tbuckley/cabot-search huggingface dataset:
Abstract P066: Cortisol/Testosterone and Cortisol/ Sex Hormone Binding Globulin Ratios With Metabolic Syndrome in Women
Authors: Ju-Mi Lee, Laura Colangelo, Joseph E Schwartz, Yuichiro Yano, David S Siscovick, Teresa Seeman, Pamela J Schreiner, Kiang J Liu, Donald M Lloyd-Jones, Philip Greenland Greenland
Journal: Circulation (2015)

Introduction: The ability to study chronic stress in humans is complicated due to measurement error of questionnaires and the inability of short-term measures of stress hormones to reflect the chronic state. Therefore considerable controversy remains about whether chronic stress influences cardiovascular disease or not. The cortisol/testosterone (C/T) ratio was suggested to be a better predictor of heart disease in men than cortisol alone, as gonadotropin and cortisol are derived from the same biochemical precursor. This ratio has never been studied with metabolic syndrome (MetS) in a U.S. epidemiologic study, especially in women. Study question: Are C/T and C/sex hormone binding globulin (SHBG) ratio associated with MetS in women? Methods: In the Coronary Artery Risk Development in Young Adults (CARDIA) study, 367 women (age range 32 to 51, mean age 40 years old) who had both cortisol from year (Y) 15 and sex hormones from serum specimen Y16 measured are included. Metabolic syndrome (MetS) from Y15, 20, 25 were assessed. Due to the instability and diurnal characteristics of cortisol, area under the curve (AUC) of six samples and slope of 1st (or 3rd) and 6th (or 5th when 6th is not available) sample of salivary cortisol collected over one day were calculated. Ratios of AUC and of slope of cortisol to total testosterone (TT), free testosterone (FT), and sex hormone binding globulin (SHBG) were computed: AUC/TT, AUC/FT, AUC/SHBG, Slope/TT, Slope/FT, and Slope/SHBG. The associations of these variables categorized into tertiles with MetS were assessed cross-sectionally by logistic regression analysis. Model I controlled for age and race. Model II controlled for model I variables plus menopause, oral contraceptive usage, diabetes mellitus, alcohol consumption, and cigarette smoking. Results: MetS was present in 53, 69, and 74 participants at Y15, Y20, and Y25, respectively. The highest tertile of AUC/SHBG ratio was associated with Y15, Y20, and Y25 MetS prevalence in model I (OR 2.17, 3.77, 2.65, 95% CI 1.02-4.61, 1.64-8.44, 1.75-9.20, respectively). This association was slightly stronger in model II (OR 3.72, 4.76, 3.26, 95% CI 1.49-9.30, 2.00-11.34, 1.55-6.85, respectively). The highest tertile of slope/FT ratio was associated with Y20 and Y25 MetS prevalence in model I (OR 2.10, 1.68, 95% CI 1.03-4.26, 0.86-3.31 respectively). This association was slightly stronger in model II (OR 2.32, 2.13, 95% CI 1.09-4.95, 1.03-4.41 respectively). Conclusions: Findings suggest that some indicators of chronic stress are cross-sectionally associated with MetS in women.
