tbuckley/cabot-search huggingface dataset:
Chylopericardium Due to Residual Lymphangiomyoma Detected on 99mTc-Sulfur Colloid Lymphoscintigraphy
Authors: Angel Hemrom, Avinash Tupalli, Arunav Kumar, Nikhil Mohan, Rakesh Kumar
Journal: Clinical Nuclear Medicine (2020)

Lymphangiomyomas are relatively rare, benign neoplasms. Many patients present with symptoms including effusions, and some cases are incidentally detected. Surgical excision is the treatment of choice, but because of its location, complete surgical resection of a lymphangioma can be technically difficult, and recurrent cases can present with symptoms including effusions. 99mTc-sulfur colloid scan can be used to confirm the leak and nature of the effusion fluid. Here, we present an 8-year-old girl with recurrent pleural and pericardial effusions after lymphocele excision and total pericardiectomy. 99mTc-sulfur colloid lymphoscintigraphy was done to rule out secondary chylopericardium.
NCOG-24. WAKE FOREST NCORP RESEARCH BASE FEASIBILITY STUDY OF RAMIPRIL FOR PREVENTING COGNITIVE DECLINE IN GLIOBLASTOMA PATIENTS RECEIVING BRAIN RADIOTHERAPY (WF-1801)
Authors: Christina Cramer, Brandi Page, Jeffrey S Wefel, Emily Dressler, Edward Ip, Steve Rapp, Edward Shaw, Kathryn Weaver, Glenn Lesser, Michael Chan
Journal: Neuro-Oncology (2020)

Abstract INTRODUCTION Chronic neuro-inflammation after brain radiotherapy (RT) contributes to radiation-induced cognitive decline (RICD). The renin angiotensin system (RAS) may mediate this inflammatory cascade after RT. Ramipril is an angiotensin-converting enzyme inhibitor used to treat hypertension and has good blood-brain barrier penetration. By blocking RAS activation, ramipril reduces neuro-inflammation and preclinical data show that ramipril administration during RT can prevent RICD. METHODS WF-1801 is an ongoing feasibility study that will enroll a total of 75 patients. Patients ≥ 18 with newly diagnosed and pathologically confirmed GBM who will receive chemoradiation are eligible. All participants take ramipril daily during RT and for 4 months thereafter. Ramipril is titrated from 1.25mg to 5mg daily over 3 weeks. A cognitive battery that includes the Hopkins Verbal Learning Test-Revised (HVLT-R), Trail Making Test (TMT), and Controlled Oral Word Association test (COWA) is administered at baseline, end of RT, and 1-month and 4-months post-RT. The co-primary endpoints are retention rate (with retention defined as compliance with &amp;gt; 75% of drug therapy doses) and neurocognitive function at 1-month post-RT. To estimate the effect of ramipril on cognitive function, performance on the cognitive battery will be compared to a historical control (cognitive data from the control arm of RTOG 0825). ApoE genotyping is being performed as a correlative study. RESULTS 31 of a planned 75 participants have been enrolled over 14 months. 20 of 31 (64.5%) are male. 21 (67.7%) are between the age of 40-64. 20 (95.6%) are white and 29 (93.6%) are not Hispanic or Latino. CONCLUSION Despite a pause in accrual due to COVID-19, we are easily meeting planned accrual goals. Community oncology-based clinical trials of interventions to prevent cognitive toxicity appear to be feasible. GBM patients seem eager to enroll in studies seeking to prevent cognitive decline. Supported by NCI grant UG1CA189824.
PATH-30. EXOSOMES AS A SOURCE OF PLASMA ctDNA TO IDENTIFY POINT MUTATIONS IN PEDIATRIC GLIOMA PATIENTS
Authors: Liana Nobre, Isabel Porto Carreiro, Aline Helen da Silva Camacho, Rafaela Reis, Leila Chimelli, Ilana Zalcberg, Sima Ferman, Sima Ferman, Barbara Monte Mor
Journal: Neuro-Oncology (2020)

