tbuckley/cabot-search huggingface dataset:
EPND-04. INVESTIGATING THE BIOLOGICAL CONSEQUENCES OF PI3K PATHWAY INHIBITION ON PAEDIATRIC EPENDYMOMA TUMOURS
Authors: Jasper Estranero, Caitlyn Ascough, Holly Duane, Rebecca Chapman, Hazel Rogers, Richard Grundy
Journal: Neuro-Oncology (2017)

INTRODUCTION: Paediatric ependymoma has a relatively poor prognosis with current therapies yielding suboptimal outcomes due to these tumours’ general chemoresistant nature. We have identified that the PI3K pathway, a cell survival signalling cascade implicated in many malignancies, was activated in 72% of primary ependymomas, suggesting it is a viable therapeutic target to treat these tumours. Pathway inhibition using a pan-PI3K enzyme inhibitor BKM120 reduced cell viability of ependymoma cell lines which supports its fundamental role in ependymoma pathogenesis. METHODS: This project will purposely expand on previous work to further elucidate the PI3K pathway’s influence on ependymoma development. We treated a panel of ependymoma cell lines with BKM120 as a tool to inhibit canonical PI3K/AKT/mTOR signalling. Assays including western blot and cell death assays were performed to analyse the biological effects of PI3K signalling loss on ependymoma behaviour. Comparison of expression data of BKM120-treated and non-treated cells through microarray analysis will enable a global identification of molecular targets associated with disease progression. RESULTS: Our western blot data showed that BKM120 inhibited mTOR signalling, a known PI3K pathway target, as indicated by the decrease in pS6 levels. Apoptotic responses were absent based on the lack of cleaved caspase-3 whereas reduction in p62 expression suggests that autophagy was induced. Other cancer studies have shown that autophagy can be cytoprotective rather than cytotoxic. To determine the relevant effect in ependymoma, we inhibited BKM120-mediated autophagy with Chloroquine (CQ). BKM120/CQ combination resulted in a cell viability increase suggesting that autophagy activation is detrimental to ependymoma survival. Gene expression analysis is ongoing to further elucidate downstream pathway targets in ependymoma cells. CONCLUSION: PI3K pathway inhibition triggers cellular mechanisms that oppose survival responses in ependymoma cells. The consequent adverse effects in these tumours implicates the pathway’s oncogenic role, highlighting its therapeutic value for the clinical management of ependymoma.
Immediate antibiotics for uncomplicated RTIs do not reduce risk of admission and death, study finds
Authors: Ingrid Torjesen
Journal: BMJ (2017)

Offering a delayed rather than an immediate prescription for antibiotics to adults with lower respiratory tract infections is associated with a lower likelihood of a subsequent GP consultation and no increased risk of hospital admission or death, a study published in The BMJ shows.1

The study included 28 779 adults presenting to UK general practice with lower respiratory tract infections, whose main symptom was acute cough for as long as three weeks. Patients with serious illness were excluded.

Outcomes including repeat consultation, hospital …
Abstract 5921: Medicare Beneficiaries with Mild to Severe Heart Failure See 15–23 Different Providers Annually
Authors: Robert L Page, Christopher Hogan, Kara Strongin, Roger Mills, JoAnn Lindenfeld
Journal: Circulation (2008)

