tbuckley/cabot-search huggingface dataset:
TMOD-33. THE ROLE OF BAFF-R SIGNALING IN THE GROWTH OF PRIMARY CENTRAL NERVOUS SYSTEM LYMPHOMA
Authors: Matthias Mulazzani, Xíaolan Zhou, Wenlong Zhang, Andreas Straube, Louisa von Baumgarten
Journal: Neuro-Oncology (2020)

Abstract Primary CNS lymphoma (PCNSL) is an aggressive brain tumor. Despite improvements in therapeutic algorithms, long-term survival remains rare, illustrating an urgent need for novel therapeutic targets. BAFF-R is a pro-survival receptor expressed on most malignant B cells, including PCNSL. To date, its role in PCNSL growth remains elusive. Here, we created a BAFF-R knockout lymphoma cell line (BAFF-R-KO) using CRISPR-Cas9. In serum-starved conditions, BAFF-R-KO cells exhibit decreased viability in vitro compared to BAFF-R+ cells. Combining an orthotopic mouse model of PCNSL with chronic cranial windows and intravital microscopy, we demonstrate a significant delay in tumor growth in mice inoculated with BAFF-R-KO cells compared to BAFF-R+ PCNSL. Additionally, median survival of BAFF-R-KO mice was significantly prolonged. Altogether, our results indicate a potential of BAFF-R as a novel treatment target for PCNSL.
Abstract 12058: Development of a Risk Score for Incident Latent Heart Failure in a Japanese General Population: The Suita Study
Authors: Yoshihiro Kokubo, Aya Higashiyama, Makoto Watanabe
Journal: Circulation (2019)

Introduction: Despite the global heart failure (HF) pandemic, there are few population-based prospective studies on heart failure (HF) in non-Western populations. We developed a novel risk score fo...
Rebuilding Trust and Relationships in Medical Centers
Authors: Reshma Gupta, Leah Binder, Christopher Moriates
Journal: JAMA (2020)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Varying Hemodynamics and Differences in Prognosis in Patients With Asymptomatic Severe Aortic Stenosis and Preserved Ejection Fraction: A Call to Review Cutoffs and Concepts⁎⁎Editorials published in the Journal of the American College of Cardiology reflect the views of the authors and do not necessarily represent the views of JACC or the American College of Cardiology.
Authors: Frank A. Flachskampf, Mohammad Kavianipour
Journal: Journal of the American College of Cardiology (2012)
SURG-09. REACTIVATION OF <i>HERPES SIMPLEX</i> VIRUS AFTER NEUROLOGIC SURGERY
Authors: Carlos Almeida, Bruna Minniti Mançano, Seila Israel Prado, Gisele Caravina Almeida, Fernanda Magalhães Souza, Lucas Dias Lourenço
Journal: Neuro-Oncology (2020)

Abstract BACKGROUND Herpes simplex virus encephalitis (HSVE) is a rare complication after neurosurgery, and its clinical picture mimics features of other most frequent infectious complications of bacterial origin. Probable triggering factors are manipulation and surgical stress, since most cases occur due to reactivation rather than primary infection. The main symptoms include fever and altered consciousness. DNA identification of HSV by PCR has accuracy. Even with adequate treatment, HSVE is associated with a mortality of 30%, and potential neurologic sequelae such as cognitive and motor. CASE REPORT: An 18-year-old male patient presented with loss of vision due to cystic craniopharyngioma. We inserted an Omaya catheter and drained the cyst. On the third day, he presented with fever, seizures, and decreased consciousness. Magnetic resonance imaging (MRI) showed high signal intensity on T2-weighted and FLAIR images in the left frontal and temporal lobe, cingulate gyrus, and corpus callosum, with mass effect. He was submitted to decompressive craniectomy and empirical antibiotic therapy. CSF and blood cultures were negative. Due to inexpressive clinical improvement after 48 hours, CSF was collected for polymerase chain reaction (PCR), and we performed a brain biopsy and started intravenous acyclovir. Histology and PCR confirmed HSVE type 1 and 2. He received antiviral for two weeks and was discharged after CSF PCR negative. CONCLUSION Clinical suspicion, CSF PCR, and imaging are of paramount importance for early diagnosis of HSVE, which should be considered in the differential diagnosis of recent postoperative neurologic surgery in cases of unexplained postoperative fever with altered consciousness.
Home From the Hospital
Authors: Shane O’Hanlon
Journal: JAMA (2020)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
IMG-17. RADIOMICS CHARACTERIZATION OF FOUR PEDIATRIC BRAIN TUMOR SUBTYPES IN PDX MOUSE MODELS
Authors: Natalie Serkova, Marina Stukova, Samuel Henehan, Jenna Steiner, Angela Pierce, Andrea Griesinger, Bethany Veo, Irina Alimova, Sujatha Venkataraman, Adam Green, Nathan Dahl, Nicholas Foreman, Rajeev Vibhakar
Journal: Neuro-Oncology (2020)

