tbuckley/cabot-search huggingface dataset:
EPID-22. IMPROVED SHORT-TERM OUTCOMES AND LONG-TERM SURVIVORSHIP IN RELATION TO IMMUNOTHERAPY FOR PATIENTS WITH GLIOBLASTOMA BASED ON ANALYSIS OF THE NATIONAL CANCER DATABASE (NCDB)
Authors: Ping Zhu, Xianglin Du, Nitin Tandon, Yoshua Esquenazi, Jay-Jiguang Zhu
Journal: Neuro-Oncology (2021)

Abstract OBJECTIVES To explore the impact of immunotherapy on short-term outcomes and long-term survival rates, and the predictors of immunotherapy receipt in patients with glioblastoma (GBM) using NCDB. METHODS A total of 74245 GBM patients were derived from the NCDB from 2004 to 2014. Analyses include short-term outcomes (at least 6-month, 1-year, or 2-year after diagnosis) and long-term survivorship (at least 3-year). The Kaplan-Meier method and accelerated failure time (AFT) models were performed for survival analysis. The multivariable binary logistic regressions were applied to identify predictors of immunotherapy receipt. Random survival forest was conducted to validate the variable importance and decision tree as well. RESULTS A total of 766 (1.0%) GBM patients received immunotherapy as the first-line treatment. The multivariable binary logistic regressions identified the significant predictors related to immunotherapy receipt, including the recent years of diagnosis (especially 2013 and 2014), age &amp;lt; 65 years, higher income, private insurance, residence-hospital distance &amp;gt;50 miles, care transition, treatment at the facility located in South regions or academic facilities, and adjuvant therapy. After adjusting socio-demographics, facility characteristics, and clinical treatments (surgery and adjuvant therapy), patients received immunotherapy experienced the significantly prolonged OS compared to those who didn’t [OS (months): 16.0 vs. 9.8, log-rank test p-value: &amp;lt; 0.001; Time Ratio (TR): 1.26 vs. 1.00 (Ref.), multivariable AFT p-value: &amp;lt; 0.001]. In multivariable logistic regressions, compared to patients without immunotherapy, the likelihoods of 6-month (OR: 3.89, p&amp;lt; 0.001), 1-year (OR: 2.38, p&amp;lt; 0.001), and 2-year (OR: 1.58, p=0.001) survival rates were significantly increased for those received immunotherapy. Regarding the long-term survivorship, immunotherapy was significantly associated with a 68% higher likelihood of 3-year survival rate (p=0.004). CONCLUSIONS Our findings demonstrated that immunotherapy in GBM patients, albeit small sample size, was significantly associated with improved short-term outcomes and 3-year survivorship after adjusting traditional clinical treatments and other covariates.
Abstract 12260: Whole Exome Molecular Autopsy With Copy Number Variant Analysis of Multiple Autopsy Negative Sudden Unexplained Deaths Among Amish Siblings Yields the Discovery of a Novel Homozygous Multi-exon Duplication in the Ryr2-Encoded Ryanodine Receptor
Authors: David J Tester, Hannah M Bombei, Kristi K Fitzgerald, John Giudicessi, Beth A Pitel, Erik C Thorland, Barbara Russell, Samantha K Hamrick, CS John Kim, Carla M Haglund-Turnquist, Christopher Johnsrude, Dianne L Atkins, Luis A Ochoa, Ian H Law, Joel Temple, Michael J Ackerman
Journal: Circulation (2019)

Background: The whole exome molecular autopsy (WEMA) may elucidate a pathogenic substrate for sudden unexplained death in the young (SUDY). We combined the WEMA with copy number variant (CNV) analy...
Abstract P394: Angiotensin-(1-7) Attenuates Diastolic Dysfunction And Cardiac Remodeling In Murine Model Of Heart Failure With Preserved Ejection Fraction
Authors: Pariya Edalat, Karina Gomes, Noura N Ballasy, Anshul S Jadli, Darrell D Belke, Vaibhav B Patel
Journal: Circulation Research (2021)

