tbuckley/cabot-search huggingface dataset:
Abstract 14480: Family Planning Care Experiences and Perceptions of Women With Congenital Heart Disease
Authors: Natalie Stokes, Olivia Stransky, Shawn C WEST, Arvind Hoskoppal, Mehret Birru Talabi, Sonya Borrero, Traci Kazmerski
Journal: Circulation (2020)

Background: Due to medical advances, women with congenital heart disease (CHD) are living longer, healthier lives and many are considering pregnancy. The hemodynamic changes of pregnancy can present high risks of morbidity and mortality for many women with CHD. As little is known about these women’s reproductive health experiences, this study examines their perceptions of pregnancy and family planning care as related to CHD. Methods: Women ages 18-45 years with a diagnosis of CHD associated with a WHO classification II-IV for pregnancy morbidity and mortality participated in individual, semi-structured interviews exploring their experiences and attitudes toward parenthood, pregnancy, contraception and family planning care provision. Interviews were audio-recorded, transcribed verbatim, and analysis was performed by two independent coders using an inductive coding approach. Results: Twenty women with CHD participated in interviews (average age 30.1 years, SD 5.85). Nine women had ever been pregnant and 14 considered becoming a parent in the future. We identified 5 key interview themes: (1) Women saw CHD as impacting their reproductive health goals and decisions; (2) Women with CHD desired tailored, disease-specific family planning information; (3) Women with CHD viewed their cardiologist as the primary source for family planning information and prefer provider-initiated reproductive health discussions starting in adolescence; (4) Women with CHD desire coordinated preconception and intrapartum care between their cardiologists and women’s health providers; and (5) Women with CHD perceived a lack of safe contraceptive methods for their condition. Conclusions: Women with CHD face a variety of disease-specific family planning concerns and desire coordinated reproductive healthcare from their cardiologists and women’s health providers. As more women with CHD reach childbearing age, these unique needs must be addressed to empower women to make informed family planning decisions. These results provide a foundation for interventions to improve patient-centered interdisciplinary reproductive healthcare for this population.
Abstract 13745: Hazardous Alcohol Use is a Common but Infrequently Addressed Problem Among Hospitalized Cardiovascular Patients
Authors: Kyle Gobeil, Theodore Medling, Paolo Tarvaez, khalid sawalha, Mohammed Abozenah, Peter Friedmann, timothy naimi, Quinn Pack
Journal: Circulation (2020)

Introduction: Excessive alcohol intake and binge drinking behavior has known detrimental cardiovascular impacts. National estimates suggest that about 7% of U.S. adults has hazardous drinking behavior, but it is unclear if this is different among the inpatient cardiac population and, furthermore, how often this issue is addressed during hospitalization. Hypothesis: Prevalence of alcohol use is underappreciated in the cardiac population due to purported health benefits, and therefore, likely to be overlooked. Methods: Disorders Identification Test (AUDIT), among patients hospitalized for cardiac surgery, heart failure (HF) or myocardial infarction (MI) between June and September 2019. Problem drinking was defined as an AUDIT score of ≥8 with binge drinking defined as 5+ drinks for men or 4+ for women on a single occasion within the past 30 days. Hazardous drinking was defined as a combination of either problem or binge drinking behavior. Results: Of 300 patients approached, a total of 290 (96.7%) completed the survey (33% non-drinkers, age 69 ± 11 years, 70% male, 4% Spanish-speaking, 31% surgical). The rate (95% CI) of problem, binge, and hazardous drinking was 12% (9-16), 16% (12-20), and 18% (14-23), respectively. Irrespective of alcohol use, 58% of patients reported being asked about alcohol use during their admission, mostly by nurses (56%). Patients with hazardous drinking were counseled more frequently about their alcohol use compared to non-hazardous drinkers, (11% vs 3%, p = 0.03), but the large majority (89%) of hazardous drinkers received no advice about their alcohol use while hospitalized and only 34 (12%) patients reported having ever been given a recommendation about alcohol consumption by a cardiologist or cardiac surgeon. Conclusions: In patients hospitalized for acute cardiac illnesses, the prevalence of problem drinking was more than double national estimates. About half of patients with problem drinking behavior were asked about their alcohol, and only a minority of patients received counseling. Our findings suggest that hazardous alcohol use is more common that previously appreciated, and that there are substantial health-system gaps in screening and counseling for this important cardiovascular risk factor.
Abstract 11494: Aldehyde Dehydrogenase-2 Regulates the Mitochondrial Translocation of Dnmt1 in Cardiomyocyte
Authors: Xiaolei Sun, Yongchao Zhao, Junbo Ge, Aijun Sun
Journal: Circulation (2019)

