tbuckley/cabot-search huggingface dataset:
Abstract 13757: Prior SARS-CoV-2 Infection is Associated With Subclinical Changes in the Cardiovascular Morphology, Function, Energetics and Exercise Capacity
Authors: Rebecca R Chamley, Jonathan Collins, Kayleigh Pierce, William Watson, Peregrine Green, David O'Brien, Robert Barker-Davies, Stefan Neubauer, Alexander Bennett, Ed D Nicol, Oliver J Rider, David A Holdsworth
Journal: Circulation (2021)

Background: COVID-19 has documented multisystem effects. Whether clinically significant cardiac involvement is related to severity of disease in a working age military population remains unknown, but has implications for occupational grading and ability to deploy. Aims: To determine in the military population 1) whether prior SARS-CoV-2 infection causes clinically significant cardiac disease and 2) whether changes are related to disease severity. Methods: 105 military personnel were recruited, 85 with prior SARS-CoV-2 infection (39±10 years, 87% male; 50 mild (community), 35 severe (hospitalized) and 20 healthy volunteers (mean age 39 ±8.4 years, 90% male) underwent comprehensive cardiopulmonary investigations including; cardiopulmonary exercise test, exercise echocardiography, cardiac MRI and 31 P-MR spectroscopy (rest and dobutamine stress). Results: Prior SARS-CoV-2 infection was related to lower VO 2 max (110±18.2 vs 133±6.7% predicted, p&lt;0.05), anaerobic threshold (45±10 vs 56±14% of peak VO2, p&lt;0.05), VO2/HR (102±21 vs 128±24% predicted, p&lt;0.05) and VE/VCO2 slope (28.3±5.0 vs 25.8±2.7, p&lt;0.05) and an increase in average E/e’ change from rest to exercise stress (+1.49±2.4 vs -0.16±3.6, p&lt;0.05). Whilst resting myocardial energetics were similar, prior SARS-CoV-2 infection was associated with a fall in PCr/ATP during stress (by 8%, p=&lt;0.01) which was not seen in healthy controls. When groups were ordered normal&gt; mild&gt; severe disease, RVEDVi, RV stroke volume, VO 2 peak, VO 2 pulse and VE/VCO 2 slope were reduced (Jonckheere-Terpstra, all p&lt;0.05). Conclusion: In a young military population, prior SARS-CoV-2 infection is associated with subclinical cardiovascular changes including; lower right ventricular volumes, reduced markers of exercise capacity and reduced myocardial energetics during stress.
Abstract P355: Comparable Impairment Of Vascular Endothelial Function By A Wide Range Of Electronic Nicotine Delivery Devices
Authors: Poonam Rao, Kelly Tan, Daniel D Han, Ronak Derakhshandeh, Matthew L Springer
Journal: Circulation Research (2021)

Introduction: Electronic nicotine delivery systems (ENDS; i.e., vaping devices) such as e-cigarettes, heated tobacco products, and newer coil-less ultrasonic vaping devices are promoted as less harmful alternatives to combustible cigarettes. However, the cardiovascular health effects of these devices are understudied. We investigated whether exposure to aerosol from a wide range of ENDS devices with and without nicotine, including a new ultrasonic vaping device, impairs endothelial function. Hypothesis: ENDS aerosols irrespective of nicotine, flavors, and heating coil impair endothelial function comparably to smoke from cigarettes. Methods: We exposed 11 groups (n=8), of anaesthetized rats to aerosol from propylene glycol (PG), vegetable glycerin (VG), PG+VG without nicotine, a USONICIG Zip ultrasonic vaping device, previous generation e-cigarettes (tank style with freebase nicotine), 5% nicotine JUUL pods of three flavors (Virginia tobacco, Mango, and Menthol), and an IQOS heated tobacco product; with Marlboro Red cigarette smoke and clean air as controls, to a single session of 10 cycles of pulsatile 5s exposure over 5 minutes. Endothelial function was quantified as arterial flow-mediated dilation (FMD) using micro-ultrasound. Results: Aerosol/smoke from all conditions except air significantly impaired FMD (Figure: each colored line denotes one rat, black horizontal bars denote means). The extent of impairment ranged from 40%-67% although there were no significant differences between groups. Nicotine absorption into the blood varied widely from these undiluted aerosols (those containing nicotine), with IQOS being the highest, and USONICIG and previous generation e-cig being the lowest. Conclusions: A single session of exposure to aerosol from a wide range of ENDS, including multiple types of e-cigarettes, a heated tobacco product, and an ultrasonic vaping device, all impair endothelial vascular function comparably to combusted cigarettes. Key words: JUUL, IQOS, ultrasonic vaping device, e-liquids, flow-mediated dilation
Aducanumab: 4 in 10 high dose trial participants experienced brain swelling or bleeding
Authors: Elisabeth Mahase
Journal: BMJ (2021)

Over 40% of trial participants who had a high dose (10 mg/kg) of the Alzheimer’s disease drug aducanumab experienced brain swelling or bleeding, research has shown.1

Aducanumab, which costs $56 000 (£42 000; €49 000) per patient per year, was controversially approved through the US Food and Drug Administration’s accelerated approval pathway earlier this year.2 The pathway is used when there are uncertainties over efficacy but an expected clinical benefit.

