tbuckley/cabot-search huggingface dataset:
AB0748 Hyperuricemia in psoriatic arthritis: a new look as a risk factor for cardiovascular events
Authors: DS Bublikov
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> According to various authors, the prevalence of hyperuricemia in patients with psoriatic arthritis constitutes up to 35% of the total patient population. Thus, seronegative spondylarthritis patients, as it is known, possess a higher incidence of cardiovascular mortality than the population in general, in particular due to life-threatening cardiac arrhythmias. <h3>Objectives</h3> To study the effect of hyperuricemia on the development of ventricular extrasystole in patients with psoriatic arthritis and the interrelation of uric acid levels and gradation of ventricular extrasystole. <h3>Methods</h3> The study involved patients with psoriatic arthritis, confirmed by CASPAR criteria (2006), n=59. The average age – 57.15±12.11 years. All patients underwent the study of myocardial contractility and treadmill test. Inclusion criteria - the presence of psoriatic arthritis for the period of at least one year, uric acid levels over 360 mkmol/L for women and more than 420 mkmol/L for men. The exclusion criteria included the presence of coronary heart disease, myocardial contractility disorders and decreased ejection fraction according to Simpson less than 55%. For all patients was recorded Holter ECG for the period of 24 hours on an outpatient basis. The level of uric acid was measured by means of the standard method of biochemical analyzer. <h3>Results</h3> The prevalence of ventricular extrasystole in patients with psoriatic arthritis and grading are shown in Table 1. Moreover, there has been discovered a direct correlation of medium strength between the uric acid levels and frequency and Lown-Wolf gradation of ventricular extrasystole (Table 1). <h3>Conclusions</h3> 1. Hyperuricemia in patients with psoriatic arthritis by exclusion of cardiogenic causes of cardiac extrasystole is an independent risk factor for ventricular extrasystole. 2. The level of hyperuricemia correlates directly with the Lown-Wolf gradation of ventricular extrasystole. <h3>Disclosure of Interest</h3> None declared
THU0231 IL-17 polarization of mait cells derive from the activation of two different pathways
Authors: G Guggino, F Ciccia, M Lo Pizzo, D Di Liberto, L Saieva, P Ruscitti, P Cipriani, G Sireci, R Alessandro, F Dieli, R Giacomelli, G Triolo
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Primary Sjogren Syndrome (pSS) is a chronic inflammatory disorder affecting exocrine glands. Both IL-23 and the downstream cytokines IL-17 and IL-22 are recognised as key players in the disease. Therefore, the identification of the cellular sources and inducers of IL-17 is crucial in the understanding of the drivers of inflammation in pSS. Mucosal-associated invariant T (MAIT) cells recognize riboflavin derivatives presented by the MHC class I-like molecule MR1. <h3>Objectives</h3> Recently, MAIT cells have been implicated in the pathogenesis of autoimmune disorders and found expanded in salivary glands of pSS patients. Their expression of IL7R and IL23R, makes them potential contributors to the pathogenesis of pSS. <h3>Methods</h3> Mononuclear cells from 16 patients with pSS and 14 subjects with non Sjogren Syndrome secca syndrome (nSS) were isolated from blood and salivary glands. We assessed the phenotype and cytokine expression of MAIT cells by surface and intracellular flow cytometry analysis. The function of MAIT cells was assessed upon <i>in vitro</i> stimulation with recombinant IL-7, IL-23 or their specific ligand lumazine (a Vitamin B2 precursor previously reported to be recognized by and specifically activate MAIT cells). <h3>Results</h3> MAIT cells were reduced in frequency in peripheral blood but not in minor salivary glands of patients with pSS, compared with nSS. <i>In vitro</i> stimulation of MAIT cells from pSS patients induced cytokine production which was dependent on priming with IL-7, IL-23 or specific antigen (lumazine) stimulation. Particularly, IL-7 and IL-23 guarantee IL-17 polarization of MAIT cells by two different pathways via the activation of STAT3 or RORc respectively. <h3>Conclusions</h3> This study confirms a potential role for MAIT cells in pSS and, for the first time, links IL-7 and IL-23 to the IL-17 polarization of MAIT cells in these patients. <h3>Disclosure of Interest</h3> None declared
Annals Story Slam - A Good Death
Authors: Nadine Abdullah
Journal: Annals of Internal Medicine (2017)

