tbuckley/cabot-search huggingface dataset:
Abstract MP02: Urinary Level of Trimethylamine-N-Oxide Predicts an Increased Risk of Coronary Heart Disease Among Urban Chinese Adults
Authors: Danxia Yu, Xiao-Ou Shu, Emilio Rivera, Xianglan Zhang, Qiuyin Cai, Marion Calcutt, Yong-Bing Xiang, Honglan Li, Yu-Tang Gao, Thomas Wang, Wei Zheng
Journal: Circulation (2019)

Introduction: Trimethylamine-N-oxide (TMAO), a diet-derived, gut microbial-host co-metabolite, has been associated with adverse cardiovascular outcomes in patient populations. However, the evidence is lacking from prospective studies conducted in general populations and in non-Western populations. Hypothesis: TMAO level is associated with risk of coronary heart disease (CHD) in general populations. Methods: We examined associations of urinary TMAO and its precursors (i.e., choline, betaine, and carnitine) with risk of CHD in a case-control study nested within two prospective cohorts of Chinese adults, including 275 incident CHD cases and 275 individually matched controls. Results: Urinary TMAO, but not its precursors, was associated with risk of CHD. Odds ratio (OR, 95% CI) for the highest vs. lowest quartiles of TMAO was 1.91 (1.08-3.35; p-trend=0.008) after adjusting for CHD risk factors including obesity, diet, lifestyles, and metabolic diseases and 1.75 (0.96-3.18; p-trend=0.03) after further adjusting for potential confounders/mediators including central obesity, dyslipidemia, low-grade inflammation, and intakes of seafood and deep-fried meat/fish, which were associated with TMAO level in our study. OR was 1.30 (1.03-1.63) per standard deviation increase in log-TMAO in the fully-adjusted model. History of diabetes modified the TMAO-CHD association. A high TMAO level (≥ vs. &lt;median) showed ORs of 6.21 (1.64-23.6) and 1.56 (1.00-2.43) among diabetic and non-diabetic participants, respectively (p-interaction=0.02). History of diabetes also modified the associations of choline, betaine, and carnitine with risk of CHD with significant positive associations being found among diabetics but null associations among total and non-diabetic participants. Conclusions: Our study suggests that TMAO may play a role in the development of CHD, highlighting the importance of diet-gut microbiota-host interplay in cardiometabolic health.
Light Physical Activity and Incident Coronary Heart Disease and Cardiovascular Disease Among Older Women—A Call for Action
Authors: Gregory W. Heath
Journal: JAMA Network Open (2019)

Andrea Z. LaCroix, PhD, MPH; John Bellettiere, MA, MPH, PhD; Eileen Rillamas-Sun, PhD, MPH; Chongzhi Di, PhD; Kelly R. Evenson, PhD, MS; Cora E. Lewis, MD, MSPH; David M. Buchner, MD, MPH; Marcia L. Stefanick, PhD; I-Min Lee, MD, ScD; Dori E. Rosenberg, PhD, MPH; Michael J. LaMonte, PhD, MPH; for the Women’s Health Initiative (WHI)
The Value of an Extensive Transrectal Repeat Biopsy with Anterior Sampling in Men on Active Surveillance for Low-risk Prostate Cancer: A Comparison from the Randomised Study of Active Monitoring in Sweden (SAMS)
Authors: Ola Bratt, Erik Holmberg, Ove Andrén, Stefan Carlsson, Linda Drevin, Eva Johansson, Andreas Josefsson, Maria Nyberg, Jonas Sandberg, Pär Stattin, David Robinsson
Journal: European Urology (2019)
Association of Leisure-Time Physical Activity Across the Adult Life Course With All-Cause and Cause-Specific Mortality
Authors: Pedro F. Saint-Maurice, Diarmuid Coughlan, Scott P. Kelly, Sarah K. Keadle, Michael B. Cook, Susan A. Carlson, Janet E. Fulton, Charles E. Matthews
Journal: JAMA Network Open (2019)