Objective: The presence of methylaition has been reported to contain mitochondrial DNA (mtDNA), but the mtDNA methylation of cardiomyocyte is unclear. We herein explored the DNMT1 expression in myo...
Abstract 14994: Discontinuation of Statins and Adverse Clinical Outcomes Post Percutaneous Coronary Intervention
Authors: Daniel E Harris, Arron Lacey, Ashley Akbari, Mike B Gravenor, Julian P Halcox
Journal: Circulation (2018)

Introduction: Statin treatment reduces cardiovascular morbidity and mortality in those with and at risk of cardiovascular disease (CVD) and is endorsed in all major clinical guidelines for the prev...
A Phase I Trial of Talimogene Laherparepvec in Combination with Neoadjuvant Chemotherapy for the Treatment of Nonmetastatic Triple-Negative Breast Cancer
Authors: Hatem Soliman, Deanna Hogue, Hyo Han, Blaise Mooney, Ricardo Costa, Marie C. Lee, Bethany Niell, Angela Williams, Alec Chau, Shannon Falcon, Nazanin Khakpour, Robert J. Weinfurtner, Susan Hoover, John Kiluk, Marilin Rosa, Hung Khong, Brian Czerniecki
Journal: Clinical Cancer Research (2020)

Talimogene laherparepvec (TVEC) is an oncolytic herpes simplex 1 virus approved for treatment of melanoma. We hypothesized intratumoral TVEC may enhance response to neoadjuvant chemotherapy (NAC). This article reports the results of a trial combining NAC with TVEC for triple-negative breast cancer (TNBC).Patients with stage II-III TNBC enrolled in a 3+3 phase I trial (NCT02779855) of two TVEC dose levels [DL; DL 1 = 106 plaque-forming units (PFU) × 5 doses; DL 2 = 106 PFUs first dose, then 108 PFUs × 4 doses] on weeks 1, 4, 6, 8, and 10 plus weekly paclitaxel (80 mg/m2) for 12 weeks, followed by doxorubicin/cyclophosphamide (60/600 mg/m2) every 2 weeks for 8 weeks. Postoperative response assessment using residual cancer burden (RCB) was performed. Primary endpoints were safety and MTD. Secondary endpoints were RCB0 rate and immune correlates. Dose-limiting toxicity (DLT) rule was grade 3-5 adverse events due to TVEC during first 5 weeks.Nine patients [DL 1 (n = 3); DL 2 (n = 6)] were enrolled. Six had stage II disease, and 3 had stage III (6 clinically N+). No DLTs occurred, and MTD was DL 2. Most common toxicities with TVEC were fever (n = 8), chills (n = 3), hematomas (n = 3), and injection site pain (n = 3). Thromboembolic events (n = 2) and bradycardia (n = 1) occurred during or after NAC. Five patients (55%) achieved RCB0, 2 had RCB1 (22%), and 2 had RCB2 (22%).The addition of TVEC to NAC was feasible at the approved dose, with manageable toxicity. The complete response rate was 55%.
Obstructive sleep apnoea and the progression of thoracic aortic aneurysm: a prospective cohort study
Authors: Thomas Gaisl, Protazy Rejmer, Maurice Roeder, Patrick Baumgartner, Noriane A. Sievi, Sandra Siegfried, Simon F. Stämpfli, Robert Thurnheer, John R. Stradling, Felix C. Tanner, Malcolm Kohler
Journal: European Respiratory Journal (2020)

