tbuckley/cabot-search huggingface dataset:
Abstract 17257: Stroke Volume Reserve Index in HFrEF: A Non-Invasive Predictor of Early Clinical Outcomes and Marker of Inotropic Reserve
Authors: Ibrahim Selevany, Florin Vaida, Eric D Adler, Timothy Morris, Paul Kim
Journal: Circulation (2020)

Introduction: We investigated whether stroke volume reserve index (SVRI), a novel non-invasive measure of inotropic reserve at submaximal exercise, would predict 1-year mortality and need for advanced therapies in heart-failure with reduced ejection fraction (HFrEF) patients. Methods: We retrospectively studied a consecutive series of 245 ambulatory patients (57±11 years, 84% men) with HFrEF at a single center who underwent cardiopulmonary exercise testing (CPET) from January 2013 to December 2018. The primary outcome was defined as heart-transplantation, urgent left ventricular assist device (LVAD) implantation or death within 1 year of evaluation. SVRI was estimated at rest and at anaerobic threshold by VO 2 (oxygen consumption)/pulse and previously validated estimates of C[a-v]O 2 (arteriovenous difference in oxygen content). Multivariate regression selected the optimal predictors. Results: Among HFrEF patients studied, 82 (33.5%) deteriorated: 34 required heart-transplantation, 20 required LVADs and 28 died. SVRI of less than 130% was the best predictor of clinical deterioration (OR 3.98, p&lt;0.005), followed by cardiac index of less than 2 L/min/m 2 (OR 3.74, p&lt;0.005), and peak VO 2 below the International Society for Heart and Lung Transplantation (ISHLT) cut-off (OR 3.01, p=0.008). Kaplan-Meier curves showed that 1-year event-free survival was significantly better amongst patients with normal SVRI, compared to patients with impaired inotropic reserve. Notably, HFrEF patients with an abnormal SVRI had a poor 1-year prognosis regardless of their peak VO 2 . Conclusions: SVRI is a non-invasive measurement that provides a measure of inotropic reserve at submaximal exercise, provides valuable prognostic information independent of other known and validated CPET parameters, and may predict deterioration in HFrEF patients more accurately than currently recommended CPET predictors. SVRI and peak VO 2 provide complementary prognostic information.
Abstract 15549: Esophagopleural Fistula Associated Regional Pericarditis Mimicking Inferior Myocardial Infarction
Authors: Iain J Thompson, Jorge Fernandez, Hiroko Beck
Journal: Circulation (2020)

Introduction: Regional pericarditis is a rare clinical entity that may mimic myocardial infarction (MI) and occurs most frequently after myocardial injury. We describe a unique case of regional pericarditis secondary to esophagopleural fistula (EPF) in a patient presenting to the catheterization lab for suspected ST-segment MI. Results: A 75-year-old man with non-small cell lung cancer presented with hypotension, weakness, dyspnea, and chest pain. The initial electrocardiogram (ECG: Figure 1) revealed normal sinus rhythm with inferior lead ST- segment elevations, a chest X-ray showed a left pleural effusion, and troponin I was &lt;0.01 ng/ml. The patient underwent emergent coronary angiography showing no evidence of obstructive coronary disease. Subsequently, the patient reported palpitations and new onset dysphagia. An ECG revealed atrial fibrillation with rapid ventricular response. A barium esophagram (Figure 2) was performed to evaluate the dysphagia and revealed the presence of an EPF with fluid collection adjacent to the inferior heart border. The patient was treated for pericarditis with colchicine and definitive treatment with esophageal stenting was performed. Conclusions: We describe a case of regional pericarditis secondary to EPF masquerading as inferior MI. Given the prevalence and severity of MI, remaining cognizant of its mimickers such as regional pericarditis is important in clinical practice. This case report highlights the utility of maintaining a broad differential and performing a thorough history and physical both at initial presentation and when new information challenges the initial diagnosis.
Functionally distinct POMC-expressing neuron subpopulations in hypothalamus revealed by intersectional targeting
Authors: Nasim Biglari, Isabella Gaziano, Jonas Schumacher, Jan Radermacher, Lars Paeger, Paul Klemm, Weiyi Chen, Svenja Corneliussen, Claudia M. Wunderlich, Michael Sue, Stefan Vollmar, Tim Klöckener, Tamara Sotelo-Hitschfeld, Amin Abbasloo, Frank Edenhofer, Frank Reimann, Fiona M. Gribble, Henning Fenselau, Peter Kloppenburg, Frank T. Wunderlich, Jens C. Brüning
Journal: Nature Neuroscience (2021)

