tbuckley/cabot-search huggingface dataset:
Increased Uptake of 68Ga-Pentixafor in Thymic Rebound After Chemotherapy in a Patient With Multiple Myeloma
Authors: Qingqing Pan, Yaping Luo, Xinxin Cao, Jian Li
Journal: Clinical Nuclear Medicine (2020)

Abstract A 38-year-old man with newly diagnosed multiple myeloma underwent 68 Ga-pentixafor PET/CT for baseline assessment. 68 Ga-pentixafor PET/CT demonstrated multiple focal bone and bone marrow lesions with intense radioactivity. After 9 cycles of chemotherapy against multiple myeloma, the patient experienced serologically complete remission of myeloma. Consistently, the follow-up 68 Ga-pentixafor PET/CT for PET response showed significantly reduced uptake in the previously chemokine receptor 4–positive bone lesions. However, intense and homogeneous uptake of 68 Ga-pentixafor was noted in the thymus with a smooth contour and slightly increased density, which is possibly caused by thymic hyperplasia after chemotherapy.
The BMJ Awards 2020: Winners share their journey to victory in online videos
Authors: Matthew Limb
Journal: BMJ (2020)

The inspirational stories behind this year’s winning teams at The BMJ Awards are now available to view with the online launch of the 2020 BMJ Awards Showcase (thebmjawards.bmj.com/showcase), which features doctors and their clinical colleagues talking about their collaborations to improve services throughout the NHS.

The BMJ Awards 2020 winners and finalists were announced in a virtual ceremony on 7 October, hosted by The BMJ ’s editor in chief, Fiona Godlee.1 She said that, in such a challenging year, …
Effect of Hydroxychloroquine on Clinical Status at 14 Days in Hospitalized Patients With COVID-19
Authors: Wesley H. Self, Matthew W. Semler, Lindsay M. Leither, Jonathan D. Casey, Derek C. Angus, Roy G. Brower, Steven Y. Chang, Sean P. Collins, John C. Eppensteiner, Michael R. Filbin, D. Clark Files, Kevin W. Gibbs, Adit A. Ginde, Michelle N. Gong, Frank E. Harrell, Douglas L. Hayden, Catherine L. Hough, Nicholas J. Johnson, Akram Khan, Christopher J. Lindsell, Michael A. Matthay, Marc Moss, Pauline K. Park, Todd W. Rice, Bryce R. H. Robinson, David A. Schoenfeld, Nathan I. Shapiro, Jay S. Steingrub, Christine A. Ulysse, Alexandra Weissman, Donald M. Yealy, B. Taylor Thompson, Samuel M. Brown
Journal: JAMA (2020)

Data on the efficacy of hydroxychloroquine for the treatment of coronavirus disease 2019 (COVID-19) are needed.
Abstract 16395: Soluble ST2 and Its Association With Echocardiographic Measures of Cardiac Structure
Authors: Alexander O Gong, Nina Balac, Sagar V Patel, Jennifer Hwang, Jennifer M McLeod, Luanda P Grazette
Journal: Circulation (2020)

