tbuckley/cabot-search huggingface dataset:
Trust in Health Care in the Time of COVID-19
Authors: David W. Baker
Journal: JAMA (2020)

Trust is foundational for the relationship between patients and clinicians.Patients often disclose profound personal information and trust this will remain confidential.Clinicians work to gain trust so patients are willing to accept their diagnoses and recommended treatments, including undergoing invasive procedures and taking medications indefinitely for chronic conditions.To achieve this level of trust, clinicians and health care systems must, above all, convince people that they put patients' best interests above any financial or nonfinancial self-interest of their own.However, trust in health care has declined during the past half-century.In a 1966 survey of adults in the US, 73% said they had great confidence in the leaders of the medical profession; but in a 2012 survey, only 34% said this. 1 Many factors are thought to contribute to the declining trust in clinicians and organized medicine, including the rise of managed care and related financial incentives, highly publicized conflicts of interest between clinicians and pharma and device manufacturers, limited time for communication, fragmentation of the patient-clinician relationship, and consumerism. 2,3Trust in health care is even lower among Black persons and people of other communities who have experienced barriers to health care access, health care disparities, and overt racism within the health care system. 4he coronavirus disease (COVID-19) pandemic has created new threats to trust.This may have been inevitable when facing a novel pathogen that defied preconceived expectations (eg, spread from asymptomatic carriers), leading to rapid advances in scientific understanding of the disease and frequently changing recommendations for prevention and treatment.However, the preexisting distrust in science was exacerbated by conflicting messages, questionable treatments reported in research publications, concerns about political interference in public health recommendations and decisions regarding the efficacy of therapeutics, and pseudoscience and conspiracy theories.In addition, Black and Latino communities faced inadequate testing, financial barriers to care, and disproportionately high rates of COVID-19 cases and deaths, further threatening their trust in physicians, the health care system, public health, and science. 5][8][9][10][11] Arora and colleagues 6 discuss concerns related to medical misinformation and offer countervailing strategies at the clinical and societal level, ranging from use of social media to spread messages supporting vacci-
COVD-13. EFFECTS OF COVID-19 PANDEMIC ON NEUROSURGICAL ONCOLOGY PRACTICES AT INOVA HEALTH SYSTEM: AN INSTITUTIONAL EXPERIENCE
Authors: Danielle Dang, Luke Mugge, Omar Awan, Emily Gunnells, Megan Vaughan, Mateo Ziu
Journal: Neuro-Oncology (2020)

Abstract INTRODUCTION Amidst the unprecedented nationwide ban on elective surgeries during the COVID-19 pandemic, concern regarding timely and safe treatment of patients with intracranial tumors has been raised in the neuro-oncology community. METHODS A retrospective chart review was performed on all patients who underwent treatment for intracranial tumors from 3/12–7/1 for 2019 and 2020. Dates aligned with declaration of State of Emergency through the multi-phase public re-opening. Primary comparative endpoints included case volume, median time to surgery, chemotherapy, and radiation, and COVID-related mortality. RESULTS Overall surgical case volume decreased by 26.6%, while a 46.9% decrease was evident during the ban on elective surgeries. Case reduction occurred only for glial (p= 0.33) and pituitary tumors (p=0.04) where volume was nearly identical for other tumors. Median time to surgery was 2.5 days (range: 0–9) for high-grade glioma patients, 3 days for metastases, 3 days for meningiomas, and 26 days (range: 0–98) for pituitary adenomas, not significantly different from 2019. Time to chemoradiation and planned number of treatments were without significant difference. Among 2,795 Covid-19 patients treated in our institution, only four had brain tumors. Only one patient experienced delayed radiation treatment (three weeks) due to inability to achieve seroconversion prior to planned simulation. Only one COVID-related mortality in our cohort occurred. DISCUSSION The pandemic did not significantly delay type and time to treatment for neuro-oncology patients at Inova. With swift implementation of PPE and strict peri-operative testing, we provided standard of care treatment without increases in COVID-19 contraction or mortality. Decreases in overall case volume are likely due to ongoing cultural avoidance of seeking medical care; deferment of endonasal surgery may be attributed to a known greater mortality for ENT procedures. Future patient care challenges include establishing clinical significance of seroconversion for asymptomatic, COVID-19 infected patients without delaying necessary systemic treatment.
