tbuckley/cabot-search huggingface dataset:
Abstract 9726: Simplified Academic Research Consortium for High Bleeding Risk Criteria Predicts Bleeding Events in Patients with Heart Failure
Authors: Yu Sato, Akiomi Yoshihisa, Ryohei Takeishi, Himika Ohara, Yukiko Sugawara, Yasuhiro Ichijo, Yu Hotsuki, Koichiro Watanabe, Satoshi Abe, Tomofumi Misaka, Takamasa Sato, Masayoshi Oikawa, ATSUSHI KOBAYASHI, Kazuhiko Nakazato, Yasuchika Takeishi
Journal: Circulation (2021)

Introduction: It has been reported that the simplified Academic Research Consortium for High Bleeding Risk (ARC-HBR) criteria in which six rare criteria are excluded are comparable to the original ARC-HBR criteria in predicting major bleeding in patients who undergo percutaneous coronary intervention. We aimed to evaluate the predictive value of the simplified ARC-HBR criteria for bleeding events in patients with heart failure (HF) including those with and without coronary artery disease (CAD). Methods and Results: A total of 2,437 patients hospitalized for HF were enrolled. Among them, 56.5%, 23.7%, 15.8%, 4.8%, 4.7%, and 3.0% presented with oral anticoagulation, anemia, renal dysfunction, thrombocytopenia, active malignancy, and stroke of major criteria. Patients were divided into two groups based on the simplified ARC-HBR criteria: patients who are at HBR (HBR group, n = 2,026, 83.1%) and those who are not (non-HBR group, n = 411, 16.9%). The HBR group was older (72.0 vs. 61.0 years old, P &amp;lt; 0.001) and had lower prevalence of CAD (31.1% vs. 36.5%, P = 0.034) than the non-HBR group. The Kaplan-Meier analysis showed that post-discharge hemorrhagic stroke and gastrointestinal bleeding rates were higher in the HBR group than in the non-HBR group ( Figure ). In the Cox proportional hazard analysis, the simplified ARC-HBR criteria predicted both hemorrhagic stroke (hazard ratio [HR] 2.827, 95% confidence interval [CI] 1.019-7.844, P = 0.046) and gastrointestinal bleeding (HR 3.565, 95% CI 1.560-8.145, P = 0.003) irrespectively of CAD (interaction P = 0.931 and 0.761, respectively). Conclusions: The simplified ARC-HBR criteria predicts high bleeding events in patients with HF.
Abstract 12560: The Association of Social Risk Factors With Hypertrophic Cardiomyopathy Treatments and Mortality: US National Inpatient Sample, 2012-2018
Authors: Daniel Y Johnson, RJ Waken, Daniel K Fox, Gmerice Hammond, Karen E Joynt Maddox, Sharon Cresci
Journal: Circulation (2021)