Abstract Pro-opiomelanocortin (POMC)-expressing neurons in the arcuate nucleus of the hypothalamus represent key regulators of metabolic homeostasis. Electrophysiological and single-cell sequencing experiments have revealed a remarkable degree of heterogeneity of these neurons. However, the exact molecular basis and functional consequences of this heterogeneity have not yet been addressed. Here, we have developed new mouse models in which intersectional Cre/Dre-dependent recombination allowed for successful labeling, translational profiling and functional characterization of distinct POMC neurons expressing the leptin receptor ( Lepr ) and glucagon like peptide 1 receptor ( Glp1r ). Our experiments reveal that POMC Lepr+ and POMC Glp1r+ neurons represent largely nonoverlapping subpopulations with distinct basic electrophysiological properties. They exhibit a specific anatomical distribution within the arcuate nucleus and differentially express receptors for energy-state communicating hormones and neurotransmitters. Finally, we identify a differential ability of these subpopulations to suppress feeding. Collectively, we reveal a notably distinct functional microarchitecture of critical metabolism-regulatory neurons.
Abstract P203: Determinants Of Perceived Factors Discouraging Electronic Nicotine Delivery Systems (ENDS) Use Among Youth
Authors: Joy L Hart, Thomas J Payne, Allison Groom, Kandi L Walker, Rose M Robertson, Anshula Kesh, Robyn L Landry, Aida L Giachello, Thanh-Huyen T Vu
Journal: Circulation (2021)

Introduction: Despite cardiovascular and other health risks, youth use of electronic nicotine delivery systems (ENDS) has reached an epidemic level. Studies have examined factors associated with ENDS use, but little is known about factors discouraging youth ENDS use. We examined youth sociodemographic and tobacco/ENDS use determinants of perceived factors discouraging ENDS use. Methods: Data from a nationwide online survey of youth were weighted to be representative of the overall U.S. population in terms of age, sex, race, ethnicity, and region. Participants selected up to 3 reasons that would discourage their use of ENDS. Results: Of 3000 participants, 55.7% were female, 20.1% Hispanic, and 13.7% non-Hispanic Black; 7.3% current ENDS only, 6.2% current cigarette/other products only, 10.8% current dual/poly, 32.1% any past product, and 43.7% never used. Health risk akin to smoking was the most often selected factor discouraging ENDS use (50.4%), followed by harmful chemicals (47.1%), device dangers (26.0%), parent disapproval (24.4%), high nicotine level (23.3%), leads to smoking (21.0%), increased expense (17.9%), doctor/nurse discouraging (17.8%), friend criticizing (11.7%), and other (7.7%) (Fig 1A). Multivariable logistic regression models revealed that perceptions significantly varied by age, sex, race/ethnicity, parental education, and particularly tobacco/ENDS use status. For example, the odds of selecting health risk as discouraging were 34% lower in boys v. girls, 38% lower for current ENDS only users v. never users, and 33% higher in those with higher parental education (Fig 1B). Conclusions: For youth, perceived health risk was most important in discouraging ENDS use. Factors discouraging ENDS use were associated with participant sociodemographic and tobacco/ENDS use status. The findings have relevance for developing communication and education strategies to prevent or reduce ENDS use--thus reducing CVD/health burden--and suggest tailoring such messaging may be key to maximizing impact.
Expanding Criteria for Prognostic Stage IA in Hormone Receptor–Positive Breast Cancer
Authors: Olga Kantor, Tari A King, Steven Shak, Christy A Russell, Armando E Giuliano, Gabriel N Hortobagyi, Harold J Burstein, Eric P Winer, Tanujit Dey, Joseph A Sparano, Elizabeth A Mittendorf
Journal: JNCI Journal of the National Cancer Institute (2021)