In fiscal year 2003, Medicare beneficiaries with heart failure (HF) accounted for 37% of all Medicare spending and nearly 50% of all hospital inpatient costs. On average, each beneficiary had 10.3 outpatient and 2 inpatient visits specifically for HF. Despite significant improvements in medical care for HF, mortality and hospital admissions remain high. No data exist regarding the number of providers ordering and providing care for this population. An analysis of fiscal year 2005 Medicare claims was conducted, using a 5% sample standard analytic and denominator file, limited data set version to extrapolate the 34,150,200 Medicare beneficiaries. Three cohorts were defined according to mild, moderate, severe HF employing the Centers for Medicare and Medicaid Services Hierarchical Condition Categories Model and Chronic Care Improvement Program definitions. HMO enrollees, persons without Part A and Part B coverage, and those outside the United States were excluded. We identified physicians by using the unique physician identification number of performing physicians. Based on inclusion criteria, 173,863 beneficiaries were identified. The average number of providers providing care in all sites were 15.9, 18.6, 23.1 for beneficiaries with mild, moderate, and severe HF, respectively; and 10.1, 11.5, and 12.1 in the outpatient setting, respectively. The average number of providers ordering care in all sites consisted of 8.3, 9.6, and 11.2 for beneficiaries with mild, moderate, and severe HF, respectively; and 6.5,7.3, and 7.8 in the outpatient setting, respectively. For beneficiaries with mild disease, only 10% of all office visits were specifically for HF, while those with moderate or severe disease, only 20% were specifically for HF. Medicare beneficiaries with HF, even those with mild disease, have a large number of providers ordering and providing care. These data highlight the importance for developing systems and processes of coordinated care for this population.
EBV-Specific Donor Cells Transduced to Express a High-Affinity WT1 TCR Can Prevent Recurrence in Post-HCT Patients with High-Risk AML
Authors: Aude Chapuis, Daniel N. Egan, Merav Bar, Thomas M Schmitt, Megan McAfee, Maurizio Perdicchio, Gunnar B. Ragnarsson, Cecilia C.S. Yeung, Hieu Nguyen, Lara Kropp, Luca Castelli, Felecia Wagener, Daniel Hunter, Kristen Cohen, Aaron Seese, Margaret (Julie) McElrath, Kieu-Thu Bui, Deborah E Banker, Natalie Duerkopp, Philip D Greenberg
Journal: Blood (2016)
Prognostic impact of IKZF1 deletions in association with vincristine–dexamethasone pulses during maintenance treatment of childhood acute lymphoblastic leukemia on trial ALL-BFM 95
Authors: L Hinze, A Möricke, M Zimmermann, S Junk, G Cario, E Dagdan, C P Kratz, V Conter, M Schrappe, M Stanulla
Journal: Leukemia (2017)

Acute lymphoblastic leukemia (ALL) is the most common malignancy of childhood and is cured by application of modern treatment protocols in more than 80% of cases. 1,2However, the ~20% of children with ALL suffering from relapse still exemplify the ongoing need for improved risk stratification and adapted treatment strategies. 1,2][5] Recently, Clappier et al. 6 from the EORTC Study Group suggested that patients with IKZF1-deleted ALL and intermediate-risk features-so-called average-risk (AR) patientstreated on the BFM-based EORTC protocol 58951 may benefit from intensification of conventional maintenance therapy by application of vincristine-glucocorticoid pulses.We previously reported that on ALL-BFM protocols IKZF1 status exerts additive value as a prognostic factor, especially in the intermediate-risk group, in which still the majority of relapses occur. 4Therefore, we investigated the impact of additional pulses during maintenance therapy for IKZF1-deleted ALL in a large cohort of intermediaterisk patients treated according to the ALL-BFM 95 protocol. 7These patients were included in the I-BFM study on pulses of vincristine and dexamethasone in BFM protocols for children with ALL. 8 Between April 1995 and December 2000, patients diagnosed with de novo ALL were enrolled in ALL-BFM 95 from Austrian, German and Swiss study centers. 7Treatment was stratified in three risk groups as follows: standard (SR), intermediate (IR) and high risk (HR).Risk group definition was as follows: HR, prednisone poor response and/or no complete remission on day 33, and/or evidence of t(9;22) (or BCR/ABL), and/or evidence of t(4;11) (or MLL/AF4); IR, no HR criteria and initial white blood cell (WBC) count 20 × 10 9 /l or more and/or age at diagnosis less than 1 or 6 years, or older, and/or T-ALL; SR, no HR criteria and initial WBC less than 20 × 10 9 /l, and age at diagnosis between 1 and 6 years, and no T-ALL.CNS status was no stratification criterion.Before start of maintenance treatment, patients of the IR group who were in complete remission were randomly assigned to receive either conventional mercaptopurine and methothrexate chemotherapy or mercaptopurine and methothrexate supplemented with additional pulses of vincristine (1.5 mg/m 2 weekly for 2 weeks) and dexamethasone (6 mg/m 2 daily for 7 days) every 10 weeks for six cycles.
Factors linked to increased stroke risk are identified in women with pre-eclampsia
Authors: Ingrid Torjesen
Journal: BMJ (2017)

Women with pre-eclampsia face a raised risk of stroke during pregnancy and postpartum if they have infections, particularly of the urinary tract, chronic hypertension, or clotting or bleeding disorders, shows a study published in the journal Stroke .1

Pre-eclampsia develops in 3-8% of pregnant women. While pre-eclampsia can be mild and symptomless, one of the most dangerous potential complications is pregnancy associated stroke.