Introduction: Hypertrophic cardiomyopathy (HCM) is the most common heritable cardiac disease. In small studies race has been associated with disparities in septal reduction therapy (SRT) but little is known about the association of social risk factors with HCM treatments and outcomes. Methods: A retrospective cohort of admissions for HCM in the National Inpatient Sample from 2012-2018 was identified using ICD-9-CM and ICD-10-CM diagnosis codes. SRT and implantable cardioverter-defibrillator (ICD) procedures were identified using ICD-9-CM and ICD-10-CM procedure codes. Logistic regression controlling for social risk factors, Elixhauser comorbidities, pre-existing ICD, and clustering by hospital-year was used to determine the association of social risk factors with HCM procedures and in-hospital mortality. Results: We identified 60,227 patients with HCM; 45.82% with obstructive HCM (oHCM). Among them, 57.25% were female, 18.65% were Black, 26.75% were in the lowest ZIP income quartile, and 14.89% lived in rural areas. ICD procedures were done on 3.07% of patients with HCM. Septal myectomy and alcohol septal ablation were received by 6.89% and 2.21% of patients with oHCM, respectively. The in-hospital mortality rate was 3.32% for HCM admissions. Compared to White patients, Black patients were less likely to receive septal myectomy (odds ratio [OR] 0.56, 95% confidence interval [0.45-0.70], p&lt;0.001) and more likely to receive ICD procedures (OR 1.17 [1.01-1.36], p=0.03). Patients in the lowest income quartile were less likely to receive septal myectomy (OR 0.81 [0.68-0.98], p=0.03) and ICD procedures (OR 0.83 [0.71-0.98], p=0.02). Rural patients were more likely than urban patients to receive septal myectomy (OR 1.39 [1.17-1.64], p&lt;0.001) and to die during hospitalization (OR 1.38 [1.19-1.59], p&lt;0.001). Female patients were less likely to receive ICD procedures (OR 0.69 [0.62-0.76], p&lt;0.001) but more likely to die during hospitalization (OR 1.19 [1.07-1.31], p&lt;0.001). Conclusions: Among 60,227 patients with HCM, social risk factors were associated with significant disparities in in-hospital mortality and in receiving septal myectomy and ICD treatment. Further research is required to identify and address the sources of these disparities.
Whole Genome Sequencing As an Unbiased and Simplified Approach to Molecular Karyotyping in AML/MDS
Authors: Xiaodong Lv, Tao Li, Dandan Zhu, Mengna Zhang, Yuexin CHENG, Zhenling Li, Yan Chen, Shiyong Li, Yinyin Chang, Mao Mao, Zunmin Zhu, Yongping Song
Journal: Blood (2021)
TMOD-17. A NOVEL GLIOBLASTOMA INVASION MODEL USING HUMAN BRAIN SLICE CULTURES
Authors: Vidyha Ravi, Kevin Joseph, Jürgen Beck, Oliver Schnell, Ulrich Hofmann, Dieter Henrik Heiland
Journal: Neuro-Oncology (2021)

Abstract OBJECTIVE Glioblastoma (GBM) is among the most common of malignant brain tumours, with a median post-surgical survival of less than one year. Over the past several decades, therapies that appeared promising in mice models have failed during clinical trials due to the differences encountered during translation of research from model organisms to humans. To partially mitigate these difficulties in translation, we present a human cortical organotypic culture based GBM model, which allows us to manipulate individual components of the tumour environment in order to investigate the influence of different cell types in the immunosuppressive tumour microenvironment. METHODS Human neocortical tissue (at least 2 cm away from the tumour core) or entry cortex from epilepsy surgery guided by intraoperative neuro navigation, was cultured for up to 14 days post resection using an optimized medium. The cultured tissue was further injected with patient derived human GBM cells to create an ex vivo human model of glioblastoma model. The role of astrocytes in the tumour microenvironment was studied using microglia loss of function model. RESULTS Our established human neo-cortical slice model can recapitulate an in-vivo characteristics of glioblastoma from functional and imaging aspect. Our data corroborate differences between astrocytes in human and murine models in different reactive states, shows that the glioblastoma microenvironment can be difficult to be accurately modelled using murine models. Results from our human microglia depletion model, provided ample evidence that complex interaction of astrocytes and microglia cells, promotes an immunosuppressive environment in Glioblastoma by releasing high concentration of IL10 and TGFbeta (p&amp;lt; 0.001). CONCLUSION Our model therefore has potential applications to the fields of neuroscience, neuro-oncology, and pharmacotherapy.
Abstract 10780: Uptake of Direct Oral Anticoagulants in Older Adults with Atrial Fibrillation in 2010-2018
Authors: Darae Ko, Joshua K Lin, Mehdi Najafzadeh, Susan Cheng, Erin Kim, Lily G Bessette, Allan J Walkey, Dae Hyun Kim
Journal: Circulation (2021)

