tbuckley/cabot-search huggingface dataset:
Abstract P064: Metabolic Risk Transitions In Obesity With The Incidence Of Heart Failure And Coronary Heart Disease: The Atherosclerosis Risk In Communities (aric) Study
Authors: Yvonne Commodore-Mensah, Sui Zhang, Justin Echouffo Tcheugui, Roberta Florido, Vijay Nambi, Erin D Michos, Wendy S Post, Gary Gerstenblith, Roger S Blumenthal, Christie M Ballantyne, Elizabeth Selvin, Chiadi E Ndumele
Journal: Circulation (2022)

Introduction: Obesity is associated with a varying spectrum of metabolic risk, from the metabolically healthy obesity (MHO) phenotype, to metabolically unhealthy obesity (MUO) with the development of metabolic syndrome (MetS) and diabetes (DM). The longitudinal association of metabolic risk with CVD phenotypes (CHD, HF) has not been well characterized. Hypothesis: Persistent MHO is independently associated with heart failure (HF) but not coronary heart disease (CHD), and regression from MUO to MHO mitigates CVD risk. Methods: We conducted a prospective analysis of 10,011 Visit 4 (1996-98) ARIC participants free of HF and CHD (mean age 63, 21% Black, 56% female). Metabolic risk among those with obesity (BMI ≥ 30 kg/m 2 ) was categorized as MHO (no MetS or DM), MUO (MetS present) and MUO with DM, with same categorizations among those without obesity. We used Cox regression models to estimate associations of cross-categories of metabolic risk status at Visit 2 (1990-92) and Visit 4 with risk of HF and CHD after Visit 4 through 12/21/19. (Reference: persistent metabolically healthy normal weight). Results: Between Visits 2 and 4, 56% of those with MHO transitioned to MUO. There were 2212 HF and 1648 CHD events, median follow-up of 20.5 years. Persistent MHO status was associated with increased risk for HF (HR:1.59, 95% CI: 1.19-2.13) but not CHD (HR: 1.08, 95% CI: 0.74-1.58) (Table). Persistent MUO with DM had the highest risk for HF (HR: 5.30, 95% CI: 4.38-6.41) and CHD (HR: 3.77, 95% CI: 3.00-4.74). Among those with MUO at Visit 2, progression to MUO with DM at Visit 4 was linked to greater risk for HF and CHD, while regression to MHO was associated with an attenuated risk for CVD. Similar patterns were seen for those without obesity (data not shown). Conclusions: Transitions in metabolic risk status are common and associated with divergent patterns of CVD risk. Progression from MHO to MUO and even persistent MHO are linked to HF risk, whereas regression from MUO to MHO may attenuate CVD risk. Primordial prevention of obesity is warranted to stave off HF.
Abstract P172: Association Of Atrial Fibrillation With Severity Of Coronary Artery Disease: The Emory Cardiovascular Biobank (emcab)
Authors: Linzi Li, Zakaria Almuwaqqat, Yi-An Ko, Vinita Subramanya, Arshed A Quyyumi, Alvaro Alonso
Journal: Circulation (2022)

