tbuckley/cabot-search huggingface dataset:
Primary angioplasty versus intravenous thrombolysis in acute myocardial infarction: can we define subgroups of patients benefiting most from primary angioplasty?: Results from the pooled data of the maximal individual therapy in acute myocardial infarction registry and the myocardial infarction registry11The individuals and institutions that participated in the MITRA and MIR studies are listed elsewhere (see references 19and 20).
Authors: Ralf Zahn, Rudolf Schiele, Steffen Schneider, Anselm K Gitt, Harm Wienbergen, Karlheinz Seidl, Thomas Voigtländer, Martin Gottwik, Gunther Berg, Ernst Altmann, Werner Rosahl, Jochen Senges
Journal: Journal of the American College of Cardiology (2001)
Factors associated with complete clip closure after endoscopic mucosal resection of large colorectal polyps
Authors: Heiko Pohl, Maria Pellisé, Oswaldo Ortiz, Douglas K. Rex, Ian S. Grimm, Matthew T. Moyer, Muhammad K. Hasan, Douglas Pleskow, B. Joseph Elmunzer, Mouen A. Khashab, Omid Sanaei, Firas H. Al-Kawas, Stuart R. Gordon, Abraham Mathew, John M. Levenick, Harry R. Aslanian, Fadi Antaki, Daniel von Renteln, Seth D. Crockett, Amit Rastogi, Jeffrey A. Gill, Ryan Law, Michael B. Wallace, Pooja A. Elias, Todd A. MacKenzie
Journal: Endoscopy (2020)

Abstract Background and study aim Delayed bleeding is a common adverse event following endoscopic mucosal resection (EMR) of large colorectal polyps. Prophylactic clip closure of the mucosal defect after EMR of nonpedunculated polyps larger than 20 mm reduces the incidence of severe delayed bleeding, especially in proximal polyps. This study aimed to evaluate factors associated with complete prophylactic clip closure of the mucosal defect after EMR of large polyps. Methods This is a post hoc analysis of the CLIP study (NCT01936948). All patients randomized to the clip group were included. Main outcome was complete clip closure of the mucosal resection defect. The defect was considered completely closed when no remaining mucosal defect was visible and clips were less than 1 cm apart. Factors associated with complete closure were evaluated in multivariable analysis. Results In total, 458 patients (age 65, 58 % men) with 494 large polyps were included. Complete clip closure of the resection defect was achieved for 338 polyps (68.4 %); closure was not complete for 156 (31.6 %). Factors associated with complete closure in adjusted analysis were smaller polyp size (odds ratio 1.06 for every millimeter decrease [95 % confidence interval 1.02–1.08]), good access (OR 3.58 [1.94–9.59]), complete submucosal lifting (OR 2.28 [1.36–3.90]), en bloc resection (OR 5.75 [1.48–22.39]), and serrated histology (OR 2.74 [1.35–5.56]). Conclusions Complete clip closure was not achieved for almost one in three resected large nonpedunculated polyps. While stable access and en bloc resection facilitate clip closure, most factors associated with clip closure are not modifiable. This highlights the need for alternative closure options and measures to prevent bleeding.
LGG-06. LONG-TERM OUTCOME OF NEWLY DIAGNOSED LOW GRADE GLIOMA
Authors: Nongnuch Sirachainan, Attaporn Boongerd, Samart Pakakasama, Usanarat Anurathapan, Ake Hansasuta, Duantida Songdej, Pongpak Pongpicha, Mantana Dhanachai, Suradej Hongeng
Journal: Neuro-Oncology (2020)