Introduction: Under-treatment with oral anticoagulants (OAC) in atrial fibrilliation (AF) is a persistent management gap, particularly in older adults. Understanding patterns of OAC adoption may enable design of implementation strategies to improve evidence-based care. Objectives: Determine changes in OAC use and overall uptake of direct oral anticoagulants (DOACs) in older adults. Methods: We analyzed administrative claims data (years 2010 to 2018) from Optum Clinformatics Data Mart to identify Medicare Advance Plan beneficiaries (aged ≥65) with AF and CHA 2 DS 2 -VASc score ≥2. We excluded patients with history of intracranial hemorrhage and end-stage renal disease. We calculated the proportion of patients prescribed a DOAC, warfarin, or no OAC each year. We examined uptake by patient subgroups, including those with dementia diagnoses and those with frailty, defined by a claims-based frailty index. Results: Our sample size ranged from 123,700 in 2010 to 398,385 in 2018. The mean age ranged 76-79 years and the proportion of women ranged 50-53%. The proportion of eligible patients receiving OAC increased from 50.9% to 53.8% for the total sample (+2.9%) (Figure A). This increase was greater for younger patients (65-79 years: 53.7% to 58.1% vs ≥80 years: 48.9 to 49.5%) (Figures B &amp; C), those with dementia (dementia: 39.6% to 44.8% vs no dementia: 52.5% to 55.3%) (Figures D &amp; E), and those with frailty (frailty: 48.1% to 52.1% vs no frailty: 53.4% to 55.3%) (Figures F &amp; G). There was a consistent decreasing trend in warfarin use in all subgroups from 2010 to 2018 (51 to 19 % in the total population, Figures A-G). Conclusion: Following the advent of DOACs, overall OAC use modestly increased in older adults, including for those with dementia and frailty. A large proportion of patients with guidelines-based eligibility for OAC remain untreated. Implementation strategies for improving OAC use are needed, particularly for high-risk older patients who stand to benefit the most.
Benefits of physical activity interventions combining self-monitoring with other components versus self-monitoring alone: a systematic review and meta-analysis
Authors: Tomas Vetrovsky, Charlotte Wahlich, Agnieszka Borowiec, Roman Jurik, Witold Smigielski, Michal Steffl, James Tufano, Wojciech Drygas, Petr Stastny, Lukasz Malek, Tess Harris
Journal: The Lancet (2021)
Activation Mediated By Peroxisome Proliferator-Activated Receptor (PPAR) Ligands and Brown Algae-Based Compounds: Different Mechanisms between Megakaryoblasts and Mature Platelets
Authors: Jin-Yeong Han, Jae-Lim Choi, Ri-Young Goh, Hyeon-Ho Lim, Joo-In Park
Journal: Blood (2017)
Abstract 11812: Hypertrophic Cardiomyopathy, in a Latin American Center
Authors: Ramon Medina, Juan Felipe Vasquez, Esther Campo, Maria Juliana Rodriquez, Claudia Jaimes
Journal: Circulation (2021)

Introduction: Hypertrophic cardiomyopathy (HCM) is the most common monogenic cardiovascular disorder, however, data from Latin-American countries are scarce. Methods: We conducted a retrospective study to characterize the population with HCM in a cardiovascular care center in Bogotá, Colombia. All cardiac magnetic resonance (CMR) performed between 2017 to 2019 were reviewed. Patients with diagnosis of HCM by imaging findings were included in the analysis. Demographic data, and clinical, and imaging characteristics, were described. Results: A total of 2636 CMR were performed between 2017-2019. The diagnostic criteria for HCM were met in 116 (4,4%) patients. The mean age of diagnosis was 63 YO, 54,3% were male. A family history of sudden cardiac death (SCD) was reported in 12%. The most frequent symptoms were dyspnea and chest pain. 26% had atrial fibrillation (table 1). The main phenotype was septal (70%) (figure 1). Most of the patients with HCM (88%) had some alteration of the mitral valve apparatus. Survival at 5 years was 87%. ICD implantation was required in 12,9% of the patients and a septal myomectomy was performed in 6,8%. Conclusions: HCM was more frequent in our cohort than that reported in the current literature, however, the clinical characteristics and prognosis were similar. In our population, HCM patients were diagnosed later than other cohorts.
Abstract P352: An Antiplatelet Agent Sarpogrelate Suppresses Pressure Overload-induced Development Of Heart Failure In A 5-ht <sub>2a</sub> Receptor-independent Manner
Authors: Kana Shimizu, Masafumi Funamoto, Yoichi Sunagawa, Yasufumi Katanasaka, Yusuke Miyazaki, Noriyuki Murai, Satoshi Shimizu, Koji Hasegawa, Tatsuya Morimoto
Journal: Circulation Research (2021)

