tbuckley/cabot-search huggingface dataset:
SAT0238 Rapid elevation of erythrocyte methotrexate-polyglutamate3 (MTX-PG3) levels related to the efficacy of mtx in patients with rheumatoid arthritis (RA).
Authors: M. Nishida, G. Tsuji, M. Takahashi, T. Saitou, Y. Noda, K. Yoneda, N. Amano, S. Sendo, A. Onishi, A. Morinobu, M. Shinohara, S. Kumagai
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background:</h3> MTX is transported into cells and retained long after polyglutamation. Recently, it has been described that the response to MTX treatment is related to the intracellular MTX-polyglutamate (MTX-PG) levels, but little is known about its details and determinants<sup>1)</sup>. <h3>Objectives:</h3> To clarify the association of erythrocyte concentrations of MTX-PGs (PG1 to PG4) with the efficacy of MTX in 35 MTX naïve patients with RA. <h3>Methods:</h3> We measured erythrocyte MTX-PGs at 4, 12, 24, and 48 weeks after administration of MTX using liquid chromatography (LC)-mass spectrometry (MS)/MS assay. The associations of MTX-PG concentrations with disease activity and the 9 SNPs including 5 SNPs reported for associations with MTX-efficacy were analyzed. <h3>Results:</h3> As shown in the figure, MTX-PG1 and PG2 elevated at week 4, and total MTX-PGs as well as MTX-PG3 and MTX-PG4 increased until week 12. The MTX-PG2 fraction (as percentage of total) was 26% to 29% and almost constant throughout the course. MTX-PG3 and MTX-PG4 fractions were gradually elevated over time, although MTX-PG1 fraction was decreased. A negative association of Disease Activity Score in 28 joints (DAS28) at week 4, 12 and 24 was observed with levels of MTX-PG2 (p=0.008), MTX-PG3 (p=0.0045), MTX-PG4 (p=0.0142) and total MTX-PG (p=0.023). On the other hand, ΔDAS28 (change in DAS28 scores from baseline) was positively correlated to fraction of MTX-PG3 (p=0.011) but negatively correlated to that of MTX-PG1 (p=0.0071). At week 12 and 24, MTX-PG2 fraction was higher (p=0.0783) in the patients who achieved the EULAR good response criteria than in those who did not. MTX-PG3 levels were associated with SLC19A1c.80G&gt;A and FMO2_c.585A&gt;G, and the fraction of MTX-PG2 in total MTX-PGs was associated with GGH c.452C&gt;T and with FMO2_c.585A&gt;G. <h3>Conclusions:</h3> This study suggests that rapid elevation of erythrocyte MTX-PG3 levels from MTX-PG1 through MTX-PG2 and higher distribution of MTX-PG3 is important to exert certain efficacy of MTX. We previously reported in retrospective study that MTX-PG concentration in RA patients keeping remission for long time was associated with several SNPs<sup>2</sup>), and some of the results were confirmed in this prospective study. <h3>References</h3> 1) de Rotte MCFJ, et al. Ann Rheum Dis, 2015;74:408–414. 2) Kumagai S, et al. Ann Rheum Dis76(Suppl2)282. doi:10.1136/annrheumdis-2017-eular.2585 <h3>Disclosure of Interest:</h3> None declared
Targeting Sec23b in COPII Vesicles Regulates T Cell Immunity
Authors: Stephanie Kim, Rami Khoriaty, Rajesh Valanparambil, Julia Wu, Austin Taylor, Hideaki Fujiwara, Dan Peltier, Yaping Sun, Israel Henig, Cynthia Zajac, Katherine Oravecz-Wilson, Stuart Brabbs, Rafi Ahmed, David Ginsburg, Pavan Reddy
Journal: Blood (2018)
AB0365 The insulin resistance, metabolic syndrome and type 2 diabetes mellitus development risk assessment in rheumatoid arthritis patients
Authors: L. Kondratyeva, T. Popkova
