tbuckley/cabot-search huggingface dataset:
Abstract 13822: Comparison of Produced Potential Delay in Superior Vena Cava During Right Pulmonary Vein Isolation Between High-power Short-duration and Conventional Settings
Authors: Naoko Hijioka, Takashi Kaneshiro, Kazuaki Amami, Shinya Yamada, Takafumi Ishida, Yasuchika Takeishi
Journal: Circulation (2020)

Background: Recently, a high-power short-duration (HP-SD) setting has been introduced in atrial fibrillation (AF) ablation. Ablation using this setting reduces collateral tissue damage by shortening the conductive heating phase compared to conventional setting. However, the lesion characteristics have not been rigorously evaluated during ablation procedure. We hypothesized that superior vena cava (SVC) potential could be affected by excessive transmural lesions in anterior-superior right pulmonary vein isolation (PVI), adjacent to posterior aspect of SVC. Therefore, we compared the produced potential delay in SVC between HP-SD and conventional settings. Methods and Results: The consecutive 42 patients (61±10 years, 32 men) who underwent PVI for drug refractory AF were analyzed. Before introduction of HP-SD setting to AF ablation in November 2018, 14 patients underwent right PVI with conventional setting with output of 20-30 W (Conventional group). In the remaining 28 patients after then, right PVI was performed using HP-SD setting with output of 45-50 W (HP-SD group). We compared total radiofrequency energy and mean contact force along the anterior superior right PVI line between the 2 groups. Moreover, the produced SVC potential delay was calculated after anterior superior right PVI and compared between the 2 groups. Total radiofrequency energy delivered (6138 J vs. 6139 J, P = 0.999) and the mean contact force (17.2 g vs. 20.2 g, P = 0.100) in the anterior superior right PV did not differ between the HP-SD and Conventional groups. However, the produced SVC potential conduction delay after anterior superior right PVI was significantly longer in Conventional group compared to HP-SD group (6.2 ms vs. 0.5 ms, P &lt; 0.001). Conclusions: Our data suggest that HP-SD setting caused less collateral tissue damage than conventional setting during PVI. The significant produced SVC potential delay might be a surrogate marker of collateral tissue damage by conductive heating phase in PVI.
Abstract 16350: Predicted versus Observed 10-year Cardiovascular Event Rates in a Rural Population-Based Health Program: The Heart of New Ulm Project
Authors: Angela Phillips, Abbey Sidebottom, Marc Vacquier, Gretchen A Benson, Scott W Sharkey, Thomas Knickelbine, Michael D Miedema
Journal: Circulation (2020)

Introduction: Assessment of 10-year ASCVD risk via the Pooled Cohorts Equation (PCE) is a standard component of the clinician-patient risk discussion to aid treatment decisions for the primary prevention of ASCVD. However, calibration of the PCE to modern populations remains a concern. Methods: We studied a sample of individuals participating in the Heart of New Ulm (HONU) Project, a population-based health program aimed at reducing ASCVD risk in a rural, agricultural community of New Ulm, Minnesota. HONU collected baseline survey data on 5,221 individuals in 2009. For this analysis, we included participants who were aged 40-79 years, free of ASCVD at baseline and had adequate data to calculate 10-year ASCVD risk. New Ulm is served by a single healthcare system, allowing surveillance via electronic health records (EHR). EHR data and state death records were used to determine rates of non-fatal myocardial infarction and stroke, and ASCVD death from 2010-2019. ASCVD event rates were compared to estimated 10-year risks calculated using the PCE, and stratified by sex and clinically relevant risk categories. Results: The sample (n=2,819, mean age 56.1 ± 9.9 years, 59.6% female) had a low prevalence of tobacco use (8.1% current smokers), diabetes (6.5%) and higher prevalence of hypertension (44.4%) and hyperlipidemia (56.6%). The median estimated 10-year ASCVD risk for the entire sample was 5.7% (interquartile range 2.3 -13.5%) with an observed 10-year ASCVD event rate of 3.4%. ASCVD rates were lower than predicted across all risk categories in both men and women, especially in those with a 10-year risk ≥7.5% (Table). Conclusion: In a rural sample exposed to ASCVD risk reduction efforts, observed rates of ASCVD were substantially lower compared to estimated ASCVD risk. The uncertainty of current risk models and the potential for significantly lower than predicted ASCVD event rates in certain populations should be included in the clinician-patient risk discussion.
Abstract 15945: Temporal Analyses of Chromatin Accessibility, Dna Methylation and Epigenomic Structure Identify Mechanisms of Locus-specific Regulation in the Heart
Authors: Manuel Rosa-garrido, Douglas J Chapski, Maximilian Cabaj, Marco Morselli, Shuxun Ren, Matteo Pellegrini, Yibin Wang, Thomas M Vondriska, Rosibel J Mason
Journal: Circulation (2020)