Web Exclusives19 September 2017Annals Story Slam - A Good DeathFREENadine Abdullah, MDNadine Abdullah, MDFrom University of Toronto, Toronto, Ontario, Canada.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/W17-0055 SectionsAboutVisual Abstract ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Video. Annals Story Slam - A Good Death "A Good Death," by Dr. Nadine Abdullah (Duration 05:39)Building on the popular Annals feature “On Being a Doctor,” storytellers share stories about the experience of doctoring on video.For more videos from and information on Annals Story Slam, visit go.annals.org/StorySlam. Comments0 CommentsSign In to Submit A Comment Author, Article, and Disclosure InformationAffiliations: From University of Toronto, Toronto, Ontario, Canada.Current Author Address: Nadine Abdullah, MD, University of Toronto, Toronto, Ontario, Canada; e-mail, nadine.[email protected]ca. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byComparing the Needs of Family Caregivers and Program Providers in Long-Term Care in Terms of Family Support Program 19 September 2017Volume 167, Issue 6Page: SS1 ePublished: 19 September 2017 Issue Published: 19 September 2017 Copyright & PermissionsCopyright © 2017 by American College of Physicians. All Rights Reserved.Loading ...
Report from the first European Dermato-Epidemiology Network forum
Authors: A. Ascott, S.M. Langan, I. García-Doval, M.A. Descalzo, S.A.J. Schmidt, T. Nijsten, L.M. Hollestein
Journal: British Journal of Dermatology (2017)

The first European Dermato-Epidemiology Network (EDEN) forum was held on 30-31 March 2017 in Madrid, Spain. Dermatoepidemiology describes the study of causes, prevention, health services research and evaluation of interventions of skin diseases. EDEN aims to promote high-quality research, share expertise and facilitate collaboration. These aims were achieved during the EDEN forum by including a preconference course on skin cancer epidemiology; having excellent world-leading guest speakers on causality, quality of care, pharmacoepidemiology and missing data analysis; and including delegates who presented and discussed innovative research findings. The meeting brought together delegates from 11 different countries. We welcome everyone with an interest in clinical research and epidemiology related to skin disease to attend next year's meeting in March 2018 in Berlin.
SAT0581 Non-tuberculous mycobacterial (NTM) infection in patients with rheumatic diseases: possible importance of pulmonary barrier function rather than systemic immune state in the development and exacerbation of NTM infection
Authors: S Takenaka, H Kameda, T Ogura, H Oshima, K Izumi, A Hirata, H Ito, Y Fujisawa
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Objectives</h3> To identify the risk factors of the development and exacerbation of NTM infection in patients with rheumatic diseases. <h3>Methods</h3> Among 7013 patients with rheumatic diseases visiting Toho University Ohashi Medical Center and Tokyo Medical Center, 20 patients were enrolled in this study by fulfilling the diagnostic criteria of NTM infection by The Japanese Society for Tuberculosis and The Japanese Respiratory Society, and being followed-up for more than 1 year. The medical records of enrolled patients were retrospectively reviewed. <h3>Results</h3> Eleven patients with rheumatoid arthritis, 4 patients with vasculitis, 3 patients with Sjögren9s syndrome and 1 patient with dermatomyositis and systemic lupus erythematosus for each were enrolled in this study. <i>Mycobacterium avium</i> complex (MAC) was detected in 13 patients, <i>M. chelonae</i> in 2 patients, <i>M. abscessus</i> and <i>M.kansasii</i> in 1 patient each, and undetermined mycobacterium in 3 patients. Notably, bronchiectasis was the predominant pulmonary complication observed in 13 patients, and interstitial lung disease was observed in 5 patients. Although 7 patients experienced the exacerbation of NTM during the observation period, immunological state on NTM diagnosis including peripheral blood leukocyte (median 5.8×10<sup>3</sup> versus 7.0×10<sup>3</sup>/μL; p=0.72), lymphocyte (median 1.3×10<sup>3</sup> versus 1.1×10<sup>3</sup>/μL; p=0.10) and the serum IgG level (median 1379 mg/dL versus 1207 mg/dL; p=0.20) were within normal ranges and comparable between ever and never exacerbated patients, respectively, as well as the treatments for rheumatic diseases such as glucocorticoids and biological agents. <h3>Conclusions</h3> NTM infection in patients with rheumatic diseases develops based on the dysfunction of pulmonary barrier rather than the systemic immunosuppression. <h3>Disclosure of Interest</h3> None declared
FRI0571 Osteoporosis and breast cancer: can frax-based risk factors accurately predict further fractures at this setting?
