tbuckley/cabot-search huggingface dataset:
MBCL-50. DISMAL OUTCOME OF HIGH RISK MEDULLOBLASTOMA TREATED WITH CHEMOTHERAPY FIRST APPROACH IN MALAYSIA
Authors: Shiao Wei Quah, E J Abdul Rahman, H Mohd Ibrahim, Z Muda, I S Othman, M N Mohamed Unni, K Gunasagaran, M P Ang, C B Goh, K H Teh
Journal: Neuro-Oncology (2020)

Abstract INTRODUCTION Patients with high risk medulloblastoma are treated either with high dose chemotherapy or hyperfractionated radiotherapy. Both approaches are not feasible in resource-limited countries. POG9031 trial has reported favourable outcome for high risk medulloblastoma using standard chemotherapy and radiotherapy only. Hence, we have adopted the protocol using chemotherapy first approach due to logistical reasons. OBJECTIVE To review the outcome of children diagnosed with high risk medulloblastoma in Hospital Kuala Lumpur. METHODS Patients diagnosed with high risk medulloblastoma between January 2015 and June 2018 treated using the chemotherapy first approach as per POG9031 protocol were identified. Data was then extracted and analysed. RESULTS Nine patients were identified, 3 boys and 9 girls. Median age was 9.3 years (range 2.6 – 15.9 years). Median follow up for survivors are 3.6 years. Five patients (55.6%) had macroscopic metastatic disease at diagnosis. All patients had significant residual disease post-op. Only 3 patients are disease free till last follow up, giving a 3 years event free survival of 16%. Of the 6 patients who had relapsed, 4 have died, giving a 3 years overall survival of 46%. Patients with no metastasis at diagnosis (M0) fared better with 3 years event free survival of 38%, but 3 years event free survival for patients with macroscopic metastatic disease (M+) was 0%. CONCLUSION Outcome of children with high risk medulloblastoma treated with chemotherapy first approach was dismal.
Clinician Perspectives on Caring for Dying Patients During the Pandemic
Authors: Deborah J. Cook, Alyson Takaoka, Neala Hoad, Marilyn Swinton, France J. Clarke, Jill C. Rudkowski, Diane Heels-Ansdell, Anne Boyle, Felida Toledo, Brittany B. Dennis, Kirsten Fiest, Meredith Vanstone
Journal: Annals of Internal Medicine (2020)

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has affected the hospital experience for patients, visitors, and staff.
SURG-12. PAEDIATRIC BRAIN TUMOUR SURGERY: HOW CAN WE REPORT OUR SURGICAL OUTCOMES AND OPERATIVE MORBIDITY?
Authors: Mitchell Foster, Dawn Hennigan, Rebecca Greystone, Kirsten van Baarsen, Geraint Sunderland, Christopher Millward, Harishchandra Srinivasan, Deborah Ferguson, Teddy Totimeh, Barry Pizer, Conor Mallucci
Journal: Neuro-Oncology (2020)

Abstract OBJECTIVE Our objective was to quantify resection outcomes and operative morbidity in paediatric brain tumour surgery using existing scales, assessing their applicability. METHODS We investigated morbidity using the Clavien-Dindo (CD) scale and the Drake classification. All paediatric patients receiving a biopsy or craniotomy for an intracranial tumour in a single tertiary paediatric neurosurgery centre between January 2008 and December 2018 were studied. Complications up to day 30 post op were graded. RESULTS There were 459 operations: 92 biopsies and 367 craniotomies comprising 166 infratentorial and 292 supratentorial tumours. Median age was 9 years (56% male). The surgical goal was achieved or exceeded in 94% of cases. Thirty-day mortality was 1.31% with all deaths related to disease and none to surgical complications. The overall CD score was 1 in 10.9% of cases, 2 in 18.9%, 3A in 1.7%, 3B in 11.8%, and 4 in 1.1%. There was no operative morbidity in 54% of cases. Using the Drake classification, meningitis was seen in 3.92% of cases, seizures in 3.92%, neurological deficit (that persisted at 30 days) in 8.5%, CSF leak in 5.01%, wound infection in 1.96%, haemorrhage 1.75 %, shunt infection in 1.53%, shunt block in 0.65%, medical complications in 2.4%, and others in 3.05%. CONCLUSIONS This is the largest series presenting morbidity from paediatric brain tumour surgery, and the first to validate the CD scale. Our morbidity on the Drake scale was comparable with other series. There is a need to develop improved tools to quantify morbidity in this high-risk specialty.
Personalizing Treatment for Rectal Cancer
Authors: Noam VanderWalde, Axel Grothey
Journal: JAMA Network Open (2020)