Background: Heart failure with preserved ejection fraction (HFpEF) is a global public health epidemic that accounts for half of the heart failure cases. Various therapeutic approaches have been tested to block the activation of the Renin-Angiotensin System (RAS), including AT1R blockers (ARBs), Angiotensin-Converting Enzyme (ACE) inhibitors (ACEi), and direct renin inhibitors (DRIs) with modest to negligible benefits. The discovery of ACE2, a novel homolog of ACE, has advanced our understanding of the RAS. ACE2 is a monocarboxypeptidase that degrades Ang II into Ang-(1-7), which works via the activation of the Mas receptor. It has been well understood that the actions of Ang-(1-7) attenuate cardiac remodeling, production of ROS, and cardiac fibrosis. Objective: To determine the therapeutic role of Ang-(1-7) in HFpEF and identify the molecular mechanism related to its action. Methods and Results: To generate a murine model of HFpEF, male WT mice (n=24) were subjected to HFD in addition to eNOS inhibition with L-NAME (0.5 g l-1 in drinking water), as previously described. The control group (n=12) received chow diet and normal tap water. The murine model of HFpEF was validated using the non-invasive transthoracic echocardiography and invasive pressure-volume (PV) loop analyses, which exhibited diastolic dysfunction as well as cardiac hypertrophy. To evaluate the effects of Ang-(1-7) on HFpEF, animals were administered with either saline (n=12) or Ang-(1-7) (n=12) (24 μg/kg/day) for four weeks. Ang-(1-7) treatment improved diastolic function by reducing LVEDP (Ctrl: 8.267±1.254; HFD+L-NAME: 17.64±1.925; Ang-(1-7): 9.100±1.578) and Tau value (Ctrl: 7.365±0.5752; HFD+L-NAME: 9.224±0.3569; Ang-(1-7): 7.381±0.3041). Furthermore, Ang-(1-7) reduced cardiac hypertrophy by reducing the phosphorylation level of MAPK ERK 1/2 (Ctrl: 0.9074±0.1088; HFD+L-NAME: 1.212±0.1369; Ang-(1-7): 0.5615±0.1502) and increasing the phosphorylation level of AMPK (Ctrl: 0.1502±0.1502; HFD+L-NAME: 0.6127±0.06414; Ang-(1-7): 0.7852±0.1006). Ang-(1-7) treatment also reduces cardiomyocytes’ size and decreases interstitial fibrosis, as indicated by WGA and PSR staining. Conclusion: Ang-(1-7) treatment attenuated the development of HFD+L-NAME-induced HFpEF, reduced cardiac hypertrophy, and improved metabolic function.
The Impact of Somatic Mutations on Allogeneic Hematopoietic Cell Transplantation in Chronic Myelomonocytic Leukemia: A Center for International Blood and Marrow Transplant Research (CIBMTR) Analysis
Authors: Matthew Mei, Raju Pillai, Soyoung Kim, Noel Estrada-Merly, Michelle Afkhami, Lixin Yang, Zhuo Meng, Ronald M. Sobecks, Betul Oran, Bart L. Scott, Wael Saber, Ryotaro Nakamura
Journal: Blood (2021)
Health Status and Cardiac Rehabilitation—Putting a Dollar Amount on Improvement
Authors: Paul A. Heidenreich
Journal: JAMA Cardiology (2021)

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CTNI-30. A SNAPSHOT OF “REAL WORLD” CURRENT NEURO-ONCOLOGY PRACTICE IN TEN UK CENTRES AND RATIONALE FOR THE TESSA JOWELL BRAIN MATRIX (TJBM) PLATFORM STUDY
Authors: Victoria Wykes, John Apps, Joshua Savage, Sara Meade, Ute Pohl, Vijay Sawlani, Amit Patel, Lucinda Billingham, Gerard Thompson, Adam Waldman, Olaf Ansorge, Colin Watts
Journal: Neuro-Oncology (2021)

