tbuckley/cabot-search huggingface dataset:
Abstract 10153: Validation of the Cost Needed to Treat Measure
Authors: Ronen Arbel, Enis Aboalhasan, Joseph Azuri, Ariel Hammerman
Journal: Circulation (2021)

Introduction: Several innovative medications have recently demonstrated significant efficacy in preventing major adverse cardiovascular events. In many situations, payers need to understand promptly whether the novel interventions provide good value for their resources invested. Cost-effectiveness analysis (CEA) is the gold standard and cornerstone of pharmacoeconomic evaluation but requires significant resources, and is not always available at the period needed for reimbursement decisions. Therefore, we suggest using the "Cost Needed to Treat" (CNT) measure as a preliminary economic figure for comparing novel preventive therapies' value until valid CEA is available. CNT represents the extra cost of therapy needed to prevent one additional adverse event. The CNT is a product of the number needed to treat (NNT) and the cost of the therapy. A lower CNT indicates more value for money. To validate the usefulness of the CNT measure, we aimed to retrospectively compare outcomes of published CNT evaluations and the later published CEAs. Hypothesis: CNT measure and CEA result in comparable recommendations. Methods: We compared the conclusions of all published CNT evaluations with available published CEA results. Results: Seven published CNT figures, based on cardiovascular outcome trial results, were identified. Four CNTs had matched CEAs. The CNT evaluation and the CEA resulted in the same conclusions in all four cases (Figure 1). Conclusions: Outcomes of the published CNT evaluations seem to correlate with published CEA results. CNT seems to be a valuable, prompt tool for comparing novel preventive interventions' economic value.
PATH-12. CLINICAL AND PATHOLOGICAL ANALYSIS OF 43 PATIENTS WITH EPITHELIOID GLIOBLASTOMA
Authors: Junjie Zhen, Mingyao Lai, Jiangfen Zhou, Shaoqun Li, Linbo Cai
Journal: Neuro-Oncology (2021)

Abstract BACKGROUND AND PURPOSE Epithelioid glioblastoma (eGBM) is a rare and aggressive subtype of glioblastoma. The clinical characteristics, pathological features and radiological findingsare still not well characterized. METHODS The clinical data of 43 patients with eGBM confirmed pathologically after surgery in Guangdong Sanjiu Brain Hospital from June 2015 to January 2021 were reviewed, and to investigate the clinical, pathological and imaging characteristics of the eGBM. RESULTS The range of patients' age was from 5 to 70 years (median 39 years). There were 24 males and 19 females. The median karnofsky performance score (KPS）at diagnosis was 70 (40-90). The most common symptom were headache (81.4%), and other common symptoms included nausea or vomiting (44.1%), limb weakness (30.2%), disturbance of consciousness (20.9%) and seizures (9.3%). Most of the tumors (97.6%) were located in the cerebral hemisphere ,except for one case located in the cerebellum,and with an average diameter of 5.3 cm (2.5-9.4 cm). There were 2 cases of intracranial metastasis and 7 cases of spinal cord metastasis in MRI. In pathologic examination, immunohistochemistry showed all the patients were IDH1 wild-type (43/43) and H3K27M wild-type(34/34). 25 (58.1%) of cases harbored BRAF mutation and 19 (44.2%) cases of MGMT positive. Most of patients were positive for GFAP, P53, Olig-2 and ATRX. CONCLUSION Epithelioid glioblastoma is more common in adults, most of which are located on the supratentorial, intracranial and spinal cord dissemination may occur. Half of patients showed BRFA mutation and maybe benefit from targeted therapy.These findings may help clinicians understand and treat epithelioid glioblastoma better.
Under-diagnosis of SARS-CoV-2 infections among children aged 0–15 years, a nationwide seroprevalence study, Israel, January 2020 to March 2021
Authors: Victoria Indenbaum, Yaniv Lustig, Ella Mendelson, Yael Hershkovitz, Aharona Glatman-Freedman, Lital Keinan-Boker, Ravit Bassal
Journal: Eurosurveillance (2021)

Until recently, children and adolescents were not eligible for COVID-19 vaccination. They may have been a considerable source of SARS-CoV-2 spread. We evaluated SARS-CoV-2 IgG antibody seroprevalence in Israeli children aged 0-15 years from January 2020 to March 2021. Seropositivity was 1.8-5.5 times higher than COVID-19 incidence rates based on PCR testing. We found that SARS-CoV-2 infection among children is more prevalent than previously thought and emphasise the importance of seroprevalence studies to accurately estimate exposure.
NCMP-04. BRAIN-UMAP: THE GENETIC INTERSECTION BETWEEN NEUROSCIENCE, NEUROLOGY, PSYCHIATRY, AND ONCOLOGY
Authors: Sonali Arora, Nicholas Nuechterlein, Siobhan Pattwell, Eric Holland
Journal: Neuro-Oncology (2021)

