tbuckley/cabot-search huggingface dataset:
Abstract 14437: Age-related Variations in Takotsubo Syndrome in the United States
Authors: SALIK NAZIR, Keerat R Ahuja, Neha J Patel, Ronak G Soni, Hitesh Raheja, Sameer Saleem, Ingrid Hsiung, Ehab Eltahawy, John E Madias
Journal: Circulation (2020)

Introduction: Several studies have described age-related variation in clinical outcomes for Takotsubo Syndrome (TTS) patients with conflicting results. The present study aimed at analyzing the influence of age on TTS outcomes from a large national database. Methods: The National Inpatient Sample (2009-2015) was used to identify patients with a primary admitting diagnosis of TTS. All patients were stratified according to age and categorized into 3 groups (younger: ≤ 50 years, middle age: 51-74 years, and older: ≥ 75 years). Data on patient demographics, comorbidities, hospital characteristics, and in-hospital complications were extracted. Results: Of 40,326 patients, 11.2% of the patients were ≤ 50 years of age, 59.95% were 51 to 74 years of age, and 29.0% were ≥75 years of age. Young patients were more likely to be male, and less likely to have hypertension, diabetes mellitus, atrial fibrillation, and heart failure (Table). Our analysis showed that in-hospital mortality was higher in the older age group compared to the middle and younger age group. However, younger patients were more likely to have cardiogenic shock, cardiac arrest, invasive ventilation, circulatory support, and ventricular arrhythmias (Table). On multivariate analysis, using middle age as a reference group, older age was independently associated with in-hospital mortality (OR, 1.68; 95% CI: 1.37-2.07), while young age was independently associated with cardiac arrest (OR, 2.92; 95% CI: 2.33-3.63), and ventricular arrhythmias (OR, 2.09; 95% CI: 1.81-2.43). Conclusions: Our study reveals that young patients with TTS are critically ill with higher rates of cardiogenic shock, cardiac arrest, circulatory support, invasive ventilation, and ventricular arrhythmias. However, in-hospital mortality was still higher in the older age group. Further studies are needed to better understand the pathophysiological mechanism of relatively poor outcomes in younger TTS patients.
Peter Sleight: visionary cardiologist and inspiring leader
Authors: John Illman
Journal: BMJ (2020)

Photo credit: Mervyn George Bishop/Fairfax Media/Getty Images

Peter Sleight, a professor at Oxford University, helped to transform heart attack treatment and prevent cardiovascular disease with angiotensin converting enzyme inhibitors and statins. He was among the first cardiologists to recognise the critical importance of large simple trials involving thousands of patients and rigorous statistical analysis of treatment outcomes.

This put him at odds with fellow cardiologists, who regarded statisticians, according to one commentator, as “aliens and Martians.” But Sleight’s reputation persuaded clinicians all over the world to enrol patients into the groundbreaking International Studies of Infarct Survival (Isis) trials.

Cardiology sceptics were finally won over in 1988 when Isis-2 showed that prompt treatment of suspected heart attacks with streptokinase and with aspirin each reduced 30 day mortality by about a quarter, while jointly halving 30 day mortality. The finding that the two clot busters, acting on clots in different ways, complemented one another was a surprise.

Having recruited some 140 000 patients, the four Isis trials had a profound impact on the emerging science of evidence based medicine. Isis methodology influenced the design of studies into other conditions, including the Recovery trial, which showed that dexamethasone reduces covid-19 mortality.

Sleight, a celebrated leader and mentor, inspired great loyalty. Moreover, unlike many eminent men, he was able, endearingly, to laugh at …
Emerging agents and regimens for multiple myeloma
Authors: Yang Yang, Yi Li, Huiyao Gu, Mengmeng Dong, Zhen Cai
Journal: Journal of Hematology & Oncology (2020)

Abstract The outcomes of multiple myeloma (MM) have been improved significantly with the therapies incorporating proteasome inhibitors (PI), immunomodulatory drugs, monoclonal antibodies (MoAb) and stem cell transplantation. However, relapsed and refractory MM (RRMM) remains a major challenge. Novel agents and regimens are under active clinical development. These include new PIs such as ixazomib, marizomib, and oprozomib; new MoAbs such as isatuximab and MOR202; novel epigenetic agent ricolinostat and novel cytokines such as siltuximab. Recently, the first XPO-1 inhibitor, selinexor, was approved for RRMM. BCMA-targeted BiTE, antibody–drug conjugates and CAR-T cells have the potential to revolutionize the therapy for RRMM. In this review, we summarized the latest clinical development of these novel agents and regimens.
Athlete health and safety at large sporting events: the development of consensus-driven guidelines
Authors: Margo Mountjoy, Jane Moran, Hosny Ahmed, Stephane Bermon, Xavier Bigard, Dominik Doerr, Alain Lacoste, Stuart Miller, Alexis Weber, Jeremy Foster, Richard Budgett, Lars Engebretsen, Louise M Burke, Vincent Gouttebarge, Marie-Elaine Grant, Brian McCloskey, Paul Piccininni, Sebastien Racinais, Mark Stuart, David Zideman
Journal: British Journal of Sports Medicine (2020)