Obstructive sleep apnoea (OSA) is associated with an increased prevalence of aortic aneurysms and it has also been suggested that severe OSA furthers aneurysm expansion in the abdomen. We evaluated whether OSA is a risk factor for the progression of ascending thoracic aortic aneurysm (TAA).Patients with TAA underwent yearly standardised echocardiographic measurements of the ascending aorta over 3 years and two level III sleep studies. The primary outcome was the expansion rate of TAA in relation to the apnoea-hypopnoea index (AHI). Secondary outcomes included surveillance for aortic events (composite end-points of rupture/dissection, elective surgery or death).Between July 2014 and March 2020, 230 patients (median age 70 years, 83.5% male) participated in the cohort. At baseline, 34.8% of patients had AHI ≥15 events·h-1. There was no association between TAA diameter and AHI at baseline. After 3 years, mean±sd expansion rates were 0.55±1.25 mm at the aortic sinus and 0.60±1.12 mm at the ascending aorta. In the regression analysis, after controlling for baseline diameter and cardiovascular risk factors, there was strong evidence for a positive association of TAA expansion with AHI (aortic sinus estimate 0.025 mm, 95% CI 0.009-0.040 mm; p<0.001 and ascending aorta estimate 0.026 mm, 95% CI 0.011-0.041 mm; p=0.001). 20 participants (8%) experienced an aortic event; however, there was no association with OSA severity.OSA may be a modest but independent risk factor for faster TAA expansion and thus potentially contributes to life-threatening complications in aortic disease.
Abstract 240: Comparison of Hemodynamics Generated by Synchronized and Interposed Compressions During Treatment of Pseudo Electro-mechanical Dissociation
Authors: Joshua W Lampe, Jill K Badin, Lyra Clark, Jeff R Gould, Karen L Moodie, Norman A Paradis
Journal: Circulation (2020)

Introduction: Pseudo electro-mechanical dissociation (P-EMD) is a cardiac arrest variant characterized by a life-threatening reduction in cardiac output in the presence of organized electrical activity. Synchronization of chest compressions to the R-wave in the ECG may be preferable to the delivery of standard CPR. However, in the bradycardic P-EMD state, synchronization may result in inadequate blood flow due to the low compression/heart rate. This pilot study examined the hemodynamic effect of interposing additional chest compressions between synchronized chest compressions during bradycardic P-EMD to increase the compression rate. Methods: P-EMD was induced via hypoxia in three female swine (~30 kg) and treated with synchronized compressions until the onset of asystole (HR&lt;12 BPM). Interposed compressions were added when the heart rate fell below 60 BPM. A chest compression was classified as synchronized or interposed depending on the presence or absence of a co-incident R-wave. Hemodynamic parameters were integrated or averaged over each compression interval. Results: Synchronized compressions tended to produce larger aortic pressures, larger carotid blood flows, and lower right atrial pressures than interposed compressions. Data from one experiment are shown in Figure 1. The relative hemodynamic benefit of a synchronized chest compression appears to depend on the effectiveness of the underlying heart contraction. The interposed chest compressions generated forward carotid blood flow and increased the compression rate during bradycardia. Discussion: During bradycardic P-EMD, synchronized compressions may generate better hemodynamics than interposed compressions, and the combination of synchronized and interposed compressions may result in more blood flow than the delivery of synchronized compressions alone. Figure 1. Comparison of hemodynamics generated by synchronized compressions (blue) and interposed compressions (red).
Somatic copy number gains in MYC, BCL2, and BCL6 identifies a subset of aggressive alternative-DH/TH DLBCL patients
Authors: Jordan E. Krull, Kerstin Wenzl, Keenan T. Hartert, Michelle K. Manske, Vivekananda Sarangi, Matthew J. Maurer, Melissa C. Larson, Grzegorz S. Nowakowski, Stephen M. Ansell, Ellen McPhail, Thomas M. Habermann, Brian K. Link, Rebecca L. King, James R. Cerhan, Anne J. Novak
Journal: Blood Cancer Journal (2020)