Purpose: The cost of new drug development is increasing year by year, and drug repositioning is being used as a strategy to develop new treatments at low-cost. We used a library of approved drugs to screen for compounds that suppress cardiomyocyte hypertrophy, and identified as a candidate the antiplatelet drug sarpogrelate, a selective serotonin-2A (5-HT 2A ) receptor antagonist. In this study, we examined the effect of sarpogrelate on cultured cardiomyocyte hypertrophy and development of heart failure. Methods &amp; Results: First, primary cultured cardiomyocytes were treated with 1 μM sarpogrelate and then stimulated with various hypertrophic stimuli (30 μM phenylephrine (PE), 0.1 μM angiotensin II and 0.1 μM endothelin 1). The results of immunofluorescence staining with anti-MHC antibody showed that sarpogrelate significantly suppressed cardiomyocyte hypertrophy induced by each stimulus. Western blotting and qPCR analysis showed that the mRNA and protein levels of 5-HT 2A receptor did not change by PE, and sarpogrelate significantly suppressed PE-induced phosphorylation of ERK1/2 and GATA4. Next, C57BL/6j male mice were subjected to a transverse aortic constriction (TAC) and sham operation. One day after the operation, the mice were randomly divided into 3 groups: sarpogrelate at 1 mg/kg or 5 mg/kg, and vehicle as a control. Daily oral administration was repeated for 8 weeks. Echocardiographic analysis showed that 5 mg/kg sarpogrelate significantly prevented a TAC-induced increase in posterior left ventricular wall thickness and a decrease in fractional shortening at 8 weeks after the operation. Five mg/kg sarpogrelate also suppressed TAC-induced increase in HW/BW ratio, cross-sectional areas, perivascular fibrosis, and mRNA levels of ANF and BNP. Moreover, the western blotting analysis showed that 5 mg/kg sarpogrelate significantly suppressed TAC-induced phosphorylation of ERK1/2. Conclusions: These results indicate that sarpogrelate significantly suppresses cardiomyocyte hypertrophy and the development of heart failure via at least, in part, by inhibition of ERK1/2-GATA4 pathway. These findings suggest that sarpogrelate may be an effective agent for heart failure therapy.
TB and COPD in low-income settings: a collision of old foes
Authors: Jamilah Meghji, Kevin Mortimer, Stellah Mpangama
Journal: Thorax (2021)

Tuberculosis (TB) remains a major global public health challenge, with 10 million incident cases estimated in 2019. Historically, national TB programmes and international TB policy frameworks have focused on the need to identify active TB cases, improve access to care and ensure treatment completion, in order to achieve microbiological cure and improve disease survival. However, in recent years as TB survival has slowly improved, there has been a growing focus on residual post-TB morbidity, with calls for TB programmes to consider the long-term physical, psychosocial and socioeconomic well-being of TB survivors even after TB treatment completion.1 Residual lung damage after pulmonary TB disease—or post-TB lung disease—is a particular concern in TB endemic settings. For patients with TB in low-income and middle-income countries (LMICs) residual respiratory symptoms may be highly stigmatising, interfere with work and livelihoods, and lead to costly health seeking after TB treatment completion. For healthcare providers the lack of access to respiratory diagnostics, treatment guidelines and established care pathways make patients with post-TB lung disease particularly challenging to manage.