Abstract Whole transcriptome sequencing (RNA-seq) is an important tool for understanding genetic mechanisms underlying human diseases and gaining a better insight into complex human diseases. Several ground-breaking projects have uniformly processed RNASeq data from publicly available studies to enable cross-comparison. One noteworthy study is the recount2 pipeline, which in 2017, has reprocessed ~70,0000 samples from Short Read Archive(SRA), The Cancer Genome Atlas (TCGA), and Genotype-Tissue Expression (GTEx). This vast dataset also includes gene expression data for GTEx-defined brain regions, neurological and psychiatric disorders (such as Parkinson's, Alzheimer’s, Huntington’s) and gliomas (such as TCGA, Chinese Glioma Genome Atlas (CGGA)). We apply uniform manifold approximation and projection (UMAP), a non-linear dimension reduction tool, to bulk gene expression data from brain-related diseases to build a BRAIN-UMAP, which allows for visualization of gene expression profiles across datasets. This UMAP shows that while gliomas form a distinct cluster, the neurological and psychiatric diseases are similar to GTEX-defined normal brain regions which exhibit tissue-specific profiles and patterns. Incorporating gliomas from various publicly available datasets also allows for the ability to observe unique clustering of particular subtypes, which can increase our genetic understanding of the disease. We also present a resource where researchers interested in mechanisms, can easily compare, and contrast the expression of a given gene and/or pathway of interest across various diseases, gliomas, and normal brain regions. Our current study, focusing on brain related diseases, offers insight into what may be possible for the broader neuroscientific community if we continually reprocess newly available brain related RNASeq samples using recount2. Additionally, if we build similar uniformly processing pipelines for other kinds of next-generation sequencing data, we would be able to use multi-omic sequencing data to find novel associations between biological entities and increase our mechanistic knowledge of the disease.
Concomitant <i> JAK2</i> and <i>BCR-ABL1</i> in Patients with Chronic Myeloid Leukemia Clinical Impact and Response to Therapy: A Systematic Review
Authors: Elrazi Awadelkarim Ali, Elabbass Abdelmahmuod, Ashraf Ahmed, Maab Faisal, Mohamed A Yassin
Journal: Blood (2021)
Abstract 9703: Prevalence and Outcomes of Low Ankle Brachial Index in ASCVD Risk Categories- from the National Health and Nutrition Examination Survey
Authors: Muchi Ditah Chobufo, Meesum Amir, Muhammad Munir, ATUL SINGLA, Abbas Ali, Wilbert S Aronow, Sudarshan balla
Journal: Circulation (2021)

Introduction: The utility of Ankle Brachial Index(ABI) as a risk-enhancer to the pooled cohort equations(PCE) in assessing cardiovascular risk for primary prevention of atherosclerotic cardiovascular disease(ASCVD) is uncertain. We aim to assess the prevalence and all-cause mortality of people with low ABI across ASCVD risk categories. Hypothesis: Would the addition of ABI to standard ASCVD risk assessment improve all cause mortality risk stratification? Methods: Participants were recruited as part of the National Health and Nutrition Examination Survey from 1999-2004 and mortality assessed on 12/31/2015. We included participants aged 40-75years with ABI values≤1.3 and data for ASCVD computation using the PCE. Persons with ABI&lt;0.9 and ABI 0.9-1.3 were classified as having low ABI and normal ABI, respectively. Results: The mean follow-up time was 156months(95%CI 154-158). Persons with low ABI were older(61 Vs 53years) and had higher mean systolic blood pressure(135 Vs 126mmHg). There was no difference in mean total cholesterol(mg/dl)[212(95%CI 210-214) vs. 208( 202-215)], LDL(mg/dl) [128 (95%CI 125-130) vs. 121(112-129)] and HDL(mg/dl) [54 (95%CI 53-54) vs. 52(50-55)] between the two ABI categories. The all-cause mortality was higher among persons with low ABI(43.1%) compared to those with normal ABI(12.2%), p&lt;0.001. The all-cause mortality in the normal ABI and low ABI categories was 4.8% and 8.8% in the low risk ASCVD group and 7.8% and 41.6% in the borderline/intermediate ASCVD risk group, respectively. Conclusions: Approximately 67% of participants with low ABI were classified as low, borderline or intermediate risk by PCE. Low ABI was associated with increased all-cause mortality in the intermediate/borderline and high ASCVD risk categories but not in the low ASCVD risk category. Our study supports the use of ABI in risk stratification for primary prevention of ASCVD in individuals with borderline or intermediate risk.
Abstract 13325: Racial Heterogeneity in Mortality and Complications Among Adult Women Presenting With ST Elevation Myocardial Infarction
Authors: Sriviji Senthil Kumaran, Juan Del Cid Fratti, Anjali R Desai, Sudhir Mungee, EKANKA MUKHOPADHYAY, Tinoy J Kizhakekuttu
Journal: Circulation (2021)