Authors: S Lopez-Salguero, JC Ordoñez, L Ranieri, M Andrés, J Ponce, I Ibero
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Women with breast cáncer (BC) are at risk for the development of bone loss and osteoporosis (OP) mainly due to adjuvant therapies, as aromatase inhibitors (AI). Thus, it would be of special interest in this group of patientes, to know at baseline wich factors can predispose to develope fragility fractures (FF) during follow-up, in order to optmize vigilance and treatment. <h3>Objectives</h3> The purpose of this study is to analyze wich risk factors at baseline that can predict the appereance of a new FF in women with BC and OP. <h3>Methods</h3> Retrospective analysis of consecutive female patients with recent breast cancer (BC) and low bone mineral density (BMD) referred to the osteoporosis outpatient clinic for assessment, as agreed with oncologists. Fort he purpose of this anaylisis, only patients with follow-up data (at least six months after baseline visit) were selected. FRAX tool [1]-derived risk factors (age, BMI, DEXA, previous fracture, parent fractured hip, smoking, alcohol, glucocorticoids, rheumatoid arthritis, secondary OP) were taken as explicative variables. Student9s t and chi-2 tests were used to perform comparisons base don the appereance of new FF in the study period. <h3>Results</h3> A total number of 156 female patients have been assessed up to January 2017. Of the 107 patients in follow-up (68.5%; median time in follow-up 2.1 years p25–75 1.2–3.2). Median age was 62.07 years old (SD±10,35), being 89% of them postmenopausal. 73 (68,2%) were on AI therapy (10 anastrozole, 59 letrozole and 4 exemestane). At baseline, 29 patients (27.1%) showed a FF (15 vertebral; 10 non vertebral; 2 hip; 2 multiple fracture). Antiosteoporotic treatment was recommended in 95 patients (88.7%). During follow-up, 13 FF were seen (12,1%; CI95% 6–19); being 8 of them vertebral, 4 not vertebral, and one multiple fracture; no new hip FF was seen. After comparison of the different risk factors according to the development of a new FF, no significant association was found (see table). <h3>Conclusions</h3> In this study no relationship between FRAX-based risk factors and the development of new FF in women with OP and BC was found. As new FF occurred in 12% of cases, it highlights the need for special attention to this singular, secondary form of OP. <h3>References</h3> Kanis JA, Johnell O, Oden A, Jonsson B, Dawson A, Dere W. Risk of hip fracture derived from relative risks: an analysis applied to the population of Sweden. Osteoporosis International 2000; 11: 120–127. <h3>Disclosure of Interest</h3> None declared
INSECTS AND WAR: II.--THE BED-BUG (Cimex lectularius)
Authors: A. E. Shipley
Journal: BMJ (1914)

Bedaquiline is a recently approved drug for the treatment of multidrug-resistant tuberculosis. Adverse cardiac and hepatic drug reactions to bedaquiline have been noted in clinical practice. The current study investigated bedaquiline metabolism in human hepatocytes using a metabolomic approach. Bedaquiline <i>N</i>-demethylation via CYP3A4 was confirmed as the major pathway in bedaquiline metabolism. In addition to CYP3A4, we found that both CYP2C8 and CYP2C19 contributed to bedaquiline <i>N</i>-demethylation. The <i>K</i><sub>m</sub> values of CYP2C8, CYP2C19, and CYP3A4 in bedaquiline <i>N</i>-demethylation were 13.1, 21.3, and 8.5 <i>µ</i>M, respectively. We also identified a novel metabolic pathway of bedaquiline that produced an aldehyde intermediate. In summary, this study extended our knowledge of bedaquiline metabolism, which can be applied to predict and prevent drug–drug interactions and adverse drug reactions associated with bedaquiline.
