the reliability of US on evaluation of PTI. <h3>Methods</h3> 27 consecutive non selected PsA patients with clinical involvement of at least one 2nd to 5th MCPj were included. A rheumatologist trained in PTI assessments obtained the US images exploring the dorsal aspect of MCPj from 2nd to 5th of both hands using a MyLab 70 XVG machine, Esaote, Genova, Italy, with a greyscale (GS) 13 MHz probe and a 7.1 MHz power Doppler (PD) frequency, PRF 750 Hz and a 60 Gain. 3–5 seconds videos of each MCPj were obtained in transversal and longitudinal views for further reliability analysis. In the inter-reader reliability analysis, performed by five readers from five different hospitals and four countries, it was scored as present or absent 1) PTI (defined as an hypoechoic swelling of the soft tissue surrounding the extensor tendon at MCPj level with or without PD) and 2) intra-articular synovitis (IAS, OMERACT definition), both in PD and GS. The consensus of true US results for every joint and lesion was achieved when at least three readers had the same opinion. Cohen9s Kappa test was used for statistical analysis. <h3>Results</h3> Clinical MCPj involvement was present in 60 (27.7%) of the 216 joints whereas US detected IAS and/or PTI in 75 (34.7%). US showed GS PTI in 41 (19%) and PD in 38 (17.6%) of the joints, while GS IAS was found in 63 (29.2%) with PD activity in 41 (19%) of the joints. The inter-reader reliability is shown in the Table. Intra-reader reliability results expressed as mean Kappa were 0.826 for PTI PD, 0.784 for PTI GS, 0.743 for IAS PD and 0.637 for IAS GS. <h3>Conclusions</h3> US examination of MCPj shows that PTI is near as frequent as IAS in PsA with reliability of its scoring at least as good as for joint synovitis. This opens the possibility of introducing US scoring of PTI, which may be of importance for the diagnosis and follow-up of PsA patients. <h3>References</h3> Gutierrez M et al. Ann Rheum Dis 2011; 70: 1111–4. Zabotti A et al. Clinical and Experimental Rheumatology 2016; 34: 459–465. <h3>Disclosure of Interest</h3> None declared
OP0229 Effect of baseline serum crp levels on clinical efficacy in rheumatoid arthritis patients treated with filgotinib: post-hoc analysis from two phase 2b studies
Authors: R Westhovens, A Kavanaugh, C Jamoul, C Tasset, P Harrison, A Van der Aa
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Filgotinib (GLPG0634, GS-6034) is an oral, selective JAK1 inhibitor that has shown a favorable safety and efficacy profile both as add-on to methotrexate (MTX) and as monotherapy in two 24-week placebo-controlled phase 2B studies in active rheumatoid arthritis (RA) patients with inadequate response to MTX (MTX-IR)<sup>1,2</sup>. <h3>Objectives</h3> To assess effect of baseline serum CRP levels on clinical efficacy in MTX-IR RA patients treated with filgotinib. <h3>Methods</h3> Patients were randomized in a double blind manner to placebo (PBO) or one of 3 daily doses of filgotinib (50mg, 100mg or 200mg) for 24 weeks. In the DARWIN 1 study, filgotinib on the background of MTX was evaluated as once (QD) or twice daily treatment. In the DARWIN 2 study once-daily filgotinib was assessed as monotherapy. The inclusion criterion for CRP was amended during the studies and decreased over time from 13.5 mg/L to 6.3 mg/L. This post hoc analysis included patients treated with the selected Phase 3 filgotinib doses, 100mg and 200mg QD, and PBO. Efficacy outcomes were analyzed by baseline CRP level (low: ≤9 mg/L and high: &gt;9 mg/L, with 9mg/L as ULN). <h3>Results</h3> Baseline disease activity was high, with mean DAS28(CRP) scores of 5.6 and 5.7 in the low CRP subgroups for DARWIN 1 and DARWIN 2, respectively, and 6.3 in the high CRP subgroups for both studies. Mean CRP levels at baseline were elevated (16.3 - 35.3 mg/L). In both low and high CRP subgroups, patients on filgotinib 100mg or 200mg QD for 12 weeks showed efficacy over PBO, as measured by change from baseline in DAS28(CRP), CDAI and HAQ-DI, and ACR20 (Table 1). Despite slight numerical differences, baseline CRP level had no consistent effect on filgotinib efficacy, neither for endpoints including CRP (DAS28(CRP) or ACR20) nor for endpoints not including CRP (CDAI). Results were similar across both studies. <h3>Conclusions</h3> Post hoc analysis of two Phase 2B studies in MTX-IR RA patients suggests that filgotinib treatment once daily at 100mg and 200mg both on the background of MTX and as monotherapy is consistently associated with improved clinical outcomes compared to placebo, regardless of baseline CRP levels. <h3>References</h3> Westhovens R et al. Ann Rheum Dis 2016;0:1–11. Kavanaugh A et al. Ann Rheum Dis 2016;0:1–11. <h3>Disclosure of Interest</h3> R. Westhovens Grant/research support from: Roche, Consultant for: Galapagos, Speakers bureau: BMS, A. Kavanaugh Consultant for: Galapagos, Pfizer, AbbVie, Amgen, Celgene, Janssen, Novartis, Eli Lilly, UCB, C. Jamoul Employee of: Galapagos NV, C. Tasset Employee of: Galapagos NV, P. Harrison Employee of: Galapagos NV, A. Van der Aa Employee of: Galapagos NV