<h3>Importance</h3> Although the benefits of leisure-time physical activity (LTPA) in middle age are established, the health effects of long-term participation and changes in LTPA between adolescence and middle age have not been documented. <h3>Objective</h3> To determine whether an association exists between LTPA life course patterns and mortality. <h3>Design, Setting, and Participants</h3> This prospective cohort study used data from the National Institutes of Health–AARP (formerly American Association of Retired Persons) Diet and Health Study established in 1995 to 1996. Data analysis was conducted from March 2017 through February 2018. Data were analyzed for 315 059 adult AARP members living in 6 states, namely, California, Florida, Louisiana, New Jersey, North Carolina, or Pennsylvania, or 2 metropolitan areas, Atlanta, Georgia, or Detroit, Michigan. <h3>Exposures</h3> Self-reported LTPA (hours per week) at the baseline interview for ages grouped as 15 to 18, 19 to 29, 35 to 39, and 40 to 61 years. <h3>Main Outcomes and Measures</h3> All-cause, cardiovascular disease (CVD)–related, and cancer-related mortality records available through December 31, 2011. <h3>Results</h3> Of 315 059 participants, 183 451 (58.2%) were men, and the participants were 50 to 71 years of age at enrollment. Ten LTPA trajectories (categorized as maintaining, increasing, and decreasing LTPA across time) were identified, and 71 377 deaths due to all causes, 22 219 deaths due to CVD, and 16 388 deaths due to cancer occurred. Compared with participants who were consistently inactive throughout adulthood, participants who maintained the highest amount of LTPA in each age period were at lower risks for all-cause, CVD-related, and cancer-related mortality. For example, compared with participants who were consistently inactive, maintaining higher amounts of LTPA was associated with lower all-cause (hazard ratio [HR], 0.64; 95% CI, 0.60-0.68), CVD-related (HR, 0.58; 95% CI, 0.53-0.64), and cancer-related (HR, 0.86; 95% CI, 0.77-0.97) mortality. Adults who were less active throughout most of the adult life course but increased LTPA in later adulthood (40-61 years of age) also had lower risk for all-cause (HR, 0.65; 95% CI, 0.62-0.68), CVD-related (HR, 0.57; 95% CI, 0.53-0.61), and cancer-related (HR, 0.84; 95% CI, 0.77-0.92) mortality. <h3>Conclusions and Relevance</h3> Maintaining higher LTPA levels and increasing LTPA in later adulthood were associated with comparable low risk of mortality, suggesting that midlife is not too late to start physical activity. Inactive adults may be encouraged to be more active, whereas young adults who are already active may strive to maintain their activity level as they get older.
Therapy of 4s Chimeric Antigen Receptor T Cells Achieves Long-Term Disease-Free Survival with No Severe CRS or Cres in Patients with Relapsed and Refractory Acute Lymphoblastic Leukemia
Authors: Sanfang Tu, Rui Huang, Lan Deng, Xuan Zhou, Yanjie He, Weijun Zhou, Jilong Yang, Chunyan Yue, Anqin Wu, Meifang Li, Zhenling Guo, Lung-Ji Chang, Yuhua Li
Journal: Blood (2018)
Targeting tumor infiltrating myeloid cells to inhibit tumor progression in pancreatic adenocarcinoma.
Authors: Timothy M. Nywening, Brian Belt, Brian M Cusworth, Roheena Z. Panni, Dominic E. Sanford, William G. Hawkins, David G DeNardo, William E. Gillanders, Peter S. Goedegebuure, David Linehan
Journal: Journal of Clinical Oncology (2015)