The latest study combined the data from 3285 participants in two international phase III clinical trials—Emerge and Engage—of whom 1029 …
NCMP-14. WHOLE BRAIN RADIOTHERAPY COMBINED WITH INTRATHECAL LIPOSOMAL CYTARABINE FOR LEPTOMENINGEAL METASTASIS – A SAFETY ANALYSIS AND VALIDATION OF THE EANO-ESMO CLASSIFICATION
Authors: Sarah Iglseder, Martha Nowosielski, Gabriel Bsteh, Armin Muigg, Johanna Heugenhauser, Meinhard Nevinny-Stickel, Elke Mayer, Astrid Grams, Guenther Stockhammer
Journal: Neuro-Oncology (2021)

Abstract BACKGROUND Although there is no proven standard therapy for leptomeningeal metastases (LM), treatment often includes intrathecal chemotherapy combined with whole brain radiation therapy (WBRT). Little is known on the toxicity of such combination therapies. We performed a retrospective safety analysis for the combination of intrathecal liposomal cytarabine with WBRT in patients with LM and validated the EANO-ESMO classification in this unique cohort. METHODS Treatment toxicities in patients diagnosed with LM between 2004 and 2014 were retrospectively analyzed according to the RTOG (Radiation Therapy Oncology Group) and NCI CTCAE V5.0 (Common Toxicity Criteria Adverse Events) toxicity criteria. Diagnostic criteria and treatment response as assessed by EANO-ESMO classification were correlated with survival by Kaplan Meier analysis and Breslow test. RESULTS 40 patients with LM who were treated with combined WBRT and intrathecal cytarabine, were identified. Ten patients (25%) experienced adverse events ≥ grade 3 according to the RTOG-toxicity criteria, in 22 patients (55%) CTCAE criteria ≥3 grade were detected. Median overall survival (mOS) was 124.0 days [72.9;175.1]. Median time to neurological progression was 52.0 days [41.1; 62.8]. When comparing the diagnostic criteria, patients with a positive CSF cytology (n=26) showed worse prognosis compared to patients with a negative CSF cytology (n=14) (mOS 84 days [44.0;124.0] versus 198.0 days [162.6;233.4] days, p=0.006, respectively). The EANO-ESMO response assessment correlated significantly with survival - “stable” (n=7) mOS 233.0 [76.5;389.5] days, “response” (n=10) mOS 206.0 [193.9;218.9] days, “progression” (n=17) mOS 45.0 [34.4;55.6] days, “suspicion of progression” (n=6) mOS 133.0 [65.8;200.2] days (overall, p&amp;lt; 0.001). CONCLUSIONS In this retrospective analysis, the treatment combination of WBRT and intrathecal liposomal cytarabine shows an acceptable safety profile. The EANO-ESMO classification for diagnosis and treatment response predicts survival
MPL S505C enhances driver mutations at W515 in essential thrombocythemia
Authors: Leila N. Varghese, Gonzalo Carreño-Tarragona, Gabriel Levy, Xabier Gutiérrez-López de Ocáriz, Inmaculada Rapado, Joaquín Martínez-López, Rosa Ayala, Stefan N. Constantinescu
Journal: Blood Cancer Journal (2021)
A failure of ambition on climate action will amplify humanitarian needs
Authors: Caroline Voûte, Maria Guevara, Patricia Nayna Schwerdtle
Journal: BMJ (2021)

A failure of ambition on climate action will amplify humanitarian needs Humanitarian actors are struggling to keep up with the demands of increasingly frequent, erratic, and overlapping crises at current levels of warming Caroline Voûte, 1 Maria Guevara, 1 Patricia Nayna Schwerdtle 1 , 2 "Can there be peace and prosperity if one third of the world literally prospers and the other two thirds of the world live under siege and face calamitous threats to their wellbeing?"(Mia Mottley, prime minister of Barbados and envoy at COP26, 2021)
NIMG-40. MRI-BASED ESTIMATION OF THE ABUNDANCE OF IMMUNOHISTOCHEMISTRY MARKERS IN GBM BRAIN USING DEEP LEARNING
Authors: Sara Ranjbar, Kyle Singleton, Deborah Boyett, Michael Argenziano, Jack Grinband, Peter Canoll, Kristin Swanson
Journal: Neuro-Oncology (2021)

