tbuckley/cabot-search huggingface dataset:
Ventricular Preexcitation in a Patient Found to Have Wolff-Parkinson-White Pattern
Authors: Anjali B. Thakkar, Melvin Scheinman, Nora Goldschlager
Journal: JAMA Internal Medicine (2020)

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AsthmaMap: An interactive knowledge repository for mechanisms of asthma
Authors: Alexander Mazein, Olga Ivanova, Irina Balaur, Marek Ostaszewski, Valeriya Berzhitskaya, Tatiana Serebriyskaya, Thomas Ligon, Jan Hasenauer, Bertrand De Meulder, Rupert W. Overall, Ludovic Roy, Richard G. Knowles, Craig E. Wheelock, Sven-Erik Dahlen, Kian Fan Chung, Ian M. Adcock, Graham Roberts, Ratko Djukanovic, Johann Pellet, Piotr Gawron, Rudi Balling, Anke H. Maitland-van der Zee, Reinhard Schneider, Peter J. Sterk, Charles Auffray
Journal: Journal of Allergy and Clinical Immunology (2020)
Validating a novel score based on interaction between ACLF grade and MELD score to predict waitlist mortality
Authors: Mohamed A. Abdallah, Yong-Fang Kuo, Sumeet Asrani, Robert J. Wong, Aijaz Ahmed, Paul Kwo, Norah Terrault, Patrick S. Kamath, Rajiv Jalan, Ashwani K. Singal
Journal: Journal of Hepatology (2020)
LGG-34. CLINICAL AND MOLECULAR CHARACTERIZATION OF A MULTI-INSTITUTIONAL COHORT OF PEDIATRIC SPINAL CORD LOW-GRADE GLIOMAS
Authors: Sydney Grob, Lianna Nobre, Kurtis Davies, Scott Ryall, Dara Aisner, Lindsey Hoffman, Shadi Zahedi, Andrew Morin, Anandani Nellan, Adam Green, Nicholas Foreman, Rajeev Vibhakar, Todd Hankinson, Michael Handler, Cynthia Hawkins, Uri Tabori, B K Kleinschmidt-DeMasters, Jean Mulcahy Levy
Journal: Neuro-Oncology (2020)

Abstract BACKGROUND The MAPK/ERK pathway is involved in cell growth and proliferation, and mutations in the BRAF paralog of this pathway have made it an oncogene of interest in pediatric cancer. Previous studies have identified that BRAF mutations as well as BRAF-KIAA1549 fusions are common in intracranial low-grade gliomas (LGGs). Fewer studies have tested for the presence of these genetic aberrations in spinal LGGs. The aim of this study was to better understand the prevalence of BRAF and other genetic aberrations in spinal LGG. METHODS We analyzed 46 spinal LGGs from children age 1–25 years from two institutions, Children’s Hospital Colorado (CHCO) and The Hospital for Sick Children (Sick Kids) for the presence of BRAF fusions or mutations. Data was correlated with clinical information. A 67 gene panel additionally screened for other possible genetic abnormalities of interest in the patient cohort from CHCO. In the Sick Kids cohort, BRAFV600E was tested for by ddPCR and IHC while BRAF fusions where detected by FISH, RT-PCR or Nanostring platform. RESULTS Of the 31 patient samples who underwent fusion analysis, 13 (42%) harbored the BRAF-KIAA1549 fusion. Overall survival (OS) for patients confirmed positive for BRAF-KIAA1549 was 100% compared to 76% for fusion negative patients. Other mutations of interest were also identified in this patient cohort including BRAFV600E, STK11, PTPN11, H3F3A, APC, TP53, PIK3CA (polymorphism), FGFR1, and CDKN2A deletion. CONCLUSION BRAF-KIAA1549 was seen in higher frequency than BRAFV600E or other genetic aberrations in pediatric spinal LGGs and trends towards longer OS although not statistically significant.
Stopping aspirin 1 to 3 mo after PCI reduces bleeding without increasing MACE vs. continued DAPT
Authors: Manoj Kesarwani
Journal: Annals of Internal Medicine (2020)

Source Citation O’Donoghue ML, Murphy SA, Sabatine MS. The safety and efficacy of aspirin discontinuation on a background of a P2Y12 inhibitor in patients after percutaneous coronary intervention: a systematic review and meta-analysis. Circulation. 2020;142:538-45. 32551860
BIOM-51. FACTORS ASSOCIATED WITH DECLINING SEX DISCREPANCY IN MENINGIOMA WITH INCREASING TUMOR AGGRESSIVENESS: RETROSPECTIVE REVIEW OF A RURAL PENNSYLVANIA COHORT
Authors: Richard Sofoluke, Sally Chu, Shane Bross, Na Tosha Gatson
Journal: Neuro-Oncology (2020)