Anup Kasi, MD, MPH; Saqib Abbasi, MD; Shivani Handa, MD; Raed Al-Rajabi, MD; Anwaar Saeed, MD; Joaquina Baranda, MD; Weijing Sun, MD
Human iPSC-Derived Cardiomyocytes of Peripartum Patients With Cardiomyopathy Reveal Aberrant Regulation of Lipid Metabolism
Authors: Martijn F. Hoes, Nils Bomer, Melanie Ricke-Hoch, Tristan V. de Jong, Karla F. Arevalo Gomez, Stefan Pietzsch, Denise Hilfiker-Kleiner, Peter van der Meer
Journal: Circulation (2020)
BIOM-36. THE UNIQUE METABOLOMICS BASED BIOMARKERS OF RESPONSE TO IMMUNOTHERAPY FOR GLIOBLASTOMA
Authors: Farhad Dastmalchi, Aida Karachi, Yusuf Mehkri, Ram Khattri, Matthew Merritt, Paul Kubilis, Duane Mitchell, Maryam Rahman
Journal: Neuro-Oncology (2020)

Abstract INTRODUCTION The adaptive immune response requires robust T cell proliferation and activation. These T cell changes are dependent on metabolic program shifts that can be measured using metabolomic analysis. The objective of this project was to identify a metabolomics profile to serve as a biomarker of response to immunotherapy for the treatment of brain tumors. METHODS GL261-gp100 tumor-bearing mice were received anti-PD1 or bone marrow-derived dendritic cell (DC) vaccine that was generated ex vivo. Urine samples were collected for Nuclear Magnetic Resonance (NMR) analysis. A more in-depth Sparse Partial Least Squares Discriminant Analysis (sPLS-DA) revealed global metabolic changes induced with immunotherapy. RESULTS The metabolic changes were most dramatic at 24 hours post DC vaccination and slowly returned to baseline at 7 days post DC vaccination. The main drivers of the differences included creatine, n-dimethyl glycine, alanine, lactate, glucose, glutamine, leucine, citrate and formate. Anti-PD1 therapy-related metabolic changes were largest around day 20 post therapy and the main drivers of the differences included dimethyl sulfone, succinate, lactate and isobutyrate. CONCLUSION Immunotherapy results in systemic metabolic changes that serve as a biomarker treatment effect. These findings have translational relevance in predicting patients who will develop an immune response to immunotherapy and ultimately have better outcomes with treatment.
Revisiting the Complexity of GLP-1 Action from Sites of Synthesis to Receptor Activation
Authors: Brent A McLean, Chi Kin Wong, Jonathan E Campbell, David J Hodson, Stefan Trapp, Daniel J Drucker
Journal: Endocrine Reviews (2020)