Background: Existing literature suggests that atrial fibrillation (AF) can lead to coronary artery disease (CAD). However, little information exists regarding the association between AF and CAD severity. Methods: We conducted cross-sectional and prospective analyses of 7819 participants in the Emory Cardiovascular Biobank (EmCAB). EmCAB recruits patients undergoing cardiac catheterization at three Emory Healthcare hospitals in the Atlanta area. At enrollment, data on AF history and four CAD severity measurements were collected: presence of ≥70% coronary stenosis, presence of ≥50% coronary stenosis, number of vessels with ≥50% coronary stenosis, and the Gensini score. To minimize the effect of missing covariates, multiple imputation by chained equation (MICE) was employed. In the imputed dataset, linear, logistic, and Poisson models were used to examine the association between the different measurements and AF history. During follow-up, the occurrence of incident MI, fatal MI, and all-cause death were obtained as primary endpoints, and Cox regression models were used to examine the association of AF history with each endpoint. Results: At baseline, the prevalence of AF history was 8.5%. Among patients with and without AF history respectively, the prevalence of ≥50% stenosis was 72% and 76%, and of ≥70% stenosis was 65% and 70%, respectively. AF patients and non-AF patients had similar numbers of vessels with ≥50% stenosis on average (1.7, vs. 1.8) and a median Gensini score (10.0 vs. 10.5). No association was found between AF and the presence of ≥50% and ≥70% stenosis, and numbers of vessels with ≥50% stenosis. AF was associated with 3.32 (95% CI -7.20, 0.57) points lower Gensini score after multivariable adjustment (demographic and clinical factors). In the longitudinal analysis, there was no evidence of an association between AF and nonfatal MI, fatal MI, and any MI. The risk of all-cause mortality among AF patients was 1.66 times (95% CI 1.37, 2.01) that among non-AF patients in the unadjusted model and was strongly attenuated after adjustment for demographic and clinical factors (HR: 1.26, 95% CI 1.03, 1.53). Conclusion: In the EmCAB, AF was associated with all-cause mortality but not with CAD severity.
Abstract P099: Fixed-dose Combination Therapy-based Protocol Compared With Nigeria’S National Hypertension Treatment Protocol: Results Of A Cluster Randomized Trial
Authors: Olutobi Sanuade, Boni Ale, IKECHUKWU ANTHONY ORJI, Tunde Ojo, Grace Shedul, Eugenia Ugwuneji, Nonye Egenti, Kasarachi Omitiran, Rosemary Okoli, Helen Eze, Ada Nwankwo, Lisa Hirschhorn, Aashima Chopra, Jiancheng Ye, Priya Tripathi, Bolanle Banigbe, Namratha Kandula, Mark D Huffman, Dike Ojji
Journal: Circulation (2022)

Abstract Importance: Out of the &gt;1.2 billion adults with elevated blood pressure globally, treatment (42.5%) and control (20.5%) rates are very low, including in Nigeria, the most populous country in Africa. A treatment protocol that includes fixed-dose combination (FDC) therapy may improve hypertension control rates more efficiently and with no increase in adverse events compared with a standard treatment protocol. Objective: To determine the efficacy and safety of a treatment protocol that uses FDC therapy for hypertension control compared with Nigeria’s 2019 National Hypertension Treatment protocol from baseline to 6 months. Design, setting, and participants: Cluster randomized (1:1) trial among 60 primary health centers in Abuja, Nigeria, stratified by median case load and control rate. Eligible patients were adults ( &gt; 18 years) who had a history of hypertension, persistently elevated blood pressure (SBP ≥140 mmHg or DBP ≥90 mmHg),or use of blood pressure lowering medications. Interventions: Sites were randomized to a protocol that started with and utilized 2- and 3-drug FDC therapy (Step 1: amlodipine 5 mg + losartan 50 mg) to a protocol that started with monotherapy (Step 1: amlodipine 5 mg) and added individuals medications. Results: Sixty sites, including 5,576 patients (mean [SD] age=49.2 [12.4] years; 70% female; mean [SD] baseline systolic/diastolic BP=155[SD]/96 [SD] mm Hg), were randomized. At 6-month follow-up, the rates of hypertension control for the FDC therapy and Nigeria’s 2019 National Hypertension Treatment protocol were 54.7% and 48.3%, respectively ( Figure 1 ). The final results will be added at a later date. Conclusion and relevance: A hypertension treatment protocol that used FDC therapy led to a higher hypertension control rate compared with a standard treatment protocol in Nigeria. These results may have relevance to protocols used in other large-scale hypertension control programs.
Re: Visualization of Tumor Heterogeneity in Advanced Medullary Thyroid Carcinoma by Dual-Tracer Molecular Imaging: Revealing the Theranostic Potential of SSTR- and PSMA-Directed Endoradiotherapy
Authors: Paulo Schiavom Duarte
Journal: Clinical Nuclear Medicine (2022)