Heart failure can be induced or ameliorated in animal models by regulation of chromatin modifying enzymes, yet the chromatin level actions of these enzymes during pathogenesis is unknown. Because many histone modifiers and transcription factors regulate gene expression, we sought to directly measure chromatin accessibility through an unbiased method (ATAC-seq) that reports the status of a given locus at any time—the sum total of all epigenetic modifiers—in a mouse model of pressure overload hypertrophy. Early compensation of pressure overload at 3 days was associated with widespread changes in chromatin accessibility and DNA methylation, primarily in noncoding regions. The majority of changes that persisted to the decompensated phase (3weeks) were already established at the earlier time point, revealing a temporal nature of epigenomic compensation to pathologic stimuli. A cardiac-specific CTCF depletion model was used to examine basal cardiac chromatin function and revealed that disruption of this structure by loss of CTCF causes widespread changes in accessibility and methylation distinct from those in pressure overload. Less than half of the gene expression changes occurring at either time point after pressure overload were explained by DNA methylation alone and accessibility was likewise an imperfect predictor of transcription. Distal enhancers were paired with genes based on chromatin structural data and the regulatory actions of these elements examined in the context of DNA methylation and accessibility: enhancer actions require specific combinations of transcription factors and histone modifications at different stages of disease and to execute aspecific transcriptional event (methylation or accessibility alone was insufficient to predict the behavior). For example, the subset of differentially accessible enhancers in both 3 weeks TACand CTCF depletion significantly overlaps with cardiac transcription factors Gata4 (p=4.13x10 -6 ),Nkx2-5 (p=2.49x10 -5 ) and P300 (p=8.38x10 -7 ). In summary, these studies characterize the logic employed at coding, regulatory, and noncoding regions to regulate chromatin accessibility and transcription, providing a resource of epigenomic data at distinct temporal stages of heart failure.
Abstract 16872: The Association of Mental Health Disorders With Heart Failure Outcomes and the Impact of Substance Abuse
Authors: Francesca Cazzulino, Marin Nishimura, Harpreet S Bhatia, Isac C Thomas
Journal: Circulation (2020)

Introduction: Depression is associated with adverse heart failure (HF) outcomes. Substance abuse disorders often co-occur with depression and other psychiatric disorders. It is unclear if associations of psychiatric disorders with HF outcomes are confounded, mediated or enhanced by substance abuse. Methods: Medical records and diagnosis codes of HF patients with reduced ejection fraction at UC San Diego between 2005 and 2016 were reviewed. Outcomes were total number of HF admissions, time to HF readmission, and all-cause mortality. Associations of mood and anxiety disorders were assessed using negative binomial regression or cox regression models with hierarchical adjustment for demographics, substance abuse, and medical co-morbidities. Effect modification by substance abuse was assessed by inclusion of multiplicative interaction terms. Results: Of 4529 patients (mean age 61.5 years, 69% male) included, 722 (16%) had an anxiety disorder and 222 (4.9%) had a mood disorder. Methamphetamine (6.6 %) and opioid (6.0%) abuse were common. Over a median follow up of 3.8 years (9999 HF admissions and 901 deaths), both anxiety and mood disorders were associated with total HF admissions and HF readmission; this was not attenuated by adjustment for substance abuse (Table, top). Adjustment for medical co-morbidities weakened the associations modestly. These associations did not vary significantly by abuse of any substance (Table, bottom). Mood disorders were associated with mortality only in patients with certain substance abuse disorders. Conclusions: Anxiety and mood disorders are associated with adverse HF outcomes. Their associations are independent of and do not vary with substance abuse, however some substances appear to enhance an association with total mortality. These results suggest that greater recognition and treatment of psychiatric disorders in HF patients, including in those with co-morbid substance abuse disorders, may improve clinical outcomes.
Fats and Mets, KRAS-Driven Lipid Dysregulation Affects Metastatic Potential in Pancreatic Cancer
Authors: Jennifer Man, Marina Pajic, Anthony M. Joshua
Journal: Cancer Research (2020)