e15217 Background: Human pancreas cancer (PC) is associated with a heavy desmoplastic reaction and bone marrow derived cell influx. Recruitment of these cells by the tumor allows for PC to create a favorable microenvironment that is immunosuppressive. Our work demonstrates that the most abundant myeloid cell in PC is granulocytes that express the chemokine receptor CXCR2. This receptor is vital for the trafficking of these cells to the tumor and selective targeting of granulocytes via CXCR2 blockade may lead to clinical benefit in patients with PC. Methods: All human samples were obtained under an IRB approved protocol at Washington University. C57BL/6 mice were injected subcutaneously or orthotopically with syngeneic PC (KCKO) cells & treated with vehicle or inhibitor daily. Tumor size was determined by caliper measurements and weight. Samples were analyzed by FACS, real time PCR, and IHC. Results: Human PC patients have elevated levels of CXCR2+ granulocytes in the peripheral blood (p = 0.02) and PC tumors (p = 0.002) compared to controls. In a murine model, CXCR2 inhibition reduces tumor infiltrating granulocytes (p = 0.02). This was associated with a reduction in tumor growth in both a subcutaneous and orthotopic model (p = 0.03). Our group has previously demonstrated that targeting the monocytic subset of myeloid cells in PC is an effective treatment strategy. Intriguingly, treatment with CCR2 inhibitor alone increased tumor infiltrating granulocytes (p < 0.05) in human PC patients. This finding was recapitulated in a murine model (p = 0.03). However, both therapies in combination resulted in a significant reduction in total tumor myeloid infiltrate (p < 0.01) and was synergistic, with and without chemotherapy (FOLFIRINOX), in regards to tumor reduction compared to either therapy alone (p < 0.01). Conclusions: Human PC has an abundant CXCR2+ granulocytic infiltrate and blockade of CXCR2 may translate to potential clinically useful therapies. Future work exploring therapies directed at targeting both the monocytic and granulocytic myeloid infiltrate may translate into beneficial treatments for patients with PC.
Abstract 020: Age-Associated Rise in Arterial Stiffness Among Hunter-Gatherers
Authors: Mingyu Zhang, Oscar Noya-Alarcon, Monica Contreras, Hirofumi Tanaka, Kunihiro Matsushita, Lawrence J Appel, Maria G Dominguez-Bello, Noel T Mueller
Journal: Circulation (2019)

Introduction: Elevated blood pressure (BP) and arterial stiffness increase cardiovascular disease risk. While BP and arterial stiffness both increase with age in most westernized populations, BP does not rise with age in isolated hunter-gatherers, including Yanomami, where vascular disease is uncommon. No studies have examined if arterial stiffness rises with age among Yanomami or the geographically collocated Yekwana. Methods: In a pilot study conducted in February 2016, we sampled participants from 5 isolated Yanomami-Sanema villages and 3 Yekwana villages in the Upper Caura River Basin, a remote area of the Venezuelan Amazon. Trained staff measured cardio-ankle vascular index (CAVI) per standard protocols, and height and weight to determine body mass index (BMI). We used ANCOVA to compare the age-CAVI association between Yanomami and Yekwana, and further compared associations with data from US whites and Japanese female volunteers for physiological studies with CAVI measurement. Results: 80 participants (63 Yekwana; 17 Yanomami) age 11-72 years had data on CAVI. A 5-year increment in age was associated with a 0.24 unit (95% CI: 0.17, 0.31) and a 0.25 unit (95% CI: 0.14, 0.35) increase in CAVI in Yekwana and Yanomami, respectively (Figure). The age-CAVI slope did not differ in these two populations (p=0.95). Compared to Yanomami and Yekwana individuals, a 5-year increment in age was associated with a significantly greater increase in CAVI in US whites (0.12, 95% CI: 0.04, 0.20) and a non-significantly greater increase in Japanese females (0.08, 95% CI: -0.02, 0.18). Estimates did not markedly change after adjusting for BMI. Conclusion: In Yekwana and Yanomami individuals with hunter-gatherer lifestyles, arterial stiffness increased with age, in a manner similar to Japanese females but less steep than US whites. Taken together with our previous finding that BP does not rise with age in Yanomami and minimally in Yekwana, our preliminary findings suggest that rise in arterial stiffness with age might be independent of BP.
Measuring population ageing: an analysis of the Global Burden of Disease Study 2017
Authors: Angela Y Chang, Vegard F Skirbekk, Stefanos Tyrovolas, Nicholas J Kassebaum, Joseph L Dieleman
Journal: The Lancet Public Health (2019)