Abstract INTRODUCTION Meningioma is the most common benign primary brain tumor in adults comprising 37% of all primary CNS tumors. Approximately 81.1% of meningiomas are grade I, 16.9% - grade II, and 1.7% - grade III. While females are 2.5 times more likely to have meningiomas, males more commonly have aggressive grades. Loss of progesterone receptor (PR) and presence of androgen receptor (AR) are associated with tumor aggressiveness. We observed a declining sex-discrepancy with increasing tumor grade. We present an ongoing assessment of a rural population to define potential factors contributing to this observation. METHODS We completed a single institutional retrospective review of 406 pathology confirmed meningiomas in rural Northeast Pennsylvania. We compared WHO grade, hormone receptors, and proliferative indices between males and females. We further evaluated tumor location and comorbid endocrine disease for possible association. RESULTS Our patient cohort had a high frequency of aggressive tumors 73.5% (n= 297) grade I, 24% (n= 99) grade II, and 2.5% (n= 10) grade III. The ratio of females versus males was 3.1:1, 1.3:1, and 1:1 in grades I, II, and III respectively. Factors contributing to closing the sex-gap were: (1) grade II: males expressed less PR than females (76% vs 94%); (2) grade III: females expressed less AR than males (0% vs 100%), while PR expression remained equivalent; and (3) males had higher tumor proliferative indices compared to females (7% and 22% vs 2% and 14%), grades I and II respectively. There was no relationship determined for tumor location or comorbid endocrine disease between the sexes. CONCLUSION The association between declining sex discrepancy in meningioma with increasing tumor aggressiveness is potentially related to the expression PR, AR, and increased tumor proliferation indices with increasing meningioma grade.
INNV-22. PROSPECTIVE ANALYSIS OF UTILIZATION OF TELEMEDICINE IN NEURO-ONCOLOGY
Authors: Aman Kalra
Journal: Neuro-Oncology (2020)

Abstract OBJECTIVE to offer neuro-oncology care to patients in rural/suburban settings that may not otherwise have access to urban amenities, specialists, and clinical trials. To test the feasibility of telemedicine in Neuro-Oncology by measuring cost savings, travel time savings, and burden of care. To screen patients for clinical trials. BACKGROUND Neuro-Oncology services are primarily available only at tertiary care hospitals. This increases the burden of care for patients who live in suburban and rural areas, as they have to travel long distances for their care. Hence, some families and patients do not seek care as travel time increases the stress on patients and their caretakers who are already dealing with the devastating diagnosis of a brain tumor. Similarly, these patient groups do not have access to clinical trials. METHODS To help ease above hardships on patients, we built a telemedicine Neuro-Oncology program that is studying the quality of care compared with daily routine visits in the cancer center. We are enrolling 30 patients in each cohort of the study, cohort A, telemedicine visits and cohort B, regular clinic visits for a total of 60 patients after obtaining written consent. We are providing them survey identifying quality measures of care (24 questions). The survey is provided to the patients and their caregivers at the end of their visit. RESULTS Survey answers are inputted into Survey Monkey. After the completion of 60 total patient visits, surveys will be evaluated and the results will be analyzed. CONCLUSION We are looking for the long-term feasibility of utilizing telemedicine care in rural/suburban settings for Neuro-Oncology patients. We anticipate that there will be cost savings, travel time savings and reduction in burden of care without compromising patient satisfaction or quality of care provided. We are also studying the feasibility of screening patients for clinical trials.
35P Toxicity and safety of novel immuno-oncology (IO) treatments after prior immune checkpoint inhibitors (ICIs) exposure
Authors: A.A. Valdivia, A. Hernando, O. Saavedra, R. Berché, I. Braña, I. Matos Garcia, A. Ázaro, M. Vieito Villar, G. Alonso, V. Galvão, H.K. Oberoi Oberoi, N.A. Wornham, L. Fariñas Madrid, N. Mulet Margalef, R. Morales Barrera, P. Iranzo Gomez, E. Muñoz Couselo, J. Tabernero, R. Dienstmann, E. Garralda
Journal: Annals of Oncology (2020)
SURG-01. RISK OF TRACT RECURRENCE WITH STEREOTACTIC BIOPSY OF BRAIN METASTASES: AN 18-YEAR CANCER CENTER EXPERIENCE
Authors: Joseph Carnevale, Graham Winston, Jacob Goldberg, Cameron Brennan, Viviane Tabar, Nelson Moss
Journal: Neuro-Oncology (2020)