Abstract Surgery consists in the mainstay of treatment in most gliomas, but in many cases, a resection is not feasible. Liquid biopsy is an ideal tool providing a minimally invasive method through plasma or CSF sampling to assess cell-free tumor DNA (ctDNA). Here we explore the feasibility of detecting DNA in plasma exosomes (exoDNA) extracted from glioma patients and further investigate its use in identifying molecular alterations. Exosomes were isolated from 2ml of plasma from 24 patients (13 LGG, 8 HGG, 3 DIPG) and fully characterized by nanoparticle tracking analysis and transmission electron microscopy. DNA was extracted from 13 samples (exoDNA) so far. Five patients had confirmed point mutations in the primary tumor (3BRAFV600E; 1FGFR1N546K; 1H3.3), additionally, 3 samples were collected from clinically diagnosed DIPG patients to inquire H3K27M mutations. DNA was extracted successfully from all exosome samples; a pre-amplification step was needed and direct sequencing was carried out for BRAFV600E. FGFR1N546K and H3K27M mutations were sought in patients with positive tumors. Wildtype BRAF fragment was identified in 12/13samples (1 patient failed sequencing). However, none of the five tumor positive patients nor the DIPG patients had mutations detected at the exo-DNA level. There is growing evidence that CSF may be the ideal source of ctDNA in brain tumor patients, therefore although we could not detect mutations in plasma DNA we are currently analyzing CSF exoDNA and cell-free DNA to evaluate if this proves a successful strategy and weather exoDNA is more representative of the tumor content.
Gadolinium Can Depict Area at Risk and Myocardial Infarction: A Double-Edged Sword?⁎⁎Editorials published in JACC: Cardiovascular Imaging reflect the views of the authors and do not necessarily represent the views of JACC: Cardiovascular Imaging or the American College of Cardiology
Authors: Andrew E. Arai
Journal: JACC. Cardiovascular imaging (2011)
Glia-Selective Deletion of Complement <i>C1q</i> Prevents Radiation-Induced Cognitive Deficits and Neuroinflammation
Authors: Mineh Markarian, Robert P. Krattli, Jabra D. Baddour, Leila Alikhani, Erich Giedzinski, Manal T. Usmani, Anshu Agrawal, Janet E. Baulch, Andrea J. Tenner, Munjal M. Acharya
Journal: Cancer Research (2020)

Abstract The adverse neurocognitive sequelae following clinical radiotherapy (RT) for central nervous system (CNS) malignancies are often long-lasting without any clinical recourse. Despite recent progress, the cellular mechanisms mediating RT-induced cognitive deficits (RICD) are poorly understood. The complement system is an immediate sensor of a disturbed inflammatory environment and a potent mediator of gliosis with a range of nonimmune functions in the CNS, including synaptic pruning, which is detrimental if dysregulated. We hypothesize that complement-mediated changes in glial cell function significantly contribute to RICD. The underlying alterations in CNS complement cascade proteins (C1q, C3), TLR4, and colabeling with glia (IBA1, GFAP) were examined using gene expression, immunofluorescence, and in silico modeling approaches in the adult mouse brain following 9 Gy cranial RT. Three-dimensional volumetric quantification showed elevated molecular signatures of gliosis at short- and long-term post-RT times. We found significant elevations in complement C1q, C3, and TLR4 post-RT accompanied by increased colabeling of astrocytes and microglia. To address the mechanism of RT-induced complement cascade activation, neuroinflammation, and cognitive dysfunction, we used a genetic approach—conditional, microglia-selective C1q (Flox) knockdown mice—to determine whether a glia-specific, upstream complement cascade contributes to RICD. C1q-Flox mice exposed to cranial RT showed no cognitive deficits compared with irradiated WT mice. Further, irradiated C1q-Flox mice were protected from RT-induced microglial activation and synaptic loss, elevation of anaphylatoxin C5a receptor, astrocytic-C3, and microglial-TLR4 expression in the brain. Our findings demonstrate for the first time a microglia-specific mechanism of RICD involving an upstream complement cascade component, C1q. Significance: Clinically-relevant radiotherapy induces aberrant complement activation, leading to brain injury. Microglia-selective genetic deletion of CNS complement C1q ameliorates radiation-induced cognitive impairments, synaptic loss, and neuroinflammation, highlighting the potential for C1q as a novel therapeutic target. See related commentary by Korimerla and Wahl, p. 1635
Abstract P189: Metabolomic Signatures Of Serum Creatinine Among Hypertensive African Americans.
Authors: Ninad S Chaudhary, Hemant K Tiwari, Nicholette Allred, Fang-Chi Hsu, Donald Bowden, Barry Freedman, Donna K Arnett, Marguerite M Irvin
Journal: Circulation (2020)