BackgroundTraditional metrics for population health ageing tend not to differentiate between extending life expectancy and adding healthy years. A population ageing metric that reflects both longevity and health status, incorporates a comprehensive range of diseases, and allows for comparisons across countries and time is required to understand the progression of ageing and to inform policies.MethodsUsing the Global Burden of Diseases, Injuries, and Risk Factors Study 2017, we developed a metric that reflects age-related morbidity and mortality at the population level. First, we identified a set of age-related diseases, defined as diseases with incidence rates among the adult population increasing quadratically with age, and measured their age-related burden, defined as the sum of disability-adjusted life-years (DALYs) of these diseases among adults. Second, we estimated age-standardised age-related health burden across 195 countries between 1990 and 2017. Using global average 65-year-olds as the reference population, we calculated the equivalent age in terms of age-related disease burden for all countries. Third, we analysed how the changes in age-related burden during the study period relate to different factors with a decomposition analysis. Finally, we describe how countries with similar levels of overall age-related burden experience different onsets of ageing. We represent the uncertainty of our estimates by calculating uncertainty intervals (UI) from 1000 draw-level estimates for each disease, country, year, and age.Findings92 diseases were identified as age related, accounting for 51·3% (95% UI 48·5–53·9) of all global burden among adults in 2017. Across the Socio-demographic Index (SDI), the rate of age-related burden ranged from 137·8 DALYs (128·9–148·3) per 1000 adults in high SDI countries to 265·9 DALYs (251·0–280·1) in low SDI countries. The equivalent age to average 65-year-olds globally spanned from 76·1 years (75·6–76·7) in Japan to 45·6 years (42·6–48·2) in Papua New Guinea. Age-standardised age-related disease rates have decreased over time across all SDI levels and regions between 1990 and 2017, mainly due to decreases in age-related case fatality and disease severity. Even among countries with similar age-standardised death rates, large differences in the onset and patterns of accumulating age-related burden exist.InterpretationThe new metric facilitates the shift from thinking not just about chronological age but the health status and disease severity of ageing populations. Our findings could provide inputs into policymaking by identifying key drivers of variation in the ageing burden and resources required for addressing the burden.FundingNational Institute on Aging of the National Institutes of Health.
Comparing Folic Acid Dosage Strengths to Prevent Reduction in Fetal Size Among Pregnant Women Who Smoked Cigarettes
Authors: Korede K. Yusuf, Hamisu M. Salihu, Roneé Wilson, Alfred Mbah, William Sappenfield, Lindsey M. King, Karen Bruder
Journal: JAMA Pediatrics (2019)

This randomized clinical trial examines the effect of folic acid supplementation in pregnant women who smoke tobacco on infant birth weight, infant status as small for gestational age, and fetal growth restriction.
Angiotensin Receptor Neprilysin Inhibitor for Functional Mitral Regurgitation
Authors: Duk-Hyun Kang, Sung-Ji Park, Sung-Hee Shin, Geu-Ru Hong, Sahmin Lee, Min-Seok Kim, Sung-Cheol Yun, Jong-Min Song, Seung-Woo Park, Jae-Joong Kim
Journal: Circulation (2019)

Background: The morbidity and mortality of patients with functional mitral regurgitation (MR) remain high, but no pharmacological therapy has been proven effective. The hypothesis of this study was that sacubitril/valsartan would be superior to valsartan alone in improving functional MR via dual inhibition of the renin-angiotensin system and neprilysin. Methods: In this double-blind trial, we randomly assigned 118 patients with heart failure with chronic functional MR secondary to left ventricular (LV) dysfunction to receive either sacubitril/valsartan or valsartan, in addition to standard medical therapy for heart failure. The primary end point was the change in effective regurgitant orifice area of functional MR from baseline to the 12-month follow-up. Secondary end points included changes in regurgitant volume, LV end-systolic volume, LV end-diastolic volume, and incomplete mitral leaflet closure area. Results: The decrease in effective regurgitant orifice area was significantly greater in the sacubitril/valsartan group than in the valsartan group (–0.058±0.095 versus –0.018±0.105 cm 2 ; P =0.032) in an intention-to-treat analysis including 117 (99%) patients. Regurgitant volume was also significantly decreased in the sacubitril/valsartan group in comparison with the valsartan group (mean difference, –7.3 mL; 95% CI, –12.6 to –1.9; P =0.009). There were no significant between-group differences regarding the changes in incomplete mitral leaflet closure area and LV volumes, with the exception of LV end-diastolic volume index ( P =0.044). We noted no significant difference in the change of blood pressure between the treatment groups, and 7 patients (12%) in the sacubitril/valsartan group and 9 (16%) in the valsartan group had ≥1 serious adverse events ( P =0.54). Conclusions: Among patients with secondary functional MR, sacubitril/valsartan reduced MR to a greater extent than did valsartan. Our findings suggest that an angiotensin receptor-neprilysin inhibitor might be considered for optimal medical therapy of patients with heart failure and functional MR. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT02687932.
Pembrolizumab (anti-PD-1) Treatment Increases Anti-Tumor Activities of XBP1/CD138/CS1-Specific Cytotoxic T Lymphocytes Against Multiple Myeloma
Authors: Jooeun Bae, Derin Keskin, Yu-Tzu Tai, Teru Hideshima, Nikhil Munshi, Kenneth C Anderson
Journal: Blood (2017)
Decision support needs analysis in newly diagnosed malignant glioma.
Authors: Lara Kunschner Ronan, Camilo E. Fadul, Heather Wishart
Journal: Journal of Clinical Oncology (2015)

