tbuckley/cabot-search huggingface dataset:
Abstract 14229: Hepatobiliary Markers in Minority Heart Failure Patients; Echocardiography and Clinical Outcomes
Authors: Joseph A Casillas, Perry Wengrofsky, Maya Srinivasan, Noah Silverstein, Inna Bukharovich
Journal: Circulation (2020)

Introduction: AHA sponsored guidelines and studies have focused on cardiac disease and particular heart failure (HF) profiles among minorities like African, Hispanic, and Asian Americans. Previous studies on liver function tests (LFT) in HF patients, like aspartate and alanine aminotransferase (AST, ALT), alkaline phosphatase (ALP), and bilirubin (Bili), have underrepresented minority groups in study cohorts. We investigated the relationship between LFT levels with echocardiographic (ECHO) findings and readmission outcomes among minority patients at the Heart Health Center (HHC) of NYC Health + Hospitals, Kings County, in Brooklyn, New York. Hypothesis: In minority HF patients, LFT levels are associated with ECHO parameters, and LFT abnormalities are associated with increased risk of admission. Methods: Retrospective review was performed of patients in the HF clinic at the HHC, and during acute HF exacerbation admission from November 2017 - November 2018, with hospitalization monitored through November 2019. Baseline and admission LFT levels were obtained. While abnormal AST, ALP, and Bili levels were classified by the hospital’s laboratory range, abnormal ALT levels were classified based on national gastroenterology guidelines. Regression analysis was used to examine the relationship between LFT levels during acute HF exacerbation and ECHO parameters. Odds ratio (OR) and confidence interval (CI) were used for analysis of readmission outcomes. Results: Among 586 HF patients, there was an increased risk of hospitalization with baseline elevations in AST (OR 2.30, CI 1.24 - 4.25, p = 0.008) and ALP (OR 1.99, CI 1.10 - 3.64, p = 0.023). In those hospitalized with acute HF (n = 147), Bili was positively correlated with mitral valve (MV) EA ratio (r = 0.28, p = 0.002) and tricuspid regurgitation max velocity (r = 0.21, p = 0.004). ALT positively correlated with mean MV e’ velocity (r = 0.23, p = 0.009) and negatively correlated with aortic valve (AV) mean velocity (r = -0.24, p = 0.001). Conclusions: Understanding the association of ECHO findings and risk of hospitalization in minority patients with baseline and acute HF LFT levels has crucial implications for the identification of high risk patients and for the development of patient centered HF care strategies.
Abstract 16495: Activation of Notch Signaling in the Heart Promotes Electrical Disturbances
Authors: Emanuele Pizzo, Daniel O Cervantes, Martina Comelli, Marianna Meo, olivier meste, Jason T Jacobson, Marcello Rota
Journal: Circulation (2020)