Background: Soluble ST2 (sST2) has emerged as a powerful prognostic marker in chronic systolic heart failure with reduced ejection fraction (HFrEF). Elevated levels of sST2 are associated with adverse cardiac remodeling and fibrosis. We have previously described the prognostic value of sST2 collected from stable patients in the ambulatory setting and correlated it with long term clinical outcomes. However, few studies have demonstrated the association between sST2 levels and echocardiographic measures of cardiac structure and function as well as outcomes. Hypothesis: Baseline circulating levels of sST2, using the partition value of 35 ng/ml, will correlate with echocardiographic measures of cardiac chamber size and function in stable stage C patients in the ambulatory setting. Methods: Single-center, retrospective observational study of subjects presenting to an ambulatory heart failure (HF) clinic from July 2014 to December 2016. There were 156 subjects with stage C heart failure and a baseline sST2 level. For purposes of this analysis in HFrEF, we excluded patients with EF &gt; 40% resulting in a study cohort of 103 subjects. The mean follow-up was 2.20 years ± 1.53 years. Analysis was performed with IBM SPSS Statistics 26. Discrete variables were expressed as counts (percentage) and were compared using the Chi-squared test. Mean differences of continuous variables were expressed as a mean ± standard deviation and compared using the unpaired Student’s t- test. Results: Patients who had baseline sST2 ≥ 35 ng/ml had a greater LA volume index (p=0.05) and RA area (p=0.01) compared to patients with sST2 &lt; 35 ng/ml. Patients with sST2 ≥ 35 ng/ml had a mean LA volume index of 62.72 ± 30.28 ml/m 2 and RA area of 24.59 ± 7.87 ml/m 2 . We also found that sST2 ≥ 35 ng/ml was associated with increased risk for atrial arrhythmias (39.0% vs. 20.5%), a higher New York Heart Association classification (2.73 vs. 2.18), lower hemoglobin (11.5 vs 13.0), and lower systolic blood pressure (109.6 vs 124.8). Conclusion: In our study, subjects with sST2 levels ≥ 35 ng/ml was associated with increased atrial size by echocardiography, increased risk for atrial arrhythmia and higher NYHA class. These findings support the utility of sST2 for risk stratification in ambulatory patients with HFrEF.
Abstract 14794: Cmr-derived Biventricular Global Function Index is Associated With Adverse Outcomes in Repaired Tetralogy of Fallot
Authors: Tarek ALSAIED, Tal Geva, Julia Graf, Lynn A Sleeper, Anne M Valente
Journal: Circulation (2020)

Introduction: Despite improvement in outcomes, patients with repaired tetralogy of Fallot (rTOF) are at risk for ventricular tachycardia and death. Cardiac magnetic resonance (CMR) derived global function index (GFI) is a new CMR parameter that integrates ventricular volume, mass, and function. This retrospective cohort study evaluated the utility of the biventricular global function index (BVGFI) for risk stratification in patients with rTOF. Methods: Patients with rTOF who had a CMR were followed for the occurrence of a composite outcome of death, resuscitated cardiac arrest, or sustained ventricular tachycardia (VT) were studied. GFI was calculated as the (ventricular stroke volume x 100) / (ventricular mean cavity volume + total ventricular myocardial volume). Ventricular mean cavity volume was defined as [(end-diastolic + end-systolic volume) /2]. BVGFI was calculated as the average of right and left GFI. Cox regression and CART analysis were used. Results: Of the 736 eligible patients (median age at CMR 25.4 years; median follow-up 28 months), 55 patients (7.4%) reached the composite outcome (41 deaths, 14 VT). Multivariable Cox regression identified BVGFI &lt;37, RV end-systolic volume index &gt;85 ml/m 2 , atrial tachycardia , and age at repair &gt;2.5 years as independent predictors of outcome with a model C-index of 0.86. RVEF &lt;40% , which is a known predictor of worse outcomes in previous studies, was not associated with the primary outcome when BVGFI is included in the analysis and only became significant when BVGFI was excluded from the model (C-index of 0.83). Similarly, CART analysis identified BVGFI as the only binary CMR parameter to identify patients at high-risk for adverse outcomes. Conclusions: We describe a novel CMR parameter that uses readily available parameters and is associated with adverse clinical outcome after adjusting for traditional CMR parameters in rTOF. BVGFI adds prognostic information and aids in risk stratification in the population.
Development of a CD8 co-receptor independent T-cell receptor specific for tumor-associated antigen MAGE-A4 for next generation T-cell-based immunotherapy
Authors: Kathrin Davari, Tristan Holland, Laura Prassmayer, Giulia Longinotti, Kenneth P Ganley, Lisa J Pechilis, Iulia Diaconu, Prashant R Nambiar, Michael S Magee, Dolores J Schendel, Daniel Sommermeyer, Christian Ellinger
Journal: Journal for ImmunoTherapy of Cancer (2021)