Abstract BACKGROUND Previously, we have reported on the development of advanced magnetic resonance imaging (MRI) protocols for mouse brain tumors. The goal of this follow-up pre-clinical study was to develop a machine-learning MRI classifier (radiomics) for four subtypes of childhood brain tumor in patient-derived xenograft (PDX) mice. METHODS MRI scans on orthotopic medulloblastoma, ependymoma, ATRT and DIPG PDX (each n=12 animals) were performed on the animal 9.4 Tesla scanner with an in-plane resolution of 47 microns. Image segmentation, as well as shape and texture based radiomics descriptors were modeled using a modified COLIAGE software for tumor classification and to characterize tumor habitat of each tumor subtype. RESULTS The mean tumor volumes were 11.2 mm3. Each MRI scan was segmented into three regions: (i) well defined tumor (including distant metastases); (ii) peritumoral edema; (iii) tumor necrosis. 360 radiomics features (capturing co-occurrence, grey-level dependence and directional gradients) were obtained for each region. The model classified four subtypes with high accuracy while achieving sufficient segmentation accuracy despite the small lesion size. A subset of fourteen tumoral, six peritumoral and five distant MRI radiomics features were found to be predictive of the tumor sub-type (p=0.0017) independently of tumor anatomical location. CONCLUSIONS MRI protocols followed by radiomics feature analysis discriminated among specific radiological features for four distinct orthotopic PDX models: medulloblastomas exhibit low ADC values, high angiogenesis and cortical metastases as compared to ependymomas (high levels of edema and olfactory bulb metastases), ATRT (the highest level of necrosis) and DIPG (highest T2 signal intensities and spinal metastases).
COVD-03. ASSESSING THE IMPACT OF CORONAVIRUS 19 PANDEMIC ON NEURO-ONCOLOGY AT GUY’S CANCER CENTRE LONDON
Authors: Jessica Little, Omar Al-Salihi, Lucy Brazil, Angela Swampillai
Journal: Neuro-Oncology (2020)

Abstract BACKGROUND Immunosuppressive treatment increases COVID-19 risk. Neuro-oncology patients may not qualify for ITU if they deteriorate, but without oncological treatment, prognosis is poor. The pandemic has seen the introduction of new guidelines; including alternative treatment schedules which balance risks of contracting COVID-19, against safely delivering effective cancer treatment. We assess COVID-19 impact on neuro-oncology treatment at Guy’s Cancer Centre, London. METHODS Notes of patients seen March-April 2020 were reviewed. Demographic data, tumour grade, treatment and changes due to COVID-19 recorded. RESULTS 111 patients were identified (69 male: 42 female, median age 51years). 65 were WHO Grade 4, 24 Grade 3, 17 Grade 2, 2 Grade 1, 1 metastatic-neuroblastoma, 1 anaplastic-medulloblastoma and 1 radiological diagnosis of high-grade-glioma. 14% (32) of consultations were in person (16 new, 7 consents, 9 attending for treatment); 86% (198) were telephone. 8 had concurrent chemo-radiotherapy, 22 radiotherapy alone, 64 chemotherapy alone, 15 had active-surveillance and 2 best-supportive-care. To minimise COVID-19 risk, 22.5% (25) had treatment altered: - A 76-year-old had a radiological diagnosis; - 4 had hypofractionated radiotherapy (30Gy in 6#) to minimise hospital visits; - 7 had no chemotherapy (5 were unmethylated /age, 2 patient choice); - 4 switched from PCV to Lomustine; - 11 stopped chemotherapy early; - 50% (36) were given prophylactic GCS-F; - No patients were recruited for trials. 19 reported possible COVID-19 symptoms – 7 had delays and 3 stopped treatment. 4 tested COVID-19 positive (although not all tested). 1 died of COVID-19 (off treatment). Review of March-April 2020 service showed similar new patient referrals compared to the same time in 2019 (16 and 19 respectively). CONCLUSION Despite concern about decreasing new referrals during the pandemic, this wasn’t the case for our service. 77.5% of patients had no treatment changes due to COVID-19 and all 22 patients on trial were able to continue treatment throughout this period.
Abstract P141: A Novel GWAS Locus Influences Microvascular Response to Acute Psychological Stress
Authors: Zakaria Almuwaqqat, Chang Liu, Jeong Hwan Kim, Qin Hui, Muhammad Hammadah, Ayman Alkhoder, Shabatun Islam, Bruno B Lima, James Bremner, Paolo Raggi, Anurag Mehta, Amit J Shah, Yan Sun, Viola Vaccarino, Arshed A QUYYUMI
Journal: Circulation (2020)