Abstract BACKGROUND Stereotactic biopsy is increasingly performed on brain metastases (BrM) as improving cancer outcomes drive aggressive multimodality treatment, however the risk of tract recurrence for such biopsies, in both the upfront and recurrent settings, are poorly defined in an era defined by focused-irradiation paradigms. As such, the rate of tract recurrence was evaluated. METHODS A retrospective review was performed to identify stereotactic biopsies performed for BrM at Memorial Sloan Kettering Cancer Center from 2002-2020. Data including surgical indications, tumor type, radiographic characteristics, stereotactic planning, pre- and post-operative CNS-directed and systemic treatments, and clinical courses were collected. Recurrence was evaluated using RANO-BM criteria. RESULTS Four-hundred-and-seventy-nine patients underwent stereotactic intracranial biopsy for any diagnosis (&amp;gt;80% were for gliomas or CNS lymphoma). Twenty-two (4.5%) were for pathologically-confirmed viable BrM and 91% of these underwent postoperative irradiation with either stereotactic radiotherapy (14/20, 70%; SBRT) in plans that did not specifically target the biopsy tract, or whole-brain irradiation (6/20, 30%; WBRT). Eleven patients (50%) had &amp;gt;/=3 months radiographic follow-up (median 11.9; 4.5-30.6), of which 6 (55%) developed discontinuous enhancement along the tract at a median 6.4 months (2.3-17.1) post-biopsy. Of these, 2 had previously been treated with SBRT and were sampled in the setting of diagnostic ambiguity (one additionally with WBRT for small cell carcinoma) and underwent intraoperative laser interstitial thermal therapy (LITT) immediately following biopsy. The remainder were treated with SBRT +/- LITT (n=3 and 4, respectively) following biopsy. Tract recurrences were treated with resection (n=2, both with pathologic confirmation), re-irradiation (n=1) or observation/systemic therapy. CONCLUSIONS In this largest reported series of biopsied BrM, we identify a nontrivial rate, higher than previously described, of recurrence along stereotactic biopsy tracts. As BrM are most commonly treated with focused radiotherapy centered on enhancing tumor margins, consideration should be made to include biopsy tracts where feasible.
MBCL-04. 5 – AZACYTIDINE IN TREATMENT OF CHILDREN WITH DE NOVO AND RELAPSED METASTATIC MEDULLOBLASTOMA: RESULTS OF INTERCENTER PILOT STUDY
Authors: Andrey Levashov, Dmitry Khochenkov, Anna Stroganova, Marina Ryzhova, Sergey Gorelyshev, Shavkat Kadirov, Svetlana Zagidullina, Stepan Babelyan, Natalya Subbotina, Georgy Mentkevich, Dmitry Sidelnikov, Vidmante Daylidite, Vasily Grigorenko
Journal: Neuro-Oncology (2020)

