tbuckley/cabot-search huggingface dataset:
Expected changes in obesity after reformulation to reduce added sugars in beverages: A modeling study
Authors: Ana Basto-Abreu, Ariela Braverman-Bronstein, Dalia Camacho-García-Formentí, Rodrigo Zepeda-Tello, Barry M. Popkin, Juan Rivera-Dommarco, Mauricio Hernández-Ávila, Tonatiuh Barrientos-Gutiérrez
Journal: PLoS Medicine (2018)

Background Several strategies have been proposed to reduce the intake of added sugars in the population. In Mexico, a 10% sugar-sweetened beverages (SSBs) tax was implemented in 2014, and the implementation of other nutritional policies, such as product reformulation to reduce added sugars, is under discussion. WHO recommends that all individuals consume less than 10% of their total energy intake (TEI) from added sugars. We propose gradually reducing added sugars in SSBs to achieve an average 10% consumption of added sugars in the Mexican population over 10 years and to estimate the expected impact of reformulation in adult body weight and obesity. Methods and findings Baseline consumption for added sugars and SSBs, sex, age, socioeconomic status (SES), height, and weight for Mexican adults were obtained from the 2012 Mexico National Health and Nutrition Survey (ENSANUT). On average, 12.6% of the TEI was contributed by added sugars; we defined a 50% reduction in added sugars in SSBs over 10 years as a reformulation target. Using a dynamic weight change model, sugar reductions were translated into individual expected changes in body weight assuming a 43% caloric compensation and a 2-year lag for the full effect of reformulation to occur. Results were stratified by sex, age, and SES. Twelve years after reformulation, the TEI from added sugars is expected to decrease to 10%, assuming no compensation from added sugars; 44% of the population would still be above WHO recommendations, requiring further sugar reductions to food. Body weight could be reduced by 1.3 kg (95% CI −1.4 to −1.2) in the adult population, and obesity could decrease 3.9 percentage points (pp; −12.5% relative to baseline). Our sensitivity analyses suggest that the impact of the intervention could vary from 0.12 kg after 6 months to 1.52 kg in the long term. Conclusions Reformulation to reduce added sugars in SSBs could produce large reductions in sugar consumption and obesity in the Mexican adult population. This study is limited by the use of a single dietary recall and by data collected in all seasons except summer; still, these limitations should lead to conservative estimates of the reformulation effect. Reformulation success could depend on government enforcement and industry and consumer response, for which further research and evidence are needed.
Abstract 19739: Decreased Resting Coronary Flow and Impaired Endothelial Function in Patients With Vasospastic Angina
Authors: Yuichi Saito, Hideki Kitahara, Takashi Nakayama, Yoshihide Fujimoto, Yoshio Kobayashi
Journal: Circulation (2017)

Introduction: Intracoronary acetylcholine (ACh) provocation test is useful to diagnose vasospastic angina (VSA). Endothelial and vascular smooth muscle dysfunction of epicardial coronary arteries play an important role in the pathogenesis of VSA. However, entire coronary circulation in patients with VSA is not fully understood. Hypothesis: We assessed the hypothesis that patients with VSA have coronary circulation dysfunction. Methods: A total of 25 patients without obstructive coronary artery disease in the left descending coronary artery undergoing ACh provocation test, were prospectively enrolled. Coronary circulation was invasively assessed with a thermodilution method by obtaining coronary flow reserve, index of microcirculatory resistance, and mean transit time (Tmn) at rest and hyperemia in the left descending coronary artery. Endothelial function was evaluated by reactive hyperemia index. The positive diagnosis of ACh provocation test was defined as total or subtotal coronary artery narrowing acco...
Abstract P317: Dietary Carbohydrate Quantity and Quality Measures and Risk of Stroke
Authors: Sally N Adebamowo, Hala B AlEssa, Donna Spiegelman, Kathryn M Rexrode, Walter C Willett
Journal: Circulation (2016)