Abstract Glucagon-like peptide-1 (GLP-1) is produced in gut endocrine cells and in the brain, and acts through hormonal and neural pathways to regulate islet function, satiety, and gut motility, supporting development of GLP-1 receptor (GLP-1R) agonists for the treatment of diabetes and obesity. Classic notions of GLP-1 acting as a meal-stimulated hormone from the distal gut are challenged by data supporting production of GLP-1 in the endocrine pancreas, and by the importance of brain-derived GLP-1 in the control of neural activity. Moreover, attribution of direct vs indirect actions of GLP-1 is difficult, as many tissue and cellular targets of GLP-1 action do not exhibit robust or detectable GLP-1R expression. Furthermore, reliable detection of the GLP-1R is technically challenging, highly method dependent, and subject to misinterpretation. Here we revisit the actions of GLP-1, scrutinizing key concepts supporting gut vs extra-intestinal GLP-1 synthesis and secretion. We discuss new insights refining cellular localization of GLP-1R expression and integrate recent data to refine our understanding of how and where GLP-1 acts to control inflammation, cardiovascular function, islet hormone secretion, gastric emptying, appetite, and body weight. These findings update our knowledge of cell types and mechanisms linking endogenous vs pharmacological GLP-1 action to activation of the canonical GLP-1R, and the control of metabolic activity in multiple organs.
NIMG-20. MULTI-HABITAT RADIOMICS UNRAVELS DISTINCT PHENOTYPIC SUBTYPES OF GLIOBLASTOMA WITH CLINICAL AND GENOMIC SIGNIFICANCE
Authors: Seung Won Choi, Hwan-ho Cho, Harim Koo, Kyung rae Cho, Karl-Heinz Nenning, Georg Langs, Julia Furtner, Bernhard Baumann, Adelheid Woehrer, Hee Jin Cho, Doo-Sik Kong, Ho Jun Seol, Jung-il Lee, Do-Hyun Nam, Hyunjin Park
Journal: Neuro-Oncology (2020)

Abstract BACKGROUNDS We aimed to evaluate the potential of radiomics as an imaging biomarker for GBM patients and explore the molecular rationale behind radiomics by radio-genomics approach. METHODS A total of 144 primary GBM patients were included in this study as a training cohort. Using multi-parametric MR images, radiomics features were extracted from multi-habitats of the tumor. We applied Cox-LASSO algorithm to build a survival prediction model and validated this model using an independent validation cohort (56 patients from Vienna). With the selected radiomics features, GBM patients were consensus clustered to reveal inherent phenotypic subtypes. The subtypes were further explored in terms of genomic signatures. RESULTS GBM patients were successfully stratified by the radiomics risk score, a weighted sum of radiomics features, corroborating the potential of radiomics as a prognostic biomarker. Using consensus clustering, we identified three distinct subtypes which significantly differed in the prognosis (‘heterogenous enhancing’, ‘rim-enhancing necrotic’, and ‘cystic’ subtype). Multi-variate cox regression analysis confirmed that radiomics subtype as an independent prognostic factor. Transcriptomic traits enriched in individual subtypes were in accordance with imaging phenotypes summarized by radiomics. For example, rim-enhancing necrotic subtype was well described by radiomics profiling (T2 autocorrelation &amp; flat shape) and highlighted by the inflammatory genomic signatures, which well correlated to its phenotypic peculiarity (necrosis). CONCLUSIONS The present study confirmed the feasibility of radiomics as an imaging biomarker for GBM patients with comprehensible biologic annotation. Imaging subtypes derived from radiomics successfully recapitulate the genomic underpinnings of GBM tumors and in turn reinforce their potential as a prognostic biomarker.
NCOG-58. IMPACT OF TIME FROM PRESENTATION TO TREATMENT INITIATION ON CLINICAL OUTCOMES IN CENTRAL NERVOUS SYSTEM LYMPHOMA
Authors: Marissa Barbaro, Peter Pan, Sara Torres, Kiran Thakur, Mary Welch
Journal: Neuro-Oncology (2020)