Abstract Double/triple hit lymphoma (DH/TH), known as high-grade B-cell lymphoma (HGBL), is an aggressive diffuse large B cell lymphoma (DLBCL), defined as having concurrent MYC , BCL2 , and/or BCL6 gene rearrangements. While gene rearrangements represent significant genetic events in cancer, copy number alterations (CNAs) also play an important role, and their contributions to rearrangements have yet to be fully elucidated. Using FISH and high-resolution CNA data, we defined the landscape of concurrent gene rearrangements and copy gains in MYC , BCL2 , and BCL6 , in a cohort of 479 newly diagnosed DLBCL. We also show that concurrent translocations and copy number alterations, in combinations similar to DH/TH, identify a unique subset of DLBCL, alternative DH/TH, that have survival outcomes similar to DH/TH DLBCL patients.
Abstract 14207: Endothelial Progenitor Cells, T Cells and Macrophages’ Peripheral Levels as Possible Predictive Biomarkers of Acute Myocardial Infarction
Authors: Amankeldi A Salybekov, Katsuaki Sakai, Makoto Natsumeda, Kosit Vorateera, Yuji Ikari, Takayuki Asahara
Journal: Circulation (2020)

Introduction: Acute myocardial infarcted (AMI) patient prognosis is strictly dependent on early diagnosis and the adoption of adequate interventions. Hypothesis: Immune cells' blood level as a possible candidate to use distinct diagnostic biomarkers of AMI (H1) with/out the combination with clinical-laboratory findings are little known (H2). Materials &amp;Methods: Eighteen patients with the diagnosis of AMI were enrolled. Patients with a history of chronic inflammatory disease excluded. All patients underwent emergent percutaneous coronary intervention via the radial artery and guided by optical coherence tomography. Peripheral blood was drawn after obtaining informed consent from patients at days three and seven (MI-D3 &amp; MI-D7) after onset AMI along with sixteen healthy volunteers as a control. The mononuclear cells isolated by density gradient centrifugation and evaluated with EPCs colony formation assay, and flow cytometry analysis (FCA). Results: FCA revealed that total mononuclear live cells were significantly lower at MI-D3 and MI-D7 in myocardial infarcted patients compared with healthy controls (55.18±6.7 vs. 77.5±2, P&gt;0.01; and 64.52±7.33 vs. 77.5±2, P&gt;0.08, respectively). An area under the ROC curve (AUC) in MI-D3 was 0.95 (P&gt;0.0007), that is, total CD34+cells/ml counts for MI-D3 vs. healthy controls whereas at MI-D7 the value of EPCs as a predictor was reduced AUC=0.71(P&lt;0.16). In correlation analysis, coronary vessels lesions number inversely correlates vs. MI-D3 total EPCs number (r= -0.45) but not at MI-D7 (r= 0.39). Correlation test showed the tendency of a positive correlation between creatine kinase myocardial band to CD8+ cells at MI-D3 (r=0.58; P&lt;0.054) but not at MI-D7. ROC curve analysis depicted a high accuracy AMI prediction rate of CD8+ cells at MI-D3 (AUC=0.94; P&gt;0.0004) and MI-D7 (AUC=0.85; P&gt;0.03). Notably, all T cells subsets negatively correlated with myeloid cell subsets such as M1 and M2 macrophages at MI-D7, indicating T cells loss in PB stream compensated by monocyte/macrophage. Conclusion: Our data demonstrated that circulating EPCs number associates with cardiac vessel lesion, whereas CD8+ cells may serve as a high accuracy biomarker of AMI with a combination of classical clinical-laboratory findings.
Abstract 108: Work of Breathing Scale to Assess Need of Intubation in Covid-19 Pneumonia
Authors: Raul J Gazmuri, Mylene Apigo, Philip Fanapour, Amin Nadeem
Journal: Circulation (2020)