Comparison of Outcomes After Transcatheter vs Surgical Aortic Valve Replacement Among Patients at Intermediate Operative Risk With a History of Coronary Artery Bypass Graft Surgery
Authors: Michael J. Reardon, Robin H. Heijmen, Nicolas M. Van Mieghem, Mathew R. Williams, Steven J. Yakubov, Daniel Watson, Neal S. Kleiman, John Conte, Atul Chawla, David Hockmuth, George Petrossian, Newell Robinson, A. Pieter Kappetein, Shuzhen Li, Jeffrey J. Popma
Journal: JAMA Cardiology (2019)

Surgical aortic valve replacement (SAVR) has increased risk for patients with aortic stenosis (AS) and a history of coronary artery bypass graft (CABG) surgery. Transcatheter aortic valve replacement (TAVR) may be an alternative.To compare TAVR with SAVR outcomes in patients at intermediate operative risk with prior CABG surgery.In this post hoc analysis of the Surgical Replacement and Transcatheter Aortic Valve Implantation (SURTAVI) noninferiority randomized clinical trial, patients with severe, symptomatic AS at intermediate operative risk were enrolled from 87 centers across the United States, Europe, and Canada from June 2012 to June 2016 and followed-up with up to July 2017. Those with a history of CABG surgery were considered for analysis. Data were analyzed from September to December 2017.A total of 1746 patients were enrolled and randomized 1:1 to self-expanding TAVR or SAVR. An implant was attempted in 1660 patients, of whom 273 had prior CABG surgery, including 136 who underwent attempted TAVR and 137 who underwent attempted SAVR.The primary outcome was all-cause mortality or disabling stroke at 1-year follow-up. Efficacy outcomes included quality of life, measured using the Kansas City Cardiomyopathy Questionnaire at 30 days, 6 months, and 1 year, and distance walked in 6 minutes, measured using the 6-minute walk test at 30 days and 1 year.Of the 136 patients in the TAVR cohort, 111 (81.6%) were male, and the mean (SD) age was 76.9 (6.5) years; of the 137 in the SAVR cohort, 117 (85.4%) were male, and the mean (SD) age was 76.6 (6.5) years. The mean (SD) Society of Thoracic Surgeons Predicted Risk of Mortality score was 5.0% (1.6%) in the TAVR cohort and 5.2% (1.7%) in the SAVR cohort. All-cause mortality or disabling stroke at 1-year follow-up was 8.9% (95% CI, 5.2-15.2) in the TAVR cohort and 6.7% (95% CI, 3.5-12.8) in the SAVR cohort (log-rank P = .53). Compared with patients receiving SAVR, the mean (SD) Kansas City Cardiomyopathy Questionnaire summary score was significantly better among patients receiving TAVR at 30 days (81.4 [19.2] vs 69.7 [22.6]; P < .001); treatments were similar at 1 year (85.7 [14.6] vs 82.8 [18.4]; P = .19). Compared with patients in the SAVR cohort, those in the TAVR cohort showed greater mean (SD) improvement in distance walked at 1 year (48.3 [120.6] m vs 16.8 [88.7] m; P = .04).Both TAVR and SAVR were safe for intermediate-risk patients with AS and prior CABG surgery. The transcatheter approach facilitated faster improvement in quality of life and better exercise capacity at 1-year follow-up.ClinicalTrials.gov identifier: NCT01586910.
AB0898 HIV AND RHEUMATOLOGICAL DISEASES. MISDIAGNOSIS OR CONSEQUENCE!
Authors: Fatma Fayed, Mai Morsy, Marwa Elkhalifa
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Human immunodeficiency virus (HIV) infection is pandemic nowadays, more than 35 million people are infected with HIV, with two-thirds being resident in Africa.<sup>(1)</sup> The incidence of rheumatic manifestations in HIV infection was reported in about 4 to 71.3% cases in different studies depending on the stage of the disease and musculoskeletal involvements.