tbuckley/cabot-search huggingface dataset:
Abstract 13429: Echocardiographic Predictors of Mitral Transvalvular Gradients After Mitraclip Insertion
Authors: Sandra Hadjadj, Afonso B. Freitas-Ferraz, Amélie Paquin, Mathieu Bernier, Kim O'Connor, Erwan Salaun, Philippe Pibarot, Marie-Annick Clavel, Josep Rodés-Cabau, Jean-Michel Paradis, Jonathan Beaudoin
Journal: Circulation (2020)

Introduction: The MitraClip procedure is a non-surgical alternative for patients with severe mitral regurgitation and high surgical risk. However, the MitraClip may lead to a reduction in the mitral valve orifice area (MVOA) and elevated transmitral mean gradients (TMG). The objectives of this study are to assess the value of baseline MVOA by different imaging methods and explore the value of MVOA indexed for left ventricular (LV) forward stroke volume (SV) to predict postprocedural TMG. Methods: Preprocedural echo images were retrospectively reviewed in 76 consecutive patients. MVOA from 2D transthoracic (MVOA TTE ), 2D transgastric (MVOA TG ) and 3D transesophageal (MVOA 3D ) echocardiography were measured and then indexed by the SV measured by Doppler in the LV outflow tract (MVOA/SV) . Postprocedural TMG was measured at one month and survival rate at one year. Results: Patients with postprocedural TMG &gt;5 mmHg (18/76, 24%) had significantly smaller preprocedural MVOA 3D (3.9±0.9 vs 5.2±1.3 cm 2 , p&lt;0.01) and MVOA TTE (4.9±1.1 vs 5.9±1.5 cm 2 , p=0.02). No significant difference was found for MVOA TG (5.5±1.4 vs 5.9±1.4 cm 2 , p=0.2). Best threshold values for MVOA 3D and MVOA TTE to predict postprocedural TMG &gt;5 mmHg were respectively 3.9 cm 2 (AUC=0.80, IC95%: 0.67-0.94, p&lt;0.01; sensitivity (Se) 62%, specificity (Sp) 87%) and 4,6 cm 2 (AUC=0.69, IC95%: 0.54-0.83, p=0.02; Se 50%, Sp 84%). MVOA/SV from each echocardiographic modality were smaller in patients with postprocedural TMG &gt;5 mmHg (3D: 80 [62-95] vs 113 [99-129] cm 2 /L; TTE: 92 [81-105] vs 130 [100-166] cm 2 /L; TG: 104 [83-123] vs 135 [104-166] cm 2 /L; p&lt;0.01 for all). MVOA/SV 3D was overall the best predictor of postprocedural TMG &gt;5 mmHg, with an optimal threshold of 96 cm 2 /L (AUC=0.86, IC95%: 0.76-0.97, p&lt;0.001; Se 84%, Sp 81%). Patients with MVOA 3D &lt;3.9 cm 2 and MVOA/SV 3D &lt;96 cm 2 /L tend to be at higher risk for mortality at one-year follow-up (69% vs 84%, p=0.14 and 67% vs 87%, p=0.11 respectively). Conclusion: Unlike preprocedural MVOAs assessed by 3D echocardiography, preprocedural MVOAs measured by 2D echocardiographic modalities were poor predictors of high TMG after MitraClip. Preprocedural MVOA 3D &lt;3.9 cm 2 and MVOA/SV 3D &lt;96 cm 2 /L were found to be the best cut-off values to predict postprocedural TMG &gt;5 mmHg.
Long-term air pollution and road traffic noise exposure and COPD: the Danish Nurse Cohort
Authors: Shuo Liu, Youn-Hee Lim, Marie Pedersen, Jeanette T. Jørgensen, Heresh Amini, Thomas Cole-Hunter, Amar J. Mehta, Rina So, Laust H. Mortensen, Rudi G.J. Westendorp, Steffen Loft, Elvira V. Bräuner, Matthias Ketzel, Ole Hertel, Jørgen Brandt, Steen S. Jensen, Jesper H. Christensen, Torben Sigsgaard, Camilla Geels, Lise M. Frohn, Maja Brboric´, Jelena Radonic´, Maja Turk Sekulic, Klaus Bønnelykke, Claus Backalarz, Mette K. Simonsen, Zorana J. Andersen
Journal: European Respiratory Journal (2021)

