tbuckley/cabot-search huggingface dataset:
AB0878 CARDIOVASCULAR GOUT
Authors: Eleanora Mikhnevich, Tatiana Pavlovich
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Gout is characterized by clinical heterogeneity and associated with multicomorbidity. In clinical practice, we can highlight a group of patients suffering from cardiovascular diseases (CVD) and requiring constant medication, in which the gout joins later. <h3>Objectives</h3> To study the group of patients with gout developing on the basis of pre-existing CVD at the gout onset. <h3>Methods</h3> 240 patients from our Center database with confirmed gout were included in our study. Comorbidities were registered before the gout onset, at its appearance. The study group consisted of 140 patients with CVD: hypertension with duration for &gt; 5 years and treated by medication, CHD, atrial fibrillation, CHF and stroke. The comparison group consisted of patients with gout, but without CVD (n=100). <h3>Results</h3> Among patients with pre-existing CVD, the gout debuted later, at the age of 60 (55-65) years (p&lt;0.001). The most frequent comorbidity was HTN – 83.6% (n=117) (OR=7.63; 95%CI 5.33-10.93; χ2 = 48.9, p &lt; 0.001). Diabetes mellitus (OR=4.47; 95%CI 3.65-5.48; F = 0.035, p = 0.005) also dominated in this group. At the same time, BMI ≥ 25 kg/m<sup>2</sup> was prevalent in comparison group (OR=19.46; 95%CI 2.84-133.2; χ2 =15.4, p &lt; 0.001). Alcohol abuse was considerably lower – 37.1% (n=52) (OR=54.72;95%CI 17.87-167.44; χ2 =88.8, p &lt; 0.001), but medication use was higher – diuretics in 16.4% (n=23) (OR=6.36; 95%CI 5.28-7.64; F=0.045, p &lt;0.001) and low-dose aspirin in 35.0% (n=49) of patients (OR=17.41; 95%CI 14.80-20.47; F=0.147, p &lt;0.001). In the study group, the urolithiasis was evidenced more often (OR=4.13; 95%CI 3.42-4.98; χ2 = 12.1, p &lt; 0.001), and the presence of CKD with GFR &lt; 60 ml/min/ 1.73 m<sup>2</sup> was observed in 15.0% (n=21) of patients (F=0.069, p &lt;0.001), but not found in the comparison group. The percentage of patients with metabolic syndrome (3 components according to ATP III) did not differ between the groups (p &gt; 0.05). The number of patients having a concentration of uric acid (UA) in blood &gt; 360 mkmol/l and &gt; 480 mkmol/l was similar in the both study and comparison groups (p &gt; 0.05). At the same time, the cases of UA &gt; 600 mkmol/l were higher in study group by 13.1% (OR=1.86; 95%CI 1.50-2 .38; χ2= 5.94, p = 0.015). <h3>Conclusion</h3> Among our patients, the gout developing on the basis of pre-existing CVD is one of the variant of a debuting gout. The group of patients with so called "cardiovascular gout" is characterized by later gout onset, comorbidities typical for CVD, prevalence of medication (low-dose aspirin, diuretic) and renal mechanisms-triggers of gout. In these patients, the maximal concentration of UA in blood (&gt; 600 mkmol/l) was registered more frequently than in patients with primary gout. <h3>Disclosure of Interests</h3> None declared
THU0669 GESTATIONAL AGE AT BIRTH AND THE RISK OF AUTOIMMUNE DISEASE
Authors: Petteri Hovi, Suvi Alenius, Pieta Näsänen-Gilmore, Mika Gissler, Eero Kajantie