Abstract Glioblastoma (GBM) is a devastating primary brain tumor known for its heterogeneity with a median survival of 15 months. Clinical imaging remains the primary modality to assess brain tumor response, but it is nearly impossible to distinguish between tumor growth and treatment response. Ki67 is a marker of active cell proliferation that shows inter- and intra-patient heterogeneity and should change under many therapies. In this work, we assessed the utility of a semi-supervised deep learning approach for regionally predicting high-vs-low Ki67 in GBM patients based on MRI. We used both labeled and unlabeled datasets to train the model. Labeled data included 114 MRI-localized biopsies from 43 unique GBM patients with available immunohistochemistry Ki67 labels. Unlabeled data included nine repeat routine pretreatment paired scans of newly-diagnosed GBM patients acquired within three days. Data augmentation techniques were utilized to enhance the size of our data and increase generalizability. Data was split between training, validation, and testing sets using 65-15-20 percent ratios. Model inputs were 16x16x3 patches around biopsies on T1Gd and T2 MRIs for labeled data, and around randomly selected patches inside the T2 abnormal region for unlabeled data. The network was a 4-conv layered VGG-inspired architecture. Training objective was accurate prediction of Ki67 in labeled patches and consistency in predictions across repeat unlabeled patches. We measured final model accuracy on held-out test samples. Our promising preliminary results suggest potential for deep learning in deconvolving the spatial heterogeneity of proliferative GBM subpopulations. If successful, this model can provide a non-invasive readout of cell proliferation and reveal the effectiveness of a given cytotoxic therapy dynamically during the patient's routine follow up. Further, the spatial resolution of our approach provides insights into the intra-tumoral heterogeneity of response which can be related to heterogeneity in localization of therapies (e.g. radiation therapy, drug dose heterogeneity).
Abstract 12034: Personal Protective Equipment and Doffing Procedures in Out-of-Hospital Practice: Assessment With a Contamination Simulation
Authors: Fabrice Pottier, Charles Groizard, Gégory Briche, Nicolas Haraczaj, Maxime Garnier, Vinciane Loones, Anna Ozguler, Michel Baer, GERALDINE BAER, Thomas Loeb
Journal: Circulation (2021)

Background: Use of personal protective equipment (PPE) by Emergency Medical Services (EMS) requires specific attention, especially when doffing contaminated clothes. The aim of this study was to evaluate which PPE was less contaminating during doffing procedures. Methodology: Six subjects tested four different PPE (pictures 1 to 4): 1) Surgical gowns (SG) 2) Full body coveralls (FBC) 3) Self-made alternative PPEs (SMP) 4) Non-surgical isolation gowns (NSIG) After donning, an invisible tracer was sprayed on the gown of each subject. Then, after doffing PPE, each subject was photographed under UV lights to show areas of fluorescent “contamination” on their body. Number of contaminated areas were noted, as well as doffing time. Results: Contamination was observed with every type of PPE and with each subject. All body areas were contaminated at least once, except the face. While doffing, SG was found to be the least contaminating PPE. Contamination was more frequent with FBCs. The mean doffing time was shorter with SG and longer with FBC (table 1). Conclusion: This study confirms that doffing is a high risk of contamination procedure. Results converge towards the selection of SG over other types of PPE, which met both contamination criteria and shorter time for doffing. Specific attention should be paid to legs and abdomino-pelvic areas. Additional protections such as protective trousers or aprons could be added.
IMMU-14. REVEALING THE MANY MYELOID STATES IN HUMAN BRAIN TUMORS AND WAYS TO PERTURB THEM
Authors: Tyler Miller, Chadi El Farran, Julia Verga, Charles Couturier, Zeyu Chen, L Nicolas Gonzalez Castro, Joshua D'Antonio, Kevin Petrecca, Mario Suva, Bradley Bernstein
Journal: Neuro-Oncology (2021)