<sup>(2,3)</sup> <h3>Objectives</h3> The aim of these study to scope the light on HIV associated rheumatic syndromes. Rheumatic disease were a misdiagnosis or not? <h3>Methods</h3> Cross sectional study of patients admitted to rheumatology unit in Alexandria University with a previous diagnosis of autoimmune rheumatic diseases, resistant to treatment, were screened for HIV. <h3>Results</h3> Three patients found to be HIV positive with low CD4+ less than 200 cells mm<sup>3</sup> among 130 screened patients. Two patients were diagnosed as behcet disease due to recurrent oral and genital ulcers. The first one, also had recurrent skin infections associated with bilateral anterior and posterior uveitis. The second one admitted by recurrent oral and genital ulcerations associated with severe oral candidiasis, arthritis, erythema nodsum and positive pethargy test. The third one diagnosed as peripheral spondyloarthritis admitted with low-grade fever, palmoplantar psoriasis as well as acute extensive anterior and posterior uveitis in left eye and chronic anterior and posterior uveitis in right eye with CMV positive. <h3>Conclusion</h3> HIV infection might be misdiagnosed as a rheumatic disease. It is important to screen patients with inflammatory autoimmune rheumatic manifestations for HIV infection for its implications in the diagnosis and management. <h3>References</h3> [1] Global AIDS Update 2016. Geneva, Switzerland: Joint United Nations Programme on HIV/AIDS. Accessed August 5, 2018. [2] Calabrese LH. Human immunodeficiency virus (HIV) infection and arthritis. Rheum Dis Clin North Am. 1993;19:477–88. [3] Fox C, Walker-Bone K. Evolving spectrum of HIV-associated rheumatic syndromes. Best Practice &amp; Research Clinical Rheumatology. 2015Apr1;29(2):244-58. <h3>Disclosure of Interests</h3> None declared
LncRNA AY promotes hepatocellular carcinoma metastasis by stimulating <i>ITGAV</i> transcription
Authors: Chun Lan Kang, Bing Qi, Qian Qian Cai, Li Sheng Fu, Ying Yang, Chang Tang, Ping Zhu, Qi Wen Chen, Jing Pan, Mei Hua Chen, Xing Zhong Wu
Journal: Theranostics (2019)

Rationale: Tumor metastasis is the main cause for cancer-related death. However, the driving molecules of metastasis remain largely unknown. Here, we aim to identify long non-coding RNAs (lncRNAs) critical for human hepatocellular carcinoma (HCC) metastasis. Methods: Microarrays were used to screen a comprehensive set of lncRNAs with differential expression profiles in sulfatide-treated cells. Mass spectrometry, protein arrays, and RNA pull-down experiments were used to identify proteins that interacted with lncRNA. Epigenetic analysis was used to study lncRNA-mediated regulation mechanisms. Results: We identified lncRNA AY927503 (AY) as a metastasis-associated molecule that was highly expressed in human hepatocellular carcinoma (HCC) and correlated with metastatic events and poor prognosis in patients with HCC. AY promoted HCC cell migration, stemness, 5-fluorouracil resistance, and metastasis in mice. However, knockdown of integrin αV (ITGAV) abolished AY-stimulated migration, cell viability in HCC cells or tube formation. AY strongly promoted ITGAV transcription and αVβ3 expression by interacting with the ITGAV promoter specifically and stimulating its activity. AY was identified to interact with histone 1FX (H1FX), but deletion of the central domain of AY (AY∆371-522) abolished H1FX binding and ITGAV promoter stimulation. AY significantly enriched H3K4Me3 and acH3K9/14 but reduced H3K27Me3 and H1FX occupancy on the ITGAV promoter, which remodeled chromatin structures for RNA polymerase II recruitment. Knockdown of H1FX abrogated ITGAV transcription stimulated by AY. Conclusions: Our findings suggested that lncRNA AY promoted HCC metastasis via induction of chromatin modification for ITGAV transcription as a pioneer factor and was a potential molecular signature for metastasis or poor prognosis in patients with HCC.