Abstract Background The prognostic significance of patients with low-risk recurrence score (RS) results in the context of the American Joint Committee on Cancer (AJCC) eighth edition pathologic prognostic staging has not been investigated. We evaluated if expanded RS criteria can be considered for downstaging in AJCC pathologic prognostic staging. Methods Using Surveillance, Epidemiology, and End Results data, we identified patients with T1-3N0-3M0 hormone receptor–positive, HER2-negative breast cancer treated from 2010 to 2015 with follow-up data through 2016. We evaluated TNM categories, grade, and RS result. The primary outcome measured was 5-year disease-specific survival (DSS) of patients with low-risk RS results not already pathologic prognostic stage IA, determined by T and N categories per AJCC eighth edition. All statistical tests were 2-sided. Results Of 154 050 patients with median follow-up of 49 months (range = 0-83), RS results were obtained in 60 886 (39.5%): RS was less than 11 in 13 570 (22.3%); 11-17 in 22 719 (37.3%); 18-25 in 16 521 (27.1%); and 26 or higher in 8076 (13.3%). Five-year DSS for pathologic prognostic stage IA patients (n = 114 910, 74.6%) was 98.8%. Among N0-1 patients with a RS less than 18 not staged as pathologic prognostic stage IA by current criteria, 5-year DSS was excellent and not statistically significantly different than for pathologic prognostic stage IA patients (97.2%-99.7%; P &amp;gt; .05). For those with a RS of 18-25, there was a small decrease in DSS for T2N0 (2.3%) and modest decrease for T1-2N1 (4.2%-6.4%) compared with pathologic prognostic stage IA patients (P &amp;lt; .001). Conclusion Patients with a RS less than 18 have excellent 5-year DSS regardless of T category for N0-1 disease suggesting further modification of the AJCC staging system using this cutoff.
Abstract 16532: Sedentary Time in Hospitalized Older Adults With Acute Cardiovascular Disease
Authors: Haroon Munir, Michael Goldfarb
Journal: Circulation (2020)

Background: Older adults may be subject to prolonged bedrest during hospitalization for acute cardiovascular (CV) disease, which can contribute to poor functional outcomes posthospitalization. Our objective was to describe mobility status in hospitalized older adults with acute CV disease. Methods: Patients aged ≥ 60 years old in the cardiac ICU and CV ward at a tertiary care academic centre in Montreal, Quebec were prospectively enrolled from April 2019 to March 2020. Activity levels were measured with an accelerometer (ActiGraph GT9 Link). Sedentary was defined as lying in bed or in a sitting position. Health-related quality of life (HRQoL) was measured with the Short-Form 36 (SF-36) questionnaire by telephone at 1 month post-hospital discharge. The primary outcome was percentage of sedentary time during hospital stay. Secondary outcomes were step counts, steps per minute, and kcal/day consumption. Results: There were 35 patients included in the analysis (75.7 6.9 years old; 45.7% females; 22.9% ischemic heart disease; 20.0% heart failure). Patients spent 91.2% ± 5.5 in the sedentary position during their hospital stay (range 80.0-100%; Figure ). There was no difference in percentage sedentary time by primary diagnosis or sex. Mean steps per minute were 1.0 ± 1.2 and mean kcals consumed per day were 116.6 ± 124.5. In the multivariable analysis, a lower percentage of sedentary time and lower steps per minute were each associated with lower total SF-36 scores at 1-month posthospitalization (both P&lt;0.05). Conclusion: Older adults with acute CV disease are sedentary for a large part of their hospital stay. Increased sedentary time is associated with worse self-reported posthospital HRQoL. Future studies are needed to determine whether interventions to increase activity during hospitalization improve posthospital HRQoL and functional outcomes.
Diverse Molecular Mechanisms Contribute to Differential Expression of Human Duplicated Genes
Authors: Colin J Shew, Paulina Carmona-Mora, Daniela C Soto, Mira Mastoras, Elizabeth Roberts, Joseph Rosas, Dhriti Jagannathan, Gulhan Kaya, Henriette O’Geen, Megan Y Dennis
Journal: Molecular Biology and Evolution (2021)