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> A preterm newborn has an immature immune system. Although preterm birth is associated with autoimmune hypothyreosis, it is unclear, whether it also could lead to an overall increased risk of autoimmune disease. <h3>Objective</h3> We assessed whether a shorter gestation increases the risk of special reimbursement for medication for hypothyreosis, rheumatic disease, or ulcerative colitis/Crohn's disease <h3>Design/Methods</h3> A total of 235 622 children were born in Finland from Jan 1987 to Sep 1990, according to the Medical birth register, which provided also gestational age (GA) at birth. Data were linked by help of the personal identity number. A register held by the Social Insurance Institution provided the data on special reimbursements. We calculated cumulative incidences within gestational age groups until December 2014 and tested statistical significance by the chi-squared –test. <h3>Results</h3> At the end of the follow-up, 1354 men and 2200 women had at least one of the specified autoimmune diseases. The cumulative incidences differed by gestational age only regarding a 50% higher incidence for hypothyreosis among all subgroups of preterm wome (P=0.05). No other clear patterns were seen regarding autoimmune diseases among preterm born or early term born subgroups. <h3>Conclusion(s)</h3> Those born preterm develop hypothyreosis more often. However, the two other composite categories of autoimmune diseases were unrelated to gestational age pointing against an overall tendency toward autoimmune disease in preterm born young adults. Cumulative incidence (1/100,000) of four groups of autoimmune diseases 202 Disseminated connective tissue disorders, rheumatoid arthritis and other rheumatic diseases (A04.6, A39.8, A50.5, D76.0, D76.3, H20.1, H30, I33.0, I40.8, J84, K50.9, K51.9, K73.2, K74.3, K83.0, L40.5, M02, M05, M06, M08, M13.9, M30–M35, M45, M46.1, M46.9, M94.1, N03, N04, Q44.2). 104 Hypothyreosis 208 Ulcerative colitis or Crohn's disease <h3>Disclosure of Interests:&nbsp;&nbsp;</h3> Petteri Hovi Consultant for: Pfizer, Paid instructor for: Pfizer, Suvi Alenius: None declared, Pieta Näsänen-Gilmore: None declared, Mika Gissler: None declared, Eero Kajantie: None declared
FRI0281 MACRO AND MICRO-VASCULAR AFFECTION IN CORRELATION TO HLA-B51 IN EGYPTIAN PATIENTSWITH BEHÇET’S DISEASE
Authors: Manal Elmeniawy, Mary Fawzy, Noha Khalil, Mohamed Hussein, Mervat Behiry, Rasmia Elgohary, Reham Abdelghany, Samar Ali, Sahar Kamal, Manal Abdelrazek
Journal: Annals of the Rheumatic Diseases (2019)

Background:  Behcet’s disease is a multisystem inflammatory disorder with unknown etiology.HLA-B51 antigen has been known as a genetic factor associated with B D(1). Vascular involvement in Behcet has been widely described to affect large & medium vessels Vascular involvement in Behcet has been widely described to affect large & medium vessels however, few studies demonstrated micro vascular affection through nailfold capillaroscopy examination (2).  Objectives:  Objective was to highlights HLA role in different clinical presentation of BD, especially the vascular point of view.  Methods:  40 Egyptian Behcet’s disease patients (according to the international study group of Behcet’s disease, 1990), and 30 age and sex matched healthy controls where enrolled in our study. All patients were subjected to history taking and clinical examination. BDCAF, CBC, ESR, CRP, liver function and lipid profile.  Genetic typing HLA B51 by PCR, carotid intima media thickness, Capillriscopy of nail capillary fold and ankle brachial index were done to both patients and controls.  Results:  There was no statistically significant correlation between HLA B51 and systemic manifestations or disease activity or Doppler findings nor capillary parameters and morphology. There was statistically significant relation between HLA B51 and ankle brachial index.  