Abstract INTRODUCTION Low grade glioma (LGG) is the most common central nervous system (CNS) tumor in children accounted for 30–50%. Regarding benign characteristic of disease, surgical management remains the mainstay of treatment. However, surgical approach is limited in some conditions such as location at brainstem or infiltrative tumor. Chemotherapy and radiation treatments have been included in order to control tumor progression. The 5-years survival rate is approach 90% especially in patients who receive complete resection. However, the outcome of children with LGG in low to middle income is limited. Therefore, the aim of the study was to determine long-term outcome of children with newly diagnosed LGG. METHODS A retrospective study enrolled children aged &amp;lt;18 years who were newly diagnosed LGG during January 2006- December 2019. Diagnosis of LGG was confirmed by histological findings of grade I and II according to WHO criteria. RESULTS A total of 40 patients, female to male ratio was 1:1.35 and mean (SD) for age was 6.7 (4.0) years. The most common location was optic chiasmatic pathway (42.5%), followed by suprasellar region (25.0%). Sixty percent of patients received at least partial tumor removal. Chemotherapy and radiation had been used in 70% and 10.0% respectively. The 10-year progression free survival was 74.1±11.4% and overall survival was 96.2±3.8%. SUMMARY: Treatment of Pediatric LGG mainly required surgical management, however, chemotherapy and radiation had been used in progressive disease. The outcome was excellent.
EPID-29. CAUSES OF DEATH FOR PRIMARY BRAIN AND CNS TUMOR PATIENTS IN THE UNITED STATES (2001 – 2016): A POPULATION BASED STUDY
Authors: Maria Penuela, Nirav Patil, Gino Cioffi, Carol Kruchko, Jill S Barnholtz-Sloan
Journal: Neuro-Oncology (2020)

Abstract BACKGROUND Population-based data on the various causes of death among Primary Brain and CNS tumor patients are lacking. We evaluated the causes of death for all eligible patients using the National Program of Cancer Registries (NPCR) data. METHODS The population-based cancer survival data collected by the Centers for Disease Control and Prevention’s National Program of Cancer Registries (NPCR) were used to analyze the causes of death for patients of all ages with primary brain and CNS tumors diagnosed between 2001 and 2016. Patients for whom the cause of death was not listed on the death certificate or whose state death certificate was not available were excluded. Additional analyses to identify factors associated with brain tumor-specific mortality for the most common malignant (Glioblastoma) and non-malignant (Meningioma) were performed using univariable and multivariable logistic regression analysis. RESULTS Major cause of death for patients with malignant tumors was death due to brain and other CNS tumors (49.29%), and for non-malignant tumors were other benign and malignant tumors (31.5%) and heart disease (17.9%). Overall mortality was 36.4% (n=331,953) in patients with Primary Brain and CNS Tumors during the study period. Specifically, 163,621 (49.29%) patients died due to brain and other CNS tumors. A significant proportion of patients with malignant tumors had brain tumor-specific mortality compared to non-malignant tumors (75.4% in malignant vs 4.2% in non-malignant). The factors associated with brain specific mortality in Glioblastoma patients were Age (p&amp;lt; 0.001), Race (p&amp;lt; 0.001) and Primary Site (p&amp;lt; 0.001). Further, the factors associated with brain specific mortality in Non-malignant Meningioma patients were Age (p&amp;lt; 0.001), Sex (p&amp;lt; 0.001), Race (p&amp;lt; 0.001) and Primary Site (P&amp;lt; 0.001). CONCLUSION Cause of death attributed to the brain tumor was significantly higher in malignant brain tumors compared to non-malignant brain tumors.
Inhibition of miR-331-3p and miR-9-5p ameliorates Alzheimer's disease by enhancing autophagy
Authors: Meng-Lu Chen, Chun-Gu Hong, Tao Yue, Hong-Ming Li, Ran Duan, Wen-Bao Hu, Jia Cao, Zhen-Xing Wang, Chun-Yuan Chen, Xiong-Ke Hu, Ben Wu, Hao-Ming Liu, Yi-Juan Tan, Jiang-Hua Liu, Zhong-Wei Luo, Yan Zhang, Shan-Shan Rao, Ming-Jie Luo, Hao Yin, Yi-Yi Wang, Kun Xia, Si-Yuan Tang, Hui Xie, Zheng-Zhao Liu
Journal: Theranostics (2020)