Background While air pollution has been linked to the development of chronic obstructive pulmonary disease (COPD), evidence on the role of environmental noise is just emerging. We examined the associations of long-term exposure to air pollution and road traffic noise with COPD incidence. Methods We defined COPD incidence for 24 538 female nurses from the Danish Nurse Cohort (age &gt;44 years) as the first hospital contact between baseline (1993 or 1999) and 2015. We estimated residential annual mean concentrations of particulate matter with an aerodynamic diameter &lt;2.5 µm (PM 2.5 ) since 1990 and nitrogen dioxide (NO 2 ) since 1970 using the Danish Eulerian Hemispheric Model/Urban Background Model/Air Geographic Information System modelling system, and road traffic noise (L den ) since 1970 using the Nord2000 model. Time-varying Cox regression models were applied to assess the associations of air pollution and road traffic noise with COPD incidence. Results 977 nurses developed COPD during a mean of 18.6 years’ follow-up. We observed associations with COPD for all three exposures with HRs and 95% CIs of 1.19 (1.01–1.41) per 6.26 µg·m −3 for PM 2.5 , 1.13 (1.05–1.20) per 8.19 µg·m −3 for NO 2 and 1.15 (1.06–1.25) per 10 dB for L den . Associations with NO 2 and L den attenuated slightly after mutual adjustment, but were robust to adjustment for PM 2.5 . Associations with PM 2.5 were attenuated to null after adjustment for either NO 2 or L den . No potential interaction effect was observed between air pollutants and noise. Conclusion Long-term exposure to air pollution, especially traffic-related NO 2 , and to road traffic noise were independently associated with COPD.
Evaluation and Management of Aortic Stenosis in Chronic Kidney Disease: A Scientific Statement From the American Heart Association
Authors: Gautam R. Shroff, Sripal Bangalore, Nicole M. Bhave, Tara I. Chang, Santiago Garcia, Roy O. Mathew, Janani Rangaswami, Julien Ternacle, Vinod H. Thourani, Philippe Pibarot
Journal: Circulation (2021)

Aortic stenosis with concomitant chronic kidney disease (CKD) represents a clinical challenge. Aortic stenosis is more prevalent and progresses more rapidly and unpredictably in CKD, and the presence of CKD is associated with worse short-term and long-term outcomes after aortic valve replacement. Because patients with advanced CKD and end-stage kidney disease have been excluded from randomized trials, clinicians need to make complex management decisions in this population that are based on retrospective and observational evidence. This statement summarizes the epidemiological and pathophysiological characteristics of aortic stenosis in the context of CKD, evaluates the nuances and prognostic information provided by noninvasive cardiovascular imaging with echocardiography and advanced imaging techniques, and outlines the special risks in this population. Furthermore, this statement provides a critical review of the existing literature pertaining to clinical outcomes of surgical versus transcatheter aortic valve replacement in this high-risk population to help guide clinical decision making in the choice of aortic valve replacement and specific prosthesis. Finally, this statement provides an approach to the perioperative management of these patients, with special attention to a multidisciplinary heart-kidney collaborative team-based approach.
Abstract 059: Pre-stroke Physical Activity Is Associated With Lower Mortality Risk After Stroke In The Atherosclerosis Risk In Communities (ARIC) Study
Authors: Mauro F Mediano, Yejin Mok, Josef Coresh, Anna Kucharska-newton, Priya Palta, Kamakshi Lakshminarayan, Wayne D Rosamond, Kunihiro Matsushita, Silvia Koton
Journal: Circulation (2021)