Abstract The aim of this study was to estimate treatment toxicity and event-free survival (EFS) according to therapeutic program, MYC/MYC-N gene amplification and MGMT/DNMT (1, 3a, 3b) proteins expression in tumor cells. From 2016 to 2018 twenty four patients were included in trial. Children underwent adjuvant therapy: craniospinal radiation (CSI) or local radiation therapy (RT) to the relapsed site up to 23.4Gy with 5-azacytidine, 2 cycles methotrexate/5-azacytidine/cisplatin/etoposide, 3 cycles 5-azacytidine/temozolomide - for relapsed group (arm A, n = 5); for patients with de novo medulloblastoma: arm B, n = 11 – vincristine/cyclophosphamide/cisplatin/etoposide (OPEC) - based induction, CSI 36Gy + local RT to the tumor bed up to 54Gy with 5-azacytidine, 1 cycle OPEC and 2 cycles thiophosphamide/carboplatin with auto stem cell transplantation (auto-SCT); arm C, n = 8 – cyclophosphamide/cisplatin - based induction, CSI 23.4 Gy followed by 2 cycles 5-azacytidine/thiophosphamide/carboplatin with auto-SCT, local RT with 5-azacytidine. The combination of 5-azacytidine with local RT or temozolomide was safety and tolerability. Arm C was discontinued due to severe gastrointestinal grade 3/4 toxicity, hemorrhagic syndrome after combination of 5-azacytidine with thiophosphamide/carboplatin. EFS was 0% in arm A, 53.0 ± 15.5%, 50.0 ± 17.7% in arms B and C, a median follow-up 8.8 ± 1.1 months (arm A), 18.8 ± 2.5 months (arm B), 25.0 ± 4.4 months (arm C). Addition of 5-azacytidine to RT or chemotherapy did not improve EFS of patients with MYC/MYC-N gene amplification positive tumor. There was not determined any prognostic significance of MGMT/DNMT (1, 3a, 3b) proteins expression in this cohort.
The Use of Cardiovascular Magnetic Resonance to Identify Adverse Cardiac Prognosis: An Important Step in Reducing Image-Related Heath Care Expenditures⁎⁎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: W. Gregory Hundley
Journal: Journal of the American College of Cardiology (2010)
EPEN-39. CLINICAL STRATIFIED TREATMENT OF LOCALIZED PEDIATRIC INTRACRANIAL EPENDYMOMA WITH COMBINED LOCAL IRRADIATION AND CHEMOTHERAPY WITHIN THE PROSPECTIVE, MULTICENTER E-HIT TRIAL – THE MOLECULAR SUBGROUP MATTERS
Authors: Katja von Hoff, Denise Obrecht, Janna Wening, Martin Mynarek, Nicolas U Gerber, Martin Benesch, B - Ole Juhnke, Brigitte Bison, Monika Warmuth-Metz, Beate Timmermann, Andreas Faldum, Ulrich Schüller, Stefan M Pfister, Marcel Kool, Torsten Pietsch, Rolf-D Kortmann, Robert Kwiecien, Kristian W Pajtler, Hendrik Witt, Stefan Rutkowski
Journal: Neuro-Oncology (2020)

Abstract BACKGROUND Pediatric ependymoma is a heterogenous disease. Subgroup-specific clinical information on prospectively treated patients will help to improve treatment stratification. METHODS Within the population based, prospective, multicenter E-HIT-trial (2001–2011) patients with localized ependymoma confirmed by neuropathological central-review, received hyperfractionated local radiotherapy (68Gy, 2x1Gy/day) followed by chemotherapy (stratum-A), or chemotherapy followed by local radiotherapy (54Gy, 1.8Gy/day) (children &amp;lt; 4years, stratum-B), or age-adapted radiotherapy with pre-/post-irradiation chemotherapy (residual tumor, diagnosis after 2005, stratum-C). Retrospective classification of DNA-methylation was available for n=164 E-HIT-trial participants, and n=80 patients with comparable treatment and prospective registration in the subsequent HIT-interim-registry (2012–2014). FINDINGS: For 291 E-HIT-trial patients, 5-year progression-free (PFS) and overall survival (OS) were 61±3%, and 81±2%. Five-year PFS/OS after complete resection were 71±4% and 87±3% in stratum-A (n=127), and 64±5% and 86±4% in stratum-B (n=86). Outcome was poor after incomplete resection, irrespective of treatment-stratum (n=78, 5-year PFS/OS: 43±6%, 68±5%). In the pooled trial- and registry-cohort, there were 152 patients with PF-EPN-A (5-year PFS/OS: 44±4%, 77±4%), 40 of them with 1q-gain (5-year PFS/OS: 28±7%, 66±8%), 21 with PF-EPN-B (5-year PFS/OS: 90±7%, 100%), 59 with ST-EPN-RELA (5-year PFS/OS: 63±7%, 87±5%), and 4 with ST-EPN-YAP1 (2 progression/relapse, no death). CONCLUSION Outcome differed between molecular subgroups and insufficient survival rates were achieved for patients with PF-EPN-A with 1q-gain, despite combined radio- and chemotherapy treatment. Treatment reduction in the context of a clinical trial may be considered for PF-EPN-B.
From Mice to Men: Commonalities in Physiology for Stem Cell-Based Cardiac Repair⁎⁎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: Marc S. Penn, Saif Anwaruddin, Ravi Nair, Stephen Ellis
Journal: Journal of the American College of Cardiology (2009)
RARE-55. CHALLENGES AND SPECIFIC STRATEGIES FOR CONSTITUTIONAL MISMATCH REPAIR DEFICIENCY SYNDROME IN LOW RESOURCE SETTINGS. ON BEHALF OF THE INTERNATIONAL RRD CONSORTIUM IN LOW RESOURCE SETTINGS PANEL
Authors: Rejin Kebudi, Nisreen Amayiri N, Malak Abedalthagafi, Asim Noor Rana, Slman Kirmani, Naureen Musthaq, Zakiya Al Lamki, Jamilla El Houdzi, Hulya Yazıcı, S El-Naggar, Melissa Edwards, Vanessa Bianchi, Carol Durno, Uri Tabori, Eric Bouffet
Journal: Neuro-Oncology (2020)