COVID-19 pneumonia presents in most patients with significant hypoxemia but without substantial impairment of lung compliance that would increase the work of breathing (WOB) to levels requiring invasive mechanical ventilation. Thus, the ability to assess the WOB independent of the oxygen needs could help guide management and possibly avoid intubation. We previously developed and implemented in our ICU a WOB scale based on respiratory physiology ranging from 1 to 7 by assigning points to the respiratory rate level and the use of respiratory accessory muscles. We analyzed the use of our WOB scale in 10 patients admitted to our ICU with severe COVID-19 pneumonia. All patients had radiographic evidence of extensive lung disease with significant hypoxemia and multiple risk factors associated with poor outcome. Hypoxemia was successfully managed using high-flow nasal cannula. The WOB level was measured every 4 hours. The maximum WOB was 4.3 ± 0.9, contributed primarily by the respiratory rate with a score of 3.6 ± 0.5 but with infrequent use of respiratory accessory muscles. All 10 patients survived without need of intubation. For comparison, three other patients who needed intubation had a maximal work of breathing within the preceding 24 hours of 5.3 ± 1.2 with a respiratory rate score of 3.7 ± 0.6, as in non-intubated patients, but with more often use of respiratory accessory muscles. Our data suggest that patients with COVID-19 pneumonia can be supported for extended periods using HFNC despite tachypnea provided there is only infrequent use of respiratory accessory muscles, corresponding to a WOB scale ≤ 4, prompting closer assessment for possible intubation when WOB &gt; 4. This approach would be especially advantageous under conditions of high disease intensity when avoidance of intubation is likely to result in a better outcome.
Abstract 17144: miR-146a-5p Induces Pulmonary Barrier Disruption via Macrophage-Derived TNFa
Authors: Huang Huang, Jiang Hu, Jing Zhu, Wei Chao, Lin Zou
Journal: Circulation (2020)

Introduction: Sepsis-induced acute lung injury (ALI) has substantial morbidity and mortality. Diffused alveolar damage as a result of increased endothelial cell (EC) permeability is a hallmark of ALI. We have previously demonstrated that certain uridine-rich extracellular (ex) miRNAs such as miR-146a activate innate immune response and possess a potent proinflammatory property, but their effect on EC function is largely unknown. Hypothesis: Pulmonary EC barrier function is impaired by miR-146a-5p. Methods: Conditioned media (CM) were collected from macrophages (Mφ) cultures treated with lipofectamine (lipo) or miR-146a-5p (50 nM) for 24 h. EC barrier function was analyzed in human pulmonary arterial endothelial cells (HPAECs) by transendothelial electric resistance (TER) using an electric cell-substrate impedance sensing system. Results: Direct miR-146a-5p treatment of HPAECs did not cause any change in TER even though it induced robust IL-6 and CXCL2 production in Mφ. To test whether miR-146a-5p affects EC function indirectly, we incubated HPAECs with miR146a-CM and observed a more than 50% reduction in TER ( Fig. A ). Lipo-CM had no such effect. This barrier effect was accompanied by VE-cadherin internalization and disrupted VE-cadherin lining following 8 hours of incubation ( Fig. B) . To determine the potential mediators in the CM responsible for the EC barrier disruption, we performed a cytokine array analysis of 111 cytokines in the CM and identified 15 differentially expressed cytokines. Among them, we found that TNFα neutralizing Ab (1μg/ml), but not control IgG (1μg/ml), partially blocked the miR-146a-CM-induced EC barrier disruption with improved VE-Cadherin integrity ( Fig. B ). Conclusion: Our data demonstrated miR-146a-5p induces HPAEC barrier dysfunction via an indirect mechanism involving Mφ production of TNFα.
Abstract 212: Effects of Therapeutic Hypothermia on Glymphatic Clearance
Authors: Padmesh Rajput, Jessica Lamb, Patrick D Lyden
Journal: Circulation (2020)

