tbuckley/cabot-search huggingface dataset:
Edoxaban versus Vitamin K Antagonist for Atrial Fibrillation after TAVR
Authors: Nicolas M. Van Mieghem, Martin Unverdorben, Christian Hengstenberg, Helge Möllmann, Roxana Mehran, Diego López-Otero, Luis Nombela-Franco, Raul Moreno, Peter Nordbeck, Holger Thiele, Irene Lang, José L. Zamorano, Fayaz Shawl, Masanori Yamamoto, Yusuke Watanabe, Kentaro Hayashida, Rainer Hambrecht, Felix Meincke, Pascal Vranckx, James Jin, Eric Boersma, Josep Rodés-Cabau, Patrick Ohlmann, Piera Capranzano, Hyo-Soo Kim, Thomas Pilgrim, Richard Anderson, Usman Baber, Anil Duggal, Petra Laeis, Hans Lanz, Cathy Chen, Marco Valgimigli, Roland Veltkamp, Shigeru Saito, George D. Dangas
Journal: New England Journal of Medicine (2021)

The role of direct oral anticoagulants as compared with vitamin K antagonists for atrial fibrillation after successful transcatheter aortic-valve replacement (TAVR) has not been well studied.We conducted a multicenter, prospective, randomized, open-label, adjudicator-masked trial comparing edoxaban with vitamin K antagonists in patients with prevalent or incident atrial fibrillation as the indication for oral anticoagulation after successful TAVR. The primary efficacy outcome was a composite of adverse events consisting of death from any cause, myocardial infarction, ischemic stroke, systemic thromboembolism, valve thrombosis, or major bleeding. The primary safety outcome was major bleeding. On the basis of a hierarchical testing plan, the primary efficacy and safety outcomes were tested sequentially for noninferiority, with noninferiority of edoxaban established if the upper boundary of the 95% confidence interval for the hazard ratio did not exceed 1.38. Superiority testing of edoxaban for efficacy would follow if noninferiority and superiority were established for major bleeding.A total of 1426 patients were enrolled (713 in each group). The mean age of the patients was 82.1 years, and 47.5% of the patients were women. Almost all the patients had atrial fibrillation before TAVR. The rate of the composite primary efficacy outcome was 17.3 per 100 person-years in the edoxaban group and 16.5 per 100 person-years in the vitamin K antagonist group (hazard ratio, 1.05; 95% confidence interval [CI], 0.85 to 1.31; P = 0.01 for noninferiority). Rates of major bleeding were 9.7 per 100 person-years and 7.0 per 100 person-years, respectively (hazard ratio, 1.40; 95% CI, 1.03 to 1.91; P = 0.93 for noninferiority); the difference between groups was mainly due to more gastrointestinal bleeding with edoxaban. Rates of death from any cause or stroke were 10.0 per 100 person-years in the edoxaban group and 11.7 per 100 person-years in the vitamin K antagonist group (hazard ratio, 0.85; 95% CI, 0.66 to 1.11).In patients with mainly prevalent atrial fibrillation who underwent successful TAVR, edoxaban was noninferior to vitamin K antagonists as determined by a hazard ratio margin of 38% for a composite primary outcome of adverse clinical events. The incidence of major bleeding was higher with edoxaban than with vitamin K antagonists. (Funded by Daiichi Sankyo; ENVISAGE-TAVI AF ClinicalTrials.gov number, NCT02943785.).
SARS-CoV-2 Infection and Associated Cardiovascular Manifestations and Complications in Children and Young Adults: A Scientific Statement From the American Heart Association
Authors: Pei-Ni Jone, Anitha John, Matthew E. Oster, Kiona Allen, Adrianna H. Tremoulet, Elizabeth V. Saarel, Linda M. Lambert, Shelley D. Miyamoto, Sarah D. de Ferranti
Journal: Circulation (2022)

Coronavirus disease 2019 (COVID-19) resulted in a global pandemic and has overwhelmed health care systems worldwide. In this scientific statement, we describe the epidemiology, pathophysiology, clinical presentations, treatment, and outcomes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and multisystem inflammatory syndrome in children and young adults with a focus on cardiovascular manifestations and complications. We review current knowledge about the health consequences of this illness in children and young adults with congenital and acquired heart disease, the public health burden and health disparities of this infection in these populations, and vaccine-associated myocarditis.
Prone Positioning of Intubated Patients with an Elevated Body-Mass Index
Authors: David Hao, Sarah Low, Raffaele Di Fenza, Erica S. Shenoy, Lillian Ananian, Laura A. Prout, Carolyn J. La Vita, Lorenzo Berra
Journal: New England Journal of Medicine (2022)