Background: The prevalence of chronic kidney disease (CKD) in African Americans (AAs) is high. Although ancestry-specific biomarkers have been identified, few translate to the clinic. Metabolomic studies may identify novel biomarkers useful for prevention, diagnosis and treatment. Methods: Plasma from 300 AA Hypertension Genetic Epidemiology Network (HyperGEN) study participants age ≥40 years with serum creatinine (SCr) &lt;2 mg/dL were assayed for an untargeted metabolomic study of SCr using an ultra-high performance liquid chromatography mass spectrometry platform (Metabolon ® ). SCr was measured using a thin-film adaptation of the amidohydrolase enzymatic method on fasting blood samples. Each metabolite was tested for normality and a rank-based inverse normal transformation was performed as appropriate. Multivariable linear regression was used to test for association between the metabolite (outcome) and SCr (exposure of interest) adjusting for age, gender, waist circumference and center. A Bonferroni correction was used to adjust for multiple testing using. The top 25 most significant metabolites were evaluated for replication in 367 participants from the African American-Diabetes Heart Study (AA-DHS). An exploratory pathway analysis was conducted among significant (p&lt; 6.0*10 -5 6.0e -5 metabolites in HyperGEN. Results: Among 300 participants from HyperGEN the mean age was 54.5 years (SD=9.5) and 58.7% were female. Mean SCr was 0.93 (SD=0.25). Eighty percent were treated for hypertension and 28% had diabetes. A total of 809 metabolites were annotated in HyperGEN samples. Of those, 391 were associated with SCr at p&lt;0.05 and 256 metabolites met the Bonferroni significance criteria (p&lt; 6.0*10 -5 ). The top SCr associated metabolites were tartonate(hydroxymalonate)(β[SE]= 2.99[0.07], p=3.98e -117 ), 1-stearoyl-GPC(18:0)(β[SE]= 2.49[0.14], p=2.28e -44 ), 2S-3R-dihydroxybutyrate)(β[SE]= 2.36[0.14],p=1.53e -40 ) and isovalerate(C5)( β[SE]= 2.30[0.15], p = 2.78e -36 ). The association of these metabolites with SCr replicated in AA-DHS [(tartonate(hydroxymalonate)(β[SE]= 0.66[0.19], p=0.001), 1-stearoyl-GPC(18:0)(β[SE]= 1.30[0.20], p=1.61 -10 ), 2S-3R-dihydroxybutyrate)(β[SE]= 1.20[0.18],p=4.69e -11 ) and isovalerate(C5)( β[SE]= 1.24[0.20], p = 1.91e -09 )]. An exploratory pathway analysis highlighted xenobiotics and the lysophospholipid pathway. Significance: Tartronate is a xenobiotic that is related to BMI, insulin resistance and adiponectin. 1-stearoyl-GPC (18:0) is a lysophospholipid metabolite found to be associated with oxidative stress. Conclusion: The current study discovered and replicated metabolites associated with SCr in a population of AAs with a high prevalence of hypertension. If validated, these could provide new insights in kidney disease pathways or aid in the treatment and prevention of CKD in the AA population.
Abstract P410: Association of Sarcopenia, Low Muscle Mass and Low Muscle Strength With Coronary Artery Calcium Scores
Authors: Claudia Szlejf, Claudia K Suemoto, Marcio S Bittencourt, Itamar S Santos, Paulo A LOTUFO, Isabela M Bensenor
Journal: Circulation (2020)