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> The insulin resistance (IR) is the known risk factor of type 2 diabetes mellitus (DM) and potential cardiovascular complications. But it's not feasable in routine practice to calculate special indices to determine IR, as insulin levels monitoring is not a standard procedure in RA pts. Metabolic syndrome (MS) criteria and questionnaires designed to assess the risk of DM development can help to differentiate a subgroup of pts, requiring more accurate evaluation of their IR status. <h3>Objectives</h3> To determine how IR relates with MS and DM development risk assessment in RA patients. <h3>Methods</h3> A total of 46 RA pts (39 women, 7 men, 57 [39; 64] years old) without established DM were enrolled in the study, including 14 pts with IR and 32 pts without IR, matched by age and sex. IR was defined as Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) index &gt;2,77. National Cholesterol Education Program/Adult Treatment Panel III (NCEP/ATPIII) and International Diabetes Federation (IDF) criteria were used to confirm MS. The abdominal obesity was determined as waist circumference (WC) ≥80 cm for women and ≥94 cm for men (by IDF), and WC ≥88 cm for women and ≥102 cm for men (by NCEP/ATPIII). If the total score of questionnaire Finnish Type 2 Diabetes Risk Assessment Form (FINDRISK) was ≥12, the DM development risk was considered as moderate or high. <h3>Results</h3> The body mass index was higher in pts with IR than in those without IR (28,5 [24,8; 32,5 kg/m<sup>2</sup> vs 22,4 [20,1; 25,4 kg/m<sup>2</sup>, p<i>&lt;</i>0,001). Abdominal obesity was documented in 100% pts with IR and in 41% pts without IR by IDF criteria (p=0,002), in 64% and 22% pts, respectively, by NCEP/ATPIII criteria (p=0,01). There were no differences in DAS28, CRP and ESR values and glucocorticoids users proportions. MS by IDF criteria was diagnosed in 57% pts with IR and 19% pts without IR (p=0,02), and MS prevalence by NCEP/ATP III criteria was similar in both groups (36% vs 16%, respectively, p=0,2). Higher rates of moderate and high risk for DM development were found in pts with IR compared to pts without IR (71,4% vs 31,2%, p=0,03). <h3>Conclusions</h3> The FINDRISK and IDF questionnaires, but not the NCEP/ATP III criteria of MS, can be helpful in selecting RA pts with potential IR. Abdominal obesity was the key factor indicative of IR in RA pts. On the other hand, IR may not be there even in the presence of several traditional DM risk factors. Therefore further clarification of potential contribution of RA-related risks is needed. <h3>Disclosure of Interest</h3> None declared
Large-Scale Linkage Analysis of Multiple Myeloma (MM) and Monoclonal Gammopathy of Undetermined Significance (MGUS) Families
Authors: Alyssa I. Clay-Gilmour, Nicola J Camp, Xiaomu Wei, Aaron D. Norman, Jason P Sinnwell, Delphine Demangel, Rosalie Griffin Waller, Charles Dumontet, James McKay, Kenneth Offit, Siwei Chen, Daniel R O'Brien, S. Vincent Rajkumar, Robert Klein, Shaji K. Kumar, Steven Lipkin, Susan L. Slager, Celine M. Vachon
Journal: Blood (2018)
SAT0105 Preliminary analysis of genetic variants in the immune system related to the body mass index in early arthritis patients
Authors: P. Moreno, N. Montes, J. Martín, D. Carmona, C.M. Mora, R.P. Gomáriz, A. Lamana, A. Triguero, A. M. Ortiz, I.G. Álvaro
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> We have observed in previous analyzes in our early arthritis (EA) cohort that patients with a higher body mass index (BMI) are, more frequently, ACPA negative and these patients carry, with a lower frequency, HLADRB1 alleles that encode for the shared epitope. <h3>Objectives</h3> To identify SNPs (Single Nucleotide Polymorphisms) of immune system genes related to BMI in EA patients. <h3>Methods</h3> The 257 patients of the PEARL (Princess Early Arthritis Register Longitudinal) cohort in which high density genotyping was available (using the Immunochip array of Ilumina Inc) were included. As a previous step, those SNPs that did not meet the requirements of a genotyping call rate lower than 98%, being out of Hardy-Weinberg equilibrium (<i>p</i>&lt;10-<sup>4</sup>) and minor allele frequency lower than 1% were excluded. IMPUTE v.2 was used for the genotype imputation of the SNPs that failed in the immunochip, using as reference the data of phase III of the 1000 G project. The association analysis of the remaining SNPs was made by linear regression adjusted by sex, age and study level with PLINK v1.9. Of the 1384 SNPs associated with BMI with a value of <i>p</i>&lt;0.01, 250 SNPs were selected according to the lowest values of the division of <i>p</i> divided by the absolute value of its β coefficient. After analyzing and excluding the SNPS that were in linkage desequilibrium, the importance of the 186 resulting SNPs was quantified with the "Random Forest" and "Boosted Regression Tree" techniques using %IncMSE (Mean Decrease Accuracy). <h3>Results</h3> Table 1 shows the selection of the 15 SNPs that were more important in both "machine learning" techniques according to BMI. Although most of these SNPs are located in non-coding regions (intergenic or intronic), some of the genes where the SNPs belong or the neighboring genes have shown association in some GWAS (Genome-Wide Association) with a minor (BMP7) or a greater (RSPO3) BMI; and some of them have shown to have a regulatory role in the immune system in patients with RA (WDFY4, BMP7). <h3>Conclusions</h3> Our preliminary approach allowed us to select 15 SNPs that may have more relevance related to BMI in patients with early arthritis. However, this is a preliminary study and it is necessary to validate these results in other populations to ensure their involvement in the relationship between the BMI and EA. <h3>Disclosure of Interest:</h3> None declared
AB1230 Patient empowerment through the use of a mobile phone application: the experience of rheumabuddy in italy
Authors: A. Alunno, L. Andreoli, L. Quartuccio, F. Carubbi
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Patient education and empowerment are cornerstones in the management of rheumatic and muscoloskeletal diseases (RMDs). In fact, they improve the physician-patient relationship and ensure a successful shared decision making process. In recent years, the esponential growth of interactive media and the progress of technology led to the parallel development of digital healthcare and the evaluation of how tools like mobile applications (app) can contribute to patient empowerment. Rheumabuddy has been developed thanks to the collaboration of the Danish association of young patients with RMDs (FNUG) and a Danish agency specialised in digital heathcare (Daman). RheumaBuddy is designed for young patients (18–35 years old) with chronic arthritis and integrates the function of a diary to monitor the main features of the disease (e.g. pain, stiffness, fatigue) and a forum to interact with other users and provide mutual help. <h3>Objectives</h3> We aimed at developing the Italian version of RheumaBuddy to make it available to Italian patients with RMDs. <h3>Methods</h3> The Italian Society of Rheumatology Committee for young rheumatologists (SIRyoung) translated the content of the app from English to Italian adapting when needed because of language incompatibility. <h3>Results</h3> The Italian version of RheumaBuddy was launched on the 12th October 2017 (World Arthritis Day) in partnership with national patient associations (ANMAR and APMAR). The app was also presented via a press release from the Italian Society of Rheumatology. To date, RheumaBuddy was downloaded by 1182 users with 822 of them currently using the app on a regular basis. The feedback collected so far highlighted the usefulness of the app and pointed out potential weaknesses and issues to be tailored to the Italian population. The gathering of feedback from users is still ongoing. <h3>Conclusions</h3> We developed the Italian version of RheumaBuddy, which is currently used by a consistent number of young patients with chronic arthritis. A board including patient representatives, rheumatologists and the app developers will be established to specifically tailor the app according to the needs and priority of Italian users and based on the feedback collected. <h3>Disclosure of Interest</h3> None declared