Background: Excessive peripheral microvascular constriction during acute psychological stress, measured using peripheral arterial tonometry reflects similar changes in coronary blood flow and is a predictor of adverse cardiovascular outcomes. The ratio of digital pulse wave amplitude during stress compared to rest (sPAT) is used to estimate the degree of microvascular response to stress. We sought to determine if genetic factors contribute to the degree of microvascular constriction during mental stress. Methods: A total of 642 post-MI and stable CAD subjects from two prospective cohort studies underwent mental stress testing with a standardized public speaking stressor. Digital pulse wave amplitude was continuously measured using PAT and the stress/rest PAT ratio (sPAT) of pulse wave amplitude during mental stress/baseline was calculated. Genotyping was performed using Illumina’s Multi-Ethnic Genotyping Array (MEGA) platform and imputed to the 1000 Genome reference panel. Race stratified genome-wide association studies (GWAS) of sPAT were conducted using linear regression of additive genetic mode adjusted for age, sex and population stratification in the two cohorts. A trans-ethnic meta-analysis integrated the four sets GWAS results. Results: Mean age was 63±9; 65% male, 35% Black. We identified two SNPs in linkage disequilibrium on chr4:185503564 and chr4:185491706 rs13353812 (with 35% and 28% allele frequency, respectively) that were associated with greater sPAT ratio ( P = 1.42E-08). The mean sPAT ratio during mental stress for subjects with none, one and two AT insertion alleles of SNP chr4:185503564 were 0.67, 0.76 and 0.93, respectively, an average of 12% (P &lt; 0.001), per allele. Results were similar for G insertion alleles of SNP rs13353812. The nearest gene of the sPAT-associated locus is CASP3 which encodes caspase, an essential protein for apoptosis signaling and brain and hematopoietic stem cell development. Conclusion: We have identified a genetic basis for stress-induced vasomotion. Presence of the chr4:185503564 allele is associated with less vasoconstriction during mental stress, and thus may be protective against long term cardiovascular risk. These findings need further exploration.
CTNI-28. A PROSPECTIVE, OBSERVATIONAL STUDY EVALUATING THE SAFETY AND QUALITY OF LIFE OF TUMOR TREATING FIELDS IN CHINESE GLIOBLASTOMA PATIENTS
Authors: Kevin Wong, Tao Jiang
Journal: Neuro-Oncology (2020)

Abstract OBJECTIVES Glioblastoma (GBM) is the most common and aggressive primary brain tumor with a median survival of 15 months. Adding Tumor Treating Fields (TTFields) to first-line therapy in GBM demonstrated improved survival in the EF-14 trial. This prospective study was designed to investigate the safety and effect on QoL of TTFields in Chinese patients with GBM. METHODS A total of 44 patients (29 newly diagnosed GBM, 15 recurrent GBM, median age 51.0 [24.0 - 81.0] years) who underwent TTFields following surgery, concurrent chemoradiotherapy were enrolled into the study. The primary endpoint was the incidence of TTFields-related skin adverse events; the secondary endpoint included quality of life (QoL), treatment adherence. RESULTS Of the 44 patients followed up for at least 3 months, 24 (54.5%) had skin adverse reactions, all of which were grade 1–2. Median time to skin AE was 1.2 months. The common skin AE were dermatitis (53.8%), ulcer (19.2%), infection (19.2%), and most of them could be resolved by symptomatic treatment (topical corticosteroid/antibiotics). In terms of QoL, noticeable improvement in overall health and clinical manifestations such as fatigue, nausea and vomiting were observed. The overall average treatment compliance was 91%: compliance (mean±SD), in newly diagnosed patients, 0.89±0.14, median 0.91; in recurrent patients, 0.86±0.13, median 0.93. CONCLUSIONS The incidence of skin adverse reactions (which could be effectively alleviated with treatment) in GBM patients treated with TTFields was acceptable. From our short follow up, TTFields appear to improve QoL and compliance in Chinese patients comparable to published data.
MBRS-26. CDK7 MEDIATED TRANSCRIPTIONAL PROCESSIVITY OF DNA REPAIR NETWORKS REGULATES SENSITIVITY TO RADIATION IN MYC DRIVEN MEDULLOBLASTOMA
Authors: Bethany Veo, Etienne Danis, Susan Fosmire, Dong Wang, Angela Pierce, Nathan Dahl, Sana Karam, Natalie Serkova, Sujatha Venkataraman, Rajeev Vibhakar
Journal: Neuro-Oncology (2020)