Macrophage-mediated vascular permeability via VLA4/VCAM1 pathway dictates ascites development in ovarian cancer
Authors: Shibo Zhang, Bingfan Xie, Lijie Wang, Hua Yang, Haopei Zhang, Yuming Chen, Feng Wang, Changqing Liu, Huanhuan He
Journal: Journal of Clinical Investigation (2020)

The development of ascites correlates with advanced stage disease and poor prognosis in ovarian cancer. Vascular permeability is the key pathophysiological change involved in ascites development. Previously, we provided evidence that perivascular M2-like macrophages protect the vascular barrier through direct contact with endothelial cells (ECs). Here, we investigated the molecular mechanism and its clinical significance in the ovarian cancer setting. We found that upon direct coculture with the endothelium, M2 macrophages tuned down their VLA4 and reduced the levels of VCAM1 in ECs. On the other hand, ectopically overexpressing VLA4 in macrophages or VCAM1 in ECs induced hyperpermeability. Mechanistically, downregulation of VLA4 or VCAM1 led to reduced levels of RAC1 and ROS, which resulted in decreased phosphorylation of PYK2 (p-PYK2) and VE-cadherin (p–VE-cad), hence enhancing cell adhesion. Furthermore, targeting the VLA4/VCAM1 axis augmented vascular integrity and abrogated ascites formation in vivo. Finally, VLA4 expression on the macrophages isolated from ascites dictated permeability ex vivo. Importantly, VLA4 antibody acted synergistically with bevacizumab to further enhance the vascular barrier. Taking these data together, we reveal here that M2 macrophages regulate the vascular barrier though the VCAM1/RAC1/ROS/p-PYK2/p–VE-cad cascade, which provides specific therapeutic targets for the treatment of malignant ascites.
EPEN-21. IMPAIRED NEURONAL-GLIAL FATE SPECIFICATION IN PEDIATRIC EPENDYMOMA REVEALED BY SINGLE-CELL RNA-SEQ
Authors: Bernhard Englinger, Johannes Gojo, Li Jiang, Jens M Hübner, McKenzie L Shaw, Olivia A Hack, Sibylle Madlener, Dominik Kirchhofer, Ilon Liu, Jason Pyrdol, Volker Hovestadt, Emanuele Mazzola, Nathan D Mathewson, Maria Trissal, Daniela Lötsch, Walter Berger, Christian Dorfer, Christine Haberler, Angela Halfmann, Lisa Mayr, Andreas Peyrl, Rene Geyeregger, Kristian W Pajtler, Till Milde, Jack E Geduldig, Kristine Pelton, Thomas Czech, Orr Ashenberg, Kai W Wucherpfennig, Orit Rozenblatt-Rosen, Sanda Alexandrescu, Keith L Ligon, Stefan M Pfister, Aviv Regev, Irene Slavc, Mario L Suva, Marcel Kool, Mariella Filbin
Journal: Neuro-Oncology (2020)

Abstract Ependymoma represents a heterogeneous disease affecting the entire neuraxis. Extensive molecular profiling efforts have identified molecular ependymoma subgroups based on DNA methylation. However, the intratumoral heterogeneity and developmental origins of these groups are only partially understood, and effective treatments are still lacking for about 50% of patients with high-risk tumors. We interrogated the cellular architecture of ependymoma using single cell/nucleus RNA-sequencing to analyze 24 tumor specimens across major molecular subgroups and anatomic locations. We additionally analyzed ten patient-derived ependymoma cell models and two patient-derived xenografts (PDXs). Interestingly, we identified an analogous cellular hierarchy across all ependymoma groups, originating from undifferentiated neural stem cell-like populations towards different degrees of impaired differentiation states comprising neuronal precursor-like, astro-glial-like, and ependymal-like tumor cells. While prognostically favorable ependymoma groups predominantly harbored differentiated cell populations, aggressive groups were enriched for undifferentiated subpopulations. Projection of transcriptomic signatures onto an independent bulk RNA-seq cohort stratified patient survival even within known molecular groups, thus refining the prognostic power of DNA methylation-based profiling. Furthermore, we identified novel potentially druggable targets including IGF- and FGF-signaling within poorly prognostic transcriptional programs. Ependymoma-derived cell models/PDXs widely recapitulated the transcriptional programs identified within fresh tumors and are leveraged to validate identified target genes in functional follow-up analyses. Taken together, our analyses reveal a developmental hierarchy and transcriptomic context underlying the biologically and clinically distinct behavior of ependymoma groups. The newly characterized cellular states and underlying regulatory networks could serve as basis for future therapeutic target identification and reveal biomarkers for clinical trials.
