tbuckley/cabot-search huggingface dataset:
Abstract MP45: Cardiovascular Health in Early Adulthood Predicts the Development of Coronary Artery Disease: 25 Year Follow Up in Individuals With Type 1 Diabetes From the Pittsburgh Epidemiology of Diabetes Complications Study
Authors: Susan M Devaraj
Journal: Circulation (2019)

Introduction: Coronary artery disease (CAD) is especially burdensome among individuals with type 1 diabetes (TID). The AHA created metrics to monitor cardiovascular health (CVH) to promote primordial prevention. CVH metrics define 3 health behaviors (diet, physical activity, and smoking), and 4 health factors (BMI, total cholesterol, blood pressure and fasting glucose) as ideal, intermediate or poor based on set criteria. These CVH metrics have been shown to be related to cardiovascular outcomes in the general population. The purpose of this research is to describe the prevalence of CVH metrics in young adults with T1D, a group at particularly high risk for CAD , and assess the hypothesis that more favorable metrics protect against future hard CAD outcomes. Methods: Data are from the longitudinal Pittsburgh Epidemiology of Diabetes Complications (EDC) study. CVH metrics are defined by an average of measures taken at first visit and first follow up visit (1986-1990, “baseline”) for participants age ≥20 at study entry without prevalent CAD. CVH metrics were scored according to AHA criteria, with HbA1c in place of fasting glucose. Total CVH score (possible range 0-14) is the sum of subscores for each metric where poor=0, intermediate=1 and ideal=2. Cox proportional hazards models were used to assess the association between baseline CVH and CAD incidence during 25 years of follow-up. Results: Characteristics of the 463 individuals analyzed after exclusions (179 age &lt;20 or prevalent CAD, 15 missing data) are shown in Table 1. No participants achieved ideal status for all 7 CVH metrics. Each unit increase in ideal CVH score was associated with 28% lower risk (95% CI: 0.63-0.82, p&lt;0.01), while each unit increase in total CVH score was associated with 23% lower risk of CAD (95% CI: 0.71-0.84, p&lt;0.01), adjusting for baseline diabetes duration, sex, race, albumin excretion rate, and triglycerides. Conclusions: CVH metric scores appear to be predictive of CAD in adults with T1D, demonstrating the value of promoting ideal CVH for CAD prevention.
Epidemiology and characteristics of gastric cancer in national cancer institute of Panama from the years 2007 to 2011.
Authors: Roberto Garcia
Journal: Journal of Clinical Oncology (2015)

e15007 Background: Gastric cancer showed substantial decrease in mortality in recent years, this propias1 their geographical variations. The lowest rates were observed in Southern and Western Europe, USA, Canada and some countries in Central America, including Mexico, Cuba, Puerto Rico. The highest rates were found Russia, Eastern and Central Europe, Japan, Korea and some countries of Latin America, including Chile, Costa Rica, Colombia and Ecuador. The Gastric cancer represents the fourth most common cancer and the second leading cause of death in worldwide. Methods: Retrospective observational study is performed, features are evaluated from the year 2008-2012, physical files used and / or electronic. Data using the survey form (Appendix) were collected; data were tabulated and analyzed by SPSS version 22.0. Results: 816 new cases of gastric cancer with histopathological review of the national cancer institute, 328 (40%) cases were found to be gastric adenocarcinoma, from the years 2007 to 2011, according to histopathologic subtype were recorded 34.5% were diffuse, 39.9% intestinal, 19 9% indeterminate and marked overexpression of epidermal growth factor receptor 2 (HER-2) 0.3%. 57.9% was recorded in the population between 61-80 years of age ( > 81 years 20.4%), 65.2% were male and 32.9% female; 92.1% of patients were classified into the mestizo ethnic group, 4.0% Caucasian, 2.4% Indian and 1.5% Black. Only blood type 30.5% of patients, 21.3% of registered registered were type B, 4.9% to 2.7% and 0.9% O type AB. Panama city was the major referral center 33.5%, 15.9% Veraguas and Cocle 12.2%. Conclusions: Today in Panama does not have an accurate record for the cancer , this study seeks to resolve certain questions regarding epidemiological behavior of gastric cancer in our country and its impact on decision- desciones for treatment.
Isidore Wolfe Crown
Authors: Barry Crown, Simon Crown
Journal: BMJ (2019)