Abstract Recent breakthroughs in immunotherapy have revolutionized treatment for many types of cancer, but unfortunately trials of these therapies have failed to provide meaningful life-prolonging benefit for brain tumor patients, potentially due to abundant immunosuppressive myeloid cells in the tumor. Our ultimate goal is to reprogram immunosuppressive tumor associated myeloid cells to an antitumor state to enable effective immunotherapy. Towards this goal, we have deeply characterized the immune microenvironment of more than 50 primary high and low grade gliomas using high-throughput single-cell RNA-sequencing to reveal recurrent myeloid cell states and immunosuppressive programs across IDH1 wild-type and mutant tumors. We have also established a brain tumor organoid model from primary patient tissue that maintains all of the tumor microenvironment, including myeloid and other immune cells. We utilize the this model to functionally test data-driven reprogramming strategies and understand how they impact the states of tumor and immune cells in the ex vivo human tumor microenvironment.
Risk for Stillbirth Among Women With and Without COVID-19 at Delivery Hospitalization — United States, March 2020–September 2021
Authors: Carla L. DeSisto, Bailey Wallace, Regina M. Simeone, Kara Polen, Jean Y. Ko, Dana Meaney-Delman, Sascha R. Ellington
Journal: MMWR Morbidity and Mortality Weekly Report (2021)

Pregnant women are at increased risk for severe COVID-19-related illness, and COVID-19 is associated with an increased risk for adverse pregnancy outcomes and maternal and neonatal complications (1-3). To date, studies assessing whether COVID-19 during pregnancy is associated with increased risk for stillbirth have yielded mixed results (2-4). Since the B.1.617.2 (Delta) variant of SARS-CoV-2 (the virus that causes COVID-19) became the predominant circulating variant,* there have been anecdotal reports of increasing rates of stillbirths in women with COVID-19.† CDC used the Premier Healthcare Database Special COVID-19 Release (PHD-SR), a large hospital-based administrative database,§ to assess whether a maternal COVID-19 diagnosis documented at delivery hospitalization was associated with stillbirth during March 2020-September 2021 as well as before and during the period of Delta variant predominance in the United States (March 2020-June 2021 and July-September 2021, respectively). Among 1,249,634 deliveries during March 2020-September 2021, stillbirths were rare (8,154; 0.65%): 273 (1.26%) occurred among 21,653 deliveries to women with COVID-19 documented at the delivery hospitalization, and 7,881 (0.64%) occurred among 1,227,981 deliveries without COVID-19. The adjusted risk for stillbirth was higher in deliveries with COVID-19 compared with deliveries without COVID-19 during March 2020-September 2021 (adjusted relative risk [aRR] = 1.90; 95% CI = 1.69-2.15), including during the pre-Delta (aRR = 1.47; 95% CI = 1.27-1.71) and Delta periods (aRR = 4.04; 95% CI = 3.28-4.97). COVID-19 documented at delivery was associated with increased risk for stillbirth, with a stronger association during the period of Delta variant predominance. Implementing evidence-based COVID-19 prevention strategies, including vaccination before or during pregnancy, is critical to reducing the impact of COVID-19 on stillbirths.
Abstract 11344: Association of Canonical Pathways with Length of Survival in Pulmonary Arterial Hypertension
Authors: Amy Webb, Hyoin An, Priscilla Correa-Jaque, Shili Lin, Zilu Liu, Hemant K Tiwari, Howard Wiener, Raymond L Benza
Journal: Circulation (2021)

Introduction: Pulmonary arterial hypertension (PAH) is a chronic, progressive disease without cure. Treatment can improve outcome, but informed predictions with clinical and genomic measurements can guide treatment and therapy choices. Previous research has focused on identifying clinical variables that could predict future outcomes. The current research aims to find genomic variants that can predict survival time. Hypothesis: Methods: Whole genome sequencing was performed on stored samples from 221 PAH patients. Samples were included with Long survival greater than 7 years and Short survival with mortality less than 5. Variants were filtered for quality, assigned to genes, and filtered for function and population frequency. Genes are grouped based on Canonical Pathways defined in Ingenuity Pathway Analysis Results: Patient were 50% IPAH, 81% female, 97% european decent with a mean age of 54 at sample acquisition. Mean Follow-up post sample acquisition was 5 years. Mean long and short survival was 8.3 and 2.1 years, respectively. Of pathways containing more than one gene mutated in 3 or more samples, 29 pathways were associated with survival length. Biologically relevant pathways include Pentose Phosphate (p=0.005), IL-22 (p=0.006), Phospholipase C signaling (p=0.007), Endocannabinoid related pathways (p=0.01), and Thioredoxin pathway (p=0.015). A Neural network model based on the top pathways was constructed (figure) that predicted Long/Short survival. Conclusions: We identified biologically relevant pathways associated with a Long/Short survival time in PAH patients. Our neural network model for predicting Long/Short survival using the 29 ident ified pathways and has achieved excellent performance.
NCOG-47. CONGRUENCE BETWEEN PROVIDER REPORTED PERFORMANCE STATUS AND BOTH OBJECTIVE AND PERCEIVED COGNITION IN A GLIOMA POPULATION
Authors: Marissa Panzer, Elizabeth Vera, Alvina Acquaye, Nicole Briceno, Anna Choi, Alexa Christ, Ewa Grajkowska, Varna Jammula, Heather Leeper, Jason Levine, Matthew Lindsley, Jennifer Reyes, Kayla Roche, James Rogers, Michael Timmer, Lisa Boris, Eric Burton, Nicole Lollo, Lily Polskin, Marta Penas-Prado, Valentina Pillai, Brett Theeler, Jing Wu, Mark Gilbert, Terri Armstrong
Journal: Neuro-Oncology (2021)