Prone positioning improves oxygenation and decreases mortality in patients with acute respiratory distress syndrome. This video demonstrates how to place an intubated patient in the prone position, with an emphasis on patients who have a body-mass index of more than 30 and for whom the prone position is necessary for a prolonged period.
Abstract P227: Adverse Childhood Environment And Cardiovascular Health Score Across The Lifecourse: The Coronary Artery Risk Development In Young Adults (CARDIA) Study
Authors: Robin Ortiz, Kiarri Kershaw, Songzhu Zhao, David Kline, Guy Brock, Sara Jaffee, Sherita H Golden, Judith Carroll, Teresa Seeman, Joshua J Joseph
Journal: Circulation (2022)

Background: Childhood adversity has been associated with poor health outcomes including cardiovascular disease (CVD) and mortality across the lifecourse. In contrast, ideal cardiovascular health (CVH) inclusive of seven lifestyle-related target metrics, has demonstrated protection from morbidity and mortality. While the relationship between adversity and CVD is hypothesized to be in part due to poor lifestyle, few studies have directly tested this. Purpose: To examine potential associations between childhood risky family environment (RFE) and CVH. Methods: The analyses included 1,987 CARDIA participants without CVD at baseline with complete data. The RFE questionnaire assessed adversities including caregiver abuse, affection, low support, substance use, household disorganization, and limited family engagement (score 0-28). CVH score was calculated as low (0-7), moderate (8-9), and high (10-14) based on AHA poor, intermediate, and ideal categories of smoking status, cholesterol, blood pressure, fasting glucose, body mass index, physical activity, and diet. We applied logistic regression for cross-sectional analyses at each year (0, 7, and 20) and logistic regression with random intercepts for longitudinal analyses across time (all years), adjusting for age, sex, income, and alcohol use. Results: The study sample was age 25.3 SD(3.5) years and 56% female at baseline. Average RFE score was 10 (IQR [8, 14], min 7, max 27). For every unit higher RFE score, the odds of high CVH decreased by 3% (OR=0.97, p=0.036) at year 0, 2% (OR=0.98, p=0.027) at year 7, and longitudinally over 20 years by 3% (OR=0.97, p=0.004). Conclusion: Adverse childhood environment is associated with sustained poor CVH across the lifecourse, suggesting that population health interventions mitigating RFE may improve lifecourse outcomes. Future work should explore if the identification of such environmental exposures may improve modifiable CVD risk factors in adulthood, even when childhood experiences may be long passed.
Neighborhood-Level Disadvantage Impacts on Patients with Fibrotic Interstitial Lung Disease
Authors: Gillian C. Goobie, Christopher J. Ryerson, Kerri A. Johannson, Erin Schikowski, Richard H. Zou, Nasreen Khalil, Veronica Marcoux, Deborah Assayag, Hélène Manganas, Jolene H. Fisher, Martin R. J. Kolb, Kevin F. Gibson, Daniel J. Kass, Yingze Zhang, Kathleen O. Lindell, S. Mehdi Nouraie
Journal: American Journal of Respiratory and Critical Care Medicine (2021)

Rationale: Fibrotic interstitial lung disease (fILD) is a group of pathologic entities characterized by scarring of the lungs and high morbidity and mortality. Research investigating how socioeconomic and residential factors impact outcomes in patients with fILD is lacking. Objectives: To determine the association between neighborhood-level disadvantage and presentation severity, disease progression, lung transplantation, and mortality in patients with fILD from the United States and Canada. Methods: We performed a multicenter, international, prospective cohort study of 4,729 patients with fILD from one U.S. and eight Canadian ILD registry sites. Neighborhood-level disadvantage was measured by the area deprivation index in the United States and the Canadian Index of Multiple Deprivation in Canada. Measurements and Main Results: In the U.S. but not in the Canadian cohort, patients with fILD living in neighborhoods with the greatest disadvantage (top quartile) experience the highest risk of mortality (hazard ratio = 1.51, P = 0.002), and in subgroups of patients with idiopathic pulmonary fibrosis, the top quartile of disadvantage experienced the lowest odds of lung transplantation (odds ratio = 0.46, P = 0.04). Greater disadvantage was associated with reduced baseline DLCO in both cohorts, but it was not associated with baseline FVC or FVC or DLCO decline in either cohort. Conclusions: Patients with fILD who live in areas with greater neighborhood-level disadvantage in the United States experience higher mortality, and patients with idiopathic pulmonary fibrosis experience lower odds of lung transplantation. These disparities are not seen in Canadian patients, which may indicate differences in access to care between the United States and Canada.
Are CRISPR Screens Providing the Next Generation of Therapeutic Targets?
Authors: Francisca Vazquez, William R. Sellers
Journal: Cancer Research (2021)

