tbuckley/cabot-search huggingface dataset:
AB0333 Use of biological dmards, but not of conventional synthetic dmards or steroids, may be relevant to increased energy intake in patients with rheumatoid arthritis
Authors: K Masuko, Y Mizukami, S Tohma, T Matsui
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Dietary and nutritional factors may modulate the onset and/or outcome and comorbidities including cardiovascular diseases in rheumatoid arthritis (RA)[1]. For instance, a potential contribution of sodium intake and the occurrence of autoimmunity has been suggested, however the role of sodium in disease activity of RA is unclear. <h3>Objectives</h3> To investigate the potential relationship between dietary intake and current medications and the disease activity of RA. <h3>Methods</h3> Patients with RA in outpatient clinic of National Hospital Organization, Sagamihara National Hospital (n=89, M/F=18/71, age 65.0±12.8 yo, mean disease duration 16.8±13.2 y) were enrolled to the study. A questionnaire regarding dietary habit and the brief-type self-administered diet history questionnaire (BDHQ) were used to assess the relationship between clinical activity, status of medication and intake of each foodstuff and nutritional factors. The results were analyzed using IBM SPSS software using Pearson9s correlation test and Levene test. <h3>Results</h3> The number of current medication was found to weakly correlate with DAS-28 (r=0.386), and negatively with intake of ethanol (r=-0.277). When users of biological disease modulating anti-rheumatic drugs (bDMARDs) were compared with non-users, the biologics-taking patients tended to have higher intake of total energy and carbohydrates than non-users. Use of oral corticosteroids, nor other anti-rheumatic DMARDs, did not significantly impact the total energy or carbo intake in RA patients. Sodium intake did not correlate with the disease status or the number of medications. <h3>Conclusions</h3> Although salt intake has been suggested to evoke autoimmunity, the amount of dairy intake of salt does not significantly modulate the current disease activity of RA. Use of biologics, but not of corticosteroids, may lead to increased energy and carbohydrate intake in RA patients. <h3>References</h3> Mizukami Y, et al. Distinct Patterns of Dietary Intake in Different Functional Classes of Patients with Rheumatoid Arthritis. Topics in Clinical Nutrition (in press). <h3>Disclosure of Interest</h3> None declared
MCT1 Inhibitor AZD3965 Increases Mitochondrial Metabolism, Facilitating Combination Therapy and Noninvasive Magnetic Resonance Spectroscopy
Authors: Mounia Beloueche-Babari, Slawomir Wantuch, Teresa Casals Galobart, Markella Koniordou, Harold G. Parkes, Vaitha Arunan, Yuen-Li Chung, Thomas R. Eykyn, Paul D. Smith, Martin O. Leach
Journal: Cancer Research (2017)

Monocarboxylate transporters (MCT) modulate tumor cell metabolism and offer promising therapeutic targets for cancer treatment. Understanding the impact of MCT blockade on tumor cell metabolism may help develop combination strategies or identify pharmacodynamic biomarkers to support the clinical development of MCT inhibitors now in clinical trials. In this study, we assessed the impact of the MCT1 inhibitor AZD3965 on cancer cell metabolism
Hypertrophic Cardiomyopathy
Authors: Ali J. Marian, Eugene Braunwald
Journal: Circulation Research (2017)

Hypertrophic cardiomyopathy (HCM) is a genetic disorder that is characterized by left ventricular hypertrophy unexplained by secondary causes and a nondilated left ventricle with preserved or increased ejection fraction. It is commonly asymmetrical with the most severe hypertrophy involving the basal interventricular septum. Left ventricular outflow tract obstruction is present at rest in about one third of the patients and can be provoked in another third. The histological features of HCM include myocyte hypertrophy and disarray, as well as interstitial fibrosis. The hypertrophy is also frequently associated with left ventricular diastolic dysfunction. In the majority of patients, HCM has a relatively benign course. However, HCM is also an important cause of sudden cardiac death, particularly in adolescents and young adults. Nonsustained ventricular tachycardia, syncope, a family history of sudden cardiac death, and severe cardiac hypertrophy are major risk factors for sudden cardiac death. This complication can usually be averted by implantation of a cardioverter-defibrillator in appropriate high-risk patients. Atrial fibrillation is also a common complication and is not well tolerated. Mutations in over a dozen genes encoding sarcomere-associated proteins cause HCM. MYH7 and MYBPC3, encoding β-myosin heavy chain and myosin-binding protein C, respectively, are the 2 most common genes involved, together accounting for ≈50% of the HCM families. In ≈40% of HCM patients, the causal genes remain to be identified. Mutations in genes responsible for storage diseases also cause a phenotype resembling HCM (genocopy or phenocopy). The routine applications of genetic testing and preclinical identification of family members represents an important advance. The genetic discoveries have enhanced understanding of the molecular pathogenesis of HCM and have stimulated efforts designed to identify new therapeutic agents.