Division of Nuclear Medicine, São Paulo Cancer Institute (ICESP), São Paulo, Brazil [email protected] Conflicts of interest and sources of funding: none declared.
Abstract P073: Does Physical Activity Modify The Association Between High-density Lipoprotein Cholesterol And All-cause Mortality?
Authors: James R Churilla, William Boyer
Journal: Circulation (2022)

Introduction: There is well-known inverse dose-response relationship between high-density lipoprotein cholesterol (HDL-C) and cardiovascular disease and all-cause mortality. However, only recently is the entire spectrum of HDL-C being examined with mortality. A similar dose-response relationship with mortality exists with physical activity (PA). Engaging in regular PA has consistently been shown to lower both CVD and all-cause mortality by 20-30%. This study examined the association between HDL-C and mortality by PA categories created around the current federal PA guidelines for United States Adults. Hypothesis: Level of PA participation will modify mortality risk across a spectrum of HDL-C levels. Methods: The study sample (n=8,535) included participants (age 20-79 years) from the 1999-2006 National Health and Nutrition Examination Survey. PA was classified into three distinct categories: Those meeting neither of the PA guidelines (category 1), those meeting only the aerobic PA guideline (category 2), and those meeting both the aerobic PA and muscular strengthening activity guidelines (category 3). HDL-C was categorized into eight groups (≤30, 31-40, 41-50, 51-60 [referent group], 61-70, 70-80, and &gt;80 mg/dL). All-cause mortality served as the dependent variable in this study. Cox proportional hazard models were used for all analyses. Results: Among those in PA category 1, a statistically significant increase in all-cause mortality risk was found for those with an HDL-C of 71-80 (HR 1.94, 95% CI 1.14-3.32) and &gt;80 mg/dL (HR 2.18, 95% CI 1.25-3.79). In those with an HDL-C &lt;30 mg/dL, a borderline significant increase in all-cause mortality risk was found (HR 1.67, 95% CI 0.96-2.89, p=0.06) Among those in PA categories 2 and 3, no significant increases in all-cause mortality risk were found. Conclusions: Results suggest that meeting at least the aerobic PA guideline mitigates the increased risk for all-cause mortality in those with very high HDL-C and potentially very low HDL-C. Future studies are warranted to investigate the effects of PA on mortality across measures of HDL-C.
Natural History and Characteristics of <i>ERBB2</i>-mutated Hormone Receptor–positive Metastatic Breast Cancer: A Multi-institutional Retrospective Case–control Study from AACR Project GENIE
Authors: Michele L. LeNoue-Newton, Sheau-Chiann Chen, Thomas Stricker, David M. Hyman, Natalie Blauvelt, Philippe L. Bedard, Funda Meric-Bernstam, Rinaa S. Punglia, Deborah Schrag, Eva M. Lepisto, Fabrice Andre, Lillian Smyth, Semih Dogan, Celeste Yu, Chetna Wathoo, Mia Levy, Lisa D. Eli, Feng Xu, Grace Mann, Alshad S. Lalani, Fei Ye, Christine M. Micheel, Monica Arnedos
Journal: Clinical Cancer Research (2022)