Autism-like behavior caused by deletion of vaccinia-related kinase 3 is improved by TrkB stimulation
Authors: Myung-Su Kang, Tae-Yong Choi, Hye Guk Ryu, Dohyun Lee, Seung-Hyun Lee, Se-Young Choi, Kyong-Tai Kim
Journal: The Journal of Experimental Medicine (2017)

Vaccinia-related kinases (VRKs) are multifaceted serine/threonine kinases that play essential roles in various aspects of cell signaling, cell cycle progression, apoptosis, and neuronal development and differentiation. However, the neuronal function of VRK3 is still unknown despite its etiological potential in human autism spectrum disorder (ASD). Here, we report that VRK3-deficient mice exhibit typical symptoms of autism-like behavior, including hyperactivity, stereotyped behaviors, reduced social interaction, and impaired context-dependent spatial memory. A significant decrease in dendritic spine number and arborization were identified in the hippocampus CA1 of VRK3-deficient mice. These mice also exhibited a reduced rectification of AMPA receptor–mediated current and changes in expression of synaptic and signaling proteins, including tyrosine receptor kinase B (TrkB), Arc, and CaMKIIα. Notably, TrkB stimulation with 7,8-dihydroxyflavone reversed the altered synaptic structure and function and successfully restored autism-like behavior in VRK3-deficient mice. These results reveal that VRK3 plays a critical role in neurodevelopmental disorders and suggest a potential therapeutic strategy for ASD.
FRI0184 The profiles of patients with rheumatoid arthritis according to their beliefs in their biological drugs. arco study
Authors: E Raya, I Monteagudo, J Calvo-Alén, G Salvador, T Vázquez-Rodriguez, J Tovar, T Salman-Monte, V Torrente-Segarra, P Vela, C Díaz-Miguel, E Giner, L Cea-Calvo, N Lozano-Rivas, C Marras
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Objectives</h3> To describe profiles of rheumatoid arthritis (RA) patients according to their beliefs in their subcutaneous biological medication (SC). <h3>Methods</h3> ARCO was a study carried out on RA Spanish patients who initiated a SC biological drug 11–18 months prior to the study visit. Patients completed the Beliefs About Medication Questionnaire (BMQ). According to the scores obtained in the necessity (N) and concerns (C) sub-scales, patients were classified into 4 groups: accepting (high N [&gt;3]/low C [≤3]), ambivalent (N&gt;3/C&gt;3), indifferent (N≤3/C≤3) and skeptical (low N [≤3]/high C [&gt;3]). We studied demographic characteristics, expectations and satisfaction with the treatment by group. <h3>Results</h3> 321 patients (77% women) completed the BMQ, 92.8% scored N&gt;3 and 58.9% C&gt;3. A higher % of men than women scored N≤3 (13.5% vs. 5.2%, p=0.031). The % who scored C&gt;3 was higher in those with low satisfaction with symptom control (71.1% vs. 56.7% in satisfied/very satisfied, p=0.098), or side effects (72.1% vs. 52.0%, p&lt;0.001), and in those with lower fulfillment of expectations of efficacy and tolerance (p=0.006 and p&lt;0.001). The combination of N and C scores identified 116 accepting (36.1%), 182 ambivalent (56.7%), 16 indifferent (5.0%) and 7 skeptical patients (2.2%). There were no differences in age, gender, or RA duration among the groups, but differences were seen in the satisfaction with the treatment and in the fulfillment of the expectations (table). Ambivalent patients showed less satisfaction and lower fulfillment of expectations with the treatment received than accepting patients. <h3>Conclusions</h3> Patients with RA have strong beliefs about the need of their biological SC medication, but a high % also expresses concerns. Beliefs, and especially concerns, seem to relate to the satisfaction and fulfillment of expectations of efficacy and tolerability or the drug, rather than to demographics or RA characteristics. Discussing expectations may be important when initiating a biological treatment. <h3>Acknowledgements</h3> Funded by MSD, Spain. <h3>Disclosure of Interest</h3> None declared