Abstract Germline biallelic mutations in one of the mismatch repair genes (MSH2/MSH6/MLH1/PMS2 results in constitutional mismatch repair deficiency (CMMRD), a condition associated with multiple tumors arising from multiple organs during childhood, and these individuals rarely reach adulthood. The paucity of information with respect to these conditions leads to mismanagement and may be a factor in the high mortality of patients with CMMRD. Two international consortia, the European CARE4CMMRD, and the international replication repair deficiency (RRD) consortium, are addressing the many challenges associated with this condition. To address specific issues surrounding the management of CMMRD in low and middle income countries (LMIC), a multidisciplinary taskforce of 11 specialists from nine countries was formed. Preliminary conclusions are: 1) Immunohistochemistry for CMMRD should be considered for all patients with suggestive clinical features. In countries where CMMRD is common, malignant gliomas, colon cancers and T cell lymphomas should be stained routinely as the prevalence of CMMRD in these tumors can exceed 40%. 2) Temozolomide should not be used in the management of malignant glioma. By contrast, preclinical studies have suggested increased sensitivity to nitrosoureas. For the management of CMMRD related lymphoma and leukemia, mercaptopurines should not be avoided or discontinued as a part of the standard of care before more data are collected. 3) Management with checkpoint inhibitors should be limited to centers with intensive care units and expertise in complex supportive care to manage side effects of immune therapy. 4) Surveillance protocols have demonstrated long term survival benefits and should be implemented in LMIC.
P79Qに関連したコアI97L変異は慢性B型肝炎患者における持続性低HBV DNAとHBs抗原クリアランスと関連している【Powered by NICT】
Authors: T Honda, M Ishigami, Y Ishizu, T Kuzuya, K Hayashi, T Ishikawa, Y Murakami, M Iwadate, H Umeyama, H Toyoda, T Kumada, Y Katano, H Goto, Y Hirooka
Journal: Clinical Microbiology and Infection (2017)
CSIG-18. CALCIUM COMMUNICATION IN GLIOMA: CRUCIAL PACEMAKER CELLS GOVERN TUMOR PROGRESSION
Authors: David Hausmann, Erik Jung, Daniel Azorin, Miriam Ratliff, Matthias Osswald, Wolfgang Wick, Frank Winkler
Journal: Neuro-Oncology (2020)

Abstract BACKGROUND Gliomas form therapy-resistant multicellular networks, using neurite-like protrusions (called Tumor Microtubes [TMs]), and display intercellular calcium transients, that drive brain tumor malignancy. METHODS A refined in vitro model was established to study calcium communication and its molecular toolkit in patient-derived glioma cells. In vitro results were then validated with longitudinal in vivo two-photon calcium imaging in awake mice. RESULTS Here we first describe the discovery of a small subpopulation of glioma cells that display intrinsically active calcium oscillations and behave like pacemakers. Accordingly, these pacemaker-like glioma cells trigger synchronized calcium activity in tumor cells that are connected with them via TMs. The application of network theory shows that glioma cell networks follow a scale-free and small-world topology, governed by a subpopulation of highly connected hub cells. Interestingly, the pacemaker cells most often act as these hubs, hence communicating with many other network members. Graph theory predicts that such network design displays a high degree of robustness, making it resistant to random damage as seen after radio- and chemotherapy – but extremely vulnerable to selective damage to key hubs. In line with this theory, laser ablation of the pacemaker-like hub cells splintered the malignant tumor network into small isolated cell clusters and led to increased cell death, whereas laser ablation of random tumor cells showed no effect. Among others, KCNN4 channels, which are upregulated in gliomas, were identified as drivers of the pacemaker-like hub cells. Suppressing their pacemaking-abilities by KCNN4 inhibition strongly reduced calcium communication and tumor growth. CONCLUSION In summary, coordinated calcium communication in glioma drives brain tumor malignancy. A specific tumor cell subpopulation was identified that acts as hubs of the multicellular network and initiates global calcium activity. The network’s vulnerability to loosing these pacemaker-like hub cells suggests a novel targeted approach against the resistant networks of gliomas.