AB1153 Osteoporosis risk factors in participants of healthy aging academy
Authors: O Brzezińska-Pawłowska, A Łuczak, D Stalmach, A Lentas, ML Kowalski, J Makowska
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Osteoporosis is a major cause of morbidity and mortality in elderly population. It is known that the mortality rate in European population within 1 year of hip fracture is about 30%, and another 30% of patients need long term nursing for the rest of their life. However, the prevalence and associated risk factors in the Polish elderly population have not been well documented. The aim of the study was to assess prevalence of osteoporosis in Polish elderly population and to assess risk factors related to osteoporotic fractures <h3>Objectives</h3> The study was based on questionnaires distributed among 645 students (61 men, 533 women and 51 not report mean age 69,42±5,88) attending the Healthy Aging Academy at Medical University. <h3>Methods</h3> Students were asked to answer 20 questions including information about endured fractures, osteoporosis risk factors, screening densitometry, treatment of osteoporosis, supplementation with vitamin D3 and calcium. Also, questions about classical risk factors for osteoporosis (loss of height (5 cm/year), family history, falls, loss of weight, treatment with steroids) were included to questionnaire. <h3>Results</h3> Fractures caused by fall from their own height were reported by 180 (27,91%). Moreover, 96 (14,88%) responders without fracture history declared more than 3cm decrease of height after their forties, what strongly suggest osteoporotic vertebral fractures. Forty three (24%) of the respondents had multiple fractures and single fractures were reported by 137 (76%) respondents. The most common localization of fractures was forearm (57%), shin bones (10,4%) and foot bones (9%). Among subjects who underwent densitometry after the fracture 32% had the diagnosis of osteopenia; 19,4% were diagnosed with osteoporosis and in 23,1% bone density was within normal limits. The strongest risk factors for osteoporotic fractures were numerous falls per year (p=0,000) and frequent drinking of alcohol (p=0,008). The risk factors of fractures (sum of risk factors for falls and osteoporosis) among people with previous fractures vs. those without fractures were statistically significant (p=0,037). Only 13% of patient with fracture and 15% of all patients with osteoporosis and osteopenia were treated by antiosteoporotic drugs (ibandronian/aledronian). Calcium supplementation was received by 30% of patients with fracture and 43% supplemented vitamin D3. <h3>Conclusions</h3> The prevalence of osteoporotic fractures in population of relatively well educated population of participants of Third Age University seems to be high. Patients with osteoporosis do not receive appropriate pharmacological prophylactic treatment, pointing at the need for education of primary care physicians and elderly population about burden and consequences of osteoporosis. <h3>Disclosure of Interest</h3> None declared
THU0514 Predictive value of subclinical synovitis detected by doppler ultrasound in relation to flare in patients with juvenile idiopathic arthritis treated with biologic therapy after tapering biologic therapy
Authors: JC Nieto-González, A Boteanu, JC Lόpez-Robledillo, P Collado, A Rodríguez, D Clemente, ML Gámir, I Monteagudo, E Naredo
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Anti-TNF therapy is effective and safe in JIA. Changes in anti-TNF doses are common when remission is achieved<sup>1</sup>. Subclinical synovitis on Doppler mode (PD) detected by ultrasound can predict flares in adult RA, but it is not yet clear in JIA<sup>2</sup> <h3>Objectives</h3> The aim of this study is to evaluate the predictive value of subclinical synovitis detected by PD-US in relation to flares in patients with JIA on remission under anti-TNF when therapy is tapered. The preliminary results were presented at the EULAR congress 2015 in Rome (FRI0520). <h3>Methods</h3> Observational, prospective and multicenter study. We included JIA patients on remission at least 6 months with anti-TNF, ETN and ADA, in whom anti-TNF was tapered due to clinical decision. ETN was tapered by increasing the injection 3 days and ADA by increasing a week. Patients were clinically assessed every 3 months and also with PD-US at baseline. Bilateral US assessment included joints and tendons. Adult synovitis definitions and semiquantitative scoring system were used, no synovitis definitions are available for JIA. We