All sport events have inherent injury and illness risks for participants. Healthcare services for sport events should be planned and delivered to mitigate these risks which is the ethical responsibility of all sport event organisers. The objective of this paper was to develop consensus-driven guidelines describing the basic standards of services necessary to protect athlete health and safety during large sporting events. By using the Knowledge Translation Scheme Framework, a gap in International Federation healthcare programming for sport events was identified. Event healthcare content areas were determined through a narrative review of the scientific literature. Content experts were systematically identified. Following a literature search, an iterative consensus process was undertaken. The outcome document was written by the knowledge translation expert writing group, with the assistance of a focus group consisting of a cohort of International Federation Medical Chairpersons. Athletes were recruited to review and provide comment. The Healthcare Guidelines for International Federation Events document was developed including content-related to (i) pre-event planning (eg, sport medical risk assessment, public health requirements, environmental considerations), (ii) event safety (eg, venue medical services, emergency action plan, emergency transport, safety and security) and (iii) additional considerations (eg, event health research, spectator medical services). We developed a generic standardised template guide to facilitate the planning and delivery of medical services at international sport events. The organisers of medical services should adapt, evaluate and modify this guide to meet the sport-specific local context.
Abstract 295: Deep Learning and Electrical Impedance Tomography in the Prediction of Interventions Needed to Resuscitate From Hypoxic Pseudo-Pulseless Electrical Activity
Authors: Alexander L Lindqwister, Weiyi Wu, Samuel Klein, Ethan K Murphy, Karen L Moodie, Saeed Hassanpour, Alexandra P Hamlin, Joseph M Minichiello, Justin E Anderson, Norman A Paradis
Journal: Circulation (2020)

Introduction: Pseudo-Pulseless Electrical Activity (p-PEA) is a form of profound cardiac shock defined as measurable cardiac activity without clinically detectable pulses. p-PEA has a distinct physiology and etiology from VF and true-PEA, and may constitute up to 40% of reported cases of cardiac arrest. Electrical impedance tomography (EIT) uses cutaneous electrodes to generate images based on cross sectional resistance. We utilized EIT to predict the number of interventions required to achieve ROSC from p-PEA. Methods: Female swine (N = 14) under intravenous anesthesia were instrumented with aortic and central venous micromanometer catheters. p-PEA was induced by ventilation with 6% oxygen in 94% nitrogen and was defined as a systolic aortic pressure less than 40 mmHg. Continuous EIT renderings were obtained from circumferential cutaneous thoracic and abdominal electrode arrays. A deep learning model was utilized to detect features within the EIT video clips of the p-PEA disease state to predict the number of treatments required to achieve ROSC. Twelve pigs were randomly selected as training data and 2 pigs as a test set. EIT images were saved as 30 second clips, resulting in 1630 clips generated. To increase generalizability, random epochs ranging from 30 - 100% of the total clip length were generated, resulting in a model capable of detecting this disease state with limited video fragments. Data were labeled based on the number of interventions required to achieve ROSC (100% O 2 , 100% O 2 + CPR, 100% O 2 + CPR + Epi, ROSC not achieved). Results: This approach yielded receiver operator characteristic curves - area under the curve (ROC-AUC, Figure 1) values of 0.75 for micro (weighted) AUC and 0.78 for macro (unweighted) AUC on a 4 class prediction model. Conclusion: EIT combined with machine learning may differentiate the required treatments needed to achieve ROSC in p-PEA.
Abstract 14362: Shifting Trends in Timing of Pacemaker Implantation After Transcatheter Aortic Valve Replacement
Authors: Anthony Mazzella, Michael Hendrickson, Sameer Arora, Mason Sanders, Quefeng Li, John Vavalle, Anil Gehi
Journal: Circulation (2020)