Background: Dietary carbohydrates with high glycemic index and low in cereal fiber have been associated with increased risk of diabetes, a risk factor for stroke. Few prospective studies have examined the relation between measures of carbohydrate quality and risk of incident stroke. The relation between carbohydrate to fiber ratio and stroke risk remains unknown. Methods: We prospectively examined the associations of dietary carbohydrate quantity and quality measures (total carbohydrate, fiber [total, cereal, fruit and vegetable], glycemic index and load, and carbohydrate/fiber ratio) and risk of incident stroke among 40,689 men in the Health Professionals Follow-up Study, aged 40 to 75 years and free of diagnosed cardiovascular disease and cancer at baseline in 1986. Diet was collected using a validated questionnaire every 4 years. We calculated the hazard ratio of total, ischemic, and hemorrhagic strokes by quintiles of energy-adjusted intake of dietary variables using multivariate Cox proportional hazard models. Multivariate models were adjusted for age, lifestyle (BMI, smoking, alcohol, physical activity, multivitamins and aspirin use), history of diseases (family history of CHD, baseline history of hypertension, diabetes and hypercholesterolemia) and diet (total energy, red meat, magnesium, polyunsaturated fat to saturated fat ratio and trans fat). Results: During 24 years of follow-up, 1,530 total stroke events (including 847 ischemic, 178 hemorrhagic and 505 unspecified types) were documented. In multivariate analyses adjusted for age, lifestyle risk factors, history of diseases and total energy intake, carbohydrate (RR=0.74, 95% CI: 0.61 - 0.91, Ptrend 0.008), cereal fiber (RR=0.77, 95% CI: 0.64 - 0.93, Ptrend 0.003) and glycemic load (RR=0.78, 95% CI: 0.64 - 0.95, Ptrend 0.03) were associated with reduced risk of total stroke, comparing the extreme quintiles. With further adjustment for dietary variables, these associations were attenuated to non-significant levels, carbohydrate (RR=0.84, 95% CI: 0.67 - 1.05, Ptrend 0.20), cereal fiber (RR=0.91, 95% CI: 0.73 - 1.14, Ptrend 0.40) and glycemic load (RR=0.84, 95% CI: 0.68 - 1.05, Ptrend 0.26). Vegetable, fruit and total fiber, glycemic index and carbohydrate to fiber ratio were also not significantly associated with incident stroke risk. The results for total stroke were relatively similar to those for ischemic and hemorrhagic stroke types. Conclusions: Consumption of high quality carbohydrate foods did not appear to confer protection against incident stroke risk among this population of US men.
Primary diffuse large B-cell lymphoma of the stomach: Prognostic factors and outcomes in Indian patients.
Authors: Shirley Christabel Lewis, Siddharth Laskar, Nehal Rishi Khanna, Jayant Sastri, Hari Menon, Sumeet Gujral, Manju Sengar, Tanuja Shet, Uma Bhaskar Dangi, Epari Shridhar, Hasmukh Jain, Mary Ann Muckaden
Journal: Journal of Clinical Oncology (2015)

e19509 Background: To evaluate the prognostic factors and treatment outcome of Indian patients with primary Diffuse Large B-Cell Lymphoma (DLBCL) of the stomach treated at a single institution. Methods: From January 1990 to December 2007, 160 patients with DLBCL of the Stomach were treated. Median age was 49 years, and majority of the patients (69%) were males.23% had a WHO performance status (PS) of 2 or more; 36% presented with stage I, 43% had stage II, and 21% had Stage III-IV disease. On initial endoscopy, 46% (n = 74) had single lesions. As per the international prognostic index (IPI), 59.5% (n = 95) were low risk, 23 % (n = 37) were low intermediate, 13 % (n = 21) were intermediate, and 4.5% (n = 4) were high risk. Treatment comprised of chemotherapy (CTh) alone for 39% (n = 62), Surgery (Sx) and CTh for 22.5% (n = 36), CTh and radiotherapy (RT) for 33% (n = 53), and all three modalities were used in 5.5% (n = 9). Amongst those receiving RT, 37% were treated using 3D-CRT technique and 64.5% received an RT dose of > 40Gy. Results: After a median follow-up of 54 months, the 5-year PFS & OS were 57 % and 68%, respectively. On multivariate analysis; age ≥ 50yrs (HR = 2.17, p = 0.013), WHO PS ≥ 2 (HR = 1.91,p = 0.045) and presence of multiple or diffuse lesions on endoscopy (HR = 2.17,p = 0.020) were found to have a significant negative influence on the OS. The IPI was also found to be a significant prognostic indicator for 5yr-OS: low = 78.5% vs. low-intermediate = 61.4% vs. intermediate = 42.4% vs. high = 28.6%, p < 0.001. Combined modality treatment resulted in a significantly better outcome than CTh alone (5yr-OS: CT+RT = 79.3% vs. Sx+CT = 73.2% vs. Sx+CT+RT = 76.2% vs. CT Alone = 55.5%, p = 0.005). On multivariate analysis, the hazard ratio for death in patients receiving CT alone was 2.31 (p = 0.010). The PFS (p < 0.001) and OS (p = 0.001) rates were significantly better for patients receiving a RT dose of > 40Gy. Conclusions: Age at diagnosis, WHO PS, Hb level, IPI, and the number of lesions in the stomach significantly influenced outcome in patients with primary gastric DLBCL. Combined modality treatment, comprising of CTh & RT (with a RT dose of 45Gy), results in satisfactory outcome in patients with this uncommon neoplasm.
An optical nanoreporter of endolysosomal lipid accumulation reveals enduring effects of diet on hepatic macrophages in vivo
Authors: Thomas V. Galassi, Prakrit V. Jena, Janki Shah, Geyou Ao, Elizabeth Molitor, Yaron Bram, Angela Frankel, Jiwoon Park, Jose Jessurun, Daniel S. Ory, Adriana Haimovitz-Friedman, Daniel Roxbury, Jeetain Mittal, Ming Zheng, Robert E. Schwartz, Daniel A. Heller
Journal: Science Translational Medicine (2018)