Abstract Purpose: We wanted to determine the prognosis and the phenotypic characteristics of hormone receptor–positive advanced breast cancer tumors harboring an ERBB2 mutation in the absence of a HER2 amplification. Experimental Design: We retrospectively collected information from the American Association of Cancer Research-Genomics Evidence Neoplasia Information Exchange registry database from patients with hormone receptor–positive, HER2-negative, ERBB2-mutated advanced breast cancer. Phenotypic and co-mutational features, as well as response to treatment and outcome were compared with matched control cases ERBB2 wild type. Results: A total of 45 ERBB2-mutant cases were identified for 90 matched controls. The presence of an ERBB2 mutation was not associated with worse outcome determined by overall survival (OS) from first metastatic relapse. No significant differences were observed in phenotypic characteristics apart from higher lobular infiltrating subtype in the ERBB2-mutated group. ERBB2 mutation did not seem to have an impact in response to treatment or time-to-progression (TTP) to endocrine therapy compared with ERBB2 wild type. In the co-mutational analyses, CDH1 mutation was more frequent in the ERBB2-mutated group (FDR &amp;lt; 1). Although not significant, fewer co-occurring ESR1 mutations and more KRAS mutations were identified in the ERBB2-mutated group. Conclusions: ERBB2-activating mutation was not associated with a worse OS from time of first metastatic relapse, or differences in TTP on treatment as compared with a series of matched controls. Although not significant, differences in coexisting mutations (CDH1, ESR1, and KRAS) were noted between the ERBB2-mutated and the control group.
Evolving Bilateral Hypermetabolic Axillary Lymphadenopathy on FDG PET/CT Following 2-Dose COVID-19 Vaccination
Authors: Joanna K. Weeks, Sophia R. O’Brien, Karen C. Rosenspire, Jacob G. Dubroff, Austin R. Pantel
Journal: Clinical Nuclear Medicine (2021)

Abstract A 50-year-old woman with stage IV sigmoid adenocarcinoma presented for restaging FDG PET/CT status post neoadjuvant chemotherapy/immunotherapy and diverting sigmoid colostomy. FDG PET/CT demonstrated FDG uptake in the known sigmoid mass and in abdominopelvic lymph node metastases. Bilateral, asymmetric, hypermetabolic axillary lymphadenopathy was also observed, an atypical pattern of spread for colon cancer. Further investigation revealed the patient had received both doses of COVID-19 vaccine in the 2 months prior to presentation. The authors discuss immunogenic nodal hypermetabolism following vaccination against COVID-19 and incorporating vaccination history to aid in PET/CT interpretation, especially in malignancies involving the axillae.
GSK3β and the aging kidney
Authors: Jordan A. Kreidberg, Valerie A. Schumacher
Journal: Journal of Clinical Investigation (2022)

Kidney function decreases with age and may soon limit millions of lives as the proportion of the population over 70 years of age increases. Glycogen synthase kinase 3β (GSK3β) is involved with metabolism and may have a role in kidney senescence, positioning it as a target for complications from chronic kidney disease. However, different studies suggest GSK3 has contrasting effects. In this issue of the JCI, Fang et al. explored the function of GSK3β and the interplay with lithium using human tissue and mouse models. Notably, GSK3β was overexpressed and activated in aging mice, and depleting GSK3β reduced senescence and glomerular aging. In this Commentary, we explore the similarities and differences between Fang et al. and previous findings by Hurcombe et al. These findings should prompt further study of lithium and other GSK3β inhibitors as a means of extending glomerular function in individuals with chronic kidney disease.
Effects of a social norm-based handwashing intervention including handwashing stations, and a handwashing station-only intervention on handwashing with soap in urban Côte d'Ivoire: a cluster randomised controlled trial
Authors: Maud A Amon-Tanoh, Jim McCambridge, Patrice K Blon, Herman A Kouamé, Patrick Nguipdop-Djomo, Adam Biran, Simon Cousens
Journal: The Lancet Global Health (2021)