Abstract Myc-driven Medulloblastoma remains a major therapeutic challenge due to frequent metastasis and a poor 5-year survival rate. Myc overexpression results in transcriptional dysregulation, proliferation, and survival of malignant cells. To identify therapeutic targets in Myc-amplified medulloblastoma we performed a CRISPR-Cas9 essentiality screen targeting 1140 genes annotated as the druggable genome. The cyclin-dependent kinase, CDK7, was identified as a top candidate. CDK7 phosphorylates the c-terminal domain of RNA Pol II facilitating transcriptional initiation and elongation. We subjected Myc-amplified cells treated with CDK7 inhibitors to whole transcriptomic analysis. The resultant data revealed gene networks mediating DNA repair were functionally repressed. Consistent with this data, ChIP-sequencing showed the most significant reduction in RNA Pol II and Myc promoter occupancy within a subset of DNA repair genes including BRCA2 and RAD51 but not across the whole genome. These data suggest that inhibition of CDK7 mechanistically limits Myc driven transcriptional processivity of DNA repair networks. Further, evaluation of genes mediating DNA repair show a muted response to DNA damage and increased cell death with CDK7 inhibition. We next evaluated Myc-amplified MB cell response to ionizing radiation in vitro and in vivo with CDK7 inhibition. Inhibition of CDK7 enhanced radiation sensitivity of Myc MB cells by potentiating DNA damage. Further, cotreatment produced decreased MRI T2 tumor volumes and enhanced survival benefit in orthotopic PDX xenografted mice compared to radiation alone. Our studies establish a mechanism for selective inhibition of Myc-driven MB by CDK7 inhibition combined with radiation as a viable therapeutic strategy for Myc-amplified medulloblastoma.
Novel Experience in Hybrid Tracers
Authors: Gianpiero Manca, Ludovico Maria Garau, Sara Mazzarri, Laura Mazzuca, Simona Muccioli, Matteo Ghilli, Giuseppe Naccarato, Patrick M. Colletti, Domenico Rubello, Manuela Roncella, Duccio Volterrani, Ielizza Desideri
Journal: Clinical Nuclear Medicine (2020)

Purpose The clinical introduction of a radioactive and fluorescent hybrid tracer allowed for preoperative lymphatic mapping and intraoperative real-time fluorescence tracing of the sentinel lymph node (SLN) by a single injection. The aim of this feasibility study is to evaluate the first-in-human use of the hybrid tracer by combining indocyanine green (ICG) and radiocolloid based on Nanotop compound ( 99m Tc Nanotop) for SLN biopsy (SLNB) in breast cancer patients. Methods The day before surgery, ICG- 99m Tc Nanotop was injected periareolarly in breast cancer patients scheduled for SLNB. Planar lymphoscintigraphic (PL) and SPECT/CT images were then acquired. An intraoperative optonuclear probe was used to detect SLN gamma and fluorescent signals. The harvested SLNs were examined by hematoxylin-eosin staining, and patients were clinically evaluated 1 month after surgery. Results Twenty-one consecutive patients were enrolled. The PL and SPECT/CT techniques identified at least 1 SLN in all patients for a preoperative sentinel detection rate of 100%. SPECT/CT revealed 3 additional lymph nodes in the same nodal basin, which had not been visualized on conventional PL (κ = 0.747; P &lt; 0.005). All 30 preoperative SLNs were localized and excised up to 16 hours after injection. The counts measured via gamma tracing showed a very strong correlation with those measured via near-infrared fluorescent tracing ( P &lt; 0.005, r = 0.964). No adverse reactions were observed. Conclusions The SLNB technique used with the ICG- 99m Tc Nanotop tracer resulted to be feasible, reliable, and safe. This hybrid compound allowed us to obtain excellent performance in terms of both preoperative lymphatic mapping and intraoperative SLN detection in breast cancer patients.
BIOM-17. BRAF MUTATION IS AN EARLY EVENT IN THE EVOLUTION OF A SUBSET OF GLIOBLASTOMAS AND IS ASSOCIATED WITH INCREASED PD-L1 EXPRESSION
Authors: Kyle Walsh, Joanne Xiu, Giselle López, Daniel Landi, Zachary Reitman, Sandeep Mittal, Andrew Brenner, Ekokobe Fonkem, Santosh Kesari, Surasak Phuphanich, Herbert Newton, Manjari Pandey, Emil Lou, Michael Glantz, Ashley Sumrall, Erin Dunbar, Macarena De La Fuente, W Michael Korn, Mustafa Khasraw, David Ashley
Journal: Neuro-Oncology (2020)