Abstract OVERVIEW The TJBM Platform Study (https://www.birmingham.ac.uk/research/crctu/trials/brain-matrix) is a programme of work aimed at improving the knowledge of, and treatment for, glioma. We present the feasibility data collected from the initial ten UK centres. METHOD The UK TJBM centres completed a multi-disciplinary feasibility questionnaire to facilitate participation and collaboration across centres. Data were collected from hospital electronic board review records, clinic letters, operative and imaging notes, MDT or personal experience. RESULTS Work load: Between 2016-2018 service provision redistribution reflects a trend towards higher volume centres. Overall, glioma workload within ten TJBM centres has remained stable. Imaging: All TJBM centres have good access to imaging techniques and neuroradiology expertise, including relevant ‘advanced’ imaging. All have RANO capability, although not widely used clinically. Neurosurgery: All centres have access to 5 ALA, perform awake craniotomy for language assessment and motor/sensory mapping are typically performed asleep, with subtle variation in techniques. Pathology: Despite molecular analysis advances, current practice is limited to the evaluation of formalin embedded tissue by traditional morphology/ immunohistochemically staining, with limited targeted testing of specific genetic changes. Clinical oncology: Oncology treatments for glioma were as per NICE guidance with some minor local variation. A relative lack of linking treatments to detailed clinical, treatment, toxicity, and quality of life data making communication of significance of findings to patients challenging. CONCLUSION Through systematic real-world data collection the TJBM platform study will provide a detailed understanding of practice within the UK, linked to molecular tumour genotype, treatment response outcome measures, and regular quality of life assessments. This infrastructure will help establish a trial-competent network for future collaborative research. Academic and industry partners will be able to use the TJBM platform through collaboration, overseen by a strong governance framework. This will maximise the opportunities and abilities to translate advances into trials and patient benefit.
NIMG-35. MACHINE LEARNING GLIOMA GRADE PREDICTION LITERATURE: A TRIPOD ANALYSIS OF REPORTING QUALITY
Authors: Sara Merkaj, Ryan Bahar, W R Brim, Harry Subramanian, Tal Zeevi, Eve Kazarian, Ming Lin, Khaled Bousabarah, Sam Payabvash, Jana Ivanidze, Jin Cui, Irena Tocino, Ajay Malhotra, Mariam Aboian
Journal: Neuro-Oncology (2021)

Abstract PURPOSE Reporting guidelines are crucial in model development studies to ensure the quality, transparency and objectivity of reporting. While machine learning (ML) models have proven themselves effective in predicting glioma grade, their potential use can only be determined if they are clearly and comprehensively reported. Reporting quality has not yet been evaluated for ML glioma grade prediction studies, to our knowledge. We measured published literature against the TRIPOD Statement, a checklist of items considered essential for the reporting of diagnostic studies. MATERIALS AND METHODS A literature review, in agreement with PRISMA, was conducted by a university librarian in October 2020 and verified by a second librarian in February 2021 using four databases: Cochrane trials (CENTRAL), Ovid Embase, Ovid MEDLINE, and Web of Science core-collection. Keywords and controlled vocabulary included artificial intelligence, machine learning, deep learning, radiomics, magnetic resonance imaging, glioma, and glioblastoma. Publications were screened in Covidence and scored against the 27 items in the TRIPOD Statement that were relevant and applicable. RESULTS The search identified 11,727 candidate articles with 1,135 articles undergoing full text review. 86 articles met the criteria for our study. The mean adherence rate to TRIPOD was 44.4% (range: 22.2% - 66.7%), with poor reporting adherence in categories including abstract (0%), model performance (0%), title (1.2%), justification of sample size (2.3%), full model specification (2.3%), participant demographics and missing data (7%). Studies had high reporting adherence in categories including results interpretation (100%), background (98.8%), study design/source of data (96.5%), and objectives (95.3%). CONCLUSION Existing publications on the use of ML in glioma grade prediction have a low overall quality of reporting. Improvements can be made in the reporting of titles and abstracts, justification of sample size, and model specification and performance.
Covid-19 and violence against women and children: time to mitigate the shadow pandemic
Authors: Helga Fogstad, Etienne V Langlois, Teesta Dey
Journal: BMJ (2021)

Covid-19 has highlighted the urgency of addressing violence against women and children, which reports suggest has increased during the pandemic.Often referred to as a "shadow pandemic," 1 the rise in violence over the past two years has been linked to lockdowns and other restrictions on movement put in place due to covid-19, which force women and children to remain at home with their abusers.
Abstract 11666: Who Could Return To Their Former Lifestyle In Comatose Survivors Of Cardiac Arrest With Asystole?
Authors: Eisuke Kagawa, Masaya Kato, Noboru Oda, Michiaki Nagai, Keigo Dote
Journal: Circulation (2021)