Introduction: Low muscle mass and low muscle strength, the defining components of sarcopenia, are associated with increased risks of cardiovascular disease and mortality. However, little is known about the association of sarcopenia with markers of subclinical atherosclerosis, such as coronary artery calcium (CAC). We assessed the hypothesis that sarcopenia and its defining components are associated with higher CAC scores in middle-aged and older adults. Methods: In this cross-sectional analysis we included 2700 participants from the São Paulo site of the Brazilian Longitudinal Study of Adult Health second wave, aged ≥ 50 years, who were submitted to CAC assessment, with no previous history of coronary artery disease and stroke, and with complete data on exposure, outcome and covariates. CAC was measured by noncontrast computed tomography scans and the Agatston method was adopted to calculate CAC scores. Muscle mass was assessed by bioelectrical impedance analysis and muscle strength by handgrip strength. Sarcopenia was defined according to the Foundation for the National Institutes of Health criteria. The association of sarcopenia and its defining components with CAC score &gt; 0 or &gt; 100 was investigated with logistic regression. We also investigated the association of continuous appendicular lean mass standardized by body mass index and handgrip strength with CAC score &gt; 0 and &gt; 100. Possible confounders included sociodemographic characteristics, clinical conditions, lifestyle and laboratory parameters. Results: Sarcopenia was found in 1% (23 out of 2700) of participants, 23% (609 out of 2700) with low muscle mass and 2% (40 out of 2700) with low muscle strength. CAC &gt; 0 and CAC &gt; 100 were found in 35% (952 out of 2700) and 13% (357 out of 2700) of participants, respectively. After adjustment for sociodemographic characteristics, clinical conditions, lifestyle and laboratory parameters, low muscle mass was associated with CAC &gt; 100 (OR = 1.37, 95%CI 1.03-1.80), but not with CAC &gt; 0 (OR = 1.17, 95% CI = 0.94-1.46). Sarcopenia and low muscle strength were not associated with CAC scores. Additionally, continuous appendicular leans mass standardized by body mass index was associated with lower odds of CAC &gt; 100 (OR = 0.15, 95% CI = 0.05-0.50), although it was not associated with CAC &gt; 0. Finally, continuous handgrip strength was not associated with CAC scores. Conclusion: In conclusion, low muscle mass is associated with higher odds of CAC score &gt; 100 in middle-aged and older adults.
MBCL-23. PRELIMINARY ANALYSIS OF TREATMENT-RELATED TOXICITIES DURING INDUCTION CHEMOTHERAPY FOR PATIENTS ON THE HEAD START 4 TRIAL
Authors: Vibhuti Agarwal, Joseph Stanek, Megan Jaeger, Girish Dhall, Jonathan Finlay
Journal: Neuro-Oncology (2020)

Abstract The currently active, prospective multi-center Head Start 4 (HS4) trial for CNS embryonal tumors differs from prior HS I-III trials by utilizing absolute phagocyte count (APC) as a measure of myeloid recovery instead of absolute neutrophil count. The aim of this study was to determine if utilization of APC resulted in unanticipated treatment-related toxicities during induction chemotherapy for patients enrolled on HS4. Review of the RedCap database was conducted for treatment-related CTCAE grade 3 and 4 toxicities. Data were summarized descriptively. Nonparametric statistical methods were used for comparisons. At the time of this most recent analysis, a total of 180 induction cycles were completed for the 57 patients enrolled. Of the 57 patients, nine voluntarily discontinued therapy after completing a median of three cycles each. These patients had a higher number of documented infections (59% versus 24%, p=0.0004). Veno-occlusive disease (VOD) occurred in five patients, three of whom voluntarily discontinued therapy. Since the protocol amendment utilizing milligram per kilogram dosing for patients less than six years of age, there have been no documented episodes of VOD. The overall toxicities for this cohort were comparable to those reported for induction chemotherapy in HS I-II trials. The toxic death rate is lower for HS4 compared to HS I-II (0.018% versus 4.7–6%) (Chi et al 2004). Other than the high rate of infection, possibly associated with shorter duration of the immediately prior cycles, the use of APC as part of a dose-compression strategy in HS4 does not appear associated with more significant toxicities.
Reply to M. Dowsett et al
Authors: Iris Noordhoek, Hein Putter, Johanneke E. A. Portielje, Gerrit-Jan Liefers
Journal: Journal of Clinical Oncology (2020)