Abstract P168: Impact of Oral Anticoagulation Choice on Healthcare Utilization for the Primary Treatment of Venous Thromboembolism
Authors: Rob F Walker, Richard F Maclehose, J'Neka Claxton, Terrence Adam, Alvaro Alonso, Neil A Zakai, Pamela L Lutsey
Journal: Circulation (2020)

Introduction: Little is known about the impact of oral anticoagulation (OAC) choice on healthcare encounters during the primary treatment of VTE. Hypothesis: Among anticoagulant-naïve VTE patients we tested the hypotheses that the number of hospitalizations, days hospitalized, emergency department visits, and outpatient office visits would be lower among users of rivaroxaban or apixaban than among users of warfarin. Methods: MarketScan databases for years 2016 and 2017 were used to identify VTE cases and comorbidities using international classification of disease codes, and prescriptions for OACs via outpatient pharmaceutical claims data. Healthcare utilization was identified in the first 6 months after initial VTE diagnoses. Results: The 23,864 individuals with VTE cases were on average (± standard deviation) 55.7 ± 16.1 years old and 50.6% female. Participants had on average 0.2 ± 0.5 hospitalizations, spent 1.3 ± 5.2 days in the hospital, had 5.7 ± 5.1 outpatient encounters, and visited an emergency department 0.4 ± 1.1 times. As compared to warfarin, rivaroxaban and apixaban were associated with fewer hospitalizations, days hospitalized, office visits and emergency department visits, after accounting for age, sex, comorbidities and medications (Table 1). For example, hospitalization rates were 24% lower [IRR: 0.76 (95% CI: 0.69, 0.83)] for patients prescribed rivaroxaban and 22% lower [IRR: 0.78 (95% CI: 0.71, 0.87)] for patients prescribed apixaban, as compared to those prescribed warfarin. When comparing apixaban to rivaroxaban, there were no differences in healthcare utilization. Conclusions: VTE patients prescribed rivaroxaban and apixaban had lower healthcare utilization than did those prescribed warfarin, while there was no difference when comparing apixaban to rivaroxaban. These findings complement existing literature supporting the use of direct OACs over warfarin given their similar effectiveness, slightly better safety profile, and perceived lower patient burden.