Introduction: Hospital length of stay with transcatheter aortic valve replacements (TAVRs) has decreased, though the rate of heart block requiring permanent pacemaker (PPM) implantation after TAVR has remained steady. It is unknown whether more patients are being readmitted for PPM after discharge from TAVR. Objective: To explore frequency, timing, and risk factors for PPM implant after TAVR in a nationally representative database. Methods: Patients who underwent TAVR from January 2012 through December 2017 were identified in the Nationwide Readmissions Database (NRD). Smoothing splines and logistic regression were used to analyze trends in length of stay and timing of PPM implantation after TAVR respectively. Multivariable logistic regression analysis was performed to identify risk factors for overall, early (during index hospitalization), and late (during subsequent hospitalization) PPM after TAVR. Results: Of the 62,083 included, 6,817 (11.0%) underwent PPM implantation [6,137 (9.9%) early and 680 (1.1%) late]. Rates of PPM remained stable between 8% and 12.5% with an increasing proportion occurring late (7% in 2012 increasing to 13% in 2017, p &lt; 0.0001 for trend) (Figure 1). Late PPM was associated with atrial fibrillation (p &lt; 0.01), diabetes mellitus (p &lt; 0.001), chronic kidney disease (p &lt; 0.05), second degree AVB (p &lt; 0.001), left bundle branch block (p &lt; 0.001), right bundle branch block (p &lt; 0.001), and bifascicular block (p &lt; 0.001). Conclusions: There has been a significant increase in the proportion of patients requiring readmission for PPM implantation after TAVR. As this high-risk population grows, algorithms for extended in-hospital observation or ambulatory cardiac monitoring post-TAVR are needed to reduce the risk for adverse events.
AB0141 MYCOPHENOLATE MOFETIL, INHIBITOR OF INOSINE-5’-MONOPHOSPHATE DEHYDROGENASE, REGULATES DIFFERENTIATION, MATURATION AND FUNCTION OF HUMAN DENDRITIC CELL SUBSETS
Authors: M. Shigesaka, T. Ito, M. Inaba, Y. Azuma, S. Tsujimoto, A. Tanaka, Y. Son, Y. Ozaki, S. Nomura
Journal: Annals of the Rheumatic Diseases (2020)

Background: Systemic lupus erythematosus (SLE) is a heterogeneous disease in which excessive inflammation, autoantibodies, and complement activation lead to multisystem tissue damage. Plasmacytoid dendritc cells (pDCs) play a central role in the pathogenesis of SLE through dysregulated type I IFN production, together with activated myeloid DCs (mDCs), amplifying vicious spiral of autoimmune disorders(1). Therefore, control of the aberrant DC activation may provide an alternative treatment strategy against SLE. Objectives: Mycophenolate mofetil (MMF), which has been used to treat lupus nephritis, specifically blocks proliferation of B and T lymphocytes by inhibition of inosine-5-monophosphate dehydrogenase (IMPDH). In addition, although there is evidence indicating the immunosuppressive effects of MMF on human monocyte-derived dendritic cells(2.3), there are no reports showing its effects on human blood DC subsets. Here we focused on the effects of MMF on the functions of the blood pDCs and mDCs. Methods: We isolated human blood DCs from healthy donors using cell sorting(4) and examined the function of mycophenolic acid (MPA), which is metabolic products of MMF, on DC subsets in response to TLR-ligands and serum from patients with active SLE. Written informed consent was obtained from all healthy adult donors and SLE patients. Results: We found that therapeutic plasma concentration range of MPA down-regulated expression of CD40, CD80 and CD86 dose-dependently on mDCs and pDCs without inducing apoptosis, in response to R848(TLR7/8 agonist) and CpG2216(TLR9 agonist), respectively. Of note, MPA profoundly suppressed IL-12 production and STAT4 expression in the mDCs and IFN-α production and IRF7 expression in the pDCs(Fig 1). We also obserbed inhibition of nuclear translocation of IRF-7 in pDCs treated with MPA by confocal microscopy(Fig 2). Furthermore,we identified that MPA had an inhibitory effect on SLE serum-induced IFN-α production by human PBMCs. Conclusion: Our data suggest that MMF can drive a wedge into the vicious spiral of autoimmune disorders through regulating the function of not only lymphocyte but also DC subsets. Thus, we unveiled a part mechanism of the therapeutic ability of MMF against SLE. References: [1]A Plasmacytoid Dendritic Cells-Type I Interferon Axis is Critically Implicated in the Pathogenesis of Systemic Lupus Erythematosus. Int. J. Mol. Sci. 2015: 16, 14158-14170. [2]Mycophenolate mofetil inhibits differentiation, maturation and allostimulatory function of human monocyte-derived dendritic cells. Clin Exp Immunol. 2003;134:63-69. [3]Mycophenolic acid inhibits maturation and function of human dendritic cells and B cells. Human Immunol. 2009;70: 692–700. [4]Miyamoto et al. Arthritis Research &amp; Therapy 2010, 12:R87. Disclosure of Interests: None declared
Abstract 16260: Thirty Days Major Adverse Cardiac Events Following Percutaneous Coronary Intervention Versus Coronary Artery Bypass Grafting in Non-ste-acute Coronary Syndrome: A Meta-analysis With Meta-regression
Authors: Kiro Barssoum, Ashish Kumar, Devesh Rai, Adnan Kharsa, Medhat Chowdhury, Samarthkumar J Thakkar, Muhammad Waqas Tahir, Mohan Rao
Journal: Circulation (2020)