THU0534 The effect of lumber stabilisation exercise on the balance and clinical health
Authors: K. Barut, E. Taştaban, F. Sendur
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Objectives</h3> The aim of this study is to investigate the effects of lumbar stabilisation exercises on chronic low back pain in term of pain, functioning, quality of life, balance and trophic improvement of lumbar multifidus muscles. <h3>Methods</h3> 66 patients with chronic low back pain were enrolled in this study. The patients were randomised and divided into two groups. Lomber stabilisation exercises, TENS and Hotpack treatments were given to the first group (n: 28) while the second group (n: 37) were treated with only TENS and Hotpack. Patients' evaluations have been carried out before and after 8 weeks following the exercises. Visuel Analogue Scale (VAS) were used to determine the pain as a numeric scale during the rest and pyhsical activity. Modified Oswestry Questionnaire Survey and Roland Morris Scale were used to evaluate of functional disability. The Short Form-36 (SF36) applied to measure of quality of life. Tetrax device has been used to evaluation the body balance. 7–15 MHZ Ultrasound has been used to evaluate the change of trophic changes of multifidus muscle's cross-sectional areas. <h3>Results</h3> Except falling risk, in all parameters we have observed significant improvement in group 1. Cross-sectional area of the multifidus muscles, physical role of SF-36, mental health and energy/vitality sub parameters were found significantly better in group 1 when compared to the other group. There was no significant difference between the groups when the fall index, VAS scores, Roland Morris Questionnaire and Oswestry Disability Index were considered. <h3>Conclusions</h3> As a result, lomber stabilisation exercises have positive effect on pain relief, improve the functional capacity and quality of life. Additionally the exercises also had benefit and increased cross-sectional areas of multifidus muscles. <h3>Disclosure of Interest</h3> None declared
Outcomes of Patients With Inflammatory Bowel Diseases Switched From Maintenance Therapy With a Biosimilar to Remicade
Authors: Akos Ilias, Kata Szanto, Lorant Gonczi, Zsuzsanna Kurti, Petra Anna Golovics, Klaudia Farkas, Eszter Schafer, Zoltan Szepes, Balazs Szalay, Aron Vincze, Tamas Szamosi, Tamas Molnar, Peter Laszlo Lakatos
Journal: Clinical Gastroenterology and Hepatology (2019)
A Small Nucleolar RNA Linked to Diamond-Blackfan Anemia
Authors: Adeline Mayeux, Nathalie Montel-Lehry, Manon Saby, Aurore Anton, Narjesse Karboul, Julie Galimand, Helene Bourdeau, Jonathan Levy, Anne-claude Tabet, Mohandas Narla, Alyson W. MacInnes, Pascale Dufourcq, Patrick Blader, Thierry Leblanc, Marie-francoise O' Donohue, Pierre-Emmanuel Gleizes, Lydie Da Costa
Journal: Blood (2018)
HIV pre-exposure prophylaxis (PrEP)
Authors: Ethan Tumarkin, Mark J Siedner, Isaac I Bogoch
Journal: BMJ (2019)

### What you need to know

A 22 year old man attends a sexual health clinic. Six months previously, he completed a course of HIV post-exposure prophylaxis for anal receptive intercourse without a condom. Since then, he reports six anal receptive sexual exposures without a condom. He has been treated at another sexual health clinic for rectal gonorrhoea. He asks if you could prescribe him PrEP. 