Introduction: In patients with initial shockable rhythms had favor outcomes than those with non-shockable rhythms, and those of asystole had worst outcomes. Purpose: The purpose of the study is to investigate the predictors of favorable outcomes in specific in the asystole rhythms. Method: Patients who were resuscitated after out-of-hospital cardiac arrest and were underwent targeted temperature management were enrolled in this study. Patients were divided into 3 groups according to initial recorded rhythms after indexed cardiac arrest. Favorable outcomes were defined as cerebral performance category of 1 or 2 after 90 days of indexed cardiac arrest. The logistic regression analysis was performed to assesses independent predictor of favorable outcomes. Results: Among the 305 study patients, 57 (19%) patients had initially recorded asystole rhythms, 149 (49%) patients had shockable rhythms, and 99 (32%) patients had pulseless electrical activity (PEA). The patients of PEA were elder (median 62 y [interquartile range 49 y - 72 y], 65 [57 - 75], and 62 [49 - 74], P = 0.03 in the patients of shockable, PEA, and asystole), the rate of male was higher in the shockable (86%, 58%, and 72%, P &lt; 0.001), the time interval from collapse to return of spontaneous circulation (ROSC) were longer in the asystole (28 min [17 - 48], 37 [24 - 53], and 46 [39 - 61], P &lt; 0.001), and the lactate of hospital arrival were higher in the asystole (10.1 mmol/l [6.1 mmol/l - 13.6 mmol/l], 12.0 [8.6 - 15.4], and 13.3 [9.6 - 18.3], P = 0.002). The rate of acute coronary syndrome as the cause of arrest were similar between the groups (45%, 34%, and 28%, P = 0.06). The rate of favorable outcome was 53%, 21%, and 12% (P &lt; 0.001), respectively. The time interval from collapse to ROSC were independently associated with favorable outcomes in the patients of all initial recorded rhythms. Conclusions: The cardiac arrest patients who were witnessed arrest or shorter interval from collapse to ROSC with initial recorded asystole rhythms had favor outcomes than those not. We could not find specific predictors in the patients with asystole.
Characterization of gut microbial structural variations as determinants of human bile acid metabolism
Authors: Daoming Wang, Marwah Doestzada, Lianmin Chen, Sergio Andreu-Sánchez, Inge C.L. van den Munckhof, Hannah E. Augustijn, Martijn Koehorst, Angel J. Ruiz-Moreno, Vincent W. Bloks, Niels P. Riksen, Joost H.W. Rutten, Leo A.B. Joosten, Mihai G. Netea, Cisca Wijmenga, Alexandra Zhernakova, Folkert Kuipers, Jingyuan Fu
Journal: Cell Host & Microbe (2021)
CSIG-25. BAI1/ADGRB1 REGULATES TGFβ1-INDUCED MESENCHYMAL SWITCH IN MEDULLOBLASTOMA
Authors: Satoru Osuka, Liquan Yang, Dan Zhu, Hideharu Hashimoto, Erwin G Van Meir
Journal: Neuro-Oncology (2021)

Abstract Medulloblastoma (MB) is the most common malignant brain tumor in children. MB tends to metastasize to the brain meninges and subarachnoid space and the spinal cord. Leptomeningeal metastasis is frequently found at initial diagnosis and leads to tumor relapse after standard treatment. Leptomeningeal metastasis remains a major challenge and is related with poor outcome. Acquiring a better knowledge of molecular defects underlying metastatic disease is essential for the development of effective therapies. Brain-specific Angiogenesis Inhibitor 1 (BAI1/ADGRB1) is a transmembrane receptor of the adhesion GPCR family widely expressed in normal brain, but its expression is lost in the majority of medulloblastoma through epigenetic silencing. We reported that BAI1 protects p53 from Mdm2-mediated degradation and regulate tumor growth in medulloblastoma (Zhu D. et al, Cancer Cell, 2018). However, it is unclear whether BAI1 loss is important for tumor invasion and the mesenchymal phenotype in MB. Microarray analysis of the published MB dataset revealed that low BAI1 mRNA expression correlates with poor outcome and with expression of many key mesenchymal genes, including Fibronectin1, SLUG, and TWIST1. Restoration of BAI1 expression in human MB cells suppresses mesenchymal gene expression in culture, and dramatically decreases brain tumor invasion. Mechanistically, we found that the N-terminal thrombospondin type 1 repeat (TSR#1) of BAI1 inhibits the maturation process of TGFβ1, a key growth factor involved in EMT. BAI1 is silenced epigenetically in MB cells by methylated CpG-binding protein MBD2, and its expression can be reactivated by KCC-07, a blood-brain barrier permeable MBD2 inhibitor. We found that restoration of BAI1 expression by KCC-07 treatment dramatically reduced tumor cell invasion of MB cells. These experiments demonstrate that epigenetic silencing of BAI1 is important for activation of the MB invasive phenotype through TGFβ1 pathway activation. Epigenetic targeting of this process by KCC-07 can reduce MB invasion.
Analyzing the impact of pregnancy on the outcomes of childbearing age women with chronic myeloid leukemia
Authors: Fernanda Maria Santos, Giovanna Ghelfond, Fernanda Salles Seguro, Andre Neder R. Abdo, Thales Dalessandro, Felipe Vieira R. Maciel, Lucas Bassolli, Vanderson Rocha, Israel Bendit
Journal: American Journal of Hematology (2021)
Mantle Cell Lymphoma: Updates in the Management of Relapsed/Refractory Disease
Authors: Mazyar Shadman
Journal: Journal of the National Comprehensive Cancer Network (2021)