Notch1 receptor signaling is active in the heart during embryonic development, is progressively silenced after birth, and it is partly restored in the adult myocardium following ischemic damage, a condition characterized by occurrence of arrhythmias. We previously reported that inducible overexpression of Notch1 intracellular domain (gain-of-function, NGoF) in adult mouse cardiomyocytes alters ionic currents and action potential profile. But the consequences of Notch1 signaling activation on electrical properties and arrhythmogenicity of the entire heart remain to be defined. For this purpose, electrocardiograms were obtained in NGoF (n=25) and corresponding control (Ctrl, n=13) mice in the conscious state, over a 10 min period. Electrical signals were obtained at baseline and following administration of an arrhythmogenic cocktail (120 mg/kg BW caffeine and 2 mg/kg BW epinephrine) to test the propensity of these animals to develop electrical disturbances. Moreover, information was also obtained in mice with inducible Notch1 gene deletion for complete silencing of Notch1 signaling (Notch1 loss-of-function, NLoF, n=5). At baseline, heart rate and QT interval duration were comparable in NGoF (689±30 bpm; 49±2 ms), Ctrl (703±29 bpm; 48±1 ms), and NLoF (697±50 bpm; 48±1 ms) animals. Only a small fraction (~8%) of NGoF mice presented isolated premature ventricular complexes (PVCs) or junctional rhythm, but these events were not observed in Ctrl and NLoF mice. Administration of the arrhythmogenic cocktail induced PVCs in the majority of Ctrl (~56%) and NLoF (~60%) mice and in almost all NGoF animals (~92%). Also recurrent PVCs (≥10/10 min) were 1.7-2.1-fold higher in NGoF mice, with respect to NLoF and Ctrl. Importantly, 77% of NGoF mice developed ventricular tachycardia (VT), whereas VT occurrence was attenuated in Ctrl (56%) and NLoF (~40%) animals. Incidence of sustained VT was 1.7-fold higher in NGoF mice, with respect to Ctrl. Similarly, bidirectional VT was higher in NGoF (~62%), with respect to Ctrl (~52%) and NLoF (~40%). Thus, Notch signaling activation in the heart of experimental animals tends to enhance the occurrence of electrical disturbances, a factor that may be involved in the arrhythmogenic behavior of the post-infarcted myocardium.
The role for high flow nasal cannula as a respiratory support strategy in adults: a clinical practice guideline
Authors: Bram Rochwerg, Sharon Einav, Dipayan Chaudhuri, Jordi Mancebo, Tommaso Mauri, Yigal Helviz, Ewan C. Goligher, Samir Jaber, Jean-Damien Ricard, Nuttapol Rittayamai, Oriol Roca, Massimo Antonelli, Salvatore Maurizio Maggiore, Alexandre Demoule, Carol L. Hodgson, Alain Mercat, M. Elizabeth Wilcox, David Granton, Dominic Wang, Elie Azoulay, Lamia Ouanes-Besbes, Gilda Cinnella, Michela Rauseo, Carlos Carvalho, Armand Dessap-Mekontso, John Fraser, Jean-Pierre Frat, Charles Gomersall, Giacomo Grasselli, Gonzalo Hernandez, Sameer Jog, Antonio Pesenti, Elisabeth D. Riviello, Arthur S. Slutsky, Renee D. Stapleton, Daniel Talmor, Arnaud W. Thille, Laurent Brochard, Karen E. A. Burns
Journal: Intensive Care Medicine (2020)
Recommended core outcome instruments for health‐related quality of life, long‐term control and itch intensity in atopic eczema trials: results of the HOME VII consensus meeting*
Authors: K.S. Thomas, C.A. Apfelbacher, J.R. Chalmers, E. Simpson, P.I. Spuls, L.A.A. Gerbens, H.C. Williams, J. Schmitt, M. Gabes, L. Howells, B.L. Stuart, E. Grinich, T. Pawlitschek, T. Burton, L. Howie, A. Gadkari, L. Eckert, T. Ebata, M. Boers, H. Saeki, T. Nakahara, N. Katoh
Journal: British Journal of Dermatology (2021)