SAT0058 DEFICIENT DNA DAMAGE RESPONSE AND REPAIR IN ACTIVE RHEUMATOID ARTHRITIS AND THE EFFECT OF TREATMENT
Authors: Maria Pappa, Nikolaos Vlachogiannis, Alexandra Argyriou, Vassilis L. Souliotis, Petros Sfikakis
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Increased endogenous DNA damage poses a serious threat to cell health, since it may lead to mutagenesis, genomic instability and cellular apoptosis. DNA damage accumulation in immune cells occurs in patients with chronic inflammatory diseases, however; little is known on the types and prevalence of endogenous DNA damage in patients with Rheumatoid arthritis (RA). <h3>Objectives:</h3> To study DNA damage response and repair network in patients with active RA and to test the hypothesis that anti-rheumatic treatment influences this network. <h3>Methods:</h3> Peripheral blood mononuclear cells were isolated from 15 patients with active RA and 65 apparently healthy controls; 8 patients were re-examined after 12-week treatment. Endogenous DNA damage was determined using alkaline comet assay. Specific markers for single-strand DNA breaks (SSBs; RPA32) and double-strand DNA breaks (DSBs; γH2Ax, 53BP1) were measured using western-blot. Formation of DNA damage was assessed by oxidative stress and abasic DNA sites measurements. Chromatin organization and the two subpathways of the fundamental nucleotide excision repair mechanism, namely, transcription-coupled repair (TCR) and global genome repair (GGR), were assessed along the N-ras gene. <h3>Results:</h3> A 3-fold increase of endogenous DNA damage levels (Olive Tail Moment reflecting both SSBs and DSBs) was evident in active RA [mean±SD; 12.8±7.5 versus 4.5±2.4, p&lt;0.001), as well as induction of RPA32, γH2Ax and 53BP1, higher oxidative stress levels and increased abasic sites, compared to controls. While TCR capacity was preserved, GGR capacity was deficient in all active RA patients. Moreover, a more condensed chromatin structure was found in active RA compared to controls. Following treatment, chromatin structure loosened, GGR capacity was restored, oxidative stress and abasic sites decreased and levels of endogenous DNA damage reached control values in all patients. <h3>Conclusion:</h3> Deregulated chromatin organization, deficient DNA repair capacity and augmented formation of DNA damage contribute to the accumulation of endogenous DNA damage in patients with active RA and are reversible after treatment. Additional studies to better understand the negative impact of DNA endogenous damage accumulation may create new therapeutic opportunities for patients with RA. <h3>Disclosure of Interests:</h3> None declared
New WHO prevalence estimates of mental disorders in conflict settings: a systematic review and meta-analysis
Authors: Fiona Charlson, Mark van Ommeren, Abraham Flaxman, Joseph Cornett, Harvey Whiteford, Shekhar Saxena
Journal: The Lancet (2019)

Existing WHO estimates of the prevalence of mental disorders in emergency settings are more than a decade old and do not reflect modern methods to gather existing data and derive estimates. We sought to update WHO estimates for the prevalence of mental disorders in conflict-affected settings and calculate the burden per 1000 population.In this systematic review and meta-analysis, we updated a previous systematic review by searching MEDLINE (PubMed), PsycINFO, and Embase for studies published between Jan 1, 2000, and Aug 9, 2017, on the prevalence of depression, anxiety disorder, post-traumatic stress disorder, bipolar disorder, and schizophrenia. We also searched the grey literature, such as government reports, conference proceedings, and dissertations, to source additional data, and we searched datasets from existing literature reviews of the global prevalence of depression and anxiety and reference lists from the studies that were identified. We applied the Guidelines for Accurate and Transparent Health Estimates Reporting and used Bayesian meta-regression techniques that adjust for predictors of mental disorders to calculate new point prevalence estimates with 95% uncertainty intervals (UIs) in settings that had experienced conflict less than 10 years previously.We estimated that the prevalence of mental disorders (depression, anxiety, post-traumatic stress disorder, bipolar disorder, and schizophrenia) was 22·1% (95% UI 18·8-25·7) at any point in time in the conflict-affected populations assessed. The mean comorbidity-adjusted, age-standardised point prevalence was 13·0% (95% UI 10·3-16·2) for mild forms of depression, anxiety, and post-traumatic stress disorder and 4·0% (95% UI 2·9-5·5) for moderate forms. The mean comorbidity-adjusted, age-standardised point prevalence for severe disorders (schizophrenia, bipolar disorder, severe depression, severe anxiety, and severe post-traumatic stress disorder) was 5·1% (95% UI 4·0-6·5). As only two studies provided epidemiological data for psychosis in conflict-affected populations, existing Global Burden of Disease Study estimates for schizophrenia and bipolar disorder were applied in these estimates for conflict-affected populations.The burden of mental disorders is high in conflict-affected populations. Given the large numbers of people in need and the humanitarian imperative to reduce suffering, there is an urgent need to implement scalable mental health interventions to address this burden.WHO; Queensland Department of Health, Australia; and Bill & Melinda Gates Foundation.