Objectives: Therapeutic hypothermia is the most potent protective therapy for cerebral ischemia in pre-clinical models, however clinical trials have failed to show a significant benefit in patient outcomes. We sought to reconcile this discrepancy by investigating whether hypothermia impaired glymphatic system mediated waste clearance from brain parenchyma in a rat model. Methods: Sprague -Dawley rats were divided into normothermia and hypothermia groups. Hypothermia was achieved using a perivascular closed-loop cooling circuit implanted one week before the experiments in both the groups. Animals in the normothermia group were kept at 37C while the hypothermia animals were cooled to 33C. Once the targeted temperature was reached, two fluorescent tracers, small molecular weight (Texas Red-Dextran 3KdA) and large molecular weight (FITC -Dextran 2MdA) were injected intracisternally in each animal. Animals in both the groups were monitored for blood pressure and blood gases. Thirty minutes after injection, animals were perfused with 4% paraformaldehyde and 50 micron sections were cut using Leica vibratome. Brain sections were mounted on slides and cover slipped using antifade Fluro gold. Sections were imaged on Carl-Zeiss apotome microscope. For each animal 12 sections were imaged, data was analyzed using NIH Image J software. Results and Discussion: Cerebrospinal fluid tracer efflux in brain was significantly reduced in the hypothermia group compared to the normothermia group. This experiment helps provide insight as to a potential reason clinical trials have failed to show benefit in stroke patients, as hypothermia may have an untoward effect of hindering the brain’s natural clearance system from clearing inflammatory molecules and other waste from brain parenchyma.
Abstract 14054: Soluble ACE2, Cardiac Biomarkers, Structure, Function and Events: The Atherosclerosis Risk in Communities (ARIC) Study
Authors: Aliza Hussain, Olive Tang, Wensheng Sun, Xiaoming Jia, Elizabeth Selvin, Vijay Nambi, Aaron R Folsom, Gerardo M HEISS, Faiez Zannad, Thomas Mosley, Salim S Virani, Joseph Coresh, Eric Boerwinkle, Bing Yu, Jonathan Cunningham, Amil M Shah, Scott Solomon, James A De Lemos, Ron C Hoogeveen, Christie M Ballantyne
Journal: Circulation (2020)

Introduction: Membrane-bound angiotensin-converting enzyme 2 (ACE2) has been identified to a have prominent role in SARS-COV-2 infection and is an important counter-regulator of renin-angiotensin system. But the association of cleaved soluble ACE2 (sACE2) with cardiovascular disease (CVD) remains unclear. We sought to identify the association of sACE2 with cardiac biomarkers, structure, function and events in the Atherosclerosis Risk in Communities (ARIC) Study. Methods: sACE2 was measured in a subset of 497 patients from a case-control study of incident heart failure (HF) at visit 5 (2011-2013), mean age 78 (SD 5.4), 53% men and 27% black. We used linear regression to evaluate the associations of sACE2 with cardiac biomarkers (hs-cTnI, hs-cTnT, NT-proBNP) and echocardiographic parameters. We used Cox regression to evaluate associations of sACE2 with risk of HF hospitalization, global CVD events (CHD, ischemic stroke or HF hospitalization) and all-cause death. Results: Over a median follow up of 6.1 (4.6, 6.8) years, 282 global CVD events and 190 all-cause deaths occurred. sACE2 levels were higher in men, blacks, those with prevalent CVD, diabetes and hypertension. Higher sACE2 levels were associated with significantly higher hs-cTnI, hs-cTnT, NT-proBNP levels, greater left ventricular (LV) mass index, impaired diastolic function ( Table ) and increased risk for HF hospitalization (adjusted HR 1.32 per log unit increase, 95% CI 1.10-1.58), global CVD events (HR 1.34, 95% CI 1.13-1.60) and all-cause death (HR 1.26, 95% CI 1.01-1.57). Conclusions: In an elderly biracial cohort, sACE2 was positively associated with biomarkers reflecting myocardial injury and neurohormonal activation, LV mass index, impaired diastolic function, CVD events and all-cause death. Future research is needed to elucidate the significance of sACE2 in development of CVD, not only in patients with SAR—COV2 infection, but the general population