From 1947 to 1948, Isidore Wolfe Crown was a casualty officer in the Victoria Hospital in Blackpool. From 1948 to 1950 he served as a captain in the Royal Army Medical Corps stationed in Neumunster, Schleswig-Holstein, Germany. After completing his national service, he did assistantships in Colindale in London, Newport in Gwent, and Battersea in London before …
Abstract P104: Impact of Cold Weather on Cardiovascular Diseases in Texas
Authors: Kai Zhang, Tsun-Hsuan Chen
Journal: Circulation (2019)

Background: Cardiovascular disease (CVD) has been estimated to account for nearly 50% of total deaths during cold seasons, and cold weather has been shown to have a significant impact on CVD. More importantly, detrimental health effects of cold were particularly pronounced in regions with mild winter climate. Texas is the second largest state in the U.S. and is associated with varying climates. This study aims to improve the understanding of how cold weather affects CVD-related mortality and morbidity in Texas. Methods: We obtained mortality data (1990-2013) and emergency hospital admissions (EHA) data (2003-2014) from the Texas Department of State Health Services and weather data from the National Climate Data Center. Our analysis included cases diagnosed as cardiovascular disease (CVD, ICD-9 390-429; ICD-10 I01-I52), ischemic heart disease (IHD, ICD-9 410-414; ICD-10 I20-I52), myocardial infarction disease (MI, ICD-9 410; ICD-10 I21, I22) and stroke (ICD-9 430-438; ICD-10 I60-I69). We first applied Poisson regression models to 12 Texas major Metropolitan Areas (MSAs) to estimate cold effects on deaths and hospital admissions related to CVDs. A random effects meta-regression analysis was then used to estimate pooled effects for the entire state. Results: With a 1°C decrease in temperature below a MSA-specific threshold, increased death risks were observed in CVDs (1.8% [95%CI: 1.1%, 2.6%]), stroke (1.2% [95%CI: -0.2%, 2.6%]), IHD 2.5% [95%CI: 1.1%, 4.0%], and MI 4.3% [95%CI: 1.2%, 7.5%]). Estimates of cold effects were lower for EHA risks, and they were 1.1% (95%CI: 0.4%, 1.8%) for CVDs, 2.3% (95%CI: -0.3%, 4.9%) for stroke, 1.7% (95%CI: -0.1%, 3.6%) for IHD, and 0.3% (95%CI: -3.5%, 4.2%) for MI. Conclusion: This is the first multi-city study in the U.S. that examined the effect of cold weather on CVD using both mortality and hospital admission data. Cold weather increases mortality risk significantly but less in EHA risk in Texas, and effects vary geographically. Our findings can provide insights to design better intervention strategies for targeted vulnerable populations towards reducing adverse health effects of cold weather.
Abstract 15021: Optical Coherence Tomography to Evaluate Plaque Burden and Morphology in Patients With Takotsubo Syndrome
Authors: Thomas Stiermaier, Tobias Graf, Christian Möller, Karl-Philipp Rommel, Charlotte Eitel, Gerhard Schuler, Holger Thiele, Steffen Desch, Ingo Eitel
Journal: Circulation (2016)

Introduction: Disrupted atherosclerotic plaques in the left anterior descending coronary artery (LAD) are discussed controversially as a potential pathophysiological mechanism in Takotsubo syndrome (TTS). Therefore, the aim of the present study was to assess plaque burden and morphology by using optical coherence tomography (OCT) in patients with TTS. Methods: A total of 23 consecutive TTS patients were included in this single-center study and underwent OCT imaging of the left main coronary artery and the LAD at acute presentation. All patients fulfilled the established diagnostic criteria for TTS and the diagnosis was confirmed with a multi-modality imaging approach including cardiac magnetic resonance in 16 patients (69.6%). Results: Atherosclerotic plaques located in the LAD or both the LAD and the left main coronary artery were detected in 16 TTS patients (69.6%) with 6 patients exhibiting multiple plaque types. In addition to the predominant fibro-calcific (52.2%) and lipid-rich plaques (30.4%), thin...
Combined Association of Body Mass Index and Alcohol Consumption With Biomarkers for Liver Injury and Incidence of Liver Disease
Authors: Alice R. Carter, Maria-Carolina Borges, Marianne Benn, Anne Tybjærg-Hansen, George Davey Smith, Børge G. Nordestgaard, Debbie A. Lawlor
Journal: JAMA Network Open (2019)