Background: The optimum revascularization modality in multi-vessel and left main disease patients presenting with non-ST elevation acute coronary syndrome (non-STE-ACS) is not well studied. The current recommendations are based on studies that primarily included patients with stable angina. Patients with non-STE-ACS were under-represented in clinical trials. We performed a meta-analysis of studies comparing coronary artery bypass grafting (CABG) vs. percutaneous coronary intervention (PCI) in non-STE-ACS, and reporting 30 days major adverse cardiac events (MACE). Methods: We searched Medline, EmCare, CINAHL, Cochrane database, and Google Scholar for relevant articles. We excluded studies that included patients with stable coronary artery disease and ST elevation myocardial infarction. Our primary outcome was 30 days MACE defined as all-cause death, stroke, repeat revascularization and re-infarction. We used the Paule-Mandel method with the Hartung-Knapp-Sidik-Jonkman adjustment to estimate risk ratio (RR) with a 95% confidence interval (CI). Heterogeneity was assessed using Higgin’s I 2 statistics. To account for heterogeneity, a meta-regression analysis was performed. Results: Five observational studies met our inclusion criteria summing to a total number of 7161 patients. At 30 days, there was no difference between CABG vs. PCI in terms of MACE, RR: 0.96, 95% CI 0.38 to 2.39, I 2 = 81% (Panel A). A meta-regression analysis reported that a history of PCI was associated with a lower risk of MACE with CABG compared to PCI (Panel B). Conclusion: At 30 days, there was no difference in MACE between the CABG and PCI groups. However, a history of PCI was associated with a lower risk of MACE in patients who underwent CABG.
Abstract 14861: Premature Menopause and Mid-life Subclinical Atherosclerosis: The Coronary Artery Risk Development in Young Adults (CARDIA) Study
Authors: Priya P Mehta, Lucia Petito, Laura A Colangelo, Cora E Lewis, Pamela SCHREINER, James G Terry, Melissa Wellons, Catherine Kim, Jamal S Rana, Donald M Lloyd-jones, Norrina B Allen, Sadiya S Khan
Journal: Circulation (2020)

Introduction: Women who experience premature menopause are known to have higher rates of long-term atherosclerotic cardiovascular disease (ASCVD). Specifically, menopause prior to age of 40 years has been identified as a risk enhancer by the 2019 AHA/ACC Primary Prevention guidelines. Coronary artery calcium (CAC) may have clinical utility for refinement of risk stratification in this high-risk group of women for the primary prevention of ASCVD. Methods: We included women from the Coronary Artery Risk Development in Young Adults (CARDIA) study who completed a coronary-gated CT scan at a baseline age of 43-55 years. We excluded women who had a myocardial infarction prior to CAC assessment. Menopausal status was self-reported as before the age of 40 years, at 40 years or older, or pre-menopausal. No significant interaction by race was observed. We performed multinomial logistic regression analysis to examine the association between premature menopause and 3 categories of CAC (0, 1-99, and ≥100 Agatston units). In separate multivariable models, we adjusted for demographic and cardiovascular risk factors at the time of CAC measurement. Results: Of 1786 women, 167 (9.4%) experienced premature menopause, 1175 (65.8%) reached menopause after the age of 40 years, and 444 (24.9%) were pre-menopausal at the time of CT. Presence of any CAC in these 3 groups was 18.0%, 19.6%, and 11.3% for premature menopause, ≥40 menopausal, and the pre-menopausal groups, respectively (FIGURE). Premature menopause was not associated with higher odds of non-zero CAC in unadjusted or adjusted analyses. Conclusions: Premature menopause was not associated with prevalent CAC score in these women in mid-life. Consideration of alternative approaches or biomarkers for risk stratification for ASCVD should be evaluated in this high-risk group.
Abstract 15169: <i>De Novo</i> Variants of <i>USP10</i> in Early Onset Bicuspid Aortic Valve Disease
Authors: Siddharth K Prakash, Angela T Yetman, Hector I Michelena, Malenka M Bissell, Yuli Y Kim, Dawn Hui, Maria G Andreassi, Ilenia Foffa, Dongchuan Guo, Rodolfo Citro, Margot De Marco, Carlo DeVicentis, Justin T Tretter, Simon C Body, Elizabeth E Blue, Deborah A Nickerson, Michael J Bamshad
Journal: Circulation (2020)