The cancer-testis antigen MAGE-A4 is an attractive target for T-cell-based immunotherapy, especially for indications with unmet clinical need like non-small cell lung or triple-negative breast cancer.
Abstract 13293: Detection of Atrial Fibrillation by Implantable Loop Recorders Following Cryptogenic Stroke: A Retrospective Study of Predictive Factors and Outcomes
Authors: Sara Samaan, Beshoy Nazeer, Heidi Stoute, Wei Zhao, Susanna Szpunar, Zain Azzo, Sohail Hassan
Journal: Circulation (2020)

Introduction: Cryptogenic strokes account for up to 40% of ischemic strokes. Atrial fibrillation (AF) is a known cause of ischemic stroke. Current data shows that occult AF can be detected by implantable devices at higher rates than conventional cardiac rhythm monitoring. There are, however, limited data available on risk factors and outcomes associated with AF detection by implantable loop recorders (ILRs). Objective: To investigate the risk factors and outcomes associated with occult AF detected by ILR in patients with cryptogenic stroke. Methods: We conducted a retrospective chart review of patients admitted with cryptogenic stroke at Ascension St John Hospital and Ascension Macomb-Oakland Hospital in Michigan who had ILRs placed from 1/1/2016 to 1/31/2020. Data were collected on demographics, comorbidities, treatment and outcomes. AF detection was defined as continuous AF for 30 seconds. Data were analyzed using Student’s t-test, the χ2 test and logistic regression. Results: We reviewed 172 patients, 52.3% male, 56.4% white, mean age 62.7 ± 13.6 years. The incidence of AF detection by ILR was 14% (24/172) over a mean follow-up of 12.75 ± 10.71 months. The mean duration of monitoring prior to AF detection was 4.5 months (range:1 day to 14 months). The median duration of AF was 6 minutes (range: 37.2 seconds to 11.3 hours). From univariable analysis, older age (p=0.03), male sex (p=0.09), embolic stroke pattern on imaging (p=0.06), and lack of AF symptoms (p=0.001) were associated with AF detection by ILR. From multivariable analysis, patients with detected AF were more likely to be older (OR=1.04, p=0.04), male (OR=3.6, p=0.03), asymptomatic (OR=6.3, p=0.01), and have an embolic stroke pattern on imaging (OR=3.3, p=0.04). 95.7% of patients with confirmed AF were started on anticoagulation for secondary stroke prevention. There was no difference in the incidence of stroke post-hospitalization between those with AF detection and those without (16% vs. 16.4%, p=0.96). Conclusions: In patients with cryptogenic stroke, age, gender, stroke pattern, and lack of AF symptoms are independent predictors of occult AF detection by ILR. Most patients with confirmed AF were started on anticoagulation for secondary stroke prevention and had low stroke recurrence rates.
Abstract PO-004: Identification of MLL4 as a novel therapeutic target of pancreatic ductal adenocarcinoma by in vivo genome-wide RNAi screening
Authors: Frederic K. C. Fung, Yinxin Zhu, Chi Hin Wong, Yangchao Chen
Journal: Cancer Research (2020)