Alzheimer's disease (AD) is currently ranked as the third leading cause of death for eldly people, just behind heart disease and cancer. Autophagy is declined with aging. Our study determined the biphasic changes of miR-331-3p and miR-9-5p associated with AD progression in APPswe/PS1dE9 mouse model and demonstrated inhibiting miR-331-3p and miR-9-5p treatment prevented AD progression by promoting the autophagic clearance of amyloid beta (Aβ). Methods: The biphasic changes of microRNAs were obtained from RNA-seq data and verified by qRT-PCR in early-stage (6 months) and late-stage (12 months) APPswe/PS1dE9 mice (hereinafter referred to as AD mice). The AD progression was determined by analyzing Aβ levels, neuron numbers (MAP2+) and activated microglia (CD68+IBA1+) in brain tissues using immunohistological and immunofluorescent staining. MRNA and protein levels of autophagic-associated genes (Becn1, Sqstm1, LC3b) were tested to determine the autophagic activity. Morris water maze and object location test were employed to evaluate the memory and learning after antagomirs treatments in AD mice and the Aβ in the brain tissues were determined. Results: MiR-331-3p and miR-9-5p are down-regulated in early-stage of AD mice, whereas up-regulated in late-stage of AD mice. We demonstrated that miR-331-3p and miR-9-5p target autophagy receptors Sequestosome 1 (Sqstm1) and Optineurin (Optn), respectively. Overexpression of miR-331-3p and miR-9-5p in SH-SY5Y cell line impaired autophagic activity and promoted amyloid plaques formation. Moreover, AD mice had enhanced Aβ clearance, improved cognition and mobility when treated with miR-331-3p and miR-9-5p antagomirs at late-stage. Conclusion: Our study suggests that using miR-331-3p and miR-9-5p, along with autophagic activity and amyloid plaques may distinguish early versus late stage of AD for more accurate and timely diagnosis. Additionally, we further provide a possible new therapeutic strategy for AD patients by inhibiting miR-331-3p and miR-9-5p and enhancing autophagy.
NFB-13. TRAMETINIB FOR PLEXIFORM NEUROFIBROMA AND RECURRENT LOW-GRADE GLIOMA
Authors: Aimee Sato, Nathan Millard, Francisco Perez, Nicholas Vitanza, Sarah Leary
Journal: Neuro-Oncology (2020)

Abstract BACKGROUND Based on early clinical efficacy data, Seattle Children’s established a standard clinical practice for MEK inhibitor therapy for children with plexiform neurofibroma (PN) or recurrent low-grade glioma (LGG). METHODS Data were collected under an IRB-approved retrospective chart review. Trametinib was prescribed off-label at 0.025 mg/kg daily for up to two years. Physical exam and laboratory monitoring were monthly for 3 months, then every 3 months. Retinal examination, ECHO/ECG were every 3 months. Tumor response was evaluated by MRI every 3 months for LGG; imaging for PN was dependent on tumor location. RESULTS 30 patients received trametinib; 17 LGG, 16 PN (3 both); 22 with Neurofibromatosis, Type-1 (NF1); 16 female/15 male; median age 11 (range 4.1–22.6). Most common tumor location was optic pathway (n=11) and face/neck (n=10). Most common adverse events (AE) were dermatologic and gastrointestinal. Ten had dose interruption/reduction, only one discontinued therapy for AE. Six received dermatology specialty care for AE. With median follow-up of 12 months, only 3 patients had progression, one with NF1. One-year EFS was 100% for PN and 88%+7 for LGG. Driver mutations were identified in 9 of 10 tumors tested (5 BRAF fusion, 1 BRAFV600E, 1 FGFR1+NF1, 1 FGFR1+PTPN11, 1 NF1). Radiology review of response will be presented. CONCLUSIONS This real-world pediatric cohort supports efficacy and tolerability of MEK inhibitor therapy for short-term control of plexiform neurofibroma and low-grade glioma with and without NF1. Further studies are warranted to evaluate comparative efficacy, combination therapy and duration of therapy.
EXTH-55. PET, IMAGE-GUIDED HDAC INHIBITION OF PEDIATRIC DIFFUSE MIDLINE GLIOMA IMPROVES SURVIVAL IN MURINE MODELS
Authors: Umberto Tosi, Harikrishna Kommidi, Oluwaseyi Adeuyan, Hua Guo, Uday Bhanu Maachani, Nandi Chen, Taojunfeng Su, Guoan Zhang, David Pisapia, Nadia Dahmane, Richard Ting, Mark Souweidane
Journal: Neuro-Oncology (2020)