The study by Kamenar et al 2 highlights the relationship between previous TB and residual chronic obstructive pulmonary disease (COPD) in LMICs. This paper is a pooled analysis of five population-based studies in LMICs, which include data from 12 396 adults from thirteen resource-poor settings in six countries, of whom 332 (2.7%) reported a history of previous TB disease. It examines the relationship between COPD—defined as a post-bronchodilator forced expiratory volume in …
Infarct Tissue Heterogeneity by Contrast-Enhanced MRI is a Novel Predictor of Mortality in Patients with Coronary Artery Disease with Reduced Left Ventricular Systolic Function
Authors: E. Watanabe, O.R. Coelho, F.P. Mongeon, M. Jerosch-Herold, R. Blankstein, H. Hatabu, Y.C. Chen, D. Mandry, B. Heydari, R.J. van der Geest, R.Y. Kwong
Journal: Circulation (2011)
PATH-11. PDGFA INITIATES ABERRANT MITOSIS AND MALIGNANT TRANSFORMATION OF NEURAL PROGENITOR CELLS
Authors: Michael Blough, Hiba Omairi, Cameron Grisdale, J Gregory Cairncross
Journal: Neuro-Oncology (2021)

Abstract BACKGROUND Imagining ways to prevent or treat glioblastoma (GBM) have been hindered by a lack of understanding of its pathogenesis. Although platelet derived growth factor-A (PDGFA) overexpression may be an early event, critical details of the biology of GBM, and tools to study its initiation have been lacking. Indeed, many PDGF-driven models replicate its microscopic appearance, but not genomic architecture. Recently, we reported an in vitro model of GBM initiation that overcomes this barrier to authenticity. METHODS We used a method developed to establish neural stem cell cultures to investigate the effects of PDGF-A on cells derived from the subventricular zone (SVZ), a putative region where the cells of origins for GBM are derived. We micro-dissect SVZ tissue from p53-null and wild-type adult mice, culture cells in media supplemented with PDGF-A, and assess cell viability, proliferation, mitotic capacity, and genome stability. RESULTS Paradoxical to its canonical role as a growth factor, we observe abrupt and substantial cell death in PDGF-A. Abnormal mitosis was the first observable alteration and occurred immediately in cells of both p53 wild-type and null genotypes: wild-type cells did not survive in PDGF-A, whereas a fraction of null cells evade apoptosis. Evading cells displayed attenuated proliferation accompanied by early chromosomal gains and losses. After approximately 100 days in PDGF-A, surviving cells suddenly proliferate rapidly, acquire growth factor independence, and become tumorigenic in immune-competent mice. Transformed cells continue to display highly abnormal mitotic phenotypes with complex karyotypes similar to GBM, had a neural progenitor cell (NPC) lineage profile, and were resistant to PDGFR-alpha inhibition. CONCLUSION Abnormal mitosis induced by PDGF-A initiates and perpetuates the genome instability that transforms p53-null neural progenitor cells to yield cancers with the types of recurring chromosomal gains and losses that characterize human GBM.
Activation of the STAT1-BCL-2/MCL-1 Axis in Leukemic Cells Carrying a SPAG9-JAK2 Fusion
Authors: Azusa Mayumi, Toshihiro Tomii, Takuyo Kanayama, Takashi Mikami, Kuniaki Tanaka, Hideki Yoshida, Itaru Kato, Machiko Kawamura, Tatsutoshi Nakahata, Junko Takita, Hajime Hosoi, Toshihiko Imamura
Journal: Blood (2021)
Abstract 13411: Vasodilatory Capacity With Regadenoson Myocardial Perfusion Imaging In Patients With End Stage Liver Disease
Authors: Thuy Nguyen, William Bradley, Miguel Hernandez Pampaloni
Journal: Circulation (2021)