HIV pre-exposure prophylaxis (PrEP) is the use of HIV antiretroviral medicines in people without HIV to prevent infection. When taken correctly, PrEP has been shown to reduce the risk of HIV infection in numerous populations, including young women, men who have sex with men, HIV uninfected members of sero-discordant couples, and injecting drug users.123 Based on this evidence, PrEP is recommended for people considered at high risk of acquiring HIV. However, availability of PrEP and access to expert advice and counselling about its use vary globally. For example, in England it is only available as part of a clinical trial, whereas it is available in the rest of the UK at sexual health clinics. Awareness of PrEP among at-risk groups is growing, and availability of the treatment is becoming more widespread; therefore generalists—as well as those working in sexual health services—require an awareness of the indications, efficacy, use, and potential harms of PrEP.

### Identify risk of HIV

Ask the patient about known or potential HIV exposures in the previous six months, particularly sexual exposures or injecting drug …
SP0081 Patient organisations’ challenges in a world that is getting older – less – more colourful
Authors: W. Koesters
Journal: Annals of the Rheumatic Diseases (2018)

<h3></h3> We have to see the demographic facts. The most important fact continues to be the birth rate, that is, how many children are born in a country. Because only when children are born, they can start their vocational training or go to college 16 to 18 years later and will be available as qualified workers a few years later. Only those people can in turn have children and bring them up in a way that is sustainable. Only those can become a member of a patient organisation, can be engaged voluntarily. When you look at the 28 countries in the EU, you will notice that on the one hand the average birth rate is 1.55 (2013) while on the other hand there are still significant differences even within Europe. To keep a population stable, we need 2.08 children per woman aged 15 to 49 years. The consequences are evident: in almost all European countries the population will shrink without further immigration from abroad or no longer grow on its own. In almost all countries more people will die than be born. This will also have repercussions on the ageing of society and naturally on the demand for products and services too, but also on the potential labour force. This will have consequences for patient organisations too. At the same time the needs will change because in all countries people continue to get older and live longer. In their old age they will therefore require services for a longer period of time than previous generations: health, nursing care, culture, leisure, housing, support and assistance, travel. The economy, all companies and professions, the public health, the organisation of daily life will have to face profound changes with long-term effects as well as the associated challenges. This also against the background of medical doctors becoming older and scarcer as well. <h3>Disclosure of Interest</h3> None declared
Abstract 20191: Cardiovascular Events and Coffe Use in Stage 1 Hypertension
Authors: Lucio Mos, Paolo Palatini
Journal: Circulation (2015)

Introduction: Controversy still exists about the long-term cardiovascular and metabolic effects of coffee consumption in hypertension. Aim of the study was to assess the predictive capacity of coffee use for cardiovascular events (CVE) and to ascertain whether the coffee-CVE association was mediated by the long-term effects of coffee on blood pressure (BP) and glucose metabolism. Design and methods: The analysis was made in 1201 participants from the HARVEST, a prospective cohort study of non-diabetic subjects aged 18-45 years, screened for stage 1 hypertension. BP was measured with ambulatory monitoring in all. Results: Among participants, 26.3% were abstainers, 62.7% were moderate coffee drinkers (1-3 cups/day) and 10.0% were heavy coffee drinkers (&gt;3 cups/day). During a 12.5 year follow-up there were 60 CVE. In multivariable Cox analyses, coffee was a significant predictor of development of hypertension needing treatment with hazard ratios (HR) of 1.5 (CI,1.1-1.9) for heavy drinkers and 1.1 (0.9-1.3) for moderate drinkers compared to abstainers. Also, coffee was a predictor of future prediabetes with HRs of 2.0 (1-3-3.1) and 1.3 (0.9-1.7), in the heavy and moderate drinkers, respectively. In multivariable Cox analyses, including other lifestyle factors, age, sex, parental CVE, BMI, total cholesterol, 24h ambulatory BP, 24h ambulatory heart rate and follow-up changes in body weight, both coffee categories were independent predictors of CVE with HRs of 4.3 (1.3-13.9) for heavy coffee drinkers and 2.9 (1.04-8.2) for moderate drinkers. Inclusion of hypertension development in the regression attenuated the strength of the coffee-CVE association with HRs of 3.9 (1.2-12.5) for heavy and of 2.8 (0.99-7.8) for moderate drinkers. When future prediabetes was also incorporated, the relationship was of boderline significance for heavy coffee drinkers (HR, 3.2, 0.94-10.9) and was no longer significant for moderate drinkers (HR, 2.3, 0.8-6.5). Conclusions: Coffee use is linearly associated with increased risk of CVE in stage 1 hypertension. The effect of coffee on CVE seems to be at least partially mediated by its long-term effects on BP and glucose metabolism. Coffee consumption should be reduced in young-to-middle-age patients with hypertension.