There was statistically significant difference between patients and controls in EDV, RI of the carotid artery, and arterial, venous limb of the capillary, also the capillary lobe and length with lower values in the patients. There was statistically significant difference between patients and controls in carotid intima media thickness with higher values in patients, insipte of the absence of significant difference in lipid.  Conclusion:  HLA B51 didn’t link to different clinical presentation in BD; it is related to peripheral arterial affection only. BD patients had poor arterial compliance and increased arterial stiffness, there is preclinical atherosclerosis in BD not to related to the level of lipid profile.  References:  [1] Marshall SE. bechet’s disease. Best Pract Res Clin Rheumatol. 2004 Jun 1;18(3):291–311.  [2] Hegab S, Al-Mutawa S. Immunopathogenesis of Behcet’s Disease. Clin Immunol. 2000;96(3):174–86.  Disclosure of Interests:  None declared
Milk polar lipids reduce lipid cardiovascular risk factors in overweight postmenopausal women: towards a gut sphingomyelin-cholesterol interplay
Authors: Cécile Vors, Laurie Joumard-Cubizolles, Manon Lecomte, Emmanuel Combe, Lemlih Ouchchane, Jocelyne Drai, Ketsia Raynal, Florent Joffre, Laure Meiller, Mélanie Le Barz, Patrice Gaborit, Aurélie Caille, Monique Sothier, Carla Domingues-Faria, Adeline Blot, Aurélie Wauquier, Emilie Blond, Valérie Sauvinet, Geneviève Gésan-Guiziou, Jean-Pierre Bodin, Philippe Moulin, David Cheillan, Hubert Vidal, Béatrice Morio, Eddy Cotte, Françoise Morel-Laporte, Martine Laville, Annick Bernalier-Donadille, Stéphanie Lambert-Porcheron, Corinne Malpuech-Brugère, Marie-Caroline Michalski
Journal: Gut (2019)

Objective To investigate whether milk polar lipids (PL) impact human intestinal lipid absorption, metabolism, microbiota and associated markers of cardiometabolic health. Design A double-blind, randomised controlled 4-week study involving 58 postmenopausal women was used to assess the chronic effects of milk PL consumption (0, 3 or 5 g-PL/day) on lipid metabolism and gut microbiota. The acute effects of milk PL on intestinal absorption and metabolism of cholesterol were assessed in a randomised controlled crossover study using tracers in ileostomy patients. Results Over 4 weeks, milk PL significantly reduced fasting and postprandial plasma concentrations of cholesterol and surrogate lipid markers of cardiovascular disease risk, including total/high-density lipoprotein-cholesterol and apolipoprotein (Apo)B/ApoA1 ratios. The highest PL dose preferentially induced a decreased number of intestine-derived chylomicron particles. Also, milk PL increased faecal loss of coprostanol, a gut-derived metabolite of cholesterol, but major bacterial populations and faecal short-chain fatty acids were not affected by milk PL, regardless of the dose. Acute ingestion of milk PL by ileostomy patients shows that milk PL decreased cholesterol absorption and increased cholesterol-ileal efflux, which can be explained by the observed co-excretion with milk sphingomyelin in the gut. Conclusion The present data demonstrate for the first time in humans that milk PL can improve the cardiometabolic health by decreasing several lipid cardiovascular markers, notably through a reduced intestinal cholesterol absorption involving specific interactions in the gut, without disturbing the major bacterial phyla of gut microbiota. Trial registration number NCT02099032 and NCT02146339 ; Results.