Abstract The prognosis of pancreatic ductal adenocarcinoma (PDAC) is extremely poor due to the lack of effective therapeutics. It is urgent to identify novel therapeutic target for PDAC. We performed in vivo genome-wide RNAi screening to identify cancer-associated candidate genes with critical roles in the tumorigenesis of PDAC. We identify mixed-lineage leukaemia 4 (MLL4 also known as KMT2B), which belongs to histone H3 lysine 4 (H3K4) methyltransferase of MLL family, as one of the cancer-associated gene to PDAC tumorigenesis. Here, we firstly report that MLL4 expression was frequently upregulated in PDAC cell lines as well as human PDAC tissue, depicting its potential role in PDAC tumorigenesis. Lysine methylation of different position of Histone is performed by SET (suppressor of variegation) domain of MLL family, aberrant expression of SET domain results in disruption of epigenetic gene regulation and leads to cancer. To characterize the in vitro tumorigenic role of SET domain of MLL4 in the development of PDAC, gain-of-function and loss-of-function approaches of SET domain of MLL4 and MLL4 were performed in PDAC cells, respectively. Ectopic SET expression promotes cell proliferation, colony formation, cell migration as well as invasion, demonstrating its oncogenic role in PDAC cells. Moreover, MLL4-depleted PDAC cells exhibited significantly reduction of tumor growth in nude mice xenograft model. Putative MLL4 activating and repressive targets were identified using gene expression microarray analysis in PDAC cell lines Capan2 and Panc-1. Expression alteration of these genes by regulated by MLL4 contribute to PDAC development and progression. To further delineate whether MLL4 regulates expression of the activating and repressing targets via H3K4 methylation, activity of H3K4 methylation was investigated in PDAC cells with MLL4 knockdown. Suppression of MLL4 reduced the H3K4Me2 and H3K4Me3 occupancies at promoter of MLL4 target genes, suggesting that MLL4 regulates downstream genes expression through H3K4 methylation. Taken together, our findings demonstrate that aberrant overexpression of MLL4 in PDAC cells alters its downstream oncogene and tumor suppressor genes, contributing to PDAC tumorigenesis. Thus, targeting MLL4 may serve as a potential therapeutic modality in the management of PDAC. Citation Format: Frederic K. C. Fung, Yinxin Zhu, Chi Hin Wong, Yangchao Chen. Identification of MLL4 as a novel therapeutic target of pancreatic ductal adenocarcinoma by in vivo genome-wide RNAi screening [abstract]. In: Proceedings of the AACR Virtual Special Conference on Pancreatic Cancer; 2020 Sep 29-30. Philadelphia (PA): AACR; Cancer Res 2020;80(22 Suppl):Abstract nr PO-004.
Abstract 11489: Replacing Saturated Fats With Unsaturated Fats From Walnuts or Vegetable Oils Favorably Affects Lipoprotein Classes Without Increasing Lipoprotein (a)
Authors: Alyssa Tindall, Penny M Kris-etherton, Kristina Petersen
Journal: Circulation (2019)

Introduction: Consumption of a healthy diet with walnuts consistently lowers total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) due to their unsaturated fatty acid and possibly ...
Abstract 15029: Atrial Arrhythmias and Pulmonary Hypertension Across Wsph Groups
Authors: Erika B Rosenzweig, Milena Radeva, Robert Frantz, Paul M Hassoun, Anna R Hemnes, Evelyn M Horn, Jane A Leopold, Franz Rischard, Wilson Tang
Journal: Circulation (2020)