Abstract 19971: Myocardial Blood Flow and Coronary Flow Reserve by 82Rubidium Cardiac Positron Tomography: Validation versus Coronary Angiography
Authors: Andrew Van Tosh, Tracy Faber, John Votow, John Anderson, Nathaniel Reichek, Kenneth J Nichols
Journal: Circulation (2010)

Objective: Absolute myocardial blood flow (MBF) and coronary flow reserve (CFR = stress MBF/rest MBF) can be quantified by analysis of dynamic PET/CT 82Rb (PET) flow data. This study compares a met...
Marshall Marinker: academic general practitioner who laid the foundations of modern general practice
Authors: Roger Jones
Journal: BMJ (2019)

Shortly before his death, Marshall Marinker spoke at an event at the Royal College of General Practitioners to honour the memory of Michael Balint, the great Hungarian psychoanalyst. The event included the unveiling of a plaque on the house in Regent’s Park, London, where Balint had lived and worked. Over 50 years earlier Marshall, then practising as a GP in Essex, had applied to join Balint’s research group and was interviewed there, at length. Balint had put his arm round Marshall’s shoulder and told him that he was accepted: “You will love the work. After all, you’re a little bit crazy.”

The contribution that Marshall made by bringing Balint’s ideas into mainstream general practice—illuminating, analysing, and valuing the central importance of the doctor-patient relationship—cannot be overstated. It was a crucial theme in the landmark publication in 1972 of The Future General Practitioner: Learning and Teaching , written by Marshall and five other giants of general practice (Pat Byrne, Paul Freeling, Conrad Harris, John Horder, and Donald Irvine). The book set the agenda for the conduct, teaching, and assessment of general practice for decades. In Marshall’s words, it defined the discipline.

Balint was one of the three men who Marshall says shaped his intellectual life. The second was his father, Izydor, born in Warsaw …
FRI0730-HPR CAROTID ATHEROSCLEROSIS AND CARDIOVASCULAR RISK FACTORS IN FEMALES WITH SYSTEMIC LUPUS ERYTHEMATOSUS
Authors: Oksana Sirenko, Olexandr Kuryata, Tetyana Lysunets
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Pts with systemic lupus erythematosus (SLE) have an increased risk for cardiovascular diseases (CVD) that cannot be explained by traditional risk factors only. Its relevant to search novel cardiovascular risk markers in those pts. <h3>Objectives</h3> We aimed to evaluate carotid atherosclerosis presence in females with SLE and its relationship with traditional and nontraditional cardiovascular risk factors. <h3>Methods</h3> 52 females with low-activity SLE (the median age – 48.2 [41.8; 52.9] years, the median duration of SLE 89.4 [68.9; 101.5] month) without verificated coronary artery disease were enrolled. Control group included 30 pts without SLE compared by risk factors profile. The cardiovascular risk was calculated using SCORE. The total cholesterol (TC), lipoproteins, triglycerides (TG) were measured in the blood. Carotid ultrasound, endothelial-dependent flow mediated vasodilatation (EDVD) by D. Celermajer method were performed. In all pts was calculated body mass index (BMI) and measured blood pressure (BP). All pts received steroid therapy. <h3>Results</h3> High levels of TC, LDL and TG were in 55.8%, 61.5% and 25% of pts with SLE (the median levels 5.9 [5.2; 6.4] mmol/l, 4.1 [3.7; 4.6] mmol/l and 1.8 [1.3; 2.4] mmol/l respectively). The obesity and hypertension were estimated in 51.9% and 63.5% respectively (median BMI – 31.6 [28.4; 33.2] kg/m<sup>2</sup>, median systolic BP – 154,2 [138.4; 162.3] mm Hg, median diastolic BP – 90.2 [82.4; 93.7] mm Hg). EDVD was impaired in 32.6% pts with SLE and 16.7% control pts (p&lt;0.05). Carotid atherosclerosis was established in 41 (78.8%) pts with SLE and 48 (54%) control group pts (p&lt;0.05). The majority of pts with SLE have stable carotid atherosclerotic plaques - 32 (61.5%), unstable plaques - 6 (11.5%) pts, in control group – 10 (33.3%) and 2 (6.7%) pts respectively. In the same time the median cardiovascular level matched by SCORE was 2.1 [1.5; 2.9]% in females with SLE, in control group - 1.8 [1.3; 2.5]% (p&gt;0.05). The presence of carotid atherosclerotic plaques in females with low-activity SLE was associated with endothelial dysfunction (OR=2.5, p=0.002), obesity (OR=1.5, p=0.004), duration of steroid therapy (OR=2.8, p=0.0005). <h3>Conclusion</h3> Females with low-activity SLE and moderate cardiovascular risk level are characterized by high frequency of carotid atherosclerosis. The carotid ultrasound may be useful additional tool for the evaluating of cardiovascular risk in these patients. <h3>Disclosure of Interests</h3> None declared
SP0023 INTRODUCTORY TALK ON CRYSTAL ANALYSIS
Authors: Anne-Kathrin Tausche
Journal: Annals of the Rheumatic Diseases (2019)

<h3></h3> Rheumatologists are used to do the arthrocentesis to diagnose (and treat) patients with joint effusions. Crystal arthropathies are the most common inflammatory joint diseases. So the prompt detection of (micro-) crystals in joint fluid by microscopic analysis is of outstanding importance to make the right diagnosis of the very common disease gout or CPPD-arthritis (1). Since many years the EULAR facilitates practical courses in microscopy of crystals to start the training of rheumatologists in that helpful technique. During the practical skill course the trainee will be shown how to properly prepare are slide of SF, analyze the preparation with ordinary light, simple and compensated microscope and learn to discriminate urate from CPPD-crystals<sup>2,3</sup>. <h3>References:</h3> [1] Zhang W, et al.; EULAR Standing Committee for International Clinical Studies Including Therapeutics. EULAR evidence based recommendations for gout. Part I: Diagnosis. Report of a task force of the Standing Committee for International Clinical Studies Including Therapeutics (ESCISIT). Ann Rheum Dis. 2006 Oct;65(10):1301-11. [2] Pascual E, et al. The ordinary light microscope: an appropriate tool for the detection and identification of crystals in synovial fluid. Ann Rheum Dis 1989; 48:983– 5. [3] Tausche AK, et al. A 3-day delay in synovial fluid crystal identification did not hinder the reliable detection of monosodium urate and calcium pyrophosphate crystals. J Clin Rheumatol 2013. <h3>Disclosure of Interests:</h3> None declared
Elevated TyG Index Predicts Progression of Coronary Artery Calcification
Authors: Kahui Park, Chul Woo Ahn, Sang Bae Lee, Shinae Kang, Ji Sun Nam, Byoung Kwon Lee, Jung Hye Kim, Jong Suk Park
Journal: Diabetes Care (2019)

OBJECTIVE To investigate the triglyceride-glucose (TyG) index association with coronary artery calcification (CAC) progression in adult Koreans. RESEARCH DESIGN AND METHODS Various cardiovascular risk factors and anthropometric profiles were assessed in 1,175 subjects who previously had a CAC evaluation at least twice by multidetector computed tomography in a health care center. The TyG index was determined using ln(fasting triglycerides [mg/dL] × fasting glucose [mg/dL]/2). The CAC progression was defined as either incident CAC in a CAC-free population at baseline or an increase of ≥2.5 units between the square roots of the baseline and follow-up coronary artery calcium scores (CACSs) of subjects with detectable CAC at baseline. RESULTS CAC progression was seen in 312 subjects (27%) during 4.2 years follow-up. On the basis of the TyG index, subjects were stratified into three groups. Follow-up CACS and incidence of CAC progression were markedly elevated with rising TyG index tertile. Logistic regression analysis adjusted for various risk factors revealed an odds ratio for CAC progression of 1.82 (95% CI 1.20–2.77; P ≤ 0.01) when the highest and lowest TyG index tertiles were compared. CONCLUSIONS The TyG index is an independent predictor of CAC progression.