NIMG-56. THE RARE CASE OF PRIMARY DURAL BASED MARGINAL ZONE B-CELL LYMPHOMA CAMOUFLAGING AS MILD FOCAL DURA THICKNESS AND PACYMENINGEAL ENHANCEMENT
Authors: Maya Hrachova, Mari Perez-Rosendahl, Xiao-Tang Kong
Journal: Neuro-Oncology (2020)

Abstract INTRODUCTION Primary Dural Based Marginal Zone B-Cell Lymphoma (MZBCL) is a subtype of PCNSL with an incidence rate ranging from 0.6 to 3% of all brain tumors. MZBCL typically presents as an extra-axial mass resembling meningioma. Here we report an unusual case of MZBCL with initial radiographic findings of mild nonspecific thickening tentorium and pachymeningeal enhancement surrounding 7th and 8th cranial nerves. CASE REPORT A 58-year old woman with clinical history of CMV infection, polyclonal gammopathy and unruptured left ICA aneurysm post coil embolization who presented for an evaluation of mild thickening and enhancement of the left tentorium cerebelli and 7th/8th nerve root complex. Differential considerations included inflammatory/autoimmune conditions (idiopathic hypertrophic pachymeningitis, neurosarcoidosis, Tolosa-Hunt syndrome), infections, structural lesion, benign or malignant neoplasm. Serum studies were normal. Multiple CSF studies were negative. Flow cytometry showed no malignant cells with few small lymphocytes. She was followed with the imaging surveillance for nine months until further increased thickening of dura on MRI. She underwent cerebellar dural biopsy that was consistent with MZBCL composed mainly of small CD20+ B-cells and negative MYD88. PET scan showed no systemic involvement. Bone biopsy revealed no evidence of lymphoma. The focal leptomeningeal enhancement improved significantly after she received four doses of systemic rituximab treatments. DISCUSSION Our case highlights the importance of surveillance and brain biopsy in cases of mild focal dura/pachymeningeal thickness and enhancement if no conclusive diagnosis has been established, as it might be one of the rare tumors such as MZBLC.
LINC-14. TREATMENT OF PEDIATRIC CNS TUMORS IN ARMENIA. 10 YEARS OF EXPERIENCE IN A 29 YEARS OLD RESOURCE-LIMITED SETTING
Authors: Martin Harutyunyan, Lilit Sargsyan, Samvel Iskanyan, Lusine Hakobyan, Ruzanna Papyan, Gevorg Tamamyan, Karen Bedirian, Samvel Danielyan, Armen Tananyan, Manushak Avagyan, Nune Karapetyan, Samvel Bardakhchyan
Journal: Neuro-Oncology (2020)

Abstract BACKGROUND Pediatric CNS tumors are the most common solid childhood malignancies with many challenges facing optimal outcome due to multimodality complex therapies, abandonment, and long-term morbidity. In our three-decades young, country the field of neuro-oncology is in its infancy. MATERIALS: The aim of our study is to assess incidence, epidemiology and treatment outcomes of children diagnosed and treated with CNS tumors within the last 10 years (2009–2019) in the Chemotherapy Clinic of “Muratsan” Hospital Complex of Yerevan State Medical University. RESULTS During these periods 20 patients with CNS tumors were treated in our clinic. 13 patients (65%) were diagnosed with medulloblastoma (2 patients were infants), two patients (10%) with optic pathway glioma, and 5 patients each with pilocytic astrocytoma, ATRT, ETANTR, DIPG, and glioblastoma. Five patients (3 patients with medulloblastoma, 1 patient with pilocytic astrocytoma, 1 patient with ATRT) had metastatic disease at the time of diagnosis. Seventeen patients (80%) had undergone surgery, 8 patients with medulloblastoma received chemo-RT with vincristine. Median follow up time was 15.5 months (range 5–94). Twelve patients (60%) are alive without evidence of disease. 5 patients had disease progression and three patients relapsed. From them, 3 patients died. Long-term survivors are mainly standard risk medulloblastoma patients. All medulloblastoma patients were treated according to HIT-MED guidelines. CONCLUSION Here we report about the pediatric brain tumors of one of the main pediatric oncology units in Armenia for a period of 10 years. The numbers are quite small for firm conclusions, but it shows the emerging need for further research.