CRISPR screens combined with molecular and genetic profiling of large panels of cell lines are helping to systematically identify cancer vulnerabilities. These large-scale screens, together with focused in vivo and isogenic cell line screens, have identified a growing number of promising targets and led directly to numerous target-specific drug discovery programs, several of which have reached clinical testing. However, systematic loss-of-function studies are still in their early stages. Genetic redundancy, the limitation of cell line models for many cancer types, and the difficulty of conducting complex in vitro and in vivo screens remain opportunities for discovery. We expect that over the next few years, efforts like the Cancer Dependency Map along with more focused screens will play a significant role in the creation of a roadmap of oncology therapeutic targets.
Abstract 038: Comparative Effects Of Aerobic, Resistance, And Combined Exercise On Sleep
Authors: Angelique G Brellenthin, Duck-chul Lee
Journal: Circulation (2022)

Introduction: Poor sleep quality is associated with high blood pressure and elevated cholesterol, and regular short sleep (&lt;7 hours) has been found to increase the risk of cardiovascular events. The American Heart Association recommends aerobic physical activity to improve sleep, although there are limited data on the effects of other popular types of physical activity, such as resistance exercise, on sleep. Hypothesis: We hypothesized that 1 year of aerobic, resistance, and combined aerobic and resistance exercise would significantly improve sleep compared to a no-exercise control group. Methods: Participants were 406 inactive adults (53% women, 35-70 years) with overweight/obesity and elevated/stage 1 hypertension at high risk of cardiovascular disease. They were randomly assigned to 1 of 4 groups: aerobic exercise (AE) only (n=101), resistance exercise (RE) only (n=102), combined AE and RE (CE) (n=101), and no-exercise control group (CON) (n=102) for 1 year. All exercise participants performed time-matched supervised exercise 3 times/week, 60 min/session (CE performed 30 min of each AE and RE), at 50-80% of their maximum intensity. Participants completed the Pittsburgh Sleep Quality Index (PSQI) at baseline and 12 months, and only participants with complete baseline data on all PSQI subscales were included (n=386). Primary outcomes were the PSQI total sleep quality score (lower scores = better sleep), sleep duration (hours), sleep efficiency (time asleep/time in bed), sleep latency (time to fall asleep), and sleep disturbances (a combination of the number and frequency of disturbances). Linear mixed effects models following the intention-to-treat principle were used to determine the effects of exercise groups on 12-month changes in sleep outcomes while adjusting for age, sex, and the baseline values of each outcome. Results: Overall, 94% of participants completed the intervention with an 83% exercise adherence rate. The PSQI total score and sleep disturbances decreased significantly in all groups, including the control group. Within groups, sleep duration increased significantly by 17 minutes in RE (p=0.005), but not in AE (p=0.73; -2 min), CE (p=0.77; -2 min), or CON (p=0.13; -11 min), among participants getting less than 7 hours of sleep at baseline (p=0.02 for between-within groups interaction). Within groups, sleep efficiency increased in RE (p=0.0005) and CE (0.03), but not in AE (p=0.97) or CON (p=0.86; p=0.04 for between-within groups interaction). Sleep latency also decreased by 3 minutes in RE (p=0.003), although the overall between-within groups interaction effect was not significant (p=0.14). Conclusions: These results indicate that resistance exercise may have superior benefits on sleep compared to aerobic exercise, which could provide a novel pathway for the role of resistance exercise in promoting cardiovascular health.
155TiP Phase II study of tarlatamab, a half-life extended bispecific T-cell engager (HLE BiTE®) immuno-oncology therapy targeting DLL3, in third-line or later small cell lung cancer (SCLC)
Authors: S.S. Ramalingam, M-J. Ahn, H. Akamatsu, F. Blackhall, H. Borghaei, H-D. Hummel, M. Johnson, M. Reck, Y. Zhang, D. Jandial, S. Cheng, L. Paz-Ares
Journal: Annals of Oncology (2022)
Neutralising antibody titres as predictors of protection against SARS-CoV-2 variants and the impact of boosting: a meta-analysis
Authors: Deborah Cromer, Megan Steain, Arnold Reynaldi, Timothy E Schlub, Adam K Wheatley, Jennifer A Juno, Stephen J Kent, James A Triccas, David S Khoury, Miles P Davenport
Journal: The Lancet Microbe (2021)