Emerging evidence links genes within human-specific segmental duplications (HSDs) to traits and diseases unique to our species. Strikingly, despite being nearly identical by sequence (>98.5%), paralogous HSD genes are differentially expressed across human cell and tissue types, though the underlying mechanisms have not been examined. We compared cross-tissue mRNA levels of 75 HSD genes from 30 families between humans and chimpanzees and found expression patterns consistent with relaxed selection on or neofunctionalization of derived paralogs. In general, ancestral paralogs exhibited greatest expression conservation with chimpanzee orthologs, though exceptions suggest certain derived paralogs may retain or supplant ancestral functions. Concordantly, analysis of long-read isoform sequencing data sets from diverse human tissues and cell lines found that about half of derived paralogs exhibited globally lower expression. To understand mechanisms underlying these differences, we leveraged data from human lymphoblastoid cell lines (LCLs) and found no relationship between paralogous expression divergence and post-transcriptional regulation, sequence divergence, or copy-number variation. Considering cis-regulation, we reanalyzed ENCODE data and recovered hundreds of previously unidentified candidate CREs in HSDs. We also generated large-insert ChIP-sequencing data for active chromatin features in an LCL to better distinguish paralogous regions. Some duplicated CREs were sufficient to drive differential reporter activity, suggesting they may contribute to divergent cis-regulation of paralogous genes. This work provides evidence that cis-regulatory divergence contributes to novel expression patterns of recent gene duplicates in humans.
Abstract P061: Dairy Consumption, Dairy Fat Biomarkers And Type 2 Diabetes Risk After Myocardial Infarction
Authors: Maria G. Jacobo Cejudo, Esther Cruijsen, Christiane Heuser, Sabita S. Soedamah-Muthu, Trudy Voortman, Johanna M. (Marianne) Geleijnse
Journal: Circulation (2021)