collected demographics (date of birth, JIA subcategory, previous and current treatments. Flare was defined as clinical signs and/or symptoms of arthritis that required increase of systemic therapy <h3>Results</h3> We included 57 patients, with 19 patients (33.33%) having a flare during the 12 months follow-up. 38 patients (66.67%) were receiving ETN and 19 (33.3%) ADA, of which 11 patients (28.95%) had a flare with ETN and 8 patients (42.11%) with ADA. Table 1 shows demographics. Median time to flare was 5.73 months (IR 2–93–8.9). Concomitant methotrexate was lower in patients with flare (26.32% vs 71.05%). In 18 patients (31.58%), a previous tapering was done and median time of remission before being included was 22 months (IR 15.5–28.5). US does not predict flare in our cohort. Global synovitis score at baseline was 4 (IQR 1.3–10.8) and 0 in BM and PD respectively, and tenosynovitis was 0 both BM and PD <h3>Conclusions</h3> Anti-TNF tapering was safe in our JIA patients in more than half of patients after 1 year follow-up. US did not predict flares in our patients. Concomitant treatment with methotrexate was more frequent in patients who remained on remission <h3>References</h3> Cai Y. Rheumatol Int.2013. Magni-Manzoni S.Ann Rheum Dis.2013. <h3>Disclosure of Interest</h3> None declared
AB0660 Characteristics of al-l light-chain and amyloid a deposition in progressive systemic sclerosis – a comparative postmortem clinicopathologic study of 12 patients
Authors: M Bély, Ά Apáthy
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Different types of amyloid deposits may be present in systemic sclerosis (SSc), as consequences (complications) of basic or associated diseases. <h3>Objectives</h3> The aim of this study was to determine the type, prevalence and extent of amyloid deposits on different tissue structures in various organs in SSc. <h3>Methods</h3> We studied histopathologically 12 SSc patients (females 11, average age: 54.82 years, range 66–32, onset of SSc: 48.86, average disease duration: 6.43 years; one male, age 65.0 years at death, onset of SSc and average disease duration not known, who died at the National Institute of Rheumatology. SSc was diagnosed clinically according to the criteria of the ACR [1]. In 1 (8.0% of 12) 67 year old female patient (onset of SSc: 66 years, disease duration: 1 year) SSc was accompanied by B-cell lymphoma and complicated by systemic AL-l light-chain amyloidosis. In 1 (8.0% of 12) 53 year old female patient (onset of SSc: 41 years, disease duration: 12 years) SSc was complicated by systemic amyloid A (aA) deposition. Amyloid deposits on different tissue structures [arteriole, small artery, medium size artery, venule, small vein, medium size vein, interstitial collagen fiber, reticulin fiber (collagen IV), and nerve] of 6 organs [heart, lungs, kidney, gastrointestinal tract, skin and brain] were determined histologically. The extent of amyloid deposition was evaluated by semi-quantitative, visual estimation on a 0 to 3 plus scale, based on the number of involved tissue structures per light microscopic field [2]. The prevalence and extent of amyloid-l light-chain and amyloid A deposits on different tissue structures were compared by Student (Welch) t-probe. <h3>Results</h3> The involvement of different tissue structures (prevalence in %) and the average extent of AL-l light-chain and amyloid A deposits (absolute value) are summarized in Table 1. <h3>Conclusions</h3> In SSc patients the prevalence and extent of l light-chain and amyloid A deposits on different tissue structures changed parallel. The higher prevalence and extent of l light-chain deposits in contrast to amyloid A may be explained with qualitative differences of l light-chain and amyloid A; l light-chain seems to have greater affinity for tissues than amyloid A protein. Infiltration of the vessel walls – regarding the amount of l light-chain and amyloid A deposits in arterioles and arteries in contrast to the veins – showed a converse tendency in SSc patients with AL-l or AAa. This may be related to sluggish blood flow or stasis (backward congestion and accumulation of circulating precursors) in both diseases. <h3>References</h3> van den Hoogen F et al: Ann Rheum Dis 2013; 72:1747–1755 doi: 10.1136/annrheumdis-2013-204424. Bély M, Apáthy Άgnes: Clinical pathology of rheumatoid arthritis. 1–440 pp. Akadémiai Kiadό, Budapest 2012 http://www.akkrt.hu. <h3>Disclosure of Interest</h3> None declared
SAT0115 Effect of biological disease modifying anti-rheumatic drugs (BDMARDS) on cardio vascular disease (CVD) risk in ra patients:three years results from a canadian cohort