2063 Background: Standard treatment pathways exist for malignant glioma, but are largely palliative. Patients face difficult non-curative treatment decisions. Oncologists may misinterpret patient goals or communicate ineffectively the risks/benefits of treatments. Shared Decision Making in which the patients’ values and goals are incorporated into informed consent is ideal in this situation. Methods: Ten patients, caregivers and two treating physicians completed questionnaire-based interviews exploring patient perceptions and understanding of standard of care treatment recommendations in the outpatient clinical setting after receiving a post-surgical diagnosis of malignant glioma. Cognitive dysfunction was evaluated with neurological examination, Trail Making Test and Hopkins Verbal Learning Test. Physical and emotional distress was scored with the FACT-BR and KPS. Results: Ten patients patients participated. Common themes in the patients’ interviews were 1. Fear of “doing nothing”, “chemotherapy”, loss of function/QOL; 2. Misperception of improvement in prognosis with treatment; 3. Loss of autonomy in decision making to physician and family members; 4. Lack of perception of any options; 5. Need for validation in decision making; 6. Lack of perception of dis/advantages of treatment. All patients and caregivers desired more information than was provided. Patients and caregivers who expressed interest in a second opinion did so with the goal of validating what the treating physician was recommending to improve confidence that the patient was making the “right” decision. The physicians emphasized the expected advantages of improved survival. Physicians and caregivers perceived increased patient independence in decision making than did patient. Conclusions: Patients had difficulty formulating and discussing the treatment information provided in a verbal format. While the information given met criteria to form the basis for informed consent and the physicians believed that Shared Decision Making occurred, in fact there was poor understanding of prognosis, advantages and disadvantages of standard of care treatment and patients felt little autonomy. A decision tool to incorporate patients' concerns is under development.
Abstract P395: Examining the Relationship Between Physical Activity Resources and Self-reported Vigorous Physical Activity in a Resource-limited Community: Data From the Washington DC Cardiovascular Health and Needs Assessment
Authors: Joniqua N Ceasar, Tiffany M Powell-Wiley, Marcus Andrews, Colby Ayers, Billy Collins, Steven Langerman, Valerie Mitchell, Kosuke Tamura
Journal: Circulation (2019)

Background: Despite well-documented evidence that one’s neighborhood environment and resource access are associated with cardiovascular (CV) risk, little is known about how physical activity (PA) resource access availability and type are related to vigorous PA (VPA) in urban communities. Methods: Using cross-sectional data from the Washington DC CV Health and Needs Assessment, a sample of 37 black adults living in low-income, limited-resource DC communities, we created one outcome: self-reported VPA hours/week. We used Geographic Information Systems to create three exposure variables: counts of parks, recreation facilities, and private gyms within 800 and 1600-meter (m) line-based road network buffers around homes. We examined the relationship between the three exposures and VPA in models adjusted for demographics (age, sex, and income) and neighborhood factors, including neighborhood deprivation index (NDI), neighborhood environment perception (NEP), or walk score (WS), separately. Results: Participants (mean age=57.65 years) reported a mean VPA hr/wk of 3.46. After separately adjusting for neighborhood factors, greater availability of parks within 800m and 1600m positively associated with VPA (p&lt;0.01) (Table). Positive associations between recreation facilities and VPA were found with 1600m buffer (p&lt;0.05), but not 800m. Private gyms had the weakest relationship with VPA. When considering WS, only the relationship with parks remained significant. Conclusions: Increased availability of parks was positively related to VPA, even after adjusting for NDI, NEP or WS. However, relationships were not as robust for recreation facilities and private gyms, perhaps due to higher likelihood of barriers to use or limited availability in these communities. Our findings suggest that DC public health professionals should consider prioritizing increased availability of PA resources, especially parks, to promote PA and ultimately improve CV health outcomes for residents within limited-resource communities.