Introduction: Bicuspid Aortic Valve (BAV), the most common congenital heart defect, is a major cause of aortic regurgitation or stenosis requiring valve replacement and thoracic aortic aneurysms predisposing to acute aortic dissections (TAD). The spectrum of BAV ranges from severe early onset valve and aortic complications to sporadic late onset disease. Hypothesis: Early onset BAV (EBAV) cases with valve or aortic complications that require intervention prior to age 30 are enriched for rare genetic variants that cause BAV and TAD. Methods: We performed whole exome sequencing of 147 EBAV cases in 141 families who were enrolled in the UTHealth Bicuspid Aortic Valve Research Registry. Candidate variants in the EBAV cohort (26% female, mean age 18, 44% with TAD) were compared to unselected controls from the Genome Aggregation Database (gnoMAD) and the Database of Genotypes and Phenotypes (dbGAP). We considered variants with minor allele frequencies (MAF) &lt; 1%, Combined Annotation Dependent Depletion (CADD) scores &gt; 25, and damaging (Polyphen-2) or deleterious (SIFT) functional prediction scores. Genomic copy number variants (CNVs) were detected using CoNIFER and prioritized when deletions involved genes with probability of loss intolerance (pLI) &gt; 0.9. Variants were validated using quantitative PCR or Sanger sequencing. Results: We identified 6 rare variants of USP10 in 6 EBAV families (4% of cohort): 4 CNVs (2 duplications and 2 deletions) that are rare in dbGAP controls (4 in 15,414) and 2 deleterious rare missense variants (MAF&lt;5x10 -5 in gnoMAD). Two of the 4 CNVs were de novo events in trios. In contrast, rare deleterious variants of the known causal BAV genes NOTCH1 (1), ROBO4 (1), GATA4 (1), GATA5 (1), and SMAD6 (4) were found in 7 total families. USP10 encodes a ubiquitin peptidase that is required for endothelial Notch signaling during vascular development. Conclusions: We identified rare and de novo variants of USP10 that implicate USP10 as a new candidate gene for BAV.
Comment on Zhou et al. Cost-effectiveness of Diabetes Prevention Interventions Targeting High-risk Individuals and Whole Populations: A Systematic Review. Diabetes Care 2020;43:1593–1616
Authors: Thirunavukkarasu Sathish, Jonathan E. Shaw, Brian Oldenburg, Ajay Mahal
Journal: Diabetes Care (2020)

In the July issue, Zhou et al. (1) published a systematic review of studies on the cost-effectiveness of interventions for the prevention of type 2 diabetes. Based on the findings from 17 studies (or study arms), from a health system perspective, lifestyle interventions and the use of metformin in high-risk individuals had a median incremental cost-effectiveness ratio (ICER) of US$12,510 per quality-adjusted life year (QALY) and US$17,089 per QALY, respectively. All these studies were conducted in high-income countries (HICs), including the U.S., the U.K., the Netherlands, Singapore, Australia, Sweden, and Hong Kong, and were published by July 2017.

These cost-effectiveness data from HICs are unlikely to be generalizable to low- …
Combined oral 5-azacytidine and romidepsin are highly effective in patients with PTCL: a multicenter phase 2 study
Authors: Lorenzo Falchi, Helen Ma, Sandra Klein, Jennifer K. Lue, Francesca Montanari, Enrica Marchi, Changchun Deng, Hye A. Kim, Aishling Rada, Alice T. Jacob, Cristina Kinahan, Mark M. Francescone, Craig R. Soderquist, David C. Park, Govind Bhagat, Renu Nandakumar, Daniel Menezes, Luigi Scotto, Lubomir Sokol, Andrei R. Shustov, Owen A. O’Connor
Journal: Blood (2020)