Abstract In this issue of Cancer Research, Rozeveld and colleagues present intriguing evidence of the importance of lipid droplets and hormone-sensitive lipase (HSL) in regulating the aggressive nature of pancreatic cancer. Initially demonstrating a dependency of preloaded lipids on an invasive phenotype, the authors then establish that oncogenic KRAS mutation downregulates HSL, thereby facilitating lipid storage during steady state. Thereafter, a phenotypic switch to oxidative metabolism with lipid utilization to fuel invasion and metastasis occurs. Experimentally, blocking the KRAS–HSL axis results in fewer lipid droplets, as well as metabolic reprogramming of the invasive cell phenotype, effectively reducing invasive capacity of KRAS-mutant pancreatic cancer. Of note, HSL overexpression in tumor cells also inhibited invasion, due to depletion of lipid droplets and the stored lipids, which are essential during invasion. Collectively, these novel findings highlight the importance of energy metabolism and its dynamic regulation in the evolution of the metastatic capacity of pancreatic cancer. See related article by Rozeveld et al., p. 4932
Abstract 12701: Combined Allometric Normalization of Ascending Aortic Diameter and Assessment of Complication Risk May Support an Earlier Prophylactic Replacement Preventive of Type a Dissection
Authors: Francisco Nistal, Carlos Juarez, Juan Miguel Redondo, arturo evangelista
Journal: Circulation (2020)

Introduction: Guideline recommendations of prophylactic surgery in ascending aortic dilation by maximum aortic diameter (MAD) fail to predict &gt; 50% of type-A dissections (AD). Assessment of post-dissection diameters as reference and lack of somatometric normalization may preclude an appropriate risk estimation. Hypothesis: The combined assessment of Z-score and Svensson-index (cross-area/height) based on pre-dissection aortic diameters may be advantageous to indicate prophylactic ascending aortic replacement. Such an approach would include information on normalized vascular dilatation together with a clinical aortic risk indicator. Methods: During two years (2018-2019), data from 515 AD-patients were prospectively recorded at 32 tertiary Spanish hospitals (Registro Español Síndrome Aórtico-III). Pre-dissection aortic diameters were estimated based on the in vitro observations made by Williams et al. on the perimeter change of normal human aortas after the creation of a dissection (PMID: 9122399). Svensson indexes were correlated with ascending aorta Z-scores using quadratic regression. Results (Figure): Setting thresholds of increased risk at Svensson-index &gt;10 cm 2 /m and aortic dilation at Z-score &gt;3, 59% of patients had low Svensson and low Z-score category, 19% low Svensson but high Z-score and 22% high Svensson and high Z-score. No patient with Svensson-index &lt;10 cm 2 /m and Z-score either &lt; or &gt; 3 had an indication for surgery according to guidelines. Among patients with Svensson-index &gt;10 cm 2 /m and aortic dilation at Z-score &gt;3, approximately 1/3 (32%) would have a surgical indication whereas 2/3 (68%) would not. Conclusions: According to current guidelines, only one third of high Svensson and high Z group (7% of the total cohort) would deserve elective surgery. More proactive guidelines, suggesting replacement of ascending aorta in patients with Svensson-index &gt;10 and Z-score&gt;3, would spare from dissection 22% of current cases.
TREATMENT OF MIGRAINE
Authors: J. L. Greig
Journal: BMJ (1924)

I adjunects in treatment.I think that the future will demon- strate that the essential chemical basis of the disease is a derangenent of calcium metabolism.In conclusion, I would emphasize that, from the practical standpoint, in rheumatoid arthritis (1) the etiological basis is a septic focus, and (2) the most important factors in treatment are the removal of the focus and the correct diagnosis of the stage of the disease, REFERENCES.
Learning to endure: A qualitative examination of the protective factors of homeless transgender and gender expansive youth engaged in survival sex
Authors: Brett Greenfield, Edward J. Alessi, Dean Manning, Caroline Dato, Meredith Dank
Journal: International Journal of Transgender Health (2020)