Diarrhoeal diseases are an important cause of mortality in children younger than 5 years in sub-Saharan Africa. We aimed to evaluate the effect of three handwashing interventions on handwashing with soap (HWWS) after toilet use.In this cluster randomised trial in Abidjan, Côte d'Ivoire, we randomly assigned communal housing compounds (1:1:1) to receive one of three interventions: a theory of normative social behaviour (TNSB) intervention, including provision of handwashing stations; handwashing stations only; and no intervention. The TNSB intervention was designed to shift the outcome expectation associated with HWWS from health to riddance of faeces-related disgust, and to increase the perceived descriptive norm and perceived handwashing publicness. Participants and fieldworkers were masked to the study objectives. The primary outcome was HWWS after toilet use, assessed at 1 month and 5 months follow-ups. Analysis was by intention to treat. This trial is registered at the Pan African Clinical Trial Registry, PACTR201501000892239.Between April 10 and May 22, 2014, we identified 92 eligible compounds, of which 75 compounds were included. Follow-up data on HWWS were available for 23 compounds for the TNSB group, 25 compounds for the handwashing station-only group, and 25 compounds for the control group. The study ended in April, 2017. Compared with a frequency of 5% (29 of 604 occasions) in the control group, HWWS after toilet use increased to 9% (49 of 557 occasions; adjusted risk ratio 1·89, 95% CI 1·16-3·08) in the handwashing station-only group, and 24% (143 of 588 occasions; 4·82, 3·06-7·59) in the TNSB group, at the 1-month follow-up. The intervention effect was only sustained in the TNSB group (98 [22%] of 450 compounds; 2·68, 1·65-4·34).A social norm-based handwashing intervention combined with disgust-inducing messages, with provision of handwashing stations, was effective at increasing HWWS after toilet use. The provision of handwashing stations alone had little effect. Future studies should investigate whether the same approach, when delivered via mass media, can have a similar effect to the face-to-face delivery used in this study.None.
Set back on the way to meet SDG targets: progress in tackling tuberculosis reversed by the pandemic
Journal: Eurosurveillance (2022)

Preview this article: Set back on the way to meet SDG targets: progress in tackling tuberculosis reversed by the pandemic, Page 1 of 1 < Previous page | Next page > /docserver/preview/fulltext/eurosurveillance/27/12/eurosurv-27-12-1-1.gif
Abstract P239: Dietary Behavior Interventions And Outcomes In Stroke Survivors: A Scoping Review
Authors: Ryan Bailey, Alfonso L Neri, Monica C Serra
Journal: Circulation (2022)

Purpose: Secondary stroke prevention is an essential but unmet need for stroke survivors. Current secondary stroke prevention guidelines from the American Heart Association recommend following a Mediterranean-type diet to reduce recurrent stroke risk. However, there is a lack of published data on dietary behavior interventions and outcomes among stroke survivors. Therefore, we conducted a scoping review to characterize published dietary behavior interventions and outcomes among community-dwelling stroke survivors to identify gaps in scientific knowledge. Methods: PubMed was used to find research articles published between January 2000 and April 2021. To be included, articles must have undergone peer-review and described both a dietary intervention and dietary outcome among community-dwelling stroke survivors. Study characteristics and dietary outcomes were extracted by 3 team members for studies that met inclusion criteria. Results: 649 articles were initially identified but 637 were excluded based on eligibility criteria. Study characteristics and outcomes of the 12 included studies are described in the table. All studies (9 randomized controlled trials, 3 cohort studies) delivered multimodal health behavior interventions that included a dietary component. Interventions were delivered weekly to every other month, lasted 1-24 months, and provided 1-132 contact hours. Dietary outcomes included food frequency questionnaires and self-reported fruit, vegetable, salt, or fat consumption. Eight studies reported improvement in dietary outcomes; 6 of which reported ≥16 contact hours. Conclusions: This review provides support for the efficacy of dietary behavior interventions in stroke survivors. Intervention format and outcomes varied greatly, which impedes the ability to determine efficacy of dietary interventions in this population and represents a gap in scientific knowledge. Comparative effectiveness studies that compare outcomes across existing interventions may narrow this knowledge gap.
68Ga-FAPI PET/CT Detected Non–FDG-Avid Gastric Stromal Tumor
Authors: Lin Qiu, Lianjun Lan, Hanxiang Liu, Jia Deng, Yue Chen
Journal: Clinical Nuclear Medicine (2021)