Abstract OBJECTIVE To examine impact of time from presentation to treatment initiation (TPT) on clinical outcomes in a cohort of patients with central nervous system lymphoma (CNSL). INTRODUCTION Earlier work in our population found that multifocal disease, cerebrospinal fluid (CSF) sampling, and use of immunomodulatory therapies were associated with longer TPT in CNSL, but impact on clinical outcomes was not assessed. METHODS We retrospectively reviewed records of patients who were diagnosed with CNSL from 2010-2018 and treated at Columbia University Irving Medical Center (CUIMC). Regression models were applied to examine the impact of age, gender, response to methotrexate (MTX), use of radiation, and TPT &amp;gt;/= 30 days on survival 1 year from diagnosis (one-year survival), overall survival (OS), and functional independence (FI, defined as Karnofsky Performance Status (KPS) &amp;gt; 70). RESULTS There were sixty-nine patients (51% men; median age at diagnosis 70 years, range 21-90). Median TPT was 24 days (range 7-372). TPT was &amp;lt; 30 days in 59 (85%) and &amp;gt;/= 30 days in 10 (15%). One-year survival was 77%, and FI rate was 78%. Negative prognostic factors for OS were age &amp;gt; 65 years (HR 5.34, CI 1.20-24.30, p=0.03) and absence of complete response to MTX (HR 2.40, CI 0.87-6.69, p=0.09). Only complete response to MTX predicted both FI (OR 4.71, CI 1.17-19.02, p=0.03) and one-year survival (OR 6.77, CI 1.98-23.13, p=0.002). Notably, OS was numerically improved among patients with TPT &amp;gt;/= 30 days vs. &amp;lt; 30 days (HR 0.31, p=0.27), though this did not meet statistical significance. CONCLUSIONS Longer TPT has been associated with worse outcomes in systemic lymphoma, but such a correlation has not always been observed in brain cancers such as glioblastoma. We found no negative impact of longer TPT on survival or FI.
Somatic reversion of pathogenic DOCK8 variants alters lymphocyte differentiation and function to effectively cure DOCK8 deficiency
Authors: Bethany A. Pillay, Mathieu Fusaro, Paul E. Gray, Aaron L. Statham, Leslie Burnett, Liliana Bezrodnik, Alisa Kane, Winnie Tong, Chrystelle Abdo, Sarah Winter, Samuel Chevalier, Romain Levy, Cécile Masson, Yohann Schmitt, Christine Bole, Marion Malphettes, Elizabeth Macintyre, Jean-Pierre De Villartay, John B. Ziegler, Joanne M. Smart, Jane Peake, Asghar Aghamohammadi, Lennart Hammarström, Hassan Abolhassani, Capucine Picard, Alain Fischer, Sylvain Latour, Benedicte Neven, Stuart G. Tangye, Cindy S. Ma
Journal: Journal of Clinical Investigation (2020)

Inborn errors of immunity cause monogenic immune dysregulatory conditions such as severe and recurrent pathogen infection, inflammation, allergy, and malignancy. Somatic reversion refers to the spontaneous repair of a pathogenic germline genetic variant and has been reported to occur in a number of inborn errors of immunity, with a range of impacts on clinical outcomes of these conditions. DOCK8 deficiency due to biallelic inactivating mutations in DOCK8 causes a combined immunodeficiency characterized by severe bacterial, viral, and fungal infections, as well as allergic disease and some cancers. Here, we describe the clinical, genetic, and cellular features of 3 patients with biallelic DOCK8 variants who, following somatic reversion in multiple lymphocyte subsets, exhibited improved clinical features, including complete resolution of infection and allergic disease, and cure over time. Acquisition of DOCK8 expression restored defective lymphocyte signalling, survival and proliferation, as well as CD8+ T cell cytotoxicity, CD4+ T cell cytokine production, and memory B cell generation compared with typical DOCK8-deficient patients. Our temporal analysis of DOCK8-revertant and DOCK8-deficient cells within the same individual established mechanisms of clinical improvement in these patients following somatic reversion and revealed further nonredundant functions of DOCK8 in human lymphocyte biology. Last, our findings have significant implications for future therapeutic options for the treatment of DOCK8 deficiency.
Abstract 12916: Exosomal RNAS as Potential Biomarkers of Cardiovascular Risk in NASA Astronauts
Authors: David Goukassian, May Truongcao, Arsen Arakelyan, Paul Mills, Ken Walsh, Sankar Addya, Angela Evans, Mathew Coleman, Kenneth Fish, Roger J Hajjar, Raj Kishore, Venkata N Garikipati
Journal: Circulation (2019)