Abstract 20209: Spontaneous Post Myocardial Infarction Arrhythmia is Potentiated by Calcium Alternans in Type I Diabetic Akita Mice
Authors: Hongwei Jin, Ho-Jin Park, Mark J Aronovitz, Bo Wang, Yali Zhang, Mark Link, Sami Noujaim, Jonas Galper
Journal: Circulation (2014)

Introduction: Myocardial infarction (MI) is the most common cause of mortality in diabetes. Diabetics have been shown to be twice as likely to die suddenly from MI out of hospital compared to non diabetic patients. The mechanism of sudden death in the diabetic population is unclear. Here we use the Akita Type I diabetic mouse as an animal model for the study of post MI ventricular tachycardia arrhythmias (VT) and the role of abnormalities of Ca2+ homeostasis in the pathogenesis of post MI VT. Methods: To determine the effect of MI on the incidence of VT, EKG transmitters were implanted into WT and Akita mice. MIs were generated by permanent ligation of the left coronary artery resulting in infarctions affecting more than 30% of the LV as demonstrated by echocardiographic analysis and TTC staining. Dual calcium-voltage optical mapping was performed on the isolated Langendorf heart after MI. Left ventricular myocytes were isolated for calcium imaging studies. Sarcomere shortening and Ca2+transients were measured by Ionoptix system and Ca2+ sparks by confocal microscopy. Results: Compared to WT, Akita diabetic mice developed a high incidence of non sustained and sustained VT in the first 30h post MI peaking at 18 h. Epicardial optical mapping demonstrated pacing induced: Ca2+ alternans which was most marked in the peri-infarction zone of Akitas and VT also originating in the peri-infarction zone in the Akita mice, but not in WT. Single cardiomyocytes from Akita displayed both contractile and Ca2+ alternans when pacing rate was increased above 3Hz, but none in cells from WT mice. Ca2+ imaging studies were performed to determine whether alterations in Sacroplasmic reticulum(SR) Ca2+ function contributes to Ca2+ alternans. In Akita myocytes, Ca2+ transient decay time( Tau) was significantly increased ( 0.171±0.01s, N=23 ) compared to WT(0.139±0.007s, N=20, P&lt;0.05), The frequency of spontaneous Ca2+ sparks in Akita mocytes increased from 0.043 ± 0.003 sparks/100μm/s (N=23) in the WT to 0.266 ± 0.023 sparks/100μm/s ( P&lt;0.05, N=36). Conclusions: The type 1 diabetic Akita mice demonstrate a high incidence of spontaneous post MI VT associated with pronounced Ca2+ alternans in the peri-infarction zone and abnormalities of Ca2+ homeostasis.
LOSS OF 18Q22.1-Q23 IS SIGNIFICANTLY ASSOCIATED WITH GCB-DLBCL AND FAILURE TO ACHIEVE EFS24
Authors: K. Wenzl, M. Manske, K. Hartert, J. Krull, V. Sarangi, P. Greipp, M. Maurer, A. Feldman, S. Ansell, J. Cerhan, A. Novak
Journal: HemaSphere (2019)
Diabetes, insulin resistance, and metabolic syndrome in women at high risk for breast cancer.
Authors: Valerie Dumais, Shailendra Verma, Benedicte Fontaine-Bisson, Julienne Lumingu, Lise Paquet
Journal: Journal of Clinical Oncology (2013)

e12522 Background: Despite the growing body of research on diabetes (Db), insulin resistance (IR) and metabolic syndrome (MetS) in association with breast cancer, the prevalence of these metabolic conditions has yet to be explored in the high risk population. Delineating the numerous factors that contribute to these women’s risk is key in the management of this vulnerable population, especially when outlining potentially modifiable risk factors. The overall objective of this prospective study was to quantify the prevalence of Db, IR and MetS in women at high risk for breast cancer. Methods: Participants consisted of 100 Caucasian women above the age of 35 with an estimated 5yr risk of ≥1.7%. This criteria was met by (a) BRCA mutation carriers, (b) history of LCIS, (c) history of ADH, (d) history of mantle radiation, or (e) calculated 5yr risk of ≥1.7% using the Gail model. A comprehensive metabolic profile was obtained for each participant based on a questionnaire, fasting blood sample and biophysical measurements. The diagnostic criteria used for Db were those established by the Candian Practice Guidelines. The threshold for IR was a HOMA-IR value of 2.29. The MetS diagnostic criteria were those set by the IDF where 3 of 5 criteria from ↑waist circumference, ↑triglycerides, ↓HDL, HTN and hyperglycemia must be met. Results: The frequency (%) of Db (n=97), IR (n=96) and MetS (n=88) was 5(5), 17(18) and 29(33) respectively. Among the components of MetS, ↑waist circumference had the highest prevalence 60(68.2), followed by HTN 33(37.5), hyperglycemia 27(30.7), ↑triglycerides 23(26.1) and ↓HDL 22(29.7). There was a significant correlation observed between the Gail score and HDL (0.37, p&lt;0.01), as well as systolic Bp (0.28, p&lt;0.01). Conclusions: The prevalence of IR and MetS in this sample of women at high risk for breast cancer is considerably higher than the prevalence of these metabolic conditions in a similar population of average risk women, based on population data. This supports the significance and feasibility of an experimental study comparing the prevalence of IR and MetS in women at high risk and average risk for breast cancer. The prevalence of Db in this sample was comparable to the prevalence described in the general population.