We presented a case of 67-year-old man with epigastric discomfort and anorexia for more than 2 months. No abnormal 18F-FDG uptake was found throughout the gastrointestinal tract on 18F-FDG PET/CT. The patient was enrolled in the 68Ga-FAPI PET/CT clinical trial, and a 68Ga-FAPI PET/CT was performed to help detect primary lesion. This examination demonstrated a nodular thickening of the gastric wall with an increased 68Ga-FAPI uptake in the greater curvature of the stomach. Finally, the pathological result confirmed the diagnosis of gastric stromal tumor. This case highlights that 68Ga-FAPI PET/CT might outperform 18F-FDG PET/CT in helping identify gastrointestinal stromal tumors.
Predicting the future: machine-based learning for MRD prognostication
Authors: Charlotte Pawlyn, Faith E. Davies
Journal: Clinical Cancer Research (2022)

The prognostic significance of minimal residual disease (MRD) detection in multiple myeloma is well established. Understanding factors that predict for MRD negativity, such as tumor burden, cytogenetic, and immune-related biomarkers, may enable us to improve outcome prediction at diagnosis, and in the future move toward tailored treatment approaches. See related article by Guerrero et al., p. 2598.
Alternative Mitophagy Protects the Heart Against Obesity-Associated Cardiomyopathy
Authors: Mingming Tong, Toshiro Saito, Peiyong Zhai, Shin-ichi Oka, Wataru Mizushima, Michinari Nakamura, Shohei Ikeda, Akihiro Shirakabe, Junichi Sadoshima
Journal: Circulation Research (2021)

Rationale: Obesity-associated cardiomyopathy characterized by hypertrophy and mitochondrial dysfunction. Mitochondrial quality control mechanisms, including mitophagy, are essential for the maintenance of cardiac function in obesity-associated cardiomyopathy. However, autophagic flux peaks at around 6 weeks of high-fat diet (HFD) consumption and declines thereafter. Objective: We investigated whether mitophagy is activated during the chronic phase of cardiomyopathy associated with obesity (obesity cardiomyopathy) after general autophagy is downregulated and, if so, what the underlying mechanism and the functional significance are. Methods and Results: Mice were fed either a normal diet or a HFD (60 kcal% fat). Mitophagy, evaluated using Mito-Keima, was increased after 3 weeks of HFD consumption and continued to increase after conventional mechanisms of autophagy were inactivated, at least until 24 weeks. HFD consumption time-dependently upregulated both Ser555-phosphorylated Ulk1 (unc-51 like kinase 1) and Rab9 (Ras-related protein Rab-9) in the mitochondrial fraction. Mitochondria were sequestrated by Rab9-positive ring-like structures in cardiomyocytes isolated from mice after 20 weeks of HFD consumption, consistent with the activation of alternative mitophagy. Increases in mitophagy induced by HFD consumption for 20 weeks were abolished in cardiac-specific ulk1 knockout mouse hearts, in which both diastolic and systolic dysfunction were exacerbated. Rab9 S179A knock-in mice, in which alternative mitophagy is selectively suppressed, exhibited impaired mitophagy and more severe cardiac dysfunction than control mice following HFD consumption for 20 weeks. Overexpression of Rab9 in the heart increased mitophagy and protected against cardiac dysfunction during HFD consumption. HFD-induced activation of Rab9-dependent mitophagy was accompanied by upregulation of TFE3 (transcription factor binding to IGHM enhancer 3), which plays an essential role in transcriptional activation of mitophagy. Conclusions: Ulk1-Rab9-dependent alternative mitophagy is activated during the chronic phase of HFD consumption and serves as an essential mitochondrial quality control mechanism, thereby protecting the heart against obesity cardiomyopathy.