Several SARS-CoV-2 variants of concern have been identified that partly escape serum neutralisation elicited by current vaccines. Studies have also shown that vaccines demonstrate reduced protection against symptomatic infection with SARS-CoV-2 variants. We explored whether in-vitro neutralisation titres remain predictive of vaccine protection from infection with SARS-CoV-2 variants.In this meta-analysis, we analysed published data from 24 identified studies on in-vitro neutralisation and clinical protection to understand the loss of neutralisation to existing SARS-CoV-2 variants of concern. We integrated the results of this analysis into our existing statistical model relating in-vitro neutralisation to protection (parameterised on data from ancestral virus infection) to estimate vaccine efficacy against SARS-CoV-2 variants. We also analysed data on boosting of vaccine responses and use the model to predict the impact of booster vaccination on protection against SARS-CoV-2 variants.The neutralising activity against the ancestral SARS-CoV-2 was highly predictive of neutralisation of variants of concern. Decreases in neutralisation titre to the alpha (1·6-fold), beta (8·8-fold), gamma (3·5-fold), and delta (3·9-fold) variants (compared to the ancestral virus) were not significantly different between different vaccines. Neutralisation remained strongly correlated with protection from symptomatic infection with SARS-CoV-2 variants of concern (rS=0·81, p=0·0005) and the existing model remained predictive of vaccine efficacy against variants of concern once decreases in neutralisation to the variants of concern were incorporated. Modelling of predicted vaccine efficacy against variants over time suggested that protection against symptomatic infection might decrease below 50% within the first year after vaccination for some vaccines. Boosting of previously infected individuals with existing vaccines (which target ancestral virus) is predicted to provide a higher degree of protection from infection with variants of concern than primary vaccination schedules alone.In-vitro neutralisation titres remain a correlate of protection from SARS-CoV-2 variants and modelling of the effects of waning immunity predicts a loss of protection to the variants after vaccination. However, booster vaccination with current vaccines should enable higher neutralisation to SARS-CoV-2 variants than is achieved with primary vaccination, which is predicted to provide robust protection from severe infection outcomes with the current SARS-CoV-2 variants of concern, at least in the medium term.The National Health and Medical Research Council (Australia), the Medical Research Future Fund (Australia), and the Victorian Government.
The IARC Perspective on Cervical Cancer Screening
Authors: Véronique Bouvard, Nicolas Wentzensen, Anne Mackie, Johannes Berkhof, Julia Brotherton, Paolo Giorgi-Rossi, Rachel Kupets, Robert Smith, Silvina Arrossi, Karima Bendahhou, Karen Canfell, Z. Mike Chirenje, Michael H. Chung, Marta del Pino, Silvia de Sanjosé, Miriam Elfström, Eduardo L. Franco, Chisato Hamashima, Françoise F. Hamers, C. Simon Herrington, Raúl Murillo, Suleeporn Sangrajrang, Rengaswamy Sankaranarayanan, Mona Saraiya, Mark Schiffman, Fanghui Zhao, Marc Arbyn, Walter Prendiville, Blanca I. Indave Ruiz, Isabel Mosquera-Metcalfe, Béatrice Lauby-Secretan
Journal: New England Journal of Medicine (2021)
Zanubrutinib, obinutuzumab, and venetoclax with minimal residual disease-driven discontinuation in previously untreated patients with chronic lymphocytic leukaemia or small lymphocytic lymphoma: a multicentre, single-arm, phase 2 trial
Authors: Jacob D Soumerai, Anthony R Mato, Ahmet Dogan, Venkatraman E Seshan, Erel Joffe, Kelsey Flaherty, Jason Carter, Ephraim Hochberg, Jeffrey A Barnes, Audrey M Hamilton, Jeremy S Abramson, Connie L Batlevi, Matthew J Matasar, Ariela Noy, Colette N Owens, M Lia Palomba, Anita Kumar, Tak Takvorian, Ai Ni, Morgan Choma, Chaya Friedman, Puja Chadha, Elizabeth Simkins, Jade Ruiters, Sidney Sechio, Daneal Portman, Lauren Ramos, Natascha Nolet, Neena Mahajan, Rosalba Martignetti, Joanna Mi, Krista Scorsune, Julia Lynch, Brianne McGree, Stephanie Hughes, Clare Grieve, Lindsey E Roeker, Meghan Thompson, P Connor Johnson, Mikhail Roshal, Jane Huang, Juliana Biondo, Qun Wu, Allison Jacob, Omar Abdel-Wahab, Andrew D Zelenetz
Journal: The Lancet Haematology (2021)
Post-transplant Malignancies Show Reduced T-cell Abundance and Tertiary Lymphoid Structures as Correlates of Impaired Cancer Immunosurveillance
Authors: Rabi R. Datta, Simon Schran, Oana-Diana Persa, Claire Aguilar, Martin Thelen, Jonas Lehmann, Maria A. Garcia-Marquez, Kerstin Wennhold, Ella Preugszat, Peter Zentis, Michael S. von Bergwelt-Baildon, Alexander Quaas, Christiane J. Bruns, Christine Kurschat, Cornelia Mauch, Heike Löser, Dirk L. Stippel, Hans A. Schlößer
Journal: Clinical Cancer Research (2022)