provided thoughtful commentary to our article, 2 in which we assessed the validity of their CTS5 calculator to predict late distant breast cancer recurrences. 3curate estimation of cancer prognosis remains a relevant topic of research and various efforts have been made to accurately determine the prognosis of patients with breast cancer.One of those is the CTS5 calculator which, as opposed to genetic profiling tests, is a free and easy-to-use tool and is, therefore, readily available in clinical practice. 3Dowsett et al 1 indicate that the calculator has been accessed more than 88,000 times, which underlines the importance of its risk estimations being validated in independent cohorts to ensure the reliability.
NCOG-27. INCREASED OVERALL SURVIVAL AMONG RACIAL MINORITIES AND SUBOPTIMAL USE OF STANDARD OF CARE TREATMENT IN GLIOBLASTOMA MULTIFORME
Authors: Stephanie Boisclair, Shenae Samuels, Arjun Khunger, Delia A Wietecha, Alejandro Lopez Cohen, Kelly King, Candice Sareli, Jessica Jacques, Mathew Salzberg, Michel Vulfovich, Brian Hunis, Luis E Raez, Atif M Hussein
Journal: Neuro-Oncology (2020)

Abstract Glioblastoma Multiforme (GBM) is the most common primary central nervous system (CNS) tumor and is always considered grade IV given its aggressive nature and poor overall survival (OS). Despite advancements in surgical techniques and cancer therapies, GBM treatment has remained the same since 2005: total resection followed by temozolomide and radiation. We hypothesized that OS has increased over the years and is similar among all races/ethnic groups without reduction of mortality based upon treatment facility. METHODS: The National Cancer Database from 2004-2016 was utilized to obtain demographic, tumor and treatment factors of GBM (excluding gliosarcomas). Multivariate Weibull regression model was used to evaluate prognostic factors for OS in months(m). RESULTS: A total of 119,496 patients were identified. There was a significant difference(P=0.000) in OS for patients diagnosed in 2012-2016 (10.2m) compared to 2008-2011 (9.2m) and 2004-2007 (8.1m). Among racial groups, the highest incidence was among whites (91.8%) whom also had the lowest OS (9.0m), followed by Blacks (10.5m), Hispanics (11.7m) and Asians (12.9m)(P=0.000). Patients with unilateral tumors (72.1%) and tumor size &amp;lt; 3cm (18.3%) had an increased OS (9.8m-10.2m and 11.2m, respectively) compared with patients having bilateral tumors or larger size ≥ 3cm (OS of 4.8m and 8.9m, respectively)(P=0.000). Increasing age (HR=1.03) and comorbidity score ≥ 3 (HR=1.40) were independent predictors of death (P=0.000), while female sex (HR=0.88), Asian ethnicity (HR=0.75) and treatment at an academic/research facility (HR=0.86) were independent predictors of survival(P&amp;lt; 0.01). Only 60.1% of patients (n=59,112) received ideal treatment (surgery, chemotherapy and radiation), while only 3.2% of all GBM patients received palliative care. DISCUSSION: Decreased OS was found among white race, large and bilateral tumors. Despite a statistically significant, although minimal, increase in OS since 2004-2007, there is notable underutilization of ideal treatment and palliative care. Further studies should focus on access inequalities and limitations to treatment.
Assessment of the Utility of Kidney Histology as a Basis for Discarding Organs in the United States: A Comparison of International Transplant Practices and Outcomes
Authors: Peter P. Reese, Olivier Aubert, Maarten Naesens, Edmund Huang, Vishnu Potluri, Dirk Kuypers, Antoine Bouquegneau, Gillian Divard, Marc Raynaud, Yassine Bouatou, Ashley Vo, Denis Glotz, Christophe Legendre, Carmen Lefaucheur, Stanley Jordan, Jean-Philippe Empana, Xavier Jouven, Alexandre Loupy
Journal: Journal of the American Society of Nephrology (2020)