Individually, higher body mass index (BMI) and alcohol consumption increase the risk of liver disease. Evidence of a joint association is mixed; however, previous studies have not used causal inference methods robust to confounding and reverse causation. Understanding any true effect is key to developing effective interventions to reduce liver disease.To investigate the joint association of BMI and alcohol consumption with liver injury biomarkers and incident liver disease using factorial mendelian randomization (MR).A population-based cohort study (Copenhagen General Population Study) recruited a random sample of Copenhagen, Denmark, residents aged 20 years or older of white, Danish descent (N = 98 643) between November 25, 2003, and July 1, 2014. Data were also obtained from ongoing links to national registers, and then analyzed from September 30, 2016, to April 23, 2018.High and low BMI and alcohol consumption categories from baseline-measured or self-reported observational data and genetic variants predicting BMI and alcohol consumption.Plasma biomarkers of liver injury (alanine aminotransferase [ALT] and γ-glutamyltransferase [GGT]) and incident cases of liver disease from hospital records were the outcomes.Of the 98 643 individuals recruited, 91 552 (54 299 [45.2%] women; mean [SD] age, 58 [13.05] years) with no baseline liver disease were included in main analyses. Individuals had a mean (SD) BMI of 26.2 (4.3) and consumed a mean (SD) of 10.6 (10.2) U/wk of alcohol. In factorial MR analyses, considering the high BMI/high alcohol group as the reference, mean circulating ALT and GGT levels were lowest in the low BMI/low alcohol group (ALT: -2.32%; 95% CI, -4.29% to -0.35%, and GGT: -3.56%; 95% CI, -5.88% to -1.24%). Individuals with low BMI/high alcohol use and high BMI/low alcohol use also had lower mean circulating ALT levels (low BMI/high alcohol use: -1.31%; 95% CI, -1.88% to -0.73%, and high BMI/low alcohol use: -0.81%; 95% CI, -2.86% to 1.22%) and GGT levels (low BMI/high alcohol use: -0.91%; 95% CI, -1.60% to -0.22%, and high BMI/low alcohol use: -1.13%; 95% CI, -3.55% to 1.30%) compared with the high BMI/high alcohol use reference group. These patterns were similar in multivariable factorial analyses. For incident liver disease (N = 580), factorial MR results were less conclusive (odds ratio of liver disease vs high BMI/high alcohol group: 1.01; 95% CI, 0.84 to 1.18, for the low BMI/high alcohol group, 1.22; 95% CI, 0.56 to 1.88 for the high BMI/low alcohol group, and 0.99 (95% CI, 0.41 to 1.56 for the low BMI/low alcohol group).Interventions to reduce both BMI and alcohol consumption might reduce population levels of biomarkers of liver injury more than interventions aimed at either BMI or alcohol use alone. However, it is not clear whether this intervention will directly translate to a reduced risk of liver disease.
Abstract MP52: Racial Disparity in Habitual Sleep Pattern Among Adolescents is Modified by Caloric Intake
Authors: Fan He, Huamei Dong, Julio Fernandez-Mendoza, Edward O Bixler, Jiangang Liao, Alexandros N Vgontzas, Duanping Liao
Journal: Circulation (2019)