The Harmonising Outcome Measures for Eczema (HOME) initiative has established a core outcome set of domains for atopic eczema (AE) clinical trials. Previous consensus meetings have agreed on preferred instruments for clinician-reported signs (Eczema Area and Severity Index, EASI) and patient-reported symptoms (Patient-Oriented Eczema Measure, POEM). This paper reports consensus decisions from the HOME VII meeting.To complete the core outcome set for AE by agreeing on core outcome instruments for the domains of quality of life (QoL), long-term control and itch intensity.A face-to-face consensus meeting was held in Tokyo, Japan (8-10 April 2019) including 75 participants (49 healthcare professionals/methodologists, 14 patients, 12 industry representatives) from 16 countries. Consensus decisions were made by presentations of evidence, followed by whole and small group discussions and anonymous voting using predefined consensus rules.It was agreed by consensus that QoL should be measured using the Dermatology Life Quality Index (DLQI) for adults, the Children's Dermatology Life Quality Index (CDLQI) for children and the Infant's Dermatology Quality of Life Index (IDQoL) for infants. For long-term control, the Recap of Atopic Eczema (RECAP) instrument or the Atopic Dermatitis Control Test (ADCT) should be used. Consensus was not reached over the frequency of data collection for long-term control. The peak itch numerical rating scale (NRS)-11 past 24 h was recommended as an additional instrument for the symptom domain in trials of older children and adults. Agreement was reached that all core outcome instruments should be captured at baseline and at the time of primary outcome assessment as a minimum.For now, the core outcome set for clinical trials in AE is complete. The specified domains and instruments should be used in all new clinical trials and systematic reviews of eczema treatments.
Hibernating Myocardium: Another Piece of the Puzzle Falls Into Place⁎⁎Editorials published in the Journal of the American College of Cardiologyreflect the views of the authors and do not necessarily represent the views of JACCor the American College of Cardiology.
Authors: Shahbudin H. Rahimtoola, Giovanni La Canna, Roberto Ferrari
Journal: Journal of the American College of Cardiology (2006)
Postdiagnostic Fruit and Vegetable Consumption and Breast Cancer Survival: Prospective Analyses in the Nurses' Health Studies
Authors: Maryam S. Farvid, Michelle D. Holmes, Wendy Y. Chen, Bernard A. Rosner, Rulla M. Tamimi, Walter C. Willett, A. Heather Eliassen
Journal: Cancer Research (2020)

Fruits and vegetables contain many bioactive components that may contribute to improved survival after diagnosis of breast cancer, however, evidence to date is insufficient. We prospectively assessed the associations of postdiagnostic fruit and vegetable consumption with breast cancer-specific and all-cause mortality among 8,927 women with stage I-III breast cancer identified during follow-up of the Nurses' Health Study (NHS; 1980-2010) and NHSII (1991-2011), using a validated food frequency questionnaire completed every 4 years after diagnosis. We prospectively documented 2,521 deaths, including 1,070 from breast cancer through follow-up until 2014 in the NHS and 2015 in the NHSII. Total fruit and vegetable and total vegetable consumption was related to lower all-cause [HR
Neratinib-Plus-Cetuximab in Quadruple-WT (<i>KRAS, NRAS, BRAF, PIK3CA</i>) Metastatic Colorectal Cancer Resistant to Cetuximab or Panitumumab: NSABP FC-7, A Phase Ib Study
Authors: Samuel A. Jacobs, James J. Lee, Thomas J. George, James L. Wade, Philip J. Stella, Ding Wang, Ashwin R. Sama, Fanny Piette, Katherine L. Pogue-Geile, Rim S. Kim, Patrick G. Gavin, Corey Lipchik, Huichen Feng, Ying Wang, Melanie Finnigan, Brian F. Kiesel, Jan H. Beumer, Norman Wolmark, Peter C. Lucas, Carmen J. Allegra, Ashok Srinivasan
Journal: Clinical Cancer Research (2020)

Abstract Purpose: In metastatic colorectal cancer (mCRC), HER2 (ERBB2) gene amplification is implicated in anti-EGFR therapy resistance. We sought to determine the recommended phase II dose (RP2D) and efficacy of neratinib, a pan-ERBB kinase inhibitor, combined with cetuximab, in patients with progressive disease (PD) on anti-EGFR treatment. Patients and Methods: Twenty-one patients with quadruple-wild-type, refractory mCRC enrolled in this 3+3 phase Ib study. Standard dosage cetuximab was administered with neratinib at 120 mg, 160 mg, 200 mg, and 240 mg/day orally in 28-day cycles. Samples were collected for molecular and pharmacokinetic studies. Results: Sixteen patients were evaluable for dose-limiting toxicity (DLT). 240 mg was determined to be the RP2D wherein a single DLT occurred (1/7 patients). Treatment-related DLTs were not seen at lower doses. Best response was stable disease (SD) in 7 of 16 (44%) patients. HER2 amplification (chromogenic in situ IHC) was detected in 2 of 21 (9.5%) treatment-naïve tumors and 4 of 16 (25%) biopsies upon trial enrollment (post-anti-EGFR treatment and progression). Compared with matched enrollment biopsies, 6 of 8 (75%) blood samples showed concordance for HER2 CNV in circulating cell-free DNA. Five SD patients had HER2 amplification in either treatment-naïve or enrollment biopsies. Examination of gene-expression, total protein, and protein phosphorylation levels showed relative upregulation of ≥2 members of the HER-family receptors or ligands upon enrollment versus matched treatment-naïve samples. Conclusions: The RP2D of neratinib in this combination was 240 mg/day, which was well tolerated with low incidence of G3 AEs. There were no objective responses; SD was seen at all neratinib doses. HER2 amplification, detectable in both tissue and blood, was more frequent post-anti-EGFR therapy.
Abstract 17136: Pulmonary Arterial and Venous Fractal Dimension as a Marker of Pulmonary Arterial Hypertension
Authors: Andrew Tsao, Pietro Nardelli, Eileen Harder, Gonzalo Vegas Sanchez-Ferrero, James C Ross, Samuel Y Ash, Inderjit Singh, Andetta Hunsaker, Aaron B Waxman, George Washko, Raul San Jose Estepar, Farbod Rahaghi
Journal: Circulation (2020)