Reducing major risk factors for chronic kidney disease
Authors: Valerie A. Luyckx, Katherine R. Tuttle, Guillermo Garcia-Garcia, Mohammed Benghanem Gharbi, Hiddo J.L. Heerspink, David W. Johnson, Zhi-Hong Liu, Ziad A. Massy, Orson Moe, Robert G. Nelson, Laura Sola, David C. Wheeler, Sarah L. White
Journal: Kidney International Supplements (2017)
OP0294 Fracture prediction using a genetic markers algorithm compared to frax in three european cohorts
Authors: S Ferrari, R Rizzoli, R Chapurlat, ML Brandi, H Martínez, M Herrero, J Vergés, M Artieda, D Tejedor, A Martínez, J Blanch, S Palacios
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Numerous genome-wide association studies (GWAS) and large meta-analyses have started to unravel the multiple gene polymorphisms associated with BMD and/or fragility fractures. However the clinical utility of these genetic markers for fracture prediction remains to be established. <h3>Objectives</h3> To develop a DNA genotyping tool for predicting osteoporotic fractures in postmenopausal women. <h3>Methods</h3> 768 SNPs previously associated with osteoporosis phenotypes were identified in silico through the NHGRI GWAS catalog and BoneKey Genetics website. They were genotyped on an Illumina GoldenGate assay in 1649 post-menopausal women aged 45+ yrs belonging to three osteoporotic fractures cohorts from Switzerland, Italy and France. SNPs potentially associated (p&lt;0.10) with prevalent and incident clinical fragility fractures in one or more of the cohorts, or in the cohorts together, were then combined in a genetic risk score (GRS). GRS association with fragility fractures was tested by forward logistic regressions adjusting for age and FN BMD. The ability of GRS for fracture prediction was evaluated by the area under the ROC curve (AUC) in the three cohorts combined, as well separately (for internal replication). For comparison, fracture probabilities were computed using FRAX clinical risk factors (without BMD) without and with the addition of GRS. <h3>Results</h3> The average prevalence of fragility fractures in the three cohorts was 25% (range 22 to 28%), of which half were major fractures (FRAX definition). After QC filtering, 632 SNPs in 1625 individuals were correctly genotyped, of which 73 were potentially associated with fractures in one or more cohorts. In single and multiple regression models, GRS was significantly associated with fractures (OR 1.09, CI 1.07–1.12, p&lt;0.0001). The GRS AUC for fracture prediction was significant (0.65) and highly consistent among the three cohorts. GRS predicted major fractures as well as FRAX clinical risk factors without BMD (AUC 0.63 vs 0.58, p=0.08), and when combined with clinical FRAX, the AUC was significantly improved (0.67, p=0.0106). <h3>Conclusions</h3> SNPs previously associated with osteoporosis phenotypes through large GWAS and meta-analyses can be replicated for association with fragility fractures in post-menopausal women from three European countries. Our results provide a proof-of-principle that a genetic risk score (GRS) based on these SNPs represents an independent risk factor for fractures and could be developed into a genetic algorithm to improve the prediction of fragility fractures, either alone or together with FRAX. <h3>Disclosure of Interest</h3> None declared
FRI0543 Which factors can help predict fragility fractures in patients diagnosed with inflammatory bowel disease? a case-control study
Authors: D Ahmed, M Bukhari
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Inflammatory Bowel Disease (IBD) is a known risk factor for developing low bone mineral density (BMD) osteoporosis, due to malabsorption and treatment with steroids. These patients are more susceptible to fragility fractures. Though the percentage of such fractures is low, they can be associated with impaired mortality and morbidity. The difficulty lies in early detection of patients at an increased risk of fractures. Currently the diagnosis of osteoporosis and predictions of fracture risk are calculated assessing patient BMD on dual energy X-ray absorptiometry (DEXA). However, previous studies suggest that despite a decreasing BMD being significantly associated with an increased risk of fracture, its measurement alone is fairly restricted in predicting them; other patient factors must also be brought into consideration (1). <h3>Objectives</h3> To identify specific factors which may assist in the prediction of fragility fractures in a cohort of patients diagnosed with IBD. <h3>Methods</h3> Patients referred to a DEXA scan in the North West of