Introduction: There is a sparsity of studies on the outcomes in women presenting with ST Elevation Myocardial Infarction (STEMI) among the different racial minorities. Methods: National inpatient sample database was used to retrospectively study primary mortality outcomes and secondary complications among the different races (Whites, Blacks, Hispanic, Asian and other races which includes native Americans) of adult female patients hospitalized from January 1 2016 to December 31 2018 with STEMI as their primary diagnosis. Adjusted odds ratio (AOR) was calculated by comparing the different races to white women. Results: In hospital mortality was highest among Asian women (17.1%) followed by African American women (14.4%). Cardiogenic shock occurred less frequently among African American (11.5%) women with no statistical difference between other subgroups. Use of mechanical circulatory support (MCS) was highest in other minority races (8.7%). All minority subgroups required longer periods of mechanical ventilation &gt; 24 hours (African Americans 6.1%; Hispanics 4.9%; Asians 5.1% and other race 4.8%). Acute kidney injury was highest among Hispanics (2.3%). Conclusions: Despite overall improvement in mortality of STEMI patients, heterogeneity in outcomes based on race persist. Our findings showed increased mortality and morbidity in the outcomes among women belonging to racial minorities. The increased need for renal replacement therapy, MCS, mechanical ventilation and higher rates for blood transfusion contribute to overall prognosis. Understanding these key differences will aid in improving outcomes and help guide management of these minority populations.
Abstract 11181: Transfemoral Transcatheter Aortic Valve Replacement in the Catheterization Lab vs the Operating Room
Authors: Jacob T Kirkland, Godly Jack, John Vavalle
Journal: Circulation (2021)

Introduction: Within the past decade, transcatheter aortic valve replacement (TAVR) has become the standard of care for the treatment of calcific aortic stenosis across the surgical risk spectrum. With increasing volumes of procedures, there has a shift in TAVRs into the cardiac catheterization lab and out of the hybrid operating room. A better understanding is needed regarding the impact this has on procedural success and outcomes. Methods: Patients undergoing transfemoral TAVR between April 2016 and April 2019 at the University of North Carolina were included retrospectively. Unpaired t-test, Fisher’s exact test, and chi square analysis were used to compare procedure characteristics and outcomes performed in the catheterization lab to TAVR performed in the OR. Results: A total of 160 transfemoral TAVRs were performed in the catheterization lab while 119 were performed in the OR. There were no significant differences in baseline or comorbidity characteristics. Table 1 includes data analysis finding no significant difference in procedure time, contrast volume, fluoroscopy time, anesthesia type, aborted procedures, conversions to open surgery, paravalvular leak, endocarditis, stroke, KCCQ-12 difference at 4-7 week follow up, and one year mortality. Figure 1 includes the location of transcatheter TAVR procedures at UNC over time. Conclusions: Transfemoral TAVR performed in the catheterization lab is as safe and efficacious as TAVR performed in the OR. This has significant implications for resource utilization, ability to expand this therapy, and the costs associated with TAVR.
IMMU-37. DISRUPTION OF PD-L1 BY ENHANCED TWO-SGRNAS CRISPR/CAS9 IN TREATMENT OF GLIOBLASTOMA
Authors: Javier Fierro, joshua Perez, Rocio Aguilar, Jake Dipasquale, An Tran, Chris Factoriza, Huanyu Dou
Journal: Neuro-Oncology (2021)