Abstract Efforts at altering the dismal prognosis of pediatric midline gliomas focus on direct-delivery strategies like convection-enhanced delivery (CED), where a cannula is implanted into tumor. Successful CED treatments require confirmation of tumor coverage, dosimetry, and longitudinal in vivo pharmacokinetics monitoring. These properties would be best determined clinically with image guided dosimetry using theranostic compounds, agents with both therapeutic and imaging properties. In this study, we combine CED with novel, molecular-grade positron emission tomography (PET) imaging. We synthesized PETobinostat, a novel PET-imageable HDAC inhibitor, and showed its effectiveness against DIPG models in vitro and in vivo. Cell studies against a library of DIPG cells show nanomolar IC50, allowing for rapid in vivo translation. When injected in mice, PET shows the need of CED to achieve high brain concentrations, as systemic delivery yields inferior brain permeation. PET also shows that CED has significant mouse-to-mouse variability: imaging is used to modulate CED infusions to maximize tumor saturation over time. By determining condition-specific clearance half-life (ranging between 60 and 120 minutes), we maximized tumor permeation above therapeutic concentrations for at least 12 hours. This PET-guided approach resulted in decrease tumor cellularity (p= 0.001), increased apoptosis (p= 0.034), decreased dividing cells (p= 0.003), and recovery of histone-3 acetylation (p &amp;lt; 0.0001) when compared against vehicle and systemic-treated controls in tumor-bearing mice. Further, the PET-guided CED of PETobinostat resulted in survival prolongation (67.5 vs. 35 days, p = 0.0001) when compared to systemic administration of another potent HDAC inhibitor (Panobinostat). CED without PET guidance failed at improving survival (37.5 vs. 35 days, p = 0.74). No significant toxicity was observed following CED of PETobinostat. This work demonstrates how personalized image-guided drug delivery of a novel HDAC inhibitor may be useful in potentiating CED-based treatment platforms, and supports a foundation for the clinical translation of PETobinostat.
IMMU-14. IMMUNE CHECKPOINT INHIBITOR THERAPY FOR TREATMENT OF SYNCHRONOUS CANCERS IN PAEDIATRIC PATIENTS WITH CONSTITUTIONAL MISMATCH REPAIR DEFICIENCY
Authors: Jacob Henderson, Daniel Morgenstern, Melissa Edwards, Sumedha Sudhaman, David Kram, Michael Osborn, Yoon-Jae Cho, Uri Tabori
Journal: Neuro-Oncology (2020)

Abstract Constitutional mismatch repair deficiency (CMMRD) is an autosomal recessive condition in which affected patients carry biallelic germline mutations in the MMR genes. This highly penetrant syndrome results in nearly universal development of malignant neoplasms at a young age, most commonly pediatric brain tumors. Importantly, in addition to brain tumors, patients frequently develop multiple metachronous or even synchronous tumors making it impossible to treat these cancers with current chemotherapeutic approaches due to the complexity of different chemoradiation regimens required, resulting in excess toxicity and lack of efficacy. We first, assessed the metachronous (defined here as serial tumors diagnosed &amp;gt;1 year apart or after completion of definitive treatment for the initial tumor) or synchronous cancers (defined here as tumors diagnosed within a year of each other or during the definitive treatment for the initial tumor) in all patients within the consortium. Strikingly, 47% developed synchronous and/or metachronous cancers leading to patient demise. Molecular analysis revealed that all synchronous tumors (n=26) harbored a hypermutational burden accompanied by high genomic microsatellite instability and the relevant signatures. We therefore treated two patients with glioblastomas who had synchronous solid tumors with checkpoint inhibitors. In both patients, objective tumor response was associated with clinical benefit and prolonged survival. Biomarker analysis revealed increased tumor mutational burden, microsatellite instability and immune cell infiltration. These cases highlight the role of universal, mechanism based and tumor-agnostic approach to treat patients with brain tumors with additional synchronous cancers in the setting of cancer predisposition.
Abstract 14745: Incidence Rates of Severe Hypertriglyceridemia in Olmsted County, Minnesota: A Population-Based Study
Authors: Harigopal Sandhyavenu, Ahmed Pasha, Medhat Farwati, Kent Bailey, Umama Gorsi, Carin Smith, Christina Wood-Wentz, Iftikhar J Kullo
Journal: Circulation (2019)