Introduction: PAH is characterized by a loss of pulmonary vascular complexity. In this study, total, arterial, and venous vasculatures of patients with PAH and with ePAH were analyzed using fractal analysis and compared against controls Methods: Data from 1514 consecutive right heart catheterizations from 4/27/2011 to 10/2/2018 representing subjects referred to our dyspnea center were searched for availability of imaging. 388 CT angiography (CTA) scans were identified (used given retrospective availability of thin slice reconstructions). Three initial cohorts (no overlap) were identified from individuals in this set. Control patients had normal resting and exercise hemodynamics and no history of cardiopulmonary disease. The second group met the current definition of PAH (resting mean pulmonary arterial pressure &gt;20mmHg, pulmonary vascular resistance &gt;3 Wood Units, pulmonary capillary wedge pressure &lt;15mmHg). The third group (ePAH) had normal resting hemodynamics but age adjusted evidence of PAH with exercise. Pulmonary vascular trees were reconstructed; total, arterial, and venous trees were separated; and fractal dimensions were measured using a 3D box counting method for each tree. Comparisons were made using the Wilcoxon Rank Sum test (R 3.5). Results: Venous fractal dimensions of controls (2.10±0.07) were higher than those of PAH (2.03±0.08; p=3e-6) and of ePAH (2.04±0.13; p=0.008). Total fractal dimension also yielded higher values for controls (2.30±0.05) compared against PAH (2.28±0.07; p=0.009) and ePAH (2.26±0.10; p=0.04). No significant differences were found between arterial fractal dimensions of controls (2.17±0.04) against those of PAH (2.16±0.07; p=0.15) and of ePAH (2.15±0.10; p=0.14). Conclusions: Fractal dimension allows for non-invasive characterization of pulmonary vascular complexity. Using this method, patients with PAH or ePAH were found to have lower total and venous vascular complexities than controls without PAH or ePAH.
Hormone Replacement Therapy
Authors: H S Jacobs
Journal: Journal of the Royal Society of Medicine (1979)

8 papers, based on the results of retrospective studies performed in the U. S., have dealt with the effects of treatment of postmenopausal women with unopposed estrogens. The studies are unanimous in showing that such treatment is associated with increased risks of developing uterine cancer. The increase in risk is related to dose and duration of treatment. The studies have produced essentially similar risk radios, which have survived independent reevaluation of the original histopathological diagnoses. Prospective clinical studies have also shown the dose and duration of unopposed estrogens to be related to increased risk of endometrial hyperplasia, the most severe form of which is believed to be a precursor to endometrial cancer.
Abstract 14997: Icosapent Ethyl Reduces Ischemic Events in Patients With Prior Coronary Artery Bypass Grafting: REDUCE-IT CABG
Authors: Subodh Verma, Deepak L Bhatt, Philippe G Steg, Michael Miller, Eliot A Brinton, Terry A Jacobson, Steven Ketchum, Rebecca Juliano, Lisa Jiao, Ralph Doyle, Craig Granowitz, C. Michael Gibson, Duane S Pinto, Robert P Giugliano, Matthew J Budoff, Preston P Mason, Jean-Claude Tardif, Christie M Ballantyne, Marco A Zenati
Journal: Circulation (2020)