Abstract Anti-glioblastoma multiform (GBM) immunotherapy poses a great challenge due to immunosuppressive brain tumor environments and the blood brain barrier (BBB). Programmed death ligand 1 (PD-L1) plays a key role in GBM immunosuppression, vitality, proliferation, and migration. Targeting PD-L1 for immunotherapy is a promising new avenue for treating GBM. CRISPR/Cas9 gene editing can be used to knockout both membrane and cytoplasmic PD-L1, leading to an enhanced immunotherapeutic strategy. We identified two sgRNA sequences located on PD-L1 exon 3. The first sgRNA recognized the forward strand of human PD-L1 near the beginning of exon 3 and cuts at approximately base pair 82 (g82). The second sgRNA recognized the reverse strand of exon 3 and cuts at base pair 165 (g165). Two sgRNAs, g82 and g165, created an 83bp deletion in PD-L1 genomic sequence. Two sgRNAs combination with a homology-directed repair template (HDR) was designed to enhance PD-L1 knockout specificity and efficiency. Both g82 and g165 were cloned into one CRISPR/Cas9 plasmid, and was co-transfected with HDR. GFP tagged CRISPR/Cas9 plasmid containing of g82 and g165 (Cas9-g82/165) was loaded into Rhodamine labeled nanoparticles (Cas9-g82/165-NPs) and then treated to GBM U87 cells. The enhanced intracellular uptake and transfection of Cas9-g82/165-NPs were detected by a fluorescence microscopy. T7E1, qRT-PCR and western blot analysis determined that the dual sgRNA CRISPR/Ca9 system knocked out both endogenous (80%) and exogenous (64%) PD-L1 in U87 cells and PD-L1 overexpression U87 cells, respectively. Deletion of PD-L1 reduced U87 migration and proliferation, while PD-L1 overexpression promoted tumor growth and tumor-associated macrophage polarization. Together, deletion of both membrane and cytoplasmic PD-L1 altered the PD-L1-associated immunosuppressive environment and prevented tumor progression and migration. Thus, two-sgRNAs CRISPR/Cas9 gene-editing system is a promising avenue for anti-GBM immunotherapy.
Abstract 12852: Acute Stenting Of Persistently Stenotic Cervical Lesions In Atherosclerotic Tandem Occlusions Does Not Improve Neurologic Outcomes
Authors: Weston Troja, Jonathan Weyhenmeyer, Nicolas W Villelli, Bradley Bohnstedt
Journal: Circulation (2021)

Introduction: There is a lack of consensus regarding the endovascular management of atherosclerotic tandem occlusions with persistent cervical stenosis during acute ischemic stroke. The aim of this study was to determine if patients who did not undergo stent placement during thrombectomy had better neurological outcomes. Methods: A retrospective analysis of consecutive mechanical thrombectomies for large vessel occlusions at our institution was conducted from 2011 to 2019. Atherosclerotic tandem occlusions with persistently severe cervical stenosis (&amp;ge 70%) before and after thrombectomy were identified and evaluated for clinical baseline data, perioperative data, and post-thrombectomy outcomes such as re-occlusion rates and modified Rankin score at 90 days. Results: A total of 69 patients with atherosclerotic tandem occlusions were identified. Thirty-five patients underwent acute carotid stent placement. Thirty-four patients did not receive a stent and had persistently severe cervical stenosis after thrombectomy. Demographics, NIHSS, reperfusion rates, and length of stay were similar between groups. Post-thrombectomy carotid re-occlusion (p = 0.434) and neurological outcomes (p = 0.82) were similar between stented and non-stented groups at 90 days after discharge. Conclusions: The acute stenting of persistently severe cervical stenosis in atherosclerotic tandem lesions does not reduce the rate of re-occlusion and is not associated with better neurologic outcomes at 90 days after discharge. Randomized clinical trials are warranted to determine a standardized means of endovascular management of atherosclerotic carotid lesions in tandem occlusions during acute ischemic stroke.
Abstract 11634: Sympathetic Neural Overdrive, Endothelial Dysfunction and Aortic Stiffness in Coronavirus Disease 2019 Survivors: A Short-Term Study of Cardiovascular Sequelae
Authors: Diego Faria, Laura Testa, Renata Moll-Bernardes, Camila Moniz, Erika Rodrigues, Abel Costa-Neto, Andrea Sousa, Amanda Rodrigues, Patricia Oliveira, Maria Janieire Alves, Gabriel Santos, Vera Salemi, Ruan Pimenta, Camila Paixão, Beatriz Santos, Maria U Rondon, Daniel Craighead, Matthew Rossman, Fernanda M Consolim-Colombo, Maria C Irigoyen, Luis A Martinez-Lemus, Jaume Padilla, Douglas R Seals, Carlos E Negrao, Allan Sales
Journal: Circulation (2021)