Introduction: During spaceflight, astronauts are exposed to stressors that have been linked to cardiovascular disease (CVD) associated morbidity and mortality. The molecular basis of spaceflight-in...
Renal Arterial Resistance Index
Authors: Lars Pape, Gisela Offner, Jochen H H Ehrich
Journal: New England Journal of Medicine (2003)

assert that the renal arterial resistance index is associated with the prognosis for renal-transplant recipients. This study raises methodologic issues. Survival data are defined in terms of the time from an initiating event (the time origin) to some terminal event. 2,3 The date of ultrasonography is a questionable time origin, since it is not a well-defined event; indeed, ultrasonography took place at a random date between 3 and 317 months after transplantation. In our opinion, the time origin should be closely related to the date of transplantation, which would uniformly define time relative to transplantation and provide a clear definition of patient subgroups (since the resistance index is time-dependent). If this approach is not taken, we suggest that survival data not be handled as binary data. Therefore, sensitivity, specificity, and receiver-operatingcharacteristic curves must not be estimated, except if ad hoc methods are used, 4 and survival rates must be derived from Kaplan–Meier curves and expressed as time-dependent percentages. In conclusion, because of these methodologic problems, the results of the study may be confounded.
RARE-59. CARDIAC REMODELING IN PATIENTS WITH CHILDHOOD-ONSET CRANIOPHARYNGIOMA – RESULTS OF HIT-ENDO AND KRANIOPHARYNGEOM 2000/2007
Authors: Panjarat Sowithayasakul, Leona Katharin Buschmann, Svenja Boekhoff, Hermann L Müller
Journal: Neuro-Oncology (2020)

Abstract BACKGROUND Hypothalamic obesity caused by childhood–onset craniopharyngioma results in long–term cardiovascular morbidity. Knowledge about clinical markers and risk factors is rare. PATIENTS AND METHODS A cross–sectional study on transthoracic echocardiographic parameters was performed to determine the associations with clinical and anthropometric parameters in 36 patients with childhood-onset adamantinomatous craniopharyngioma. RESULTS Body mass index (BMI) correlated with the thickness of interventricular septum in diastole (IVSd) (r=0.604, p&amp;lt;0.001) and left ventricular diastolic posterior wall in diastole (LVPWd) (r=0.460, p=0.011). Due to wide range of disease duration, 17 pediatric and 19 adult patients were analyzed separately. In the adult subgroup (age at study ≥18 years), BMI correlated with IVSd (r=0.707, p=0.003), LVPWd (r=0.592, p=0.020) and left ventricular internal diameter in diastole (LVIDd) (r=0.571, p=0.026). In the pediatric subgroup (age at study &amp;lt;18 years), no correlation between cardiac parameters and BMI was observed. Only LVIDd correlated with disease duration (r=0.645, p&amp;lt;0.001). All cardiac functions were within the normal range, indicating no association with severe functional impairments. CONCLUSIONS Cardiac remodeling in patients with childhood-onset craniopharyngioma correlates with the degree of hypothalamic obesity and disease duration. However, echocardiography has limited sensitivity in craniopharyngioma patients with obesity, so cardiac magnetic resonance imaging (MRI) should be considered as an alternative diagnostic approach for patients with craniopharyngioma and hypothalamic obesity.
Refining the Baveno VI elastography criteria for the definition of compensated advanced chronic liver disease
Authors: Margarita Papatheodoridi, Jean Baptiste Hiriart, Monica Lupsor-Platon, Fabrizio Bronte, Jerome Boursier, Omar Elshaarawy, Fabio Marra, Maja Thiele, Georgios Markakis, Audrey Payance, Edgar Brodkin, Laurent Castera, George Papatheodoridis, Aleksander Krag, Umberto Arena, Sebastian Mueller, Paul Cales, Vincenza Calvaruso, Victor de Ledinghen, Massimo Pinzani, Emmanuel A. Tsochatzis
Journal: Journal of Hepatology (2020)
STEM-04. PLATELETS DRIVE GLIOBLASTOMA ONCOGENESIS BY ENHANCING THE GLIOMA STEM CELL PHENOTYPE
Authors: Anthony Sloan, Christine Lee-Poturalski, Theresa Elder, Peggy Harris, Gino Cioffi, Alankrita Raghavan, John Willis, Jeremy Rich, Amber Kerstetter-Fogle, Jill S Barnholtz-Sloan, Eckhard Jankowsky, Andrew E Sloan
Journal: Neuro-Oncology (2020)