Introduction: Dairy consumption, especially yogurt, and circulating biomarkers of dairy fat (odd chain fatty acids, OCFAs), have been associated with a lower risk of type 2 diabetes (T2D) in population-based studies. Whether these associations are also present in post-myocardial infarction (MI) patients is unknown. Hypothesis: We hypothesized that dairy consumption and circulating OCFAs (pentadecanoic [15:0] plus heptadecanoic acid [17:0]) may be inversely associated with incident T2D after MI. Methods: We included 3347 Dutch post-MI patients from the Alpha Omega Cohort, who were initially free of T2D. At baseline (2002-2006), dairy consumption was estimated with a 203-item food frequency questionnaire and plasma OCFAs were measured in cholesteryl esters using gas chromatography. Incident T2D was ascertained through self-reported physician diagnosis and medication use. Multivariable Cox models were used to obtain hazard ratios (HRs) and 95% confidence intervals (CI) for incident T2D and dairy types and OCFAs (per 1 standard deviation (SD) increment). Results: At baseline, patients were on average 68.9 years old (± 5.5 SD), 80% were men and 87% used statins (2684 and 2908 of 3347 patients respectively). During a median follow-up time of 40 months (10,550 person-years), 181 patients developed T2D. Almost all patients consumed dairy (3300 of 3347), with a median intake of 273 g/d for total dairy. After multivariable adjustment, dairy and its subtypes consumption was not associated with T2D incidence, with HRs ranging from 1.01 to 1.07 per 1-SD increment (all p&gt; 0.05). When analysed in categories (highest vs lowest intake), HRs (95% CI) were 1.05 (0.73-1.52) for milk and 1.08 (0.77-1.51) for yoghurt intake. In line with these findings, no significant association was found for circulating OCFAs 0.97 (0.83-1.12)( Figure 1 ). Conclusion: Dairy consumption, based on self-report and plasma biomarkers, was neutrally associated with T2D incidence in a population of Dutch post-MI patients with a relatively high habitual dairy intake.
Admission Urinary and Serum Metabolites Predict Renal Outcomes in Hospitalized Patients With Cirrhosis
Authors: Jasmohan S. Bajaj, Guadalupe Garcia‐Tsao, K. Rajender Reddy, Jacqueline G. O’Leary, Hugo E. Vargas, Jennifer C. Lai, Patrick S. Kamath, Puneeta Tandon, Ram M. Subramanian, Paul Thuluvath, Andrew Fagan, Tejasav Sehrawat, Randolph de la Rosa Rodriguez, Leroy R. Thacker, Florence Wong
Journal: Hepatology (2021)

Acute kidney injury (AKI) has a poor prognosis in cirrhosis. Given the variability of creatinine, the prediction of AKI and dialysis by other markers is needed. The aim of this study is to determine the role of serum and urine metabolomics in the prediction of AKI and dialysis in an inpatient cirrhosis cohort.
Follicular Epithelial Dysplasia as Hashimoto Thyroiditis-Related Atypia: a Series of 91 Specimens
Authors: Ivana Kholová, David Kalfert, Jarkko Lintusaari, Erja Rajakorpi, Marie Ludvíková
Journal: Endocrine Pathology (2021)

Follicular epithelial dysplasia (FED) is described as Hashimoto thyroiditis-related atypia and is thought to be a possible precancerous lesion. Dysplasia as an interface between normal state and carcinoma is described in a wide range of diseases and carcinogenesis chains. On the other hand, inflammation-related atypia and cancerogenesis is also widely studied. In this study, we retrospectively analyzed 91 specimens of thyroid gland surgical resections with FED during a 10-year-period at the university hospital pathology department. The study population consisted of 68 females and 15 males aged between 22 and 86 years. The preoperative cytology diagnoses had mainly been in the indeterminate categories with prevailing AUS/FLUS results in the FED-only group (p = 0.005) and suspicious for malignancy and malignant in the group with FED plus adjacent malignancy. The decision for surgery was malignancy related in 48.2% of the cases. The lesions were sized 0.1-3.5 mm and multifocal in 45.1% of the cases. Immunohistochemically, the atypical cells were cyclin D1-positive in 67.5%, galectin-3 in 72.7%, CK19 in 85.7%, and HBME-1 in 87.0% of cases. In conclusion, FED is suggested to be a pathogenetic link between inflammation-related atypia and papillary carcinoma and thus a premalignant precursor of papillary carcinoma in HT as 36.1% of the specimens contained also papillary carcinoma in the present study. Both histopathological nuclear features and the immunoprofile of FED are widely shared with that of papillary carcinoma.
Demographic and Social Factors Associated with COVID-19 Vaccination Initiation Among Adults Aged ≥65 Years — United States, December 14, 2020–April 10, 2021
Authors: Ari Whiteman, Alice Wang, Kelly McCain, Betsy Gunnels, Robin Toblin, James Tseryuan Lee, Carolyn Bridges, Laura Reynolds, Bhavini Patel Murthy, Judy Qualters, James A. Singleton, Kimberley Fox, Shannon Stokley, LaTreace Harris, Lynn Gibbs-Scharf, Neetu Abad, Kathryn A. Brookmeyer, Susan Farrall, Cassandra Pingali, Anita Patel, Ruth Link-Gelles, Sharoda Dasgupta, Radhika Gharpure, Matthew D. Ritchey, Kamil. E. Barbour
Journal: MMWR Morbidity and Mortality Weekly Report (2021)