Introduction: Racial-ethnic minorities have been reported to sleep shorter and have worse sleep quality compared to non-Hispanic whites. Furthermore, nutrition intake has been associated with markers of inadequate habitual sleep. However, the role of nutrition intake on the racial disparity in habitual sleep has been rarely investigated, especially among adolescents. Hypothesis: We hypothesize that nutrition intake modifies the association between race/ethnicity and habitual sleep pattern in adolescents. Methods: We analyzed the data obtained from 421 adolescents who completed the follow-up examination of the Penn State Child Cohort (PSCC) study. We collected actigraphy-measured sleep durations on 7 consecutive nights and computed the intra-individual mean and standard deviation (SD), as measures of habitual sleep duration (HSD) and habitual sleep variability (HSV), respectively. We also measured participants’ daily macro-nutrients intakes, including total calorie, total fat, carbohydrates, and protein, through the Youth/Adolescent Food Frequency Questionnaire. Adjusted mean HSD and HSV among non-Hispanic whites and minorities were computed and compared by using analysis of covariance (ANCOVA), while controlling for age, sex, BMI percentile, total caloric intake, and socioeconomic status. The significance of an interaction between race/ethnicity and nutrition intake was further tested in ANCOVA models to assess the effect modification of nutrition intake on the racial differences in habitual sleep. Results: The mean (SD) age of the study population was 16.7 (2.3) years. The study population consisted of 79.3% non-Hispanic White, 13.0% African American, 4.6% Hispanics, 2.2% Asian, and 0.9% American Indian. After controlling for major covariates, adolescents who were self-identified as racial-ethnic minorities showed significantly shorter HSD (β(SE): 15.9 (6.7) minutes/night, p=0.02) and higher HSV (β(SE): 9.7 (4.8) minutes/night, p=0.04) compared to non-Hispanic whites. More importantly, nutrient intakes played a significant effect modification role in the racial-ethnic difference in HSV. Specifically, racial difference in HSV was significantly more pronounced among adolescents with higher caloric intake, especially from carbohydrates (p for interaction &lt; 0.05). Conclusion: Adolescents belong to racial-ethnic minorities sleep objectively shorter and with greater night-to-night variability than non-Hispanic whites. The racial-ethnic difference in habitual sleep variability is more pronounced among adolescents with high caloric intake, particularly from carbohydrates. If confirmed, these data may suggest that the inter-relationship among habitual sleep duration, sleep variability, and caloric intake may contribute to the disproportionate cardiovascular disease risks among racial-ethnic minorities.
Molecular markers and potential therapeutic targets in non-WNT/non-SHH (group 3 and group 4) medulloblastomas
Authors: Otília Menyhárt, Felice Giangaspero, Balázs Győrffy
Journal: Journal of Hematology & Oncology (2019)

Childhood medulloblastomas (MB) are heterogeneous and are divided into four molecular subgroups. The provisional non-wingless-activated (WNT)/non-sonic hedgehog-activated (SHH) category combining group 3 and group 4 represents over two thirds of all MBs, coupled with the highest rates of metastases and least understood pathology. The molecular era expanded our knowledge about molecular aberrations involved in MB tumorigenesis, and here, we review processes leading to non-WNT/non-SHH MB formations. The heterogeneous group 3 and group 4 MBs frequently harbor rare individual genetic alterations, yet the emerging profiles suggest that infrequent events converge on common, potentially targetable signaling pathways. A mutual theme is the altered epigenetic regulation, and in vitro approaches targeting epigenetic machinery are promising. Growing evidence indicates the presence of an intermediate, mixed signature group along group 3 and group 4, and future clarifications are imperative for concordant classification, as misidentifying patient samples has serious implications for therapy and clinical trials. To subdue the high MB mortality, we need to discern mechanisms of disease spread and recurrence. Current preclinical models do not represent the full scale of group 3 and group 4 heterogeneity: all of existing group 3 cell lines are MYC-amplified and most mouse models resemble MYC-activated MBs. Clinical samples provide a wealth of information about the genetic divergence between primary tumors and metastatic clones, but recurrent MBs are rarely resected. Molecularly stratified treatment options are limited, and targeted therapies are still in preclinical development. Attacking these aggressive tumors at multiple frontiers will be needed to improve stagnant survival rates.
MGMT (0<sup>6</sup>-methylguanine-DNA methyltransferase) promoter hypermethylation in the context of colorectal cancer.
Authors: Elisabeth Luporsi-Gely, Amandine Cadènes, Myriam Bronner, Hélène de Romémont, Dominique Saint Dizier, Ludovic Mansuy, Pierre Lehair, Philippe Jonveaux
Journal: Journal of Clinical Oncology (2015)