Abstract Karnofsky performance status (KPS) scale, a clinician-reported measure, is used to assess patients’ functional ability and as a metric for trial eligibility. Glioma patients often have a degree of neurologic deficit which can invariably affect performance status. There is little research comparing KPS, patient-reported cognitive outcomes, and objective cognitive outcomes. 273 primary brain tumor patients enrolled in the NOB Natural History Study were included in this report. We evaluated Pearson correlations between KPS (range 40-100), dichotomized as Good KPS (KPS ≥ 90) and Poor KPS (KPS ≤ 80), and MDASI-BT cognitive symptom factor, NeuroQoL Cognitive Function t-score, EQ-5D-3L index score, and objective MoCA test. The majority of patients were white (81%), male (58%) with a median 50 years of age (range 24-79). Most had high grade gliomas (74%), 22% were on active treatment, and 55% had prior tumor recurrences. Providers reported a poor KPS in 37% of patients. KPS correlated with the MDASI-BT cognitive symptoms (r = -0.32), NeuroQoL (r = 0.39), and EQ-5D-3L index score (r = 0.55) (all p &amp;lt; 0.01). Patients with poor KPS reported moderate-severe cognitive symptoms on the Neuro-QoL Cognitive Function (40%), moderate-severe difficulty remembering on the MDASI-BT (37%), and difficulty with usual activities on the EQ-5D-3L (83%). In a subset of 27 patients, MoCA scores were assessed but no significant correlation was found with KPS (r = 0.19, p = 0.352). Patient-reported and objective cognitive dysfunction was seen in up to 36% of those with good KPS. These data demonstrate that perceived cognitive testing is associated with poor KPS but may also occur in those with good performance status. The results underscore the need for alternative measures of cognitive functioning to further explore the impact in those with good KPS and the use of the MoCA in a larger sample.
Abstract 10718: Prevalence, Correlates and Associated Mortality of Undiagnosed Angina in People Without Established Cardiovascular Disease in Us Adults: From the National Health and Nutrition Examination Survey 2001-2018
Authors: Muchi Ditah Chobufo, Ebad Rahman, ATUL SINGLA, Mohammed Osman, Muhammad Zia khan, Wilbert S Aronow, Sudarshan balla
Journal: Circulation (2021)

Background: The prevalence, correlates and associated mortality of undiagnosed angina in persons without established cardiovascular disease in the USA has not been established. We set out to establish the prevalence and correlates as well as assess mortality outcomes. Methods and Results: Included in our study were National Health and Nutrition Examination Survey (NHANES) participants from 2001-2018, aged ≥40years and free of established cardiovascular disease. The diagnosis of angina was established using the Rose Angina Questionnaire. The prevalence of undiagnosed angina was 1.99% (95% confidence interval (CI) 1.79- 2.20), corresponding to 2.6 million (95% CI 2.3 - 2.9) persons. In multivariable analysis, female sex (aOR 1.75, 1.37-2.25), lower education attainment (aOR 1.59, 1.08-2.33), obesity (aOR 2.68, 1.19-2.37), ever smokers (aOR, 1.51, 1.17-1.94), low income(Poverty index ratio &lt;3) aOR 1.89, 1.44-2.47), and hypertension (aOR 1.48, 1.12-1.96) were independent correlates of undiagnosed angina. Only 3.8% of all participants with undiagnosed angina were concomitantly on beta blockers, aspirin and a statin. The death rate was 1.08 per 1,000 person months and 1.71 deaths per 1000 person months among those without angina and those with angina, respectively. Conclusion: The prevalence of undiagnosed angina among US adults ≥40years and older was 2%. Female sex, hypertension, obesity, low income, smoking and low education were associated with undiagnosed angina. Harboring undiagnosed angina was associated with higher risk of mortality.