Introduction: Severe hypertriglyceridemia (SHTG), defined as plasma triglyceride (TG) level ≥ 500 mg/dl, is a risk factor for atherosclerotic cardiovascular disease and pancreatitis. However, the i...
Dyserythropoiesis Evaluated By Red Score and Hepcidin/Ferritin Levels Predicts Response to Epoetin Zeta in Lower Risk MDS
Authors: Olivier Kosmider, Frederic Maloisel, Bernard Drenou, Nicolas Chapuis, Anne Sophie Alary, Alice Rousseau, Cecile Bouilloux, Sarah Ducamp, Frederique Verdier, Thibaud Lefebvre, Zoubida Karim, Marie-Christine Jacob, Agathe Debliquis, Agnes Charpentier, Pierre Fenaux, Emmanuel Gyan, Bruno Anglaret, Cecile Leyronnas, Selim Corm, Borhane Slama, Stephane Cheze, Kamel Laribi, Shanti Ame, Christian Rose, Florence Lachenal, Andrea Toma, Gian Matteo Pica, Martin Carre, Frederic Garban, Brigitte Pegourie, Jean-Yves Cahn, Mathieu Meunier, Orianne Wagner Ballon, Olivier Herault, Francois Dreyfus, Valerie Bardet, Michaela Fontenay, Sophie Park
Journal: Blood (2017)
The hidden army: how a GP-patient volunteer group responded to covid-19
Authors: Chris Jenner, Carly Szasz, Jacqui Martin, Laura Herman, Josh Bekhor
Journal: BMJ (2020)

When the UK government declared a national lockdown on 23 March 2020, staff at Elliott Hall Medical Centre in Harrow recognised that many of their vulnerable patients would find it difficult to cope. To help them, the practice called on volunteers within its patient community to assist. Here they describe what they did and how they continue to work with patient volunteers in the next phase of the pandemic.
The S1 protein of SARS-CoV-2 crosses the blood–brain barrier in mice
Authors: Elizabeth M. Rhea, Aric F. Logsdon, Kim M. Hansen, Lindsey M. Williams, May J. Reed, Kristen K. Baumann, Sarah J. Holden, Jacob Raber, William A. Banks, Michelle A. Erickson
Journal: Nature Neuroscience (2020)
ST6GAL1 Is a Novel Serum Biomarker for Lenvatinib-Susceptible FGF19-Driven Hepatocellular Carcinoma
Authors: Yuta Myojin, Takahiro Kodama, Kazuki Maesaka, Daisuke Motooka, Yu Sato, Satoshi Tanaka, Yuichi Abe, Kazuyoshi Ohkawa, Eiji Mita, Yoshito Hayashi, Hayato Hikita, Ryotaro Sakamori, Tomohide Tatsumi, Ayumu Taguchi, Hidetoshi Eguchi, Tetsuo Takehara
Journal: Clinical Cancer Research (2020)