An increased risk to develop cancer is one of the most challenging negative side effects of long-term immunosuppression in organ transplant recipients and impaired cancer immunosurveillance is assumed as underlying mechanism. This study aims to elucidate transplant-related changes in the tumor immune microenvironment (TME) of cancer.Data from 123 organ transplant recipients (kidney, heart, lung, and liver) were compared to historic data from non-immunosuppressed patients. Digital image analysis of whole section slides was used to assess abundance and spatial distribution of T cells and tertiary lymphoid structures in the TME of 117 tumor samples. Expression of programmed cell death 1 ligand 1 (PD-L1) and human-leucocyte-antigen class I (HLA-I) was assessed on tissue microarrays.We found a remarkably reduced immune infiltrate in the center tumor regions (CT) as well as the invasive margins (IM) of post-transplant cancers. These differences were more pronounced in the IM than in the CT and larger for CD8+ T cells, than for CD3+ T cells. The Immune-score integrating results from CT and IM was also lower in transplant recipients. Density of tertiary lymphoid structures was lower in cancer samples of transplant recipients. The fraction of samples with PD-L1 expression was higher in controls whereas decreased expression of HLA-I was more common in transplant recipients.Our study demonstrates the impact of immunosuppression on the TME and supports impaired cancer immunosurveillance as important cause of post-transplant cancer. Modern immunosuppressive protocols and cancer therapies should consider the distinct immune microenvironment of post-transplant malignancies.
CRISPR and cardiovascular diseases
Authors: Kiran Musunuru
Journal: Cardiovascular Research (2022)

Abstract CRISPR technologies have progressed by leaps and bounds over the past decade, not only having a transformative effect on biomedical research but also yielding new therapies that are poised to enter the clinic. In this review, I give an overview of (i) the various CRISPR DNA-editing technologies, including standard nuclease gene editing, base editing, prime editing, and epigenome editing, (ii) their impact on cardiovascular basic science research, including animal models, human pluripotent stem cell models, and functional screens, and (iii) emerging therapeutic applications for patients with cardiovascular diseases, focusing on the examples of hypercholesterolaemia, transthyretin amyloidosis, and Duchenne muscular dystrophy.
18F-FDG PET/CT in a Patient With Matrix-Producing Carcinoma of the Breast
Authors: Xueqi Chen, Guoqian Chen, Zhanli Fu, Qian Li
Journal: Clinical Nuclear Medicine (2021)

Abstract A 47-year-old woman presented with a large mass in the upper inner quadrant of the left breast. 18 F-FDG PET/CT revealed a low-density left breast mass with heterogeneous ring-like 18 F-FDG uptake. Core needle biopsy of the tumor revealed a rare subtype of metaplastic breast carcinoma, matrix-producing carcinoma. The tumor size slightly decreased after 6 cycles of neoadjuvant chemotherapy with docetaxel and epirubicin. The left breast was entirely resected subsequently, and the matrix-producing carcinoma of the breast was ultimately diagnosed.