England were identified and those with a referral reason of IBD were studied. Factors measured at BMD scanning include patient age, height, weight, lumbar and femoral head bmd, BMI, smoking history, alcohol use, family history of fractures, steroid exposure, rheumatoid arthritis and secondary osteoporosis. Patients where assorted into cases and controls after adjusting for age and gender. They were then analysed using T tests for continuous variables and Chi squared tests for categorical variables. Univariate and multivariate logical regression models were then utilised to identify factors predicting fractures. <h3>Results</h3> 938 patients were identified of which 721 (76.9%) were female with an average age of 58 as compared to an average age of 53 in men. 274 patients (29%) had fractures of which 238 were females (87%), at an average age of 63 compared to 60 in men. Men were shown to have a greater risk of fractures. Results of the univariate analysis are shown below. In the multivariate analysis, statistically significant variables were BMI (OR 1.05, 95% CI 1.01–1.08) and steroids (OR 0.49, 95% CI 0.35–0.69) with steroids being protective against fractures. <h3>Conclusions</h3> In the univariate analysis several risk factors are shown to be associated with fractures. These include femoral neck BMD, steroid use, lumbar BMD and the patient age at the time of the scan. The multivariate analysis showed that the biggest predictor after adjusting for age and gender is steroids and BMI with steroids being protective. <h3>References</h3> Marshall D, Johnell O, Wedel H. Meta-analysis of how well measures of bone mineral density predict occurrence of osteoporotic fractures. BMJ. 1996;312(7041):1254–9. <h3>Disclosure of Interest</h3> None declared
RILOMET-1: An international phase III multicenter, randomized, double-blind, placebo-controlled trial of rilotumumab plus epirubicin, cisplatin, and capecitabine (ECX) as first-line therapy in patients with advanced MET-positive gastric or gastroesophageal junction (G/GEJ) adenocarcinoma.
Authors: David Cunningham, Salah-Eddin Al-Batran, Irina Davidenko, David H. Ilson, André M. Murad, Niall C. Tebbutt, Yizhou Jiang, Elwyn Loh, Sarita Dubey
Journal: Journal of Clinical Oncology (2013)

TPS4153 Background: Rilotumumab is an investigational, fully human monoclonal antibody to hepatocyte growth factor/scatter factor that inhibits signaling through the MET receptor. In a randomized phase II study in patients with advanced G/GEJ adenocarcinoma, addition of rilotumumab every 3 weeks (Q3W) to ECX showed trends toward improved overall survival (OS) and progression-free survival (PFS) compared with ECX alone. In patients with high tumor MET expression and high rilotumumab exposure, the treatment effect of rilotumumab combined with ECX was significantly enhanced. Methods: In this phase III study, patients (planned N=450) are randomized 1:1 to ECX (intravenous [IV] epirubicin 50 mg/m 2 on day 1, IV cisplatin 60 mg/m 2 on day 1, and oral capecitabine 625 mg/m 2 twice daily on days 1−21) plus double-blind rilotumumab 15 mg/kg or placebo IV Q3W. Randomization is stratified by disease extent (locally advanced vs metastatic) and Eastern Cooperative Oncology Group (ECOG) score (0 vs 1). Key eligibility criteria include previously untreated, pathologically confirmed unresectable locally advanced or metastatic G/GEJ adenocarcinoma; ECOG score 0 or 1; ≥18 years old; MET-positive by centralized immunohistochemistry; HER2-negative; adequate organ function; and ≥6 months since neoadjuvant/adjuvant therapy. The primary endpoint is OS. Key secondary endpoints include PFS, 12-month survival rate, objective response, OS in MET expression tertiles, safety, and pharmacokinetics. An exploratory objective is to assess associations between outcomes and tumor and circulating biomarkers. Enrollment began in November 2012, and the trial continues to accrue. An independent data monitoring committee will conduct planned interim reviews for safety and efficacy. Status: recruiting participants. Sponsored by Amgen Inc. Clinical trial information: NCT01697072.
Addressing Minority Representation in Dermatology
Authors: Shawn G. Kwatra, Alice He, Manisha J. Loss, Ginette A. Okoye
Journal: JAMA Dermatology (2017)

This study uses course evaluation responses and anecdotal feedback to assess a pilot program that includes direct mentorship to encourage inner-city high school students from populations underrepresented in medicine to consider careers in dermatology.
A dual role for the class III PI3K, Vps34, in platelet production and thrombus growth
Authors: Colin Valet, Marie Levade, Gaëtan Chicanne, Benoit Bilanges, Cendrine Cabou, Julien Viaud, Marie-Pierre Gratacap, Frédérique Gaits-Iacovoni, Bart Vanhaesebroeck, Bernard Payrastre, Sonia Severin
Journal: Blood (2017)