A nanoreporter noninvasively detects endolysosomal lipids, revealing that short-term changes in diet have enduring effects on hepatic macrophages.
Donor APOL1 high-risk genotypes are associated with increased risk and inferior prognosis of de novo collapsing glomerulopathy in renal allografts
Authors: Dominick Santoriello, Syed A. Husain, Sacha A. De Serres, Andrew S. Bomback, Russell J. Crew, Elena-Rodica Vasilescu, Geo Serban, Eric S. Campenot, Krzysztof Kiryluk, Sumit Mohan, Gregory A. Hawkins, Pamela J. Hicks, David J. Cohen, Jai Radhakrishnan, Michael B. Stokes, Glen S. Markowitz, Barry I. Freedman, Vivette D. D’Agati, Ibrahim Batal
Journal: Kidney International (2018)
TET2 Deficiency Causes Germinal Center Hyperplasia, Impairs Plasma Cell Differentiation, and Promotes B-cell Lymphomagenesis
Authors: Pilar M. Dominguez, Hussein Ghamlouch, Wojciech Rosikiewicz, Parveen Kumar, Wendy Béguelin, Lorena Fontán, Martín A. Rivas, Patrycja Pawlikowska, Marine Armand, Enguerran Mouly, Miguel Torres-Martin, Ashley S. Doane, María T. Calvo Fernandez, Matt Durant, Veronique Della-Valle, Matt Teater, Luisa Cimmino, Nathalie Droin, Saber Tadros, Samaneh Motanagh, Alan H. Shih, Mark A. Rubin, Wayne Tam, Iannis Aifantis, Ross L. Levine, Olivier Elemento, Giorgio Inghirami, Michael R. Green, Maria E. Figueroa, Olivier A. Bernard, Said Aoufouchi, Sheng Li, Rita Shaknovich, Ari M. Melnick
Journal: Cancer Discovery (2018)

Abstract TET2 somatic mutations occur in ∼10% of diffuse large B-cell lymphomas (DLBCL) but are of unknown significance. Herein, we show that TET2 is required for the humoral immune response and is a DLBCL tumor suppressor. TET2 loss of function disrupts transit of B cells through germinal centers (GC), causing GC hyperplasia, impaired class switch recombination, blockade of plasma cell differentiation, and a preneoplastic phenotype. TET2 loss was linked to focal loss of enhancer hydroxymethylation and transcriptional repression of genes that mediate GC exit, such as PRDM1. Notably, these enhancers and genes are also repressed in CREBBP-mutant DLBCLs. Accordingly, TET2 mutation in patients yields a CREBBP-mutant gene-expression signature, CREBBP and TET2 mutations are generally mutually exclusive, and hydroxymethylation loss caused by TET2 deficiency impairs enhancer H3K27 acetylation. Hence, TET2 plays a critical role in the GC reaction, and its loss of function results in lymphomagenesis through failure to activate genes linked to GC exit signals. Significance: We show that TET2 is required for exit of the GC, B-cell differentiation, and is a tumor suppressor for mature B cells. Loss of TET2 phenocopies CREBBP somatic mutation. These results advocate for sequencing TET2 in patients with lymphoma and for the testing of epigenetic therapies to treat these tumors. See related commentary by Shingleton and Dave, p. 1515. This article is highlighted in the In This Issue feature, p. 1494
Transcription Factor 7-Like 2 (<i>TCF7L2</i>) Gene Polymorphism and Progression From Single to Multiple Autoantibody Positivity in Individuals at Risk for Type 1 Diabetes
Authors: Maria J. Redondo, Andrea K. Steck, Jay Sosenko, Mark Anderson, Peter Antinozzi, Aaron Michels, John M. Wentworth, Mark A. Atkinson, Alberto Pugliese, Susan Geyer
Journal: Diabetes Care (2018)