Background: Patients with a prior history of coronary artery bypass grafting (CABG) are at high risk for future ischemic events despite statin therapy. Methods: REDUCE-IT, a multicenter, double-blind, placebo-controlled trial, randomized statin-treated patients with elevated triglycerides (135-499 mg/dL), controlled LDL (41-100 mg/dL), and either established cardiovascular disease or diabetes plus other risk factors to receive icosapent ethyl 4g daily or placebo. In the overall trial, the primary composite endpoint (cardiovascular death, myocardial infarction, stroke, coronary revascularization, hospitalization for unstable angina) and the key secondary composite endpoint (cardiovascular death, myocardial infarction, stroke) were significantly reduced. Here we examine the subgroup of patients with a history of CABG. Results: A total of 8,179 randomized patients were followed for 4.9 years (median), 1837 (22.5%) of whom had a prior CABG, with a median of 5.1 years (0.7 months to 33.3 years) from CABG to randomization (in the 1263 patients who had the date of CABG recorded). The rate of the primary endpoint was reduced by 24% [22.0% with icosapent ethyl versus 28.2% with placebo (hazard ratio [HR]=0.76; 95% confidence interval [CI], 0.63-0.92; p=0.004; number needed to treat [NNT]=16)]. The rate of the key secondary endpoint was reduced by 31%: [14.7% with icosapent ethyl versus 20.7% with placebo (HR=0.69; 95% CI, 0.56-0.87; p=0.001; NNT=17)]. Conclusions: In statin-treated patients with a history of prior CABG, the addition of icosapent ethyl significantly reduced ischemic events, with both large relative and absolute risk reductions.
Abstract 14201: The Application of Hipsc-derived Cardiomyocytes Paced by Re-entrant Waves for Drug Assessment
Authors: Junjun Li, Itsunari Minami, Shigeru Miyagawa, Xiang Qu, YING HUA, Yoshiki Sawa, Li Liu
Journal: Circulation (2020)

Introduction: How to precisely evaluate response in newly developed medications in vitro may be a great concern in drug screening. We modified normal low-attachment culture dish and created closed-loop tissue ring from single hiPSC-CMs. We hypothesized that the re-entrant wave (ReW) could originate and pace the cardiac tissue ring, and the CMs under pacing could be matured and used for drug assessment. Methods: PDMS wells and pillars were mounted in low-attachment petri dishes (Figure 1A). 4 х 10 5 hiPSC-CMs were plated into the wells to form tissue ring where the ReW could spontaneously originate. After cultivation for 14 days, the hiPSC-CMs were evaluated by immunostaining and gene expression. Micro electrode array (MEA) were used to evaluating the CM response to different drugs. Results: The electrical signal recorded by MEA indicated that the ReWs could make the CMs beat at a much higher rate than the Control group (Figure 1B, 123.26 ± 10.36 bpm vs. 14.08 ± 4.53 bpm, p&lt;0.0001). After 14 day culture, the ReW group demonstrated significantly higher expression of Troponin T (TnT2), myosin heavy chain 7 (β-MHC), and α-actinin. Interestingly, the α-actinin staining indicated alignment of CMs within the ReW group (Figure 1C). The CMs under ReW pacing showed robust response to several cardiac compounds including E4031, (hERG K+ channel blocker, Figure 1D and E), isoproterenol (β adrenoceptor agonist) and propranolol (beta-blocker). Both the field potential as well as the Ca 2+ transients showed correlated dose-dependent change and the recovering after washout of the drugs. Conclusions: The ReWs could spontaneously originate in the cultured cardiac tissue ring with enhancement of the maturation in the hiPSC-CMs and robust response to various drugs, indicating the system as a robust drug assessment system with multiple read-out methods.
Abstract 15015: Eicosapentaenoic Acid, but Not Docosahexaenoic Acid or a Mixed Omega-3 Fatty Acid Supplement, Inhibits Low-density Lipoprotein Oxidation in a Time-dependent Manner
Authors: Samuel Sherratt, Peter Libby, Deepak L Bhatt, Preston Mason
Journal: Circulation (2020)