Abstract 2295: Influence of endocrine therapy on the ratio of androgen receptor (AR) to estrogen receptor (ER) positive circulating epithelial tumor cells (CETCs) in breast cancer
Authors: Monika Pizon, Dorothea Schott, Daniel Lux, Ulrich Pachmann, Katharina Pachmann
Journal: Cancer Research (2019)

Abstract Background: The androgen receptor (AR) is expressed in the majority of breast cancers and across the main breast cancer subtypes. Despite the high frequency of AR expression in breast cancer its appraisal remains controversial because its role is complex, dependent on the hormonal milieu. The aim of the current study was to investigate the frequency of AR and ER positive CETCs in breast cancer patients. Material and Methods: The number of vital CETCs was determined from blood of 66 patients suffering from breast cancer and the expression of AR and ER on these cells was investigated using the maintrac method. Results: Numbers of CETCs/ml blood were significantly higher in patients with advanced disease as compared to patients with early stage disease. The fraction of AR positive CETCs was significantly higher than the fraction of ER positive CETCs (90% vs. 50%; p&amp;lt;0.001). Patients with positive lymph nodes had less AR positive CETCs as compared to patients with negative lymph node status. The AR:ER ratio was higher in patients receiving tamoxifen therapy as compared to patients without tamoxifen therapy whereas treatment with aromatase inhibitor had no influence on AR:ER ratio. Conclusions: The ratio of AR to ER positive CETCs, obviously, is influenced by endocrine therapy, more specifically therapy with tamoxifen. Since AR expression seems to be responsible to resistance to endocrine therapy this may provide a new biomarker to select patients who might benefit from combination treatment of ER and AR inhibitors. Note: This abstract was not presented at the meeting. Citation Format: Monika Pizon, Dorothea Schott, Daniel Lux, Ulrich Pachmann, Katharina Pachmann. Influence of endocrine therapy on the ratio of androgen receptor (AR) to estrogen receptor (ER) positive circulating epithelial tumor cells (CETCs) in breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2295.
Abstract 4472: The hippo pathway effector TAZ regulates ferroptosis in renal cell carcinoma
Authors: Wen-Hsuan Yang, Jen-Tsan Chi
Journal: Cancer Research (2019)

Abstract Ferroptosis is a newly appreciated lipid peroxidation-dependent regulated cell death with relevance for many human diseases, which may be a tumor suppression mechanism and may have antitumor potential. Elucidation of the mechanism is therefore important. Here, we reported that ferroptosis sensitivity is significantly influenced by cell density. The effectors of the Hippo pathway, YAP/TAZ, are the molecular sensors of cell density that regulate cell proliferation, survival, and organ size determination. Therefore, we determined the potential role of YAP/TAZ in regulating ferroptosis sensitivities. RCC cell lines and RCC PDX tumor cells mainly express TAZ that undergoes density-dependent nuclear translocation. Importantly, the removal of TAZ confers ferroptosis resistance, while the expression of constructively active TAZ sensitizes cells to ferroptosis. Mechanistically, we found that TAZ knockdown reduced ferroptosis through the repression of its target gene, EMP1. EMP1 affects ferroptosis through the regulation of NOX4 and lipid peroxidation. Collectively, we have shown that the ferroptosis can be regulated by non-genetic factors, such as cell density, through the Hippo pathway and suggest the therapeutic potential of ferroptosis-inducing agent, such as erastin, for TAZ-activated tumors. Citation Format: Wen-Hsuan Yang, Jen-Tsan Chi. The hippo pathway effector TAZ regulates ferroptosis in renal cell carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4472.