The type 2 diabetes-associated alleles at the TCF7L2 locus mark a type 1 diabetes phenotype characterized by single islet autoantibody positivity as well as lower glucose and higher C-peptide measures. Here, we studied whether the TCF7L2 locus influences progression of islet autoimmunity, from single to multiple (≥2) autoantibody positivity, in relatives of patients with type 1 diabetes.We evaluated 244 participants in the Type 1 Diabetes TrialNet Pathway to Prevention study with confirmed single autoantibody positivity at screening and Immunochip single nucleotide polymorphism data (47.5% male; median age 12.8 years, range 1.2-45.9; 90.2% white). We analyzed risk allele frequency at TCF7L2 rs4506565 (in linkage disequilibrium with rs7903146). Altogether, 62.6% participants carried ≥1 risk allele. Univariate and multivariable Cox proportional hazards models and Kaplan-Meier statistical methods were used.During follow-up (median 5.2 years, range 0.2-12.6), 62% of the single autoantibody-positive participants developed multiple autoantibody positivity. In the overall cohort, the TCF7L2 locus did not significantly predict progression to multiple autoantibody positivity. However, among single GAD65 autoantibody-positive participants (n = 158), those who carried ≥1 risk allele had a lower rate of progression to multiple autoantibody positivity (hazard ratio [HR] 0.65, P = 0.033) than those who did not, after adjustment for HLA risk haplotypes and age. Among subjects who were either IA-2 or insulin autoantibody positive only, carrying ≥1 TCF7L2 risk allele was not a significant factor overall, but in overweight or obese participants, it increased the risk of progression to multiple autoantibody positivity (HR 3.02, P = 0.016) even with adjustment for age.The type 2 diabetes-associated TCF7L2 locus influences progression of islet autoimmunity, with differential effects by autoantibody specificity and interaction by obesity/overweight.
Frequency and Associations of Prescription Nonsteroidal Anti-inflammatory Drug Use Among Patients With a Musculoskeletal Disorder and Hypertension, Heart Failure, or Chronic Kidney Disease
Authors: Zachary Bouck, Graham C. Mecredy, Noah M. Ivers, Moumita Barua, Danielle Martin, Peter C. Austin, Joshua Tepper, R. Sacha Bhatia
Journal: JAMA Internal Medicine (2018)

<h3>Importance</h3> International nephrology societies advise against nonsteroidal anti-inflammatory drug (NSAID) use in patients with hypertension, heart failure, or chronic kidney disease (CKD); however, recent studies have not investigated the frequency or associations of use in these patients. <h3>Objectives</h3> To estimate the frequency of and variation in prescription NSAID use among high-risk patients, to identify characteristics associated with prescription NSAID use, and to investigate whether use is associated with short-term, safety-related outcomes. <h3>Design, Setting, and Participants</h3> In this retrospective cohort study, administrative claims databases were linked to create a cohort of primary care visits for a musculoskeletal disorder involving patients 65 years and older with a history of hypertension, heart failure, or CKD between April 1, 2012, and March 31, 2016, in Ontario, Canada. <h3>Exposure</h3> Prescription NSAID use was defined as at least 1 patient-level Ontario Drug Benefit claim for a prescription NSAID dispensing within 7 days after a visit. <h3>Main Outcomes and Measures</h3> Multiple cardiovascular and renal safety-related outcomes were observed between 8 and 37 days after each visit, including cardiac complications (any emergency department visit or hospitalization for cardiovascular disease), renal complications (any hospitalization for hyperkalemia, acute kidney injury, or dialysis), and death. <h3>Results</h3> The study identified 2 415 291 musculoskeletal-related primary care visits by 814 049 older adults (mean [SD] age, 75.3 [4.0] years; 61.1% female) with hypertension, heart failure, or CKD, of which 224 825 (9.3%) were followed by prescription NSAID use. The median physician-level prescribing rate was 11.0% (interquartile range, 6.7%-16.7%) among 7365 primary care physicians. Within a sample of 35 552 matched patient pairs, each consisting of an exposed and nonexposed patient matched on the logit of their propensity score for prescription NSAID use (exposure), the study found similar rates of cardiac complications (288 [0.8%] vs 279 [0.8%]), renal complications (34 [0.1%] vs 33 [0.1%]), and death (27 [0.1%] vs 30 [0.1%]). For cardiovascular and renal-safety related outcomes, there was no difference between exposed patients (308 [0.9%]) and nonexposed patients (300 [0.8%]) (absolute risk reduction, 0.0003; 95% CI, −0.001 to 0.002;<i>P</i> = .74). <h3>Conclusions and Relevance</h3> While prescription NSAID use in primary care was frequent among high-risk patients, with widespread physician-level variation, use was not associated with increased risk of short-term, safety-related outcomes.
Hospital Volumes of Percutaneous Radiofrequency Ablation Associated with its Treatment Outcomes for Patients with Hepatocellular Carcinoma
Authors: Y.-Y. Shao, L.-C. Lu, R.N.C. Kuo, Z.-Z. Lin, Y.-C. Yeh, W.-Y. Shau, C.-H. Hsu, A.-L. Cheng, M.-S. Lai
Journal: Annals of Oncology (2012)
Healthy Homes and Obesogenic Genes in Young Children
Authors: Myles S. Faith, Leonard H. Epstein
Journal: JAMA Pediatrics (2018)