Background: Eicosapentaenoic acid (EPA), an omega-3 fatty acid (O3FA), reduces oxidation of low-density lipoproteins (LDL) in patients with hypertriglyceridemia, an effect that may contribute to lower cardiovascular (CV) events as reported in the REDUCE-IT trial. By contrast, DHA-containing products have failed to show a reduction in CV events, which may be due, in part, to differences in antioxidant activity. We compared the effects of EPA versus DHA and a mixed O3FA (EPA/DHA) supplement on oxidation of human LDL in vitro . Methods: LDL was isolated from human plasma by isopycnic centrifugation, separated into test samples of 100 μg/mL, and incubated at 37°C for 30 min in the absence (vehicle) or presence of EPA, DHA, or mixed O3FA supplement at equimolar levels (2.5 μM). All samples were then subjected to copper-induced oxidation (20 μM) as measured by formation of malondialdehyde (MDA). The FA content of the O3FA supplement was measured using gas chromatography/mass spectrometry. Results: EPA significantly inhibited LDL oxidation in a time-dependent manner compared with vehicle; after 4 hours, EPA inhibited MDA levels by 96% compared with the vehicle oxidation level (0.51 ± 0.01 vs 11.4 ± 0.4 μM; p &lt;0.001). While DHA exhibited antioxidant activity at 2 hours at a level below EPA (2.5 ± 0.1 vs 11.4 ± 0.4; p &lt;0.001), even this level of activity was lost by 4 hours. The mixed O3FA supplement failed to show any antioxidant activity through 4 hours (11.4 ± 0.5 μM). Fatty acid analysis showed that the O3FA supplement, in addition to EPA and DHA, contained more than 30 other fatty acids, including saturated fats, that may have nullified any potential benefits. Conclusions: These data support potent LDL antioxidant effects of EPA that were sustained over time compared with DHA, which had a weaker, transient effect, or a mixed O3FA supplement, which had no beneficial effect at all. This potent antioxidant mechanism of EPA may contribute to reduced CV risks seen in REDUCE-IT compared with negative findings from trials using DHA-containing formulations.
Abstract 14846: Artificial Intelligence and Clinical Stability After the Norwood Operation
Authors: Alaa Aljiffry, Yanbo Xu, Shenda Hong, Justin Long, Jimeng Sun, Kevin Maher
Journal: Circulation (2020)

Background: Postoperative management of the neonate following the Norwood operation is among the most complex and challenging in pediatric critical care. Artificial intelligence is poised to assist in management of this complex population. Methods: We developed a convolutional neural network (CNN) model trained on electrocardiogram (ECG) waveforms collected from 45 neonates after the Norwood procedure. Waveforms from the first two postoperative days (critical) and the day prior to transfer out of the ICU (stable) were used for training. The model was validated on 10 post-Norwood neonates. Models were compared to traditional machine learning algorithms on non-waveform data, heart rate variability, and then combined in a final model to optimize performance. Retrospective clinical observation scoring was completed for comparison. Results: The CNN model on 3-lead ECG yielded an area under the curve of the receiver operating characteristic (AUC-ROC) of 0.97 ( 0.02). The final model combining predictions from the CNN, random forest on vital signs, and logistic regression on pH, lactic acid, and base deficit values achieved 0.98 ( 0.02). Retrospective clinical observations agreed with the final model 78% of the time. Conclusions: Application of this novel combined machine learning model can accurately detect changes in clinical status as patients progress from critically ill to stable following the Norwood procedure, yielding impressive clinical insights from the ECG beyond what is currently possible. This work provides the basis for the development of a novel bedside monitoring tool and suggests new ways artificial intelligence may influence clinical care beyond predicting deterioration events.