Introduction: Previous reports have shown that atrial and ventricular arrhythmias (VA) are common in all forms of pulmonary hypertension (PH) with prevalence of supraventricular arrhythmias ranging from 13-25% and VA 27%. Arrhythmias are also associated with clinical worsening events. Reports have limited numbers of patients with a variety of forms of PH and limited data comparing the prevalence of atrial arrhythmias across WSPH groups and whether advancing age, WHO FC, echocardiographic, exercise capacity and hemodynamic patterns are associated with a higher prevalence of atrial arrhythmias. Methods: As part of the PVDOMICS program, we enrolled 1195 PH participants, controls and PH comparators and prospectively collected electrocardiograms (ECGs) at enrollment for 1147 of them. Comparisons across participants with and without atrial fibrillation/atrial flutter (afib/flutter) used analysis of variance (ANOVA) or Kruskal-Wallis test in continuous variables based on distribution with statistics presented as mean + SD or median [P25, P75] respectively. Pearson’s chi-square test was used for categorical variables. Results: Of 732 PH participants (467F) who had ECGs available at baseline, 527 (72.0%) were in normal sinus rhythm and 62 had afib/flutter (8.5%). Afib/flutter participants were older (75 + 8 vs 57 + 14 years; p&lt;0.001), most commonly in WSPH group 2 (28.1%) vs. WSPH 1 (3.3%), WSPH 3(6.5%) and WSPH group 4 (3.7%), had predominantly WHO FC II/III symptoms (89.5%), higher RAP (12.6 + 5 vs.7.8 + 5mmHg; p&lt;0.001) and PCWPm (17.8 + 5.8 vs. 12.3 + 6.2mmHg; p&lt;0.001) and lower CO (4.3+ 1.5 vs. 5.2 +1.8L/min;p&lt;0.001). Participants with afib/flutter had lower 6MWD 277 + 117 vs.356 + 134meters (p&lt;0.001) than PH participants without. Echocardiography demonstrated increase in LA volume index (mL/m2), RA volume (mL) and tricuspid regurgitation severity with reduced TAPSE and LVEF (54 + 10 vs. 61 + 10%;p&lt;0.001). ProBNP was higher in afib/flutter participants 2029 [1073, 2964] vs.268 [100, 1074]pg/ml; P&lt;0.001) Conclusions: In this analysis of atrial arrhythmias in a large cohort of PH participants across all WSPH groups, afib/flutter was present most often in older WSPH group 2 patients who demonstrated clinical and hemodynamic features of worse heart failure.
Abstract 14687: Achieved Eicosapentaenoic Acid (EPA) Levels Predicts Regression of Coronary Plaque Volumes by Coronary Computed Tomography Angiography (CCTA) in the EVAPORATE Trial
Authors: Suvasini Lakshmanan, Chandana Shekar, April Kinninger, Ilana Golub, Suraj Dahal, Divya Birudaraju, Lavanya Cherukuri, Vahid Rezvanizadeh, Sajad Hamal, Khadije Ahmad, Sion Roy, John R Nelson, Deepak L Bhatt, Matthew J Budoff
Journal: Circulation (2020)

Background: Despite the beneficial effects of statins on progression of coronary atherosclerosis and cardiovascular (CV) events, significant CV risk persists in patients with hypertriglyceridemia. In REDUCE-IT (Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention Trial), icosapent ethyl (IPE) added to statins reduced initial and total CV events by 25% and 30%, but the mechanisms of benefit are unclear. In a follow-up analysis, degree of CV benefit from IPE was predominantly related to achieved serum EPA levels. Methods: EVAPORATE is a randomized, placebo-controlled trial, using CCTA to evaluate the effects of IPE as an adjunct to statins on coronary plaque volumes in a cohort with elevated triglycerides. Here, we present the 18-month, pre-specified secondary end-point analysis on association of achieved serum EPA levels, and change in coronary plaque volumes in the pooled cohort. Results: 80 patients were enrolled, and 68 completed the 18-month visit. Median (IQR) level of serum EPA for the pooled cohort was 20.6 (13.8) ug/ml at baseline and 25.3 (55.5) ug/ml at follow up. At 18 months, EPA levels &gt; 26 ug/ml predicted regression of fibro-fatty plaque (logβ: - 0.75± 0.36), total non-calcified plaque (TNCP) (logβ: - 0.77± 0.33), and total plaque (TP) (logβ: - 0.63± 0.28) volumes (mm3), after adjustment for age, sex, diabetes, hypertension, and baseline TGL levels (p &lt; 0.05 for all). Conclusions: Higher serum EPA levels predict regression of prognostically relevant coronary plaque volumes, TNCP, and TP on CCTA. This provides important mechanistic correlation to the CV benefits of IPE.
Prevention of Thromboembolic Events After Bioprosthetic Aortic Valve Replacement: What Is the Optimal Antithrombotic Strategy?⁎⁎Editorials published in the Journal of the American College of Cardiology reflect the views of the authors and do not necessarily represent the views of JACC or the American College of Cardiology.
Authors: Richard P. Whitlock, John W. Eikelboom
Journal: Journal of the American College of Cardiology (2012)
Propolis: A useful agent on psychiatric and neurological disorders? A focus on CAPE and pinocembrin components
Authors: Cinthia C. S. Menezes da Silveira, Diandra A. Luz, Carla C. S. da Silva, Rui D. S. Prediger, Manoela D. Martins, Marco A. T. Martins, Enéas A. Fontes‐Júnior, Cristiane S. F. Maia
Journal: Medicinal Research Reviews (2020)