Mantle cell lymphoma remains incurable despite recent treatment advances, and most patients experience relapsed/refractory disease. BTK inhibitors are the preferred choice in the relapsed setting, especially in patients with early relapse. For patients with high-risk features such as TP53 mutation, early referral for CAR T-cell therapy should be considered, even in those with stable disease on a BTK inhibitor. Patients without high-risk features may be monitored and initiate CAR T-cell therapy after clinical disease progression. CAR T-cell therapy is an effective treatment with high rate of complete remissions. For patients who do not achieve a complete remission 3 months after CAR-T therapy, bridging therapy with chemotherapy or targeted therapy agents and referral for allogeneic transplant are recommended.
Abstract 9609: Pioneering Cardiac Radioablation With the Use of an MRI Linear Accelerator. Can We Use a Gamma Knife <i> <sup>®</sup> </i> to the Heart as We Do in the Brain?
Authors: Robert W Biederman, Emerson Liu, Danny Lee, Seungjong Oh, Daniel Pavord, Mark Trombetta, Martin Fast, Tom Colonias, Joost Verhoeff, Mark Doyle, George Shaw, Amit Thosani, David Parda, Jason Sohn
Journal: Circulation (2021)

Introduction: VT is often refractory to medical therapy and on rare but critical cases, even EP ablation. Despite investigation into endocardial, mesocardial and occasionally even epicardial ablation for these recalcitrant and deadly arrhythmias, there remains an inability to more effectively, non-invasively, treat VT. Hypothesis: We propose that, paralleling a Gamma Knife ® approach, the use of a novel MRI linear accelerator (MR Linac), the Unity ® (Elekta AB, Stockholm, Sweden), a proof of concept could be applied to highly selected pts with obstinate VT. Methods: A multi-center team with EP, Radiation Oncology and CMR (GE 1.5T) in joint development with Pittsburgh, PA and Utrecht, The Netherlands, developed a completely EP-CMR-guided method for non-invasive VT ablation utilizing S tereo T actic A rrhythmia R adioablation (STAR) with 25 Gy in a single fraction via MR Linac. Results: To evaluate deliverability and applicability of MR Linac plans, four IMRT per clinical scan were developed with varying delivery parameters (7A: 7-beams: 52 o in 70 segments (seg), 7B: 7-beams: 52 o in 100 seg, 15A: 15-beams: 24 o in 70 seg, and 15B: 15-beams: 24 o in 100 seg). We used a 0.2 cm dose grid and a 1% uncertainty via Monte Carlo ® dose calculation. Pt specific QA/QC used ArcCHECK ® (Sun Nuclear, FL) to evaluate individual IMRT plans. 3D CMR with LGE scar fusion for lesion integration guided non-invasive MR LinAc ablation. Accordingly, all IMRT plans were clinically acceptable (&gt;97% of 7-beams and ≥98.0% of 15-beams in 3%/3mm gamma) for MR LinAc VT-ablation successfully with pt target effective arrhythmogenic myocardial ROI volume as ascertained via CMR of 63-99cm 3 . All 4 pts tolerated the 25±5min procedure without esophageal, pericardial or pro-arrhythmic complications and were alive at 30d FU with marked attenuation of VT burden. At 30d FU, no SAE's occurred to include pro-arrhythmias, pericardial effusions or esophageal fistulas. Conclusions: Refractory, complex and anatomically endocardially-remote VT has the potential to be curative, incorporating an analogous Gamma Knife ® approach via MR Linac radioablation heralding a migration to the Unity ® platform. This nearly first-in-man p r oof of concept approach may shepherd a new methodologic era into heretofore intractable VT.