Background: Transgender and gender expansive (TGE) youth face a number of adversities that are associated with deleterious consequences, including mental health problems, substance misuse, suicide, and homelessness. However, there is evidence that TGE youth still demonstrate resilience under extraordinary conditions.Aims: Therefore, this study examined how TGE youth who are homeless and engaging in survival sex describe and understand the protective factors present in their lives.Methods: In-depth qualitative interviews were conducted with 57 TGE youth living in a large U.S. city. Participants were 17-26 years old (M = 19.88, SD = 1.55), and identified as transgender woman (53%), transgender man (16%), and other (32%; gender-queer, gender-fluid, androgynous, or non-binary). Youth identified as Black (40%), multiracial (35%), Latinx (16%), White (5%), and as another race (3%). Researchers conducted a secondary analysis of qualitative data using thematic analysis.Results: We identified three themes to capture youth's understanding of their protective factors: relying on oneself and others to avoid violence, accessing gender-affirming health and mental health care, and proactively maintaining sexual health. Participants described strategies for mitigating risk of harm while attempting to meet their basic needs. Additionally, they discussed the importance of having gender-affirming health and mental health services. Participants also expressed keen awareness of their sexual health risks and making calculated, often proactive decisions about their sexual health.Conclusion: The protective factors described by TGE youth reflect the unique ways in which hyper-marginalized youth must navigate their own survival and well-being, and align with literature suggesting resilience is not mutually exclusive from risk. By focusing on TGE youth, this research privileges the experiences of individuals historically underrepresented in research and encourages future research to incorporate these perspectives into policies and programs.
Implementation of a Pooled Surveillance Testing Program for Asymptomatic SARS-CoV-2 Infections on a College Campus — Duke University, Durham, North Carolina, August 2–October 11, 2020
Authors: Thomas N. Denny, Laura Andrews, Mattia Bonsignori, Kyle Cavanaugh, Michael B. Datto, Anastasia Deckard, C. Todd DeMarco, Nicole DeNaeyer, Carol A. Epling, Thaddeus Gurley, Steven B. Haase, Chloe Hallberg, John Harer, Charles L. Kneifel, Mark J. Lee, Raul Louzao, M. Anthony Moody, Zack Moore, Christopher R. Polage, Jamie Puglin, P. Hunter Spotts, John A. Vaughn, Cameron R. Wolfe
Journal: MMWR Morbidity and Mortality Weekly Report (2020)

On university campuses and in similar congregate environments, surveillance testing of asymptomatic persons is a critical strategy (1,2) for preventing transmission of SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19). All students at Duke University, a private research university in Durham, North Carolina, signed the Duke Compact (3), agreeing to observe mandatory masking, social distancing, and participation in entry and surveillance testing. The university implemented a five-to-one pooled testing program for SARS-CoV-2 using a quantitative, in-house, laboratory-developed, real-time reverse transcription-polymerase chain reaction (RT-PCR) test (4,5). Pooling of specimens to enable large-scale testing while minimizing use of reagents was pioneered during the human immunodeficiency virus pandemic (6). A similar methodology was adapted for Duke University's asymptomatic testing program. The baseline SARS-CoV-2 testing plan was to distribute tests geospatially and temporally across on- and off-campus student populations. By September 20, 2020, asymptomatic testing was scaled up to testing targets, which include testing for residential undergraduates twice weekly, off-campus undergraduates one to two times per week, and graduate students approximately once weekly. In addition, in response to newly identified positive test results, testing was focused in locations or within cohorts where data suggested an increased risk for transmission. Scale-up over 4 weeks entailed redeploying staff members to prepare 15 campus testing sites for specimen collection, developing information management tools, and repurposing laboratory automation to establish an asymptomatic surveillance system. During August 2-October 11, 68,913 specimens from 10,265 graduate and undergraduate students were tested. Eighty-four specimens were positive for SARS-CoV-2, and 51% were among persons with no symptoms. Testing as a result of contact tracing identified 27.4% of infections. A combination of risk-reduction strategies and frequent surveillance testing likely contributed to a prolonged period of low transmission on campus. These findings highlight the importance of combined testing and contact tracing strategies beyond symptomatic testing, in association with other preventive measures. Pooled testing balances resource availability with supply-chain disruptions, high throughput with high sensitivity, and rapid turnaround with an acceptable workload.
Association Between State Medicaid Expansion and Emergency Access to Acute Care Hospitals in the United States
Authors: David J. Wallace, Julie M. Donohue, Derek C. Angus, Lindsay M. Sabik, Billie Davis, Jonathan Yabes, Jeremy M. Kahn
Journal: JAMA Network Open (2020)