Anatomical site differences of sodium lauryl sulfate‐induced irritation: randomized controlled trial
Authors: D. Leskur, J. Bukić, A. Petrić, L. Zekan, D. Rušić, A. Šešelja Perišin, I. Petrić, M. Stipić, N. Puizina‐Ivić, D. Modun
Journal: British Journal of Dermatology (2019)

Sodium lauryl sulfate (SLS)‐induced contact dermatitis is a commonly used model for testing the effects of different topical formulations. According to the guidelines, the volar forearms are the preferred testing site; however, other anatomical locations have been used in previous research, particularly the upper back as the clinically used site for testing different antigens. To investigate the existence of anatomical variations of the skin response to irritation and its effects on the response to treatment. Irritation was induced with SLS on symmetrical sites on both forearms and sides of the upper back with additional sites exposed to water as controls. Half of the sites were treated with emollient cream while the other half were left untreated. Irritation was assessed using bioengineering methods and clinical scoring. The trial was registered at ClinicalTrials.gov as NCT03231813. Upper back skin showed higher reactivity to irritants with stronger barrier disruption (measured by Tewameter®, 80·2 ± 18·3 vs. 48·0 ± 24·2 g m−2 h−1), more pronounced erythema (measured by Mexameter®, 186·5 ± 88·4 vs. 92·1 ± 58·2 arbitrary units) and dryness (measured by Corneometer®, –28·6 ± 14·5 vs. 2·7 ± 16·9 arbitrary units). Skin recovery rates were also influenced by anatomical location with the upper back showing faster recovery (316·7 ± 223·1 vs. 156·2 ± 198·5). Treatment did not lead to improvement in measured parameters, regardless of anatomical location. The skin's reaction to irritant and recovery was dependent on anatomical location. The location where testing was conducted should always be reported, as treatments tested across different locations could not be directly compared with each other.
Comparative Analysis of Independent Ex Vivo functional Drug Screens Identifies Predictive Biomarkers of BCL-2 Inhibitor Response in AML
Authors: Brian S. White, Suleiman A. Khan, Muhammad Ammad-ud-din, Swapnil Potdar, Mike J Mason, Cristina E. Tognon, Brian J. Druker, Caroline A Heckman, Olli Kallioniemi, Stephen E Kurtz, Kimmo Porkka, Jeffrey W. Tyner, Tero Aittokallio, Krister Wennerberg, Justin Guinney
Journal: Blood (2018)
SP0107 What can bayesian statistics contribute to measuring patient perspectives?
Authors: V. Ritschl
Journal: Annals of the Rheumatic Diseases (2018)

<h3></h3> Thomas Bayes (1701–1761) founded the Bayesian approach, published as "Essay Towards Solving a Problem in the Doctrine of Chances" in 1763 as a new philosophy in inferential statistics opposed to the classical, frequentist approach. Frequentists test whether a hypothesis is true or false with a certain probability. The Bayesian approach depends on conditional probability which takes prior knowledge (a prior distribution of probabilities) into account. An example for the use of the Bayesian approach is a self-reported instrument that assesses function in rheumatic and musculoskeletal diseases. This instrument produces worse scores with higher age due to the increasing incidence of physical disability. The prior knowledge (higher age leading to a worse function score) should be taken into account when the scores of the instruments are interpreted. <h3>Disclosure of Interest</h3> None declared