Compared with other age groups, older adults (defined here as persons aged ≥65 years) are at higher risk for COVID-19-associated morbidity and mortality and have therefore been prioritized for COVID-19 vaccination (1,2). Ensuring access to vaccines for older adults has been a focus of federal, state, and local response efforts, and CDC has been monitoring vaccination coverage to identify and address disparities among subpopulations of older adults (2). Vaccine administration data submitted to CDC were analyzed to determine the prevalence of COVID-19 vaccination initiation among adults aged ≥65 years by demographic characteristics and overall. Characteristics of counties with low vaccination initiation rates were quantified using indicators of social vulnerability data from the 2019 American Community Survey.* During December 14, 2020-April 10, 2021, nationwide, a total of 42,736,710 (79.1%) older adults had initiated vaccination. The initiation rate was higher among men than among women and varied by state. On average, counties with low vaccination initiation rates (<50% of older adults having received at least 1 vaccine dose), compared with those with high rates (≥75%), had higher percentages of older adults without a computer, living in poverty, without Internet access, and living alone. CDC, state, and local jurisdictions in partnerships with communities should continue to identify and implement strategies to improve access to COVID-19 vaccination for older adults, such as assistance with scheduling vaccination appointments and transportation to vaccination sites, or vaccination at home if needed for persons who are homebound.† Monitoring demographic and social factors affecting COVID-19 vaccine access for older adults and prioritizing efforts to ensure equitable access to COVID-19 vaccine are needed to ensure high coverage among this group.
Abstract 17449: Predictive Value of Growth Hormone Levels in Cardiogenic Shock Patients
Authors: Priyanka Boettger, Linda Bingener, Michael Buerke
Journal: Circulation (2020)

Introduction: Despite improved supportive care, cardiogenic shock still has a significantly high mortality. Among many factors, multiple changes in the neuroendocrine system, are responsible for the high morbidity and mortality. Reduced circulating level of insuline-like growth factor and an elevated level of growth hormone are the reported characteristic findings early in the course of sepsis and. The role of insuline-like growth factor and growth hormone levels in patients with cardiogenic shock has not been described. Methods: The aim of this study was to evaluate the changes of growth hormone/ insuline-like growth factor 1 axis in patients with cardiogenic shock. Results: When admitted, the average GH value of the patient collective was 2.86 μg / l ± 0.78. The values of the majority of the patients (31/41 = 75.6%) were within the normal range. There we no differences among survivors and non-survivors over the 96h observational period. We did not observe differences between either elder and younger patients or female and male CS patients. On admission IGF-1 levels were 76.23 ± 5.67 μg/l (normal range 70– 270 μg/l) at the lower end of the normal range. Over the next 48-72 hours, the value dropped to 66.8 μg/l. However, the drop was not significant (p = 0.14). Non-survivors showed a more rapid decline compared to survivors which stayed within the normal range.Considering the subgroup analysis, it emerges that the average IGF-1 value of male patients remains above 70 μg/l and thus within the normal range, while the IGF-1 level of the female patients during the course which was up to 55.3 μg/l decreases in the course. Clearly female CS patients showed a steeper decline compared to the male patients. Further younger CS patients showed higher levels compared to patients above 70 years. Conclusion: There were no significant changes of growth hormone levels over time and we observed a decrease of insuline-like growth factor 1 in cardiogenic shock patients. In addition, in non-survivors we detected even lower levels of growth hormone and lower levels of insuline-like growth factor 1. We think that both growth hormone and insuline-like growth factor 1 may have l prognostic value to serve as a marker in cardiogenic shock.