<h3>Importance</h3> State decisions not to expand Medicaid under the Patient Protection and Affordable Care Act could reduce emergency access to acute care hospitals. <h3>Objective</h3> To determine the relationship between state Medicaid expansion and emergency access to acute care hospitals in the United States. <h3>Design, Setting, and Participants</h3> This cross-sectional study linked hospital-level data from the Centers for Medicare &amp; Medicaid Services from 2007 to 2017 to US Census data for all 50 US states and the District of Columbia. Geospatial analyses and difference-in-differences regression models were used to compare temporal changes in the size of the population without 30-minute access to acute care hospitals between 32 states that expanded Medicaid with the population without access in 19 that did not, before and after expansion. Analyses focused on the total population and those with low incomes; secondary analyses examined emergency access to safety-net hospitals. <h3>Exposures</h3> State-level Medicaid expansion. <h3>Main Outcomes and Measures</h3> Population without emergency access to an acute care hospital, defined as living outside a 30-minute drive of any hospital. <h3>Results</h3> States that did not expand Medicaid experienced an increase in the population without access to hospitals overall (without expansion: 6.76% to 6.79% [0.03%]; vs with expansion: 5.65% to 5.35% [–0.30%]; difference-in-differences, 0.33%; 95% CI, 0.33%-0.34%;<i>P</i> &lt; .001) and for low-income persons (without expansion: 7.43% to 7.39% [–0.04%]; vs with expansion: 6.25% to 6.15% [–0.10%]; difference-in-differences, 0.06%; 95% CI, 0.05%-0.07%;<i>P</i> &lt; .001). If access changes in nonexpansion states were the same as expansion states, an estimated 421 000 more persons overall and 48 000 more low-income persons would have retained access. States that did not expand Medicaid experienced an increase in the population without access to safety-net hospitals overall (46.91% to 47.70% [0.79%] vs 33.94% to 33.07% [–0.87%]; difference-in-differences, 1.66%; 95% CI, 1.64%-1.66%;<i>P</i> &lt; .001) and for low-income persons (45.28% to 46.14% [0.86%] vs 33.00% to 32.23% [–0.77%]; difference-in-differences, 1.63%; 95% CI, 1.63%-1.67%;<i>P</i> &lt; .001). If access changes in nonexpansion states were the same as expansion states, an estimated 2 242 000 more persons overall and 364 000 more low-income persons would have retained access. <h3>Conclusions and Relevance</h3> States that did not expand Medicaid under the Patient Protection and Affordable Care Act were associated with worse emergency access to acute care hospitals compared with states that expanded Medicaid.
Abstract 15084: A Retrospective Analysis of Atrial Fibrillation Patients Aged 80 Years and Older Prescribed a Low-dose Non-vitamin K Antagonist Anticoagulant
Authors: Usman A Chaudhry, Michael Ezekowitz, Edward J Gracely, Catrina M Wolfe, Grace M Harper, Glenn Harper
Journal: Circulation (2020)

Background: The very elderly and those receiving low doses of the direct-acting oral anticoagulants (DOACs) were underrepresented in trials leading to the approval of Apixaban 2.5 mgs BID (A), Rivaroxaban 15mgs daily (R) and Edoxaban 30 mgs daily (E). Approval of dabigatran 75mgs BID (D) was based entirely on pharmacokinetic studies. Methods: Retrospective analysis of the electronic medical record of a multi-disciplinary practice of 396,064 patients between 1/1/11 (when first DOAC available) and 5/31/17. Results: 9,446 patients had Atrial Fibrillation (AF), with 2,660 prescribed a DOAC and 846 at the low dose with 514 ≥ 80 yrs (range 80 – 98) with a mean CHA 2 DS 2 -VASc score of 4.5, which did not differ between patients prescribed D, R or A (p = 0.66 by ANOVA). Fifty-three patients received D, first used on 2/26/11, 223 R, first used on 12/15/11, and 236 A, first used on 6/19/12, and one patient received E. Among 28 baseline variables there were no clinically relevant differences among D, R, and A. All outcomes were reported as time to first event. All-cause mortality, n = 5 (5.5%/yr) for D, n =15 (4.2%) for R, and n = 23 (9.5%) for A, p = 0.031 by log rank test (with A &gt; R by pairwise log-rank, p = 0.013). Major bleeding n = 13 (14.3%/yr) for D, n = 50 (14.1%) for R, and n = 22 (9.1%) for A, p = 0.048 by log rank test (with A &lt; R, p = 0.017). Intracranial bleeding n = 2 (2.2%/yr) for D, n = 6 (1.7%) for R, and n = 2 (0.8%) for A, p = 0.53. There were 7 ischemic strokes or systemic embolic events (SSE) in total (1.1%/yr): D, R, and A (p = 0.94). Comparisons involving D may be underpowered. 245 patients (47.7%) remained on their prescribed drug without an event for the observation period (p = 0.55). Conclusion: D, R and A were well tolerated in patients ≥ 80 yrs, with low SSE and intracranial bleed rates. Major bleeds were the most frequent outcome, lowest in patients prescribed A. A had a higher all-cause mortality.