Background: The association between pre-stroke PA and long-term stroke outcomes is still unclear. We examined the association of pre-stroke PA with adverse health outcomes after incident stroke in the ARIC study. Methods: We included 881 participants with incident ischemic or hemorrhagic stroke occurring between 1993-1995 and December 31 st , 2016. Follow-up for all-cause and cardiovascular disease (CVD) mortality, CVD or recurrent stroke occurred through December 31 st , 2017, allowing for at least 1-year of follow-up after incident stroke. Pre-stroke total and domain-specific (work, sports and leisure) PA was assessed with the modified Baecke questionnaire at the baseline visit (1987-1989) and in 1993-1995. The total PA score was calculated by summing scores at both visits. Distribution-based tertiles of the summed score were derived. Cox proportional hazards models estimated the hazard ratios of adverse outcomes by tertiles of pre-stroke PA, adjusted for demographic and clinical characteristics. Results: During a median follow-up of 3.1 years after incident stroke, 77% participants developed adverse outcome. Compared to low pre-stroke PA, high pre-stroke PA was associated with a lower risk of all-cause mortality (HR=0.78; 95% CI: 0.63-0.97, Table). In the analysis by domain-specific PA, the risk of all-cause mortality was lowest among participants in the highest tertile of work PA (HR; 95% CI=0.77; 0.62-0.96) and leisure PA (HR=0.72; 95% CI: 0.58 to 0.89) compared to the lowest tertiles. The risk of CVD mortality was also lower in the highest tertile of work PA (HR=0.45; 95% CI: 0.29-0.70) compared to the lowest tertile. Conclusions: Higher levels of total pre-stroke PA, as well as work and leisure PA, were associated with a lower risk of mortality after incident stroke. Strategies to increase lifetime PA should be encouraged to decrease long-term mortality after stroke.
Abstract 13033: C-src Phosphorylates the Mitochondrial Ca <sup>2+</sup> Uniporter in Nonischemic Cardiomyopathy
Authors: An Xie, Gyeoung-Jin Kang, Eun Ji Kim, Iuliia Polina, Feng Feng, Bong Sook Jhun, Jin O-uchi, Samuel C Dudley
Journal: Circulation (2020)

Introduction: We have described previously an arrhythmic mechanism in nonischemic heart failure (NI-HF) involving an increased mitochondrial Ca 2+ uptake that results in QT prolongation and lethal arrhythmias. This arrhythmic mechanism is associated with mitochondrial Ca 2+ uniporter (MCU) tyrosine phosphorylation (p-Tyr). Hypothesis: Here, we determined which kinase was responsible for MCU phosphorylation in cardiomyopathy. Methods: NI-HF was induced by hypertension in Wt C57BL6 mice by unilateral nephrectomy, deoxycorticosterone acetate (DOCA) treatment and substituting drinking water with 1% saline for six weeks. Western blot, immunoprecipitation, fluorescence resonance energy transfer (FRET) and patch-clamp techniques were employed in isolated mouse cardiomyocytes. Results: When compared to control hearts, the protein level of p-Src S17 increased significantly accompanied by significant enhancement of tyrosine but not serine/threonine phosphorylation of MCU in NI-HF mouse hearts. In a heterologous expression system, c-Src could bind MCU and tyrosine phosphorylate MCU. This phosphorylation was blocked by a c-Src inhibitor, PP1. Overexpression of constitutive active c-Src (Src-Y527F) significantly increased MCU inward current at -160 mV. It suggested that c-Src activation was directly related to mitochondrial-mediated arrhythmic risk. Downregulation of C-terminal Src kinase (CSK), a regulatory kinase inversely related to c-Src activity, increased p-Src, enhanced mitochondrial and SR contact, and facilitated mitochondrial Ca 2+ uptake in NI-HF mouse cardiomyocytes. Proline-rich tyrosine kinase 2 (Pyk2) did not contribute more phosphorylated MCU during cardiomyopathy as the protein expression of PyK2, p-PyK2 Y402 and p-PyK2 Y579/580 did not change during NI-HF. Correlation using human heart tissue showed that NI-HF patients had significantly increased p-Src S17 associated with an increased incidence of QTc elongation and arrhythmia. Conclusions: During cardiomyopathy, c-Src activation directly tyrosine phosphorylated MCU, increased MCU current, and increased mitochondrial/SR contact, suggesting this kinase is responsible for the increase in mitochondria-mediated arrhythmic risk seen in NI-HF.
Abstract 16658: Serum Potassium and Risk of Death in Patients With HFpEF: An Analysis of PARAGON-HF
Authors: Joao Ferreira, Faiez ZANNAD, Akshay S Desai, Karola Jering, Marc A Pfeffer, Jean L Rouleau, Sanjiv J Shah, Jean L Rouleau, Dirk J Van Veldhuisen, Scott Solomon, John J McMurray
Journal: Circulation (2020)