e14654 Background: This study reports an incidental finding we observed by studying MLH1 promoter methylation in patients (pts) suspected with Lynch Syndrome by MS-MLPA. In 58% of the cases, MGMT promoter was hypermethylated alone or together with MLH1 promoter in tumor tissues. We also reported 3 cases with a constitutional hypermethylation (HM) of MGMT. Methods: 62 pts who had 1 or 2 cancers were studied: colorectal (CRC) (45 tumors), endometrial (14), caecal (4) or small intestine (2). Among them were 38 women (w) (61.3%) and 24 men (m) (38.7%). MLH1promoter HM was explored in 2 situations: 1 – to assess if patients with microsatellite instability (MSI) should undergo molecular analysis of MMR genes 2 – when MLH1molecular analysis did not show any deleterious mutation. Results: The population was split in 4 groups: 1) no HM (17 pts: 41.2% w , 58.8% m) 2) HM of MLH1alone (8 pts: 87.5% w, 12.5% m) 3) HM of both MLH1 and MGMT (28 Pts: 78.6% w, 21.4% m) 4) HM of MGMTalone (9 Pts: 22.2% w, 77.8% m). All but 5 tumors were MSI-H. The MSS tumors showed a loss of MLH1 protein by immuno-histochemistry. HM of MGMTpromoter was found in 24 w tumors (63% of all w tumors) and in 13 m tumors (54% of all m tumors). However, among 9 tumors showing HM of MGMT promoter alone, we reported 7 m tumors (77.8%) and 2 w tumors (22.2 %). Three patients with MSI-H tumors and loss of expression of MLH1 protein (without MLH1 constitutional mutation) showed somatic and constitutional MGMTpromoter HM. One of them developed a CRC at age 27 with no familial history of CRC, the 2 others developed a CRC at age 44 and 69 (both with familial history of CRC). Conclusions: Previous studies indicate that MGMT promoter HM acts as a defect field, predisposing to the development of CRC. In 58% of our cohort, MGMTpromoter was HM. Concordant with other studies, we showed that more w tumors have MGMT HM than m tumors. But we also observed that more m tumors showed HM of MGMT promoter alone while more w tumors showed both MLH1 and MGMTpromoters HM. We report here 3 pts with no MLH1 mutations showing somatic and constitutional MGMT promoter HM. These incidental findings point out that MGMT analysis could be of interest for patients with familial history of CRC for whom no MMR mutation were identified.
Which Aspirin to Choose?
Authors: Tomaso Gnecchi-Ruscone, Domenico Restifo Pecorella
Journal: JAMA Surgery (2019)

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Abstract P037: Independent and Joint Associations of 25-Hydroxy Vitamin D and Parathyroid Hormone Levels With Cardiometabolic Biomarkers Among American White and Black Postmenopausal Women
Authors: Jin Xia, Wanzhu Tu, JoAnn E Manson, Hongmei Nan, Aladdin H Shadyab, Jennifer W Bea, Ting-Yuan D Cheng, Lifang Hou, Yiqing Song
Journal: Circulation (2019)

Introduction: Despite evidence of racial disparities in independent relationships of 25-hydroxyvitamin D (25[OH]D) and parathyroid hormone (PTH) status with cardiovascular risk, little is known about their joint associations with intermediate cardiovascular biomarkers. Hypothesis We hypothesized that there are White-Black differences in the direction and shape of the associations of total 25(OH)D and PTH with cardiovascular biomarkers of insulin resistance, beta cell function, systemic inflammation, and renal function among postmenopausal women. Methods: A random subcohort of 2,800 American White (n=1,500) and Black (n=1,300) postmenopausal women without cardiovascular disease (CVD) at baseline was selected from the Women’s Health Initiative Observational Study (N=93,676). We assessed plasma total 25(OH)D, PTH, high-sensitive C-reactive protein (hs-CRP), as well as creatinine-based glomerular filtration rate (GFR). Fasting glucose and insulin were measured to derive the homeostasis model assessment of insulin resistance (HOMA-IR) and beta cell function (HOMA-B). Weighted linear regression analyses were performed to assess independent and joint associations after adjusting for age, race/ethnicity, clinical center, education, body mass index, season of blood draw, smoking status, physical activity, alcohol consumption, postmenopausal hormone therapy use, and family history of CVD. Results: Total 25(OH)D levels were inversely associated with HOMA-IR among White women only (5.6% decrease per 1 SD increase in 25[OH]D; P for linear trend = 0.001). This association persisted among White women with PTH ≤65 pg/mL (5.9% decrease per 1 SD increase in 25[OH]D; P for linear trend = 0.001). While there was a linear trend towards higher 25(OH)D levels associated with lower GFR levels among White women with PTH ≤65 pg/mL (P for linear trend = 0.045), we found a non-linear relationship between total 25(OH)D and GFR among Black women with PTH &gt;65 pg/mL (P for non-linearity = 0.001). Conclusions: Higher levels of total 25(OH)D, independently and jointly with PTH, were associated with lower HOMA-IR in White postmenopausal women. The shapes of the associations between total 25(OH)D and GFR markedly differed between White and Black women after accounting for PTH, suggesting potential racial disparities in vitamin D/PTH mechanisms underlying cardiovascular health.