Community prevalence of SARS-CoV-2 in England from April to November, 2020: results from the ONS Coronavirus Infection Survey
Authors: Koen B Pouwels, Thomas House, Emma Pritchard, Julie V Robotham, Paul J Birrell, Andrew Gelman, Karina-Doris Vihta, Nikola Bowers, Ian Boreham, Heledd Thomas, James Lewis, Iain Bell, John I Bell, John N Newton, Jeremy Farrar, Ian Diamond, Pete Benton, Ann Sarah Walker, Koen B. Pouwels, A. Sarah Walker, Derrick Crook, Philippa C. Matthews, Tim Peto, Emma Pritchard, Nicole Stoesser, Karina-Doris Vihta, Alison Howarth, George Doherty, James Kavanagh, Kevin K. Chau, Stephanie B. Hatch, Daniel Ebner, Lucas Martins Ferreira, Thomas Christott, Brian D. Marsden, Wanwisa Dejnirattisai, Juthathip Mongkolsapaya, Sarah Hoosdally, Richard Cornall, David I. Stuart, Gavin Screaton, David Eyre, John Bell, Stuart Cox, Kevin Paddon, Tim James, Thomas House, John N. Newton, Julie V. Robotham, Paul Birrell, Helena Jordan, Tim Sheppard, Graham Athey, Dan Moody, Leigh Curry, Pamela Brereton, Jodie Hay, Harper Vansteenhouse, Iain Bell, Ian Diamond, Alex Lambert, Pete Benton, Emma Rourke, Stacey Hawkes, Sarah Henry, James Scruton, Peter Stokes, Tina Thomas, John Allen, Russell Black, Heather Bovill, David Braunholtz, Dominic Brown, Sarah Collyer, Megan Crees, Colin Daglish, Byron Davies, Hannah Donnarumma, Julia Douglas-Mann, Antonio Felton, Hannah Finselbach, Eleanor Fordham, Alberta Ipser, Joe Jenkins, Joel Jones, Katherine Kent, Geeta Kerai, Lina Lloyd, Victoria Masding, Ellie Osborn, Alpi Patel, Elizabeth Pereira, Tristan Pett, Melissa Randall, Donna Reeve, Palvi Shah, Ruth Snook, Ruth Studley, Esther Sutherland, Eliza Swinn, Heledd Thomas, Anna Tudor, Joshua Weston, Shayla Leib, James Tierney, Gabor Farkas, Raf Cobb, Folkert Van Galen, Lewis Compton, James Irving, John Clarke, Rachel Mullis, Lorraine Ireland, Diana Airimitoaie, Charlotte Nash, Danielle Cox, Sarah Fisher, Zoe Moore, James McLean, Matt Kerby
Journal: The Lancet Public Health (2020)
Examination of the Neck Veins
Authors: Taweevat Assavapokee, Kunlawat Thadanipon
Journal: New England Journal of Medicine (2020)

Examination of the neck veins is routinely performed to evaluate right atrial pressure and to estimate intravascular volume in patients with dyspnea, edema, or hypovolemia. This video demonstrates how to examine the neck veins and to perform the abdominojugular reflux test at the bedside.