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Abstract 14364: Hemodynamic Evaluation of 30 Y-Graft Fontan Completions
Authors: Phillip M Trusty, Maria Restrepo, Mark A Fogel, Kirk Kanter, Ajit P Yoganathan, Timothy C Slesnick
Journal: Circulation (2015)

Background: Fontan completion, resulting in a total cavopulmonary connection (TCPC), is accomplished using either a traditional baffle or bifurcated Y-graft. The use of Y-grafts was originally hypothesized to provide more even hepatic blood flow distribution to the lungs, a factor related to pulmonary arteriovenous malformations. This study evaluates the hemodynamic performance of the largest Y-graft cohort to date, compares those results with a traditional baffle, and highlights Y-graft cases that exhibit both favorable and poor performance. Methods: Thirty Y-graft and 30 traditional baffle Fontan patients were analyzed. TCPC anatomies and vessel flow waveforms were reconstructed using cardiac magnetic resonance (CMR) images and phase-contrast CMR. Computational fluid dynamic simulations were performed to quantify TCPC power loss, resistance, and hepatic flow distribution (HFD). Comparisons between graft types and subanalysis of favorable versus poor performing Y-grafts were investigated. Results: The TCPC resistance distribution, HFD distribution, and the effect of LPA stenosis on power loss for Y-grafts and traditional baffles are shown in Fig. 1A-1C. TCPC resistance was significantly lower in traditional baffle patients. HFD was similar overall, with median and range of 40 (1-77) and 51 (1-99) for the traditional baffle and Y-graft, but show a discrepancy at extreme values with more unbalanced flow in the Y-graft cohort. Power loss was more sensitive to LPA stenosis in the Y-graft cohort. Prediction of Y-graft HFD is multi-factorial and six representative cases are shown in Fig. 1D. Conclusions: Y-grafts do not inherently provide more balanced HFD than traditional baffles. Traditional baffles are more energetically favorable and less sensitive to PA stenosis. Graft type should be considered on an individual basis as hemodynamic performance is based on a combination of factors, including global flow distribution, PA stenosis and SVC positioning.
Conservative conference: May announces new cancer strategy to boost survival rates
Authors: Gareth Iacobucci
Journal: BMJ (2018)

The prime minister has announced a new cancer strategy for the NHS, aimed at increasing early detection and improving survival rates in the UK.

In her keynote speech to the Conservative Party’s annual conference in Birmingham on 3 October, Theresa May said that the government would lower the age of bowel cancer screening from 60 to 50 and invest in new equipment as part of a “step change” in how cancer is diagnosed.

She told delegates that the investment pledged to coincide with the NHS’s 70th birthday would …
Upendra Devkota: Nepal’s first neurosurgeon
Authors: Terence Hope
Journal: BMJ (2018)

On the morning of 25 April 2015 Nepal was hit by an earthquake measuring 7.8 on the Richter scale, causing the deaths of nearly 9000 people. It was typical of Upendra Devkota that within hours he was able to care for hundreds of people in the grounds of his hospital, giving food and shelter for weeks. The area around his birthplace of Gorka was particularly affected, but within days he had organised a health camp.

When his daughters were asked what they particularly associated with their father, they answered “serving and always trying to do his best.”

Upendra was born into a poor family in the remote area of Gorka, where his father was an Ayurvedic physician. One of six children, he was educated at a new missionary school to which he often returned in later life. There were no roads or electricity. He was always proud of his origins and the fact that, as a good Brahmin, he was required to learn …