Abstract Purpose: Hepatocellular carcinoma (HCC) is characterized by high intertumor heterogeneity of genetic drivers. Two multitarget tyrosine kinase inhibitors (TKI), lenvatinib and sorafenib, are used as standard-of-care chemotherapeutics in patients with advanced HCC, but a stratification strategy has not been established because of a lack of efficacious biomarkers. Therefore, we sought biomarkers that indicate lenvatinib-susceptible HCC. Experimental Design: We performed genetic screening of HCC driver genes involved in TKI susceptibility using a novel HCC mouse model in which tumor diversity of genetic drivers was recapitulated. A biomarker candidate was evaluated in human HCC cell lines. Secreted proteins from HCC cells were then screened using mass spectrometry. Serum and tumor levels of the biomarker candidates were analyzed for their association and prediction of overall survival in patients with HCC. Results: We found that lenvatinib selectively eliminated FGF19-expressing tumors, whereas sorafenib eliminated MET- and NRAS-expressing tumors. FGF19 levels and lenvatinib susceptibility were correlated in HCC cell lines, and FGF19 inhibition eliminated lenvatinib susceptibility. Lenvatinib-resistant HCC cell lines, generated by long-term exposure to lenvatinib, showed FGF19 downregulation but were resensitized to lenvatinib by FGF19 reexpression. Thus, FGF19 is a tumor biomarker of lenvatinib-susceptible HCC. Proteome and secretome analyses identified ST6GAL1 as a tumor-derived secreted protein positively regulated by FGF19 in HCC cells. Serum ST6GAL1 levels were positively correlated with tumor FGF19 expression in patients with surgically resected HCC. Among patients with serum ST6GAL1-high HCC who underwent TKI therapy, lenvatinib therapy showed significantly better survival than sorafenib. Conclusions: Serum ST6GAL may be a novel biomarker that identifies lenvatinib-susceptible FGF19-driven HCC.
TMOD-29. ESTABLISHMENT OF PATIENT-DERIVED XENOGRAFTS FROM RARE PRIMARY BRAIN TUMORS
Authors: Noriyuki Kijima, Yoshikazu Nakajima, Daisuke Kanematsu, Tomoko Shofuda, Yuichiro Higuchi, Hiroshi Suemizu, Kanji Mori, Yoshinori Kodama, Masayuki Mano, Atsushi Sasaki, Takeshi Inoue, Junko Hirato, Haruhiko Kishima, Yonehiro Kanemura
Journal: Neuro-Oncology (2020)

Abstract Patient derived xenografts are essential tools for translational research and preclinical development of novel therapeutic strategies of primary brain tumors. Recent advances in genomics of primary brain tumors revealed molecular classification of primary brain tumors, thus establishment of patient derived xenografts from each subtype of primary brain tumors is urgently needed. However, currently available patient derived xenografts are limited and are from specific subtype of primary brain tumors such as glioblastoma IDH wild type. In this study, we aim to establish patient derived xenografts from primary brain tumors with various molecular characteristics, especially rare primary brain tumors. We got primary brain tumor tissues from patients, dissociated those tissue into single cells, and orthotopically injected those cells into NOD/Shi-scid IL2Rγ KO mouse. We successfully established rare patient-derived xenografts from atypical teratoid rhabdoid tumor and CNS Ewing sarcoma family tumor with CIC alteration, which is recently described as new entity of primitive neuroectodermal tumors of the CNS. We also analyzed histopathological characteristics of these xenografts and found that each xenograft well recapitulated histopathological features of original patients’ resected tumors. These xenografts have advantages for translational research and preclinical development of novel therapeutic strategies for rare primary brain tumors. In addition, further efforts are needed to establish other types of rare primary brain tumors.
Abstract 16490: Circulating sEPCR Levels Are a Biomarker of Bioprosthetic Valve Calcification
Authors: Nicolas Gendron, Richard Chocron, Benoit Védie, Alain Carpentier, David M Smadja
Journal: Circulation (2018)

Introduction: After 10 years of implantation, 20 to 30% of valvular bioprosthesis show signs of dysfunction mostly due to calcification. Hypothesis: Because of bioprosthesis valve endothelial recov...