Introduction: Coronavirus disease 2019 (COVID-19) has become one of the more dramatic health problems in the century. This disease has enormous consequence for the health care worldwide. In addition to high mortality rate, patients recovered from COVID-19 present short and long-term cardiovascular sequelae including chest pain, myocardial dysfunction, arrhythmia, dyspnea, breathlessness, postural tachycardia syndrome, and thrombotic complications. The explanations for these clinical manifestations are still uncertain but can involve a constellation of physiological alterations. Hypothesis: To test if COVID-19 survivors have augmented sympathetic outflow, diminished endothelial function, elevated aortic stiffness, and reduced physical capacity compared to healthy individuals. Methods: Nineteen COVID-19 survivors [age: 47.0±2.3 years, BMI: 30.1±1.2 Kg/m 2 ] and eighteen well-matched healthy controls (age: 44.0±2.0 years, BMI: 28.4 ±1.2 Kg.m 2 ] were included in study. COVID-19 survivors were evaluated within 6 months of original diagnosis by RT-PCR. Muscle sympathetic nerve activity (MSNA) from fibular nerve (Microneurography), brachial artery flow-mediated dilation (BAFMD; Doppler-Ultrasound), carotid-femoral pulse wave velocity (cf-PWV; Complior), beat-to-beat blood pressure (Peripheral BP; Finometer), heart rate (HR; Electrocardiography) and peak oxygen uptake (VO 2peak , Cardiopulmonary exercise testing) were measured in both groups. Results: MSNA was higher in COVID-19 survivors compared to controls (33.0±1.0 vs. 22.0±1.0 bursts/min, p =0.001). Both BAFMD and VO 2peak were lower in COVID-19 survivors compared to controls (4.6±0.7 vs. 8.2 ±0.8%, p =0.005 and 22.2±1.5 vs. 29.7±1.6 mL/Kg/min p =0.001, respectively). Although COVID-19 survivors had greater cf-PWV than controls (8.6±0.5 m/s vs. 7.4±0.4 m/s, p =0.03), BP and HR were not different between groups. Conclusions: Our study revealed that patients recently recovered from COVID-19 have abnormal neurovascular control, vascular alterations and reduced physical capacity. These findings strongly indicate the need of further long-term investigations to uncover cardiovascular sequelae provoked by COVID-19.
Abstract 10774: A Single Center Study Investigating the Relationship Between Atrial Fibrillation and Sleep Apnea Testing
Authors: Zara Latif, Anna Modest, Hieu Tieu, Patricia Tung
Journal: Circulation (2021)

Introduction: Sleep apnea is recognized as a predictor of incident atrial fibrillation (AF); it has been associated with decreased response to antiarrhythmic drugs, and higher rates of AF recurrence after cardioversion and catheter ablation. However, it is not known whether widespread screening for sleep apnea in patients with AF affects arrhythmia outcomes. Objective: to evaluate the effect of universal sleep apnea screening on AF outcomes. Methods: We conducted a prospective study of all patients referred to electrophysiology clinic at our center for management of AF and referred for sleep apnea testing between March 2018 and March 2021. Screening was performed using home sleep testing (HST) and polysomnography (PSG). Patients were assessed for progression of AF as defined by any of the following: change from paroxysmal to persistent AF, change in antiarrhythmic drug, ablation, or cardioversion. Results: Among 321 patients evaluated for atrial fibrillation, 78% (251) of patients were tested for sleep apnea with HST or PSG. Of these, 6% (16) had no sleep apnea, 83% (208) had either obstructive or mixed apnea, and 11% (27) were inconclusive. Among those with sleep apnea, 56% (116) had OSA, 42% (87) had mixed apnea, and 2% (5) had pure central apnea.As the time from AF diagnosis to sleep apnea testing increased, the risk of AF progression also increased (p &lt;0.0001). This effect was observed even when stratified by obstructive versus mixed apnea(OSA p= 0.04, mixed p=0.0005). Conclusions: Sleep apnea was present in the vast majority of patients with AF. Of those with sleep apnea, almost half had mixed central and obstructive sleep apnea. Duration of greater than 24 months from atrial fibrillation diagnosis to sleep apnea testing was associated with higher rates of AF progression. Thus, early, universal screening for sleep apnea may improve outcomes in patients with AF. Table I. The relationship between time from AF diagnosis to sleep apnea (SA) testing on AF outcomes.
General Characteristics and Association of Myeloid Neoplasm with Thyroid Cancer
Authors: Shehab Fareed Mohamed, Naveen Pemmaraju, Koji Sasaki, Gautham Borthakur, Tareq Abuasba, Maliha Khan, Hyunsoo Hwang, Xuemei Wang, Srdan Verstovsek, Naifa Busaidy
Journal: Blood (2021)