Authors: M Khraishi, C Molta, A Lewis
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> RA patients have a higher risk for developing CV Diseases (e.g. IHD and stroke) than the general population.We reported previously (ACR, EULAR) the results CV risk in our patients treated with bDMARDs for 1&amp; 2 years. <h3>Objectives</h3> To assess the effect of bDMARDs treatment on 10-year CV disease risk in patients with RA after 36 months and evaluate the impact of their use on the incidence of CV events <h3>Methods</h3> A cohort of RA patients was followed prospectively.Demographics, disease activity parameters, inflammatory markers, CV events, CVD 10 year risk assessment [Framingham Risk Score (FRS)] were ascertained at the baseline and every six months, up to 36 months.Statistical analysis utilized SPSS (IBM version 24) software. <h3>Results</h3> 321 patients were included, of those 270 patients were followed for three years. Eight BDMARDs were included evaluating their effect on disease activity and CV risk in 233 patients who continued on their prospective biologic for the three years. Significant overall reduction in disease activity in all groups was obtained as compared to baseline. The whole group DAS improved from 3.996 to 3.118. The HAQ also improved significantly (1.201 to 0.857) and the CRP improved significantly (12.91 mg/L to 7.3). Overall, Total cholesterol (TC) changed from 5.195 mmol/L at baseline to 4.992 (P 0.001). High Density Lipoprotein Cholesterol (HDL-C) increased significantly at 36 months from 1.336 to 1.376. However, the Atherogenic Index (AI) for the whole cohort changed from 3.636 to 3.845. The overall 10 year risk of cardiovascular event increased from 12.878 to 13.8 The cohort included 321 patients. Eight bDMARDs were evaluated to assess their effect on disease activity and CVD risk. The outcomes in 233 patients who continued their prospective biologic for the three years were reported (table). 77% were females, median RA duration was 11 ys. Significant reduction in disease activity in all groups was achieved vs. baseline. The DAS improved from 3.996 to 3.118, the HAQ improved significantly (1.201 to 0.857) and the CRP also improved significantly (12.91 mg/L to7.3). Overall, Total cholesterol (TC) changed from 5.195 mmol/L at baseline to 4.992 (P 0.001). High Density Lipoprotein Cholesterol (HDL-C) increased significantly at 36 months from 1.336 to 1.376. The Atherogenic Index (AI) for the cohort changed from 3.636 to 3.845. The overall 10 year risk of cardiovascular event increased from12.878 to 13.8. <h3>Conclusions</h3> The bDMARDS studied were effective in controlling the disease activity of RA. Although the overall CVD risk was not reduced in the group as a whole at 36 months, bDMARDS may still play a role in reducing the CVD risk in these patients <h3>Disclosure of Interest</h3> M. Khraishi Grant/research support from: Roche Canada, C. Molta: None declared, A. Lewis: None declared
KEYNOTE-059 cohort 2: Safety and efficacy of pembrolizumab (pembro) plus 5-fluorouracil (5-FU) and cisplatin for first-line (1L) treatment of advanced gastric cancer.
Authors: Yung-Jue Bang, Kei Muro, Charles S. Fuchs, Talia Golan, Ravit Geva, Hiroki Hara, Shadia Ibrahim Jalal, Christophe Borg, Toshihiko Doi, Zev A. Wainberg, Jiangdian Wang, Minori Koshiji, Rita P. Dalal, Hyun Cheol Chung
Journal: Journal of Clinical Oncology (2017)

4012 Background: Preliminary analyses from the global, multicohort, phase 2 KEYNOTE-059 (NCT02335411) study suggested that safety of pembro + 5-FU + cisplatin is manageable as 1L therapy in pts with advanced gastric or gastroesophageal junction (G/GEJ) cancer (cohort 2). We present efficacy and updated safety data from KEYNOTE-059 cohort 2. Methods: Cohort 2 enrolled pts ≥18 y with HER2 – recurrent or metastatic G/GEJ adenocarcinoma, measurable disease, no prior therapy for metastatic/advanced disease, and ECOG PS 0-1. Pts received pembro 200 mg on day 1 of each 21-day cycle + cisplatin 80 mg/m 2 for 6 cycles + 5-FU 800 mg/m 2 (or capecitabine 1000 mg/m 2 in Japan) Q3W for up to 2 y or until disease progression, investigator/pt decision to withdrawal, or unacceptable toxicity. PD-L1 + pts had expression in ≥1% tumor or stromal cells using IHC (22C3 antibody). End points were safety and tolerability (primary), ORR (RECIST v1.1, by central review), DOR, PFS, and OS (secondary). Results: Of 25 enrolled pts, 64% were men, 68% were Asian, and 64% had PD-L1 + tumors. Median age was 64 y. At data cutoff (Oct 19, 