Introduction: Hyper- and hypo-kalemia have each been associated with higher risk of death in in heart failure with reduced ejection fraction but the relationship between serum potassium and risk of death in heart failure with preserved ejection fraction (HFpEF) is not well established. We assessed the risk associated with high and low potassium in patients with HFpEF enrolled in the PARAGON-HF trial. Aim: To explore the association between serum potassium and mortality in patients with HFpEF and examine the interaction with renal function. Methods: Repeated events, Cox and mixed-effects models. The primary outcome in this analysis was death from any cause. Results: Patients: mean age 73 years, 52% female. Higher potassium was not associated with higher risk of death: adjusted time-updated HR (95%CI) for potassium &gt;5.0 mmol/l =1.06 (0.85-1.32); p=0.61 (potassium 4-5 mmol/l referent HR=1.0). However, lower potassium was associated with higher risk of death: adjusted HR for potassium &lt;4.0 mmol/l=1.51 (1.21-1.87); p&lt;0.001. However, the risk related to potassium was modified by baseline renal function (p for interaction &lt;0.05), whereby the excess mortality in patients with low potassium was most prominent in patients with an eGFR &lt;60 ml/min/1.73m 2 (Figure). Conclusion: In adjusted analyses, low potassium was independently associated with mortality in patients with HFpEF, especially in the context of renal impairment.
4MO_PR HER2-low breast cancer: Evolution from primary breast cancer to relapse
Authors: F. Miglietta, G. Griguolo, M. Bottosso, T. Giarratano, M. Lo Mele, M. Fassan, M. Cacciatore, E. Genovesi, D. De Bartolo, G. Vernaci, P.F. Conte, V. Guarneri, M.V. Dieci
Journal: Annals of Oncology (2021)
Abstract 15156: Comparison of Left Atrial D <i>-</i> dimer Level in Patients With Atrial Fibrillation Administering Dabigatran, Apixaban and Edoxaban
Authors: Tetsuya Watanabe, Kouichi Tachibana, Yukinori Shinoda, Tomoko Minamisaka, Hidetada Fukuoka, Hirooki Inui, Keisuke Ueno, Shiro Hoshida
Journal: Circulation (2020)

Introduction: Atrial fibrillation causes cerebral infarction and systemic embolism. Increased D-dimer level indicates the hyperactivation of secondary fibrinolysis, showing thrombosis tendency in the vessel. Hypothesis: To clarify the effects of anticoagulation therapy, we planned to compare the D-dimer levels of peripheral and left atrial (LA) blood in patients scheduled for atrial fibrillation ablation during administration of dabigatran (D), apixaban (A) and edoxaban (E). Methods and Results: We analyzed 141 patients with non-valvular atrial fibrillation (D, n=30; A, n= 47; E, n=64; median age: 68[38-84] years, male: 60%) after exclusion of patients on dialysis. Peripheral venous blood was collected immediately before ablation and LA blood was collected immediately after the Brockenbrough method. We examined laboratory and echocardiographic parameters such as D-dimer and protein C levels, and LA diameter. Anticoagulation therapy was discontinued on the day of ablation. There were no significant differences in ejection fraction, LA diameter and peripheral C-reactive protein levels among the three groups treated with D, A and E. After adjusting for baseline characteristics, D-dimer level in the left atrium treated with E was significantly higher among the three groups (D, 0.550±0.078 vs. A, 0.603±0.052 vs. E, 0.774±0.046), although there were no significant differences in peripheral D-dimer levels (Table). Protein C levels of peripheral blood in group E were significantly suppressed among the three groups (D, 130.17±4.84 vs. A, 102.13±3.59 vs. E, 91.92±2.11, p&lt;0.001). Conclusions: In the edoxaban group, the D-dimer level in the left atrium was higher than that in the apixaban group, suggesting that the anticoagulatory effect of left atrium is better in apixaban as compared to edoxaban in patient with non-valvular atrial fibrillation.
Bioactive small molecules produced by the human gut microbiome modulate <i>Vibrio cholerae</i> sessile and planktonic lifestyles
Authors: Heidi Pauer, Felipe Lopes Teixeira, Avery V. Robinson, Thiago E. Parente, Marília A. F. De Melo, Leandro A. Lobo, Regina M. C. P. Domingues, Emma Allen-Vercoe, Rosana B. R. Ferreira, Luis Caetano M. Antunes
Journal: Gut Microbes (2021)