Abstract Propolis consists of a honeybee product, with a complex mix of substances that have been widely used in traditional medicine. Among several compounds present in propolis, caffeic acid phenethyl ester (CAPE), and pinocembrin emerge as two principal bioactive compounds, with benefits in a variety of body systems. In addition to its well‐explored pharmacological properties, neuropharmacological activities have been poorly discussed. In an unprecedented way, the present review addresses the current finding on the promising therapeutic purposes of propolis, focusing on CAPE and pinocembrin, highlighting its use on neurological disturbance, as cerebral ischemia, neuroinflammation, convulsion, and cognitive impairment, as well as psychiatric disorders, such as anxiety and depression. In addition, we provide a critical analysis, discussion, and systematization of the molecular mechanisms which underlie these central nervous system effects. We hypothesize that the pleiotropic action of CAPE and pinocembrin, per se or associated with other substances present in propolis may result in the therapeutic activities reported. Inhibition of the pro‐inflammatory cascade, antioxidant activity, and positive neurotrophic modulatory effects consist of the main molecular targets attributed to CAPE and pinocembrin in health benefits.
Abstract 16759: In-Hospital Outcomes of Coronary Artery Bypass Grafting Candidates Undergoing Percutaneous Coronary Intervention During the Intensive Care Unit Restricted Covid-19 Pandemic: The Multi-Centre Prospective UK-REVASC Registry
Authors: Thomas A Kite, Colum Owens, Alexander Chase, Abdul Mozid, Helen Routledge, Stephen P Hoole, Nick Palmer, Mohaned Egred, Divaka Perera, Mouyis Kyriacos, Manas Sinha, Tom Cahill, Luciano Candilio, Brijesh Anantharam, Aengus Murphy, Fath-Ordoubadi Farzin, Paul Das, Paul Morris, Nick Curzen, Diana Gorog, Angela Hoye, Sharon Kean, Peter Ludman, Gregg W Stone, Colin Berry, Anthony H Gershlick
Journal: Circulation (2020)

Introduction: The COVID-19 pandemic has restricted availability of ICU resources. Symptomatic patients with coronary artery disease (CAD) normally considered surgical candidates have therefore required alternative revascularization with percutaneous coronary intervention (PCI). The UK-REVASC registry describes the demographics and in-hospital clinical outcomes of this novel patient cohort. Methods: From 1 st March to 31 st May 2020, anonymised data of 171 patients from 38 UK centres were enrolled in a prospective, observational registry. All were on surgical waiting lists or considered for surgery. Results: The demographics, procedural characteristics and outcomes are shown in Tables 1-3. A comparison with routine PCI British Cardiovascular Intervention Society (BCIS) data and UK isolated coronary bypass surgical data are listed, where available and appropriate. The median age was 68 (IQR 60-76) years. There was significantly more previous MI, PCI and CABG in the routine PCI database than in ReVasc Registry patients, perhaps suggesting a more acute presentation with accelerated symptoms in the test group. These were however complex patients with a mean SYNTAX Score (SS) of 27.8 (range 9-65) and &gt;20x the number of LMS plus multi-vessel disease compared to the routine PCI group, which is reflected in a high use of adjunctive imaging. Radial access was very high at 94.1%. PCI success was 97.0%. Complete revascularization was achieved in 52% with the mean residual SS 1.42 (0-20) in these. There were 2 deaths, however the mortality rate was comparable with published surgical data. Furthermore, a 50% reduction in in-patient stay was observed. Conclusion: In this multi-centre UK registry, in-hospital outcomes following PCI for patients with complex coronary disease, who would typically be treated with CABG, compared well with the surgical data. This suggests that the role of PCI could be extended. Future longer term follow-up however is required and planned.