FRI0725 Prediction of interstitial lung disease in mixed connective tissue disease
Authors: S Reiseter, R Gunnarsson, TM Aaløkken, MB Lund, J Corander, Ø Molberg
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Mixed Connective Tissue Disease (MCTD) is characterized by high levels of autoantibodies against U1 small nuclear ribonucleoprotein (RNP) and clinical manifestations also found in Systemic Sclerosis, Systemic Lupus Erythematosus, Rheumatoid Arthritis and Polymyositis. Interstitial Lung Disease (ILD) is a severe complication in MCTD and has been reported to affect between 35% and 85% (1) in different cohorts. <h3>Objectives</h3> Here we present a predicting model of ILD in an unselected nationwide MCTD cohort aiming to assist clinicians in identifying MCTD patients with ILD. <h3>Methods</h3> 135 patients with high resolution computed tomography (CT) available for systematic evaluation were included from our nationwide MCTD cohort. Abnormal CT findings of ground glass attenuation and reticular patterns were defined as ILD. Pulmonary function tests were performed within 2 months of the HRCT examination. Serum levels of anti-RNP and Ro-52 autoantibody were determined by line immunoassay (ANA Profile 5 Euroline Blot test kit, Euroimmun, Lübeck, Germany). Logistic regression analyses were used to find the predictive factors of ILD. Variables at a significant level of <i>P</i>&lt;0.25 where considered a candidate in the prediction model by manual backward elimination procedure in addition to age and gender. <h3>Results</h3> Results: 52 patients (38%) had evidence of ILD on HRCT. The predictive model is shown in Table 1. <i>P</i>=0.55 for goodness of fit test and <i>P</i>=0.80 for area under ROC curve. <h3>Conclusions</h3> Risk factors of ILD in MCTD are DLCO less than 60% of predicted, high titer RNP antibodies, no previous arthritis and increasing age. <h3>References</h3> Gunnarsson R, Hetlevik SO, Lilleby V, Molberg O. Mixed connective tissue disease. Best Pract Res Clin Rheumatol. 2016;30(1):95–111. <h3>Disclosure of Interest</h3> None declared
SAT0722-HPR Familial risks of rheumatoid arthritis: evidence from the malaysian epidemiological investigation of rheumatoid arthritis case-control study
Authors: CL Too, LK Tan, AF Nurul Aain, S Salsabil, H Heselynn, S Wahinuddin, IS Lau, SC Gun, S Nor-Shuhaila, M Eashwary, MS Mohd-Shahrir, M-M Ainon, R Azmillah, O Muhaini, C Bengtsson, L Padyukov, L Alfredsson, L Klareskog, M Shahnaz
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Family history of rheumatoid arthritis (RA) is a surrogate for an individual9s genetic and partly environmental risk of developing RA. It is assessed daily in clinical practice and its magnitude and pattern of distribution may provide information on the RA etiology. <h3>Objectives</h3> We investigated the association between family history of RA and the risk of anti-citrullinated peptide antibody (ACPA)-positive and ACPA-negative RA in the Malaysian population. <h3>Methods</h3> Data from the Malaysian Epidemiological Investigation of Rheumatoid Arthritis (MyEIRA) population-based case-control study involving 1,055 early RA cases and 1,055 age, sex and residential area-matched controls were analyzed. Information from interview-reported family history of RA or rheumatic stiff back among first degree relatives was used to estimate the risk of developing ACPA-positive and ACPA negative