2016), median duration of follow-up was 12.2 mo (range, 1.8 to 19.6) and 84% of pts had discontinued treatment, mainly owing to clinical or radiologic disease progression (64%). ORR (CR + PR) was 60% (95% CI, 38.7-78.9) in all pts. Overall, 32% of pts had SD (95% CI, 14.9-53.5), 4% had PD (95% CI, 0.1-20.4), and 4% were not evaluable (95% CI, 0.1-20.4). ORR was 68.8% (95% CI, 41.3-89.0) in PD-L1 + pts and 37.5% (95% CI, 8.5-75.5) in PD-L1 – pts. Median DOR (range) was 4.6 mo (2.6 to 14.4+) in all pts, 4.6 mo (3.2 to 14.4+) in PD-L1 + pts, and 5.4 mo (2.8 to 8.3+) in PD-L1 – pts. Median PFS was 6.6 mo (95% CI, 5.9-10.6); median OS was 13.8 mo (95% CI, 7.3-not estimable). Grade 3-4 treatment-related adverse events (TRAEs) occurred in 76% of pts. TRAEs led to discontinuation in 3 pts (grade 3 stomatitis, grade 2 hypoacusis, and grade 1 creatinine increase). No TRAEs were fatal. Conclusions: Pembro + 5-FU + cisplatin showed manageable safety and encouraging antitumor activity as 1L therapy for pts with advanced G/GEJ cancer. Further exploration of pembro + 5-FU + cisplatin in this setting is warranted. Clinical trial information: NCT02335411.
OP0162-PARE An exploration of lived experiences amongst adults with rheumatoid arthritis using an online research community platform: a pilot study
Authors: SR Stones, S Bull, S Becerra
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Online technology has revolutionised the way in which people connect and share their experiences. It also brings new opportunities to engage patients in health and social care research through the use of an online research community platform (ORCP). For example, it can improve the accuracy and usefulness of information gathered about research priorities, and it can be used to understand behaviours and preferences. Given an increasing prevalence of long-term conditions including rheumatoid arthritis, online technology represents a novel route for participation and engagement in research. <h3>Objectives</h3> To explore the benefits and limitations of an ORCP through understanding lived experiences of adults with rheumatoid arthritis. <h3>Methods</h3> We used a purposive sampling approach to ensure variation of key attributes amongst people with rheumatoid arthritis. A total of eight individuals used the ORCP during the pilot study. Qualitative data were collected through online focus groups, conducted as semi-structured interviews and asynchronous threaded discussions. The study was conducted in line with fieldwork guidelines, and written informed consent was obtained. <h3>Results</h3> The closed ORCP enabled a physically disconnected group to share their experiences of living with rheumatoid arthritis, describing the symptoms, diagnostic experience and support they received. In addition, participants shared their experiences and opinions about treatment delivery and adherence, the impact of rheumatoid arthritis, and the experiences of transitional care from paediatric to adult health services, where appropriate. Reasons and feeling about research participants and drug development processes were also discussed. <h3>Conclusions</h3> Our pilot study provided important accounts from people living with rheumatoid arthritis, highlighting the substantial impact of the disease on their daily lives. The ORCP removed physical contact between the researcher and participants, the absence of which may enable a richer data collection. However, it also has its limitations, primarily because the researcher is less able to gauge participants9 attitudes and concerns. ORCPs represent a novel route of data collection, enabling researchers to immerse themselves into a community of individuals, whether they be patients, carers or professionals. <h3>Acknowledgements</h3> The authors would like to thank the individuals who contributed their thoughts and experiences to the pilot study. <h3>Disclosure of Interest</h3> S. Stones Employee of: McCann Complete Medical., S. Bull Employee of: McCann Complete Medical., S. Becerra Employee of: McCann Complete Medical.
Genetic and epigenetic studies of adiposity and cardiometabolic disease
Authors: Michael V. Holmes, Sara L. Pulit, Cecilia M. Lindgren
Journal: Genome Medicine (2017)

Over 300 million adults are obese, but little is known about the impact of obesity on cardiovascular health. We discuss recent genetic and epigenetic studies of adiposity that indicate a causal role for general and central adiposity in cardiometabolic disease, and highlight potential mechanisms including insulin resistance and gene expression.