US researchers looked …
Tele-medicine: a new promised land, just to save resources?
Authors: Nicolino Ambrosino, Dewi Nurul Makhabah
Journal: European Respiratory Journal (2017)

In industrialised countries there is a 95% probability that in 2030, male life expectancy at birth will be in excess of 80 years [1]. As a consequence, there will be an increasing incidence of chronic and non-communicable diseases, as well as an increasing worldwide population of "chronically critical" patients due to respiratory diseases. These conditions, combined with high and sometimes unrealistic citizens' expectations, have already led to high burdens for healthcare systems. For example, under the current law, in the USA health expenditure is projected to grow at an average 5.6% annual rate from 2016 to 2025 and represent 19.9% of gross domestic product by 2025 [2]. Therefore it is no surprise if governments are or will be unable to sustain the past level of welfare, and are looking for new models of care with better cost/benefit ratios. Unfortunately, it seems that some of these models seek to only reduce the numerator, the costs, and not increase the denominator, the benefit. We need much more evidence before tele-medicine can be considered real progress in healthcare <http://ow.ly/Xu4J30aDeHX>
Learning the hard way: clinical trials in juvenile idiopathic arthritis
Authors: Roberta A Berard, Ronald M Laxer
Journal: Annals of the Rheumatic Diseases (2017)

There have been unprecedented advances in the treatments and outcomes reported for patients living with juvenile idiopathic arthritis (JIA) over the last 20 years. The future direction of care with multinational collaborations (Paediatric Rheumatology International Trials Organisation (PRINTO), Pediatric Rheumatology Collaborative Study Group (PRCSG), Childhood Arthritis and Rheumatology Research Alliance) and advances in precision medicine will undoubtedly continue to revolutionise our approach to diagnosis, treatment and perhaps ultimately cure of JIA. In this issue of the Annals of the Rheumatic Diseases , Brunner et al report on the use of subcutaneous golimumab for children with active polyarticular course JIA.1 This trial, no doubt associated with immense direct and indirect costs, produced negative results, as it did not achieve its primary end point. Despite this, there is widespread international opinion that golimumab, like other tumour necrosis factor (TNF) inhibitors, is effective and should be added to the therapeutic armamentarium for children with JIA. We must reflect on this outcome as we consider further studies with new agents in the treatment of children with JIA.

To date, three trials of anti-TNF agents (etanercept, infliximab and adalimumab),2–4 one of a selective T cell costimulation modulator (abatacept),5 and an interleukin-6 receptor inhibitor6 (tocilizumab) have shown efficacy and safety in the treatment of polyarticular course JIA in spite of the fact that primary end point of efficacy was not met in the infliximab trial. Amarilyo et al 7 published a meta-analysis of randomised withdrawal trials which evaluated the five separate …
Effect of sub-concussive impacts sustained throughout a contact-sport season on quiet stance centre of pressure
Authors: Jonathan D Smirl, Jill K Dierijck, Alexander D Wright, Kelsey Bryk, Paul van Donkelaar
Journal: British Journal of Sports Medicine (2017)