Abstract INTRODUCTION BRAF is a RAF-family kinase that regulates MAPK/ERK signaling. Activating BRAF mutations, including V600E, are common in circumscribed low-grade gliomas of childhood and young adulthood, but are uncommon in infiltrative astrocytomas, including glioblastoma. Their role in glioblastoma initiation and progression requires analysis of large datasets given the low frequency (1.0%) in TCGA IDH-wild-type glioblastomas. METHODS Molecular profiling was done on 4679 FFPE gliomas by next-generation sequencing at Caris Life Sciences, of which 3170 underwent RNA-sequencing for gene fusion and 4603 DNA-sequencing for mutations. MGMT promoter methylation was tested by pyrosequencing and PD-L1 IHC was performed using the SP142 clone. RESULTS Excluding variants of uncertain significance, BRAF mutations/fusions were most common in pleomorphic xanthoastrocytoma (PXA; N=12/24, 50%), glioneuronal tumors (N=6/13, 46%), pilocytic astrocytoma (PA; N=15/48, 31%), and ganglioglioma (n=5/18, 28%). BRAF fusions were uncommon (N=17), most frequent in PA (N=8/31, 26%) where they were associated with older age at daignosis (P=0.043), and typically involved KIAA1549 as fusion partner (70%). BRAF-mutated/fused glioblastoma patients (N=59/3126, 2%) were younger than BRAF-wild-type glioblastoma patients (54 versus 59 years, P=3.5x10-3); more likely to be MGMT-unmethylated (75% versus 56%, P=5.0x10-3); and 3x more likely to express PD-L1 (55% versus 17%, P=2.1x10-10). In tumors harboring a V600E mutation, the variant allele frequency (VAF) was similar in glioblastoma as in PXA, PA, ganglioglioma, and glioneuronal tumors (median VAF=35%). CONCLUSIONS BRAF-mutated glioblastoma were 3x more likely to express PD-L1 than BRAF-wild-type glioblastoma. We observed no differences in BRAF V600E clonality in BRAF-mutated glioblastoma compared to BRAF-mutated PXA, PA, ganglioglioma, and glioneuronal tumors, suggesting BRAF mutation is an initiating event in the clonal evolution of a subset of glioblastoma. There is rationale to evaluate combined BRAF inhibition with checkpoint inhibition in BRAF-mutated glioblastoma, potentially synergizing the complete response profile of the former with the durable response profile of the latter.
BIOM-32. HIGH AFFINITY FLUORESCENT NANOPARTICLES FOR DETECTION IL13Rα2-POSITIVE EXTRACELLULAR VESICLES AND CELLS
Authors: Vladimir Khristov, Achuthamangalam Madhankumar, Brad Zacharia, James Connor
Journal: Neuro-Oncology (2020)

Abstract Glioblastoma (GBM) is both the most common and deadly malignant primary brain tumor with a 1-year survival of 37.2% and a 5-year survival of just 5.1%. The standard of care for GBM is surgical excision followed by radiation with concurrent and adjuvant temozolomide-centered chemotherapy (TMZ). Despite advances in imaging technology, early identification of treatment failure or impending resistance remains problematic. A unique characteristic of GBM is the overexpression of the α2 variant of IL-13 receptor (IL13Rα2) in 78–96% of patients while virtually undetectable in normal brain tissue. We hypothesize that the blood of patients with GBM contains sufficient IL13Rα2-positive extracellular vesicles (EV) to inform the clinical picture regarding disease status such as tumor recurrence and response to therapy. To detect IL13Rα2 as a specific molecular target for diagnostic testing, we have developed a modified version of IL-13 with increased affinity and specificity for IL13Rα2, and conjugated this ligand to fluorescent/ magnetic nanoparticles using an 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC) linker. Furthermore, we demonstrated that the EV plasma fraction of patients with GBM is enriched for the IL13Rα2 receptor. We also demonstrated the ability of the ligand-bound nanoparticles to aggregate with IL13Rα2-positive cells and EVs in vitro. This ligand-based affinity purification particle has the potential to both quantify IL13Rα2 EV levels in patient blood and isolate these EVs for further interrogation of genomic and proteomic molecular markers.