Background Many kidneys donated for transplant in the United States are discarded because of abnormal histology. Whether histology adds incremental value beyond usual donor attributes in assessing allograft quality is unknown. Methods This population-based study included patients who received a deceased donor kidney that had been biopsied before implantation according to a prespecified protocol in France and Belgium, where preimplantation biopsy findings are generally not used for decision making in the allocation process. We also studied kidneys that had been acquired from deceased United States donors for transplantation that were biopsied during allocation and discarded because of low organ quality. Using donor and recipient characteristics, we fit multivariable Cox models for death-censored graft failure and examined whether predictive accuracy (C index) improved after adding donor histology. We matched the discarded United States kidneys to similar kidneys transplanted in Europe and calculated predicted allograft survival. Results In the development cohort of 1629 kidney recipients at two French centers, adding donor histology to the model did not significantly improve prediction of long-term allograft failure. Analyses using an external validation cohort from two Belgian centers confirmed the lack of improved accuracy from adding histology. About 45% of 1103 United States kidneys discarded because of histologic findings could be accurately matched to very similar kidneys that had been transplanted in France; these discarded kidneys would be expected to have allograft survival of 93.1% at 1 year, 80.7% at 5 years, and 68.9% at 10 years. Conclusions In this multicenter study, donor kidney histology assessment during allocation did not provide substantial incremental value in ascertaining organ quality. Many kidneys discarded on the basis of biopsy findings would likely benefit United States patients who are wait listed.
TAMI-22. VARIATION AMONG INTACT TISSUE SAMPLES REVEALS THE CORE TRANSCRIPTIONAL IDENTITIES OF CELL TYPES IN THE GLIOMA MICROENVIRONMENT
Authors: Patrick Schupp, Michael Oldham
Journal: Neuro-Oncology (2020)

Abstract Adult low-grade gliomas generally progress to glioblastoma, a more aggressive CNS tumor with an extremely poor prognosis. Despite intensive efforts, numerous promising glioma therapies have failed to provide survival benefits. These failures reflect many factors, including intertumoral heterogeneity and immunosuppression by the tumor microenvironment (TME). We propose a novel approach to addresses these challenges through integrative deconvolution of bulk gene expression data generated from more than 5000 human gliomas and 7000 normal human brain samples. Inherent variation in the cellular composition and cellular activities of these samples allowed us to identify highly correlated modules of genes that represent specific cell types and cell states. By comparing gene coexpression modules in glioma vs. normal human brain, we have identified cell type-specific gene expression changes in the glioma TME that are highly reproducible. In contrast to single-cell methods, which sample only a fraction of the tumor tissue and fail to capture major nonmalignant cell-types, our results derive from billions of cells and thousands of individuals and are therefore highly robust. We find that a number of genes encoding cell-surface proteins are specifically up-regulated in immune and vascular cells of the glioma TME. Surprisingly, among those genes up-regulated in glioma vasculature are multiple members of the angiotensin pathway, suggesting non-canonical roles for these proteins in the glioma setting. We propose that these proteins may form a specific ‘zip code’ for glioma within the brain’s vasculature that can be targeted directly or by conjugation with existing drugs. More generally, our analytical approach has revealed reproducible gene expression changes in specific cell types of the glioma TME that provide more stable therapeutic targets than those that are expressed by genetically mutable malignant cells. We have also discovered novel, aberrantly coexpressed genes in microglia, oligodendrocytes, and astrocytes which we are testing in state-of-the-art human brain assembloid systems.