Objective To examine how sub-concussive head trauma throughout a contact-sport season affects quiet stance centre of pressure (COP) sway Design Prospective cohort Setting Laboratory Participants : Twenty-four elite male football players (age range 18–22) were recruited for the study Intervention Quiet stance data was collected at the start and at the end of the competitive season. One-minute trials were performed with eyes-open and eyes-closed on a force plate (NDI True Impulse) with feet hip-width apart and hands-on-hips. Biomechanical head-impact exposure was indexed using the xPatch (X2 Biosystems) Outcome measures COP measures: Anterior/posterior (AP) and medial/lateral (ML) root-mean-square displacement (RMSd) and mean velocity. Biomechanical head-impact data: For hits above 20g, peak linear acceleration (PLA), and peak rotational acceleration (PRAwere estimated across the competitive season. Independent variables included time (2) and condition (2) Results RM-ANOVA reveal an effect of condition (eyes-open vs eyes-closed) in AP-RMSd (p=0.035, 95% CI: 0.006, 0.159), ML-RMSd (p&lt;0.0001, CI: 0.083, 0.250), and ML mean velocity (p&lt;0.0001, 95% CI: 0.111, 0.308). However, despite exposure to a cumulative 8147.2±6215.5 g in linear acceleration and 34.5 x 106 ± 59.0x106 rad/s2 in rotational acceleration, there were no significant differences between conditions for COP measures at post-season Conclusions In contrast to the prolonged COP alterations observed following acute concussions, there were no discernable effects of sub-concussive trauma on COP sway during quiet stance in the same population. This is an important finding as it reveals that participation in contract-sport does not impair quiet stance balance Competing interests None.
MEDU-43. EFFECTS OF DISULFIRAM/CU ON MEDULLOBLASTOMA
Authors: Rosamaria Ruggieri, Yaodong Zhao, Stephen Marcus, Marc Symons
Journal: Neuro-Oncology (2017)

Medulloblastoma is the most common malignant pediatric brain tumor that comprises at least 4 subgroups based on molecular characterization: WNT, SHH, group 3 and 4. Group 3 medulloblastoma is the most aggressive subtype with the worst prognosis due to its propensity to metastasize and resistance to therapy. Disulfiram (DSF) is a drug used in the treatment of chronic alcoholism that has been shown to have antineoplastic effects in a number of different cancers including glioblastoma. Its potency has been shown to be enhanced by copper. We tested two established medulloblastoma cell lines, UW228 and D425MED group 3 cells, and two primary cultures, IMB187 WNT and IMB226 SHH cells, for their sensitivity to DSF/Cu using the WST in vitro assay. We found that, whereas DSF on its own has little effect on medulloblastoma cells, in combination with a low concentration (350 nM) of Cu, which on its own has no effect, DSF strongly inhibited the viability of all tested medulloblastoma cells. The IC50 for DSF ranges between 60 nM and 230 nM, with UW228 cells being the most sensitive and the D425MED the least sensitive. DSF/Cu also has been shown to sensitize tumor cells to chemotherapy in a number of different settings. Studies to examine the therapeutic efficacy of DSF/Cu in the D425MED orthotopic animal model of medulloblastoma, both as monotherapy and in combination with the chemotherapeutic cisplatin, are in progress.
The global state of psoriasis disease epidemiology: a workshop report
Authors: C.E.M. Griffiths, J.M. van der Walt, D.M. Ashcroft, C. Flohr, L. Naldi, T. Nijsten, M. Augustin
Journal: British Journal of Dermatology (2017)

The International Psoriasis Council, a global nonprofit organization dedicated to innovation across the full spectrum of psoriasis, led a symposium to discuss the current state of psoriasis epidemiology and to introduce the vision and development of a Global Psoriasis Atlas. The symposium was held on 9 September 2015 at the 45th annual meeting of the European Society for Dermatological Research, Rotterdam, the Netherlands. Collectively, these presentations highlighted challenges associated with assessing psoriasis epidemiology and emphasized the urgent need for an authoritative resource to clarify psoriasis disease burden on a global scale.
How to interpret post-concussion symptom severities of scat3 in professional ice hockey players
Authors: Timo Hänninen, Jari Parkkari, Markku Tuominen, Grant L Iverson, Matti Vartiainen, Juha Öhman, Teemu M Luoto
Journal: British Journal of Sports Medicine (2017)