Association of Weight Loss Interventions With Changes in Biomarkers of Nonalcoholic Fatty Liver Disease
Authors: Dimitrios A. Koutoukidis, Nerys M. Astbury, Kate E. Tudor, Elizabeth Morris, John A. Henry, Michaela Noreik, Susan A. Jebb, Paul Aveyard
Journal: JAMA Internal Medicine (2019)

Nonalcoholic fatty liver disease (NAFLD) affects about 25% of adults worldwide and is associated with obesity. Weight loss may improve biomarkers of liver disease, but its implications have not been systematically reviewed and quantified.To estimate the association of weight loss interventions with biomarkers of liver disease in NAFLD.MEDLINE, Embase, PsycINFO, CINAHL, Cochrane, and Web of Science databases along with 3 trial registries were searched from inception through January 2019.Randomized clinical trials of people with NAFLD were included if they compared any intervention aiming to reduce weight (behavioral weight loss programs [BWLPs], pharmacotherapy, and surgical procedures) with no or lower-intensity weight loss intervention. The review followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines.Two independent reviewers screened the studies, extracted the data, and assessed the risk of bias using the Cochrane tool. Pooled mean differences or odds ratios (ORs) were obtained from random-effects meta-analyses.Blood, radiologic, and histologic biomarkers of liver disease.Twenty-two studies with 2588 participants (with a mean [SD] age of 45 [14] years and with approximately 66% male) were included. Fifteen studies tested BWLPs, 6 tested pharmacotherapy, and 1 tested a surgical procedure. The median (interquartile range) intervention duration was 6 (3-8) months. Compared with no or lower-intensity weight loss interventions, more-intensive weight loss interventions were statistically significantly associated with greater weight change (-3.61 kg; 95% CI, -5.11 to -2.12; I2 = 95%). Weight loss interventions were statistically significantly associated with improvements in biomarkers, including alanine aminotransferase (-9.81 U/L; 95% CI, -13.12 to -6.50; I2 = 97%), histologically or radiologically measured liver steatosis (standardized mean difference: -1.48; 95% CI, -2.27 to -0.70; I2 = 94%), histologic NAFLD activity score (-0.92; 95% CI, -1.75 to -0.09; I2 = 95%), and presence of nonalcoholic steatohepatitis (OR, 0.14; 95% CI, 0.04-0.49; I2 = 0%). No statistically significant change in histologic liver fibrosis was found (-0.13; 95% CI, -0.54 to 0.27; I2 = 68%). Twelve studies were at high risk of bias in at least 1 domain. In a sensitivity analysis of the 3 trials at low risk of bias, the estimates and precision of most outcomes did not materially change.The trials, despite some heterogeneity, consistently showed evidence of the association between weight loss interventions and improved biomarkers of liver disease in NAFLD in the short to medium term, although evidence on long-term health outcomes was limited. These findings appear to support the need to change the clinical guidelines and to recommend formal weight loss programs for people with NAFLD.
Assessing the effectiveness of artificial intelligence methods for melanoma: A retrospective review
Authors: Xiaoyu Cui, Ran Wei, Lixin Gong, Ruiqun Qi, Zeyin Zhao, Hongduo Chen, Kaixin Song, Amer A.A. Abdulrahman, Yining Wang, John Z.S. Chen, Shuo Chen, Yue Zhao, Xinghua Gao
Journal: Journal of the American Academy of Dermatology (2019)