Introduction: The sensitivity and specificity of myocardial perfusion imaging in end stage liver disease (ESLD) patients ranges between 35-37% and 63-88%, respectively. Despite high levels of endogenous catecholamines and angiotensin, ESLD induced arterial vasodilation may exhaust the vasodilatory capacity of common pharmacologic stress agents. Reduced heart rate (HR) response to vasodilator stress test has been associated with increased major adverse cardiac events (MACE) in pre-transplant end stage renal disease patients but there is limited data in ESLD. We hypothesize that the hemodynamic response, measured as a change in HR and systolic blood pressure (SBP), during regadenoson stress test will be more robust when associated with low level exercise. Method: Forty-five subjects with ESLD referred for pre-transplant risk stratification were assigned to 1 of 3 groups: regadenoson alone or associated with low level treadmill or bicycle maneuver. Regadenoson was injected 2 minutes after low level exercise in the treadmill and bicycle groups. Myocardial perfusion images and hemodynamic changes were performed and interpreted as part of the standard clinical protocol. Results: There were 21 subjects in the regadenoson alone group, 10 in the low level treadmill group, and 14 in the bicycle maneuver group. There were no perfusion abnormalities in any of the groups and LVEF were greater than 50%. There was a statistically significant difference in HR response between the 3 groups (p = 0.015), but not in percentage SBP change between the 3 groups (p = 0.4). Pairwise comparison of regadenoson alone vs. low level treadmill percentage HR change showed statistical significance (p = 0.011). There was no MACE at 6-month follow-up. Conclusions: Low level exercise achieved a higher HR response than the other groups with a similar SBP response. The increased HR response may represent a more physiologic assessment of the true vasodilatory capacity remaining in ESLD patients.
Abstract 12642: Heart Failure Prognosis in Diabetic Patients on SGLT2 (Sodium-Glucose Cotransporter-2) Inhibitors: A Systematic Review and Meta-Analysis
Authors: Nso Nso, KELECHI EMMANUEL, Mahmoud Nassar, Hakeem Ayinde
Journal: Circulation (2021)

Introduction: Cardiovascular disease complications predominantly increase the incidence of mortality and hospitalizations in the setting of type-2 diabetes. This systematic review and meta-analysis aimed to evaluate the therapeutic impact of SGLT-2 (sodium-glucose cotransporter-2) inhibitors on heart failure prognosis in patients with type-2 diabetes. Methods: We systematically explored PubMed/Medline, JSTOR, Google Scholar, and Cochrane Library for relevant randomized controlled trials published between January 2015 and April 2020, evaluating the effect of SGLT-2 inhibitors on cardiovascular outcomes. The main outcomes included (1) overall MACEs (MI, stroke, cardiovascular death), (2) overall CV death, (3) overall hospitalization for heart failure, (4) overall kidney outcomes (worsening kidney disease, need for dialysis or transplant, and death due to kidney disease), (5) adverse outcomes (each of genital infections, hypoglycemia, and amputation risk). Results: We extracted nine studies that included a total of 1,33,276 adult patients with type-2 diabetes and a predisposition for heart failure complications. Compared to placebo, patients receiving SGLT2 inhibitors had a lower incidence of MACE (OR: 0.80 [95% CI 0.71, 0.90]), cardiovascular deaths (OR: 0.85 [95% CI 0.77, 0.94]), worsening kidney disease, need for dialysis/transplant, death due to kidney disease (OR 0.65 [95% CI 0.48, 0.87]), and all-cause mortality (OR: 0.86 [95% CI 0.80, 0.94] p=0.0007). The patients on SGLT2 inhibitors did not experience a reportable reduction in genital infections, hypoglycemia, and amputation risk compared to placebo. The moderate heterogeneity of most studies was determined by their (31%-80%) I-square values. Conclusions and Relevance: This meta-analysis revealed moderately heterogeneous but statistically significant outcomes confirmed the role of SGLT-2 inhibitors in reducing the incidence of worsening kidney disease, all-cause mortality, overall kidney outcomes, hospitalization for heart failure, cardiovascular deaths, and overall MACEs in the setting of diabetes mellitus.
Serum Neurofilament Light Chain and Contactin-1 Levels Are Not Potential Serum Biomarkers in Anti-MAG IgM Paraprotein Related Peripheral Neuropathy
Authors: Karima Amaador, Luuk Wieske, Marleen J.A. Koel-Simmelink, Charlotte E. Teunissen, Keon de Heer, Monique C. Minnema, Nicolette C. Notermans, Filip Eftimov, Marie José Kersten, Josephine M.I. Vos
Journal: Blood (2021)