Abstract Glioblastoma (GBM) is recognized as one of the deadliest forms of cancer, despite aggressive therapy consisting of maximal surgical resection followed by concurrent radiation and chemotherapy, the median survival remains ~12 months. Glioma stem cells (GSCs) possess potent tumor-initiating properties and comprise a cellular hierarchy that is responsible for treatment resistance and progression. Specifically targeting GSCs has been considered a promising therapeutic approach, however no clear method has been identified. Histologically, it is known that GSCs are found in perivascular and pseudsopalisading regions of GBM. Similarly, platelet aggregates are often found in pseudsopalisading necrotic regions, suggesting a potential interaction between platelets and GSCs due to their spatial locations. High platelet counts have been associated with poor clinical outcome in many cancers including ovarian and endometrial cancer. While platelets are known to affect progression of other tumors, mechanisms by which platelets influence GBM oncogenesis are unknown. Our work aimed to understand the crosstalk between GSCs and platelets within GBM solid tumors that work to enhance disease progression and treatment resistance. Our clinical studies suggest elevated platelet counts positively correlate with tumor growth and negatively correlate to overall patient survival. We found platelets and GSC co-localization in GBM solid tissue; platelet exposure to GSCs results in increased proliferation of GSCs specifically, by increasing the self-renewing capacity of GSCs in a dose dependent manner, and resulted in an increased “Stem-like” transcriptional pattern. Inhibiting the GSC-platelet interaction results in a decrease in GSC renewal and stemness. These results introduce a novel interaction between GSCs and platelets and elucidate a novel therapeutic approach specifically targeting GSCs by disrupting the GSC-platelet interaction.
Connecting the Dots: The Relevance of Scar in Nonischemic Cardiomyopathy**Editorials published in the Journal of the American College of Cardiologyreflect the views of the authors and do not necessarily represent the views of JACCor the American College of Cardiology.
Authors: Alan H. Kadish, Jason C. Rubenstein
Journal: Journal of the American College of Cardiology (2009)
EPEN-49. RESPONSE OF RECURRENT EPENDYMOMA TO MEMMAT BASED METRONOMIC ANTIANGIOGENIC COMBINATION THERAPY UTILIZING TAPERED BEVACIZUMAB AND MAINTENANCE THERAPY WITH CELECOXIB AND FENOFIBRATE
Authors: Eileen Gillan
Journal: Neuro-Oncology (2020)

Abstract Recurrent ependymomas have a dismal prognosis (2 year survival rates 29% OS and 23% EFS) and are relatively resistant to conventional chemotherapy. We previously reported five relapsed ependymoma patients treated with a MEMMAT based metronomic antiangiogenic combination therapy. All patients are currently alive, including four patients who were multiply relapsed with at least three recurrences. These four patients received between 44–52 weeks of therapy with minimal toxicity. Three had recurrent disease within an average of 44 months (median 42 months) after discontinuation of therapy. One patient who received the following tapering bevacizumab schedule: q3 weeks x 3, q4 weeks x 4 and q5 weeks x 5 followed by maintenance therapy with fenofibrate and celecoxib is in complete remission 12 months post treatment. This regimen was well tolerated with good quality of life in this patient population. Our results suggest that the chosen anti-angiogenic drug combination prolonged the time to progression in these multiply relapsed patients and thus may be particularly beneficial for patients with recurrent ependymoma. Tapered bevacizumab and maintenance therapy with celecoxib and fenofibrate may be modifications worth further investigation for prolonged disease free survival in relapsed ependymoma patients.