Objective To characterise the baseline to post-concussion variation of each SCAT3 symptom. Design Prospective cohort. Setting Finnish professional ice hockey league. Participants SCAT3 baseline testing has been mandatory in the Finnish hockey league since 2013. The league recommends day of injury testing for all players with suspected concussion. Of the reported day of injury SCAT3s, between seasons 2013–2016, a total of 29 concussions were confirmed by the teams’ medical staff. Intervention Outcome measures The day of concussion symptom severities for each of the 22 symptoms were compared to (i) the league’s normative reference values [based on 2013–2014 preseason baselines (n=270)] and (ii) the baseline scores of the 29 concussed players. The change between day of concussion score and players’ individual baseline score was compared to: (i) the reference variation of the league’s two preseason baselines [2013–2014 and 2014–2015 (n=179)], and (ii) the variation between two preseason baselines of the concussed players. Main results The most prevalent post-concussion symptoms were: “Don’t feel right” (100%), headache (97%), and pressure in the head (90%). In addition, these symptoms were the most common to worsen on the day of concussion compared to players’ individual baseline. “Feeling like in a fog”, confusion, and dizziness were common on the day of injury (each reported by 72%) but rare on baselines (1–2%). Fatigue or low energy and neck pain were the most common and unstable baseline symptoms in the league. Conclusions Headache and “Don’t feel right” were the most useful symptoms on the SCAT3 in acute concussion recognition. Competing interests None. Timo Hnninen, Jari Parkkari, Markku Tuominen, Matti Vartiainen, Juha hman, Teemu M. Luoto: None. Grant L. Iverson has been reimbursed by the government, professional scientific bodies, and commercial organisations for discussing or presenting research relating to mild TBI and sport-related concussion at meetings, scientific conferences, and symposiums. He has a clinical and consulting practice in forensic neuropsychology involving individuals who have sustained mild TBIs (including professional athletes). He has received research funding from several test publishing companies, including ImPACT Applications, Inc., CNS Vital Signs, and Psychological Assessment Resources (PAR, Inc.). He has not received research support from a test publishing company in the past 5 years.
The symbol of medicine: Aesculapius or cadeuceus
Authors: R. N. Pejic
Journal: JAMA (1996)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
GERM-03. IMMATURE TERATOMA WITH DICER1 MUTATIONS: A CASE REPORT
Authors: Yoshiko Nakano, Daiichiro Hasegawa, Suguru Uemura, Akihiro Tamura, Atsuro Saito, Atsufumi Kawamura, Yoshiyuki Kosaka, Junko Hirato, Koichi Ichimura
Journal: Neuro-Oncology (2017)

BACKGROUND: Recurrent somatic Dicer1 mutations were observed in patients with pulmonary blastoma, Sertoli-Leydig cell tumor and less commonly in several rare cancers including pineoblastoma and pituitary blastoma. Some of the patients have germline Dicer1 mutations, known as a Dicer1 syndrome. Here, we report the first case in the literature of immature teratoma harboring Dicer1 mutation. CASE REPORT: A week-old boy was admitted for paraplegia. His prenatal period and family history were unremarkable. MRI showed extradural tumor extended from L2 to sacral region. Levels of serum AFP and hCG were not elevated. The tumor was hemorrhagic and partially resected at the initial operation. Pathologically, the tumor consisted of immature mesenchymal tissue and primitive neuroepithelial elements. Primitive cartilage and skeletal muscle components were also observed. The tumor was diagnosed as immature teratoma after central pathology review. The patient received one course of chemotherapy with etoposide and carboplatin and then underwent total resection. Eight months later, however, the tumor recurred. The patient received partial resection and following local radiotherapy (45Gy) and chemotherapy with cisplatin, cyclophosphamide and etoposide. Although the patient transiently responded to the salvage therapy, he died of the disease with intracranial dissemination 25 months after initial diagnosis. MOLECULAR ANALYSIS: Analysis of frozen tumor sample by Ion Torrent sequencing revealed Dicer1 mutations (p.Arg745* in exon14 and p.Glu1813Lys in exon 25), confirmed by Sanger sequencing. Matched non-neoplastic material was not available. DISCUSSIONS AND CONCLUSIONS: The existence of Dicer1 mutation may reflect some embryonal components in the immature teratoma. Furthermore, the mutation in exon 14 may be germline mutation because previously reported somatic Dicer1 mutations are almost always restricted in RNaseⅢ domain (exon 24 and 25). Our case suggests that a subset of immature teratoma may