Humans live in symbiosis with a diverse community of microorganisms, which has evolved to carry out many specific tasks that benefit the host, including protection against invading pathogens. Within the chemical diversity of the gastrointestinal tract, small molecules likely constitute chemical cues for the communication between the microbiota and pathogens. Therefore, we sought to investigate if molecules produced by the human gut microbiota show biological activity against the human pathogen Vibrio cholerae. To probe the effects of the gut metabolome on V. cholerae, we investigated its response to small-molecule extracts from human feces, from a complex bacterial community cultivated in vitro, and from culture supernatants of Enterocloster citroniae, Bacteroides thetaiotaomicron, and Bacteroides vulgatus. Using RNA sequencing, we determined the impact of the human gut metabolome on V. cholerae global gene expression. Among the genes downregulated in the presence of the fecal extract, the most overrepresented functional category was cell motility, which accounted for 39% of repressed genes. Repression of V. cholerae motility by the fecal extract was confirmed phenotypically, and E. citroniae extracts reproduced this phenotype. A complex in vitro microbial community led to increased motility, as did extracts from B. vulgatus, a species present in this community. Accordingly, mucin penetration was also repressed by fecal and E. citroniae extracts, suggesting that the phenotypes observed may have implications for host colonization. Together with previous studies, this work shows that small molecules from the gut metabolome may have a widespread, significant impact on microbe–microbe interactions established in the gut environment.
Exploiting unique features of the gut-brain interface to combat gastrointestinal cancer
Authors: Alyssa Schledwitz, Guofeng Xie, Jean-Pierre Raufman
Journal: Journal of Clinical Investigation (2021)

The gastrointestinal tract comprises a complex ecosystem with extensive opportunities for functional interactions between neoplastic epithelial cells and stromal, immune, neuronal, glial, and other cell types, as well as microorganisms and metabolites within the gut lumen. In this Review, we focus on interactions between gastrointestinal cancers and elements of the central and enteric nervous systems. This previously understudied but rapidly emerging area of investigation has blossomed in recent years, particularly with respect to improved understanding of neural contributions to the development and progression of esophageal, gastric, pancreatic, and colon neoplasia. Cancer neuroscience offers great promise to advance our understanding of how neural-cancer interactions promote alimentary tract neoplasia. The resulting mechanistic insights can be leveraged to identify diagnostic and prognostic biomarkers, and to develop novel therapeutic interventions.
Abstract 14803: Activin A Directly Impaired Human IPSC-cardiomyocyte Contractility and Electrophysiology
Authors: Jake S Megna, Scott MacDonnell, Qin Ruan, Lori G MORTON
Journal: Circulation (2020)