RA. The odds ratio (OR) with 95% confidence interval (CI) was calculated. <h3>Results</h3> In this study, 64% of the RA patients were ACPA-positive and 40% of the overall RA carried HLA-DRB1 shared epitope (SE) alleles. Family history of RA was significantly associated with an increased risk of developing RA in the Malaysian population (RA versus controls, 17.0% vs. 7.7%, OR 2.4, 95% CI 1.8–3.2, p&lt;0.0001). The association between positive family history and risk of RA was uniformly observed for the ACPA-positive RA (OR 2.5, 95% CI 1.8–3.3, p&lt;0.0001) and ACPA-negative RA (OR 2.3, 95% CI 1.6–3.2, p&lt;0.0001) subsets, respectively. A dramatically increased risk for ACPA-positive RA was seen in individuals who both were having positive family history of RA and carried HLA-DRB1 SE alleles (OR 14.7, 95% CI 7.7–27.8). We also observed a lesser risk magnitude in the ACPA-negative RA patients (OR 5.7, 95% CI 2.7–11.9). <h3>Conclusions</h3> Our data demonstrate that family history of RA remains an important clinical risk factor for RA. In addition, positive family history of RA was associated with an increased risk of developing both the ACPA-positive and ACPA-negative RA in the Malaysian population, suggesting that the two RA subsets are similar in genetic risk factors that overlap with these diseases. <h3>References</h3> Frisell T, Saevarsdottir S, Askling J. Family history of rheumatoid arthritis: an old concept with new developments. Nat Rev Rheumatol. 2016 Jun;12(6):335–43. Frisell T, Hellgren K, Alfredsson L, Raychaudhuri S, Klareskog L, Askling J. Familial aggregation of arthritis-related diseases in seropositive and seronegative rheumatoid arthritis: a register-based case-control study in Sweden. Ann Rheum Dis. 2016 Jan;75(1):183–9. <h3>Disclosure of Interest</h3> None declared
Allergan transfers Restasis patent to Mohawk tribe to deter challenges from generics
Authors: Owen Dyer
Journal: BMJ (2017)

The Dublin based drug maker Allergan is transferring the patents for its dry eye treatment Restasis (ciclosporin ophthalmic emulsion) to the Saint Regis Mohawk Tribe, hoping that the native people’s sovereign status under US law will enable them to fight off patent challenges from generic makers.

The Mohawks, who live in upstate New York near the Canadian border, will immediately grant exclusive licenses for Restasis back to Allergan and will file a motion seeking to dismiss an inter partes review of the drug’s patent currently pending before the federal Patent Trial and Appeal Board.

This expedited form of patent review, available since 2011, has been called a form of “double jeopardy” by Allergan, which is already defending its Restasis patent in a Texas federal court against Mylan, Pfizer, and Teva …
A polymicrobial view of disease potential in Crohn's-associated adherent-invasive <i>E. coli</i>
Authors: Wael Elhenawy, Alexander Oberc, Brian K. Coombes
Journal: Gut Microbes (2017)

The human gut is home to trillions of bacteria and provides the scaffold for one of the most complex microbial ecosystems in nature. Inflammatory bowel diseases, such as Crohn's disease, involve a compositional shift in the microbial constituents of this ecosystem with a marked expansion of Enterobacteriaceae, particularly Escherichia coli. Adherent-invasive E. coli (AIEC) strains are frequently isolated from the biopsies of Crohn's patients, where their ability to elicit inflammation suggests a possible role in Crohn's pathology. Here, we consider the origins of the AIEC pathovar and discuss how risk factors associated with Crohn's disease might influence AIEC colonization dynamics within the host to alter the overall disease potential of the microbial community.