55P MOREL: Multicenter observational study on treatment and PD-L1 testing in patients (pts) with newly diagnosed stage IV NSCLC in Spain
Authors: B. Rubio-Viqueira, M. Majem Tarruella, M.E. Lazaro, S. Vazquez Estevez, J.F. Cordoba-Ortega, I. Maestu Maiques, J.J. Garcia Gonzalez, A. Blasco Cordellat, J. Valdivia-Bautista, C. Gonzalez Arenas, J.M. Sanchez Torres
Journal: Annals of Oncology (2020)
TAMI-52. G-CSF SECRETED BY EPIGENETICALLY REPROGRAMMED MUTANT IDH1 GLIOMA STEM CELLS, REVERSES THE MYELOID CELLS’-MEDIATED IMMUNOSUPPRESSIVE TUMOR MICROENVIRONMENT
Authors: Mahmoud Alghamri, Ruthvik Avvari, Rohit Thalla, Li Zhang, Maria Ventosa, Ayman Taher, Felipe Núñez, Jason Heth, Daniel Orringer, Pedro Lowenstein, Maria Castro
Journal: Neuro-Oncology (2020)

Abstract Mutation in isocitrate dehydrogenase (mIDH) is the main genetic lesion that defines clinical glioma subtypes and prognosis. This gain of function mutation is associated with the production of the oncometabolite, R-2-hydroxyglutarate, that inhibits α-ketoglutarate dependent enzymes such as TET2 and the Jumonji-C domain containing demethylases. The resultant epigenetic modifications elicit profound effects on the tumor biology and on the glioma-infiltrating immune cells. Here, we report that in genetically engineered mouse glioma models(1), IDH1 mutation caused an expansion of tumor infiltration granulocytes. Upon phenotypic and functional characterization, we uncovered that granulocytes in mIDH1 glioma express low level of immunosuppressive molecules and did not inhibit T-cell function. Single-cell sequencing revealed that these granulocytes are heterogeneous and composed of three distinct populations; neutrophils, pre-neutrophils, and a small fraction of immunosuppressive PMN-MDSCs. Moreover, primary human gliomas showed a higher cellular fraction exhibiting the PMN-MDSCs gene signature in wtIDH1 tumors than the mIDH1 tumors. The mechanism by which mIDH1 mediates non-immune suppressive granulocytes expansion involves epigenetic reprogramming which leads to enhanced expression of granulocyte colony-stimulating factor (G-CSF) in stem-like cells. High G-CSF gene expression is correlated with favorable patient outcome solely in LGG-astrocytoma with mIDH1. Thus, G-CSF represents a potential therapeutic that can be harnessed to improve immunotherapeutic responses in wild type IDH1 glioma patients.
EPID-07. ACCESS TO GLIOBLASTOMA CLINICAL TRIALS FOR RURAL PATIENTS IN THE UNITED STATES FROM 2010–2020
Authors: Kathryn Nevel, Samuel Capouch, Lisa Arnold, Katherine Peters, Nimish Mohile, Alissa Thomas
Journal: Neuro-Oncology (2020)

Abstract BACKGROUND Patients in rural communities have less access to optimal cancer care and clinical trials. For GBM, access to experimental therapies, and consideration of a clinical trial is embedded in national guidelines. Still, the availability of clinical trials to rural communities, representing 20% of the US population, has not been described. METHODS We queried ClinicalTrials.gov for glioblastoma interventional treatment trials opened between 1/2010 and 1/2020 in the United States. We created a Structured Query Language database and leveraged Google application programming interfaces (API) Places to find name and street addresses for the sites, and Google’s Geocode API to determine the county location. Counties were classified by US Department of Agriculture Rural-Urban Continuum Codes (RUCC 1–3 = urban and RUCC 4–9 = rural). We used z-ratios for rural-urban statistical comparisons. RESULTS We identified 406 interventional treatment trials for GBM at 1491 unique sites. 8.7% of unique sites were in rural settings. Rural sites opened an average of 1.7 trials/site and urban sites 2.8 trials/site from 1/2010–1/2020. Rural sites offered more phase II trials (63% vs 57%, p= 0.03) and fewer phase I trials (22% vs 28%, p= 0.01) than urban sites. Rural locations were more likely to offer federally-sponsored trials (p&amp;lt; 0.002). There were no investigator-initiated or single-institution trials offered at rural locations, and only 1% of industry trials were offered rurally. DISCUSSION Clinical trials for GBM were rarely open in rural areas, and were more dependent on federal funding. Clinical trials are likely difficult to access for rural patients, and this has important implications for the generalizability of research as well as how we engage the field of neuro-oncology and patient advocacy groups in improving patient access to trials. Increasing the number of clinical trials in rural locations may enable more rural patients to access and enroll in GBM studies.