Activin A is a homo-dimeric TGF-β family member involved in embryonic development, tissue morphogenesis, and cellular differentiation. Levels of activin A correlate with NYHA functional classification and age dependent cardiac dysfunction; however, no data are available to demonstrate a direct role for activin A in regulating human cardiomyocyte dysfunction. The purpose of this study was to characterize the functional impact of chronic activin A on human cardiomyocyte electrophysiology, contractility, calcium handling, and gene expression. Methods: Human iPSC-cardiomyocytes (iPSC-CM) were supplied by Fujifilm Cellular Dynamics. Calcium transients were captured using the FLIPR Tetra imager and impedance/electrophysiology by the Nanion CardioExcyte96. Cells were plated (50k/well), allowed to reach a stable synchronous monolayer, and dosed with 1nM of activin A (A) at each media change alongside a media control (C) or in the presence of inhibitory anti-activin A antibodies. Gene expression was determined using Taqman. Results: Activin A reduced contractile impedance amplitude (C=9.82±0.30, A=6.82±0.21 Ohms, p&lt;0.01) and slowed relaxation velocity kinetics (C=48.78±2.65, A=35.07±1.07 Ohms/sec, p&lt;0.01). Elongated extracellular field potential durations were observed with activin A treatment compared to control (C=0.49±0.02, A=0.56±0.01 sec, p&lt;0.01). Impaired calcium handling peak amplitude (C=609±99, A= C=447±33 RFU, p&lt;0.05) was also observed alongside slower calcium flux falling times (C=0.52±0.05, A=0.70±0.04 sec, p&lt;0.01). An inhibitory activin-A antibody restored all parameters to control values. Chronic exposure of iPSC-CM to activin A reduced expression of calcium handling genes RYR2 (C=1.01±0.07, A=0.75±0.03, p&lt;0.01) and ATP2A2 (C=1.00±0.05, A=0.89±0.05, p&lt;0.05). Conclusions: Chronic activin A treatment reduced cardiomyocyte contractile amplitude, slowed contractile kinetics, impaired cardiomyocyte calcium handling, elongated the action potential, and reduced expression of genes regulating key calcium handling proteins. These data demonstrate that elevated levels of activin A can directly act on cardiomyocytes and therefore may contribute to cardiac dysfunction in heart failure and aged populations.
Frequency and Duration of Advertising on Popular Child-Directed Channels on a Video-Sharing Platform
Authors: Samantha L. Yeo, Alexandria Schaller, Michael B. Robb, Jenny S. Radesky
Journal: JAMA Network Open (2021)

This cross-sectional study quantifies the number and duration of distinct advertisements that appear during child-directed videos on a video-sharing platform as well as the frequency of age-inappropriate ads.
Abstract 16824: Circulating Microvesicles in Heart Failure Patients Prior to, and Following LVAD Implantation
Authors: William K Cornwell, Kelly A Stockelman, Noah DeSouza, Jared Greiner, chris desouza
Journal: Circulation (2020)

Introduction: Elevated levels of circulating endothelial and platelet (EMV and PMV) microvesicles are associated with endothelial dysfunction and thrombosis/inflammation, respectively. EMVs and PMVs are elevated in patients with heart failure with reduced ejection fraction (HFrEF) and are associated with clinical outcomes. We sought to characterize longitudinal changes in EMV and PMV following LVAD implantation in these patients. Methods: Blood samples were obtained from patients with advanced HFrEF (59±9years, N=9 males) during an invasive hemodynamic assessment with Swan-Ganz catheterization 2.7±4.1 and 4.3±1.3 months prior to, and following CF-LVAD implantation, respectively. Circulating concentrations of total MV, EMVs (CD31+) and PMVs (CD42b+) were determined by flow cytometry. Results: Demographics and hemodynamics pre- and post-LVAD implantation are displayed in the table . Prior to LVAD, four patients were on inotropes. Six patients received a Heartware VAD, and four patients received a Heartmate 3 VAD. As demonstrated in the figure , there was a significant reduction in total MV concentration, as well as EMVs and PMVs following LVAD implantation. Conclusion: Circulating concentrations EMVs and PMVs decline significantly in HFrEF patients following LVAD implantation. These findings are indicative of improvements in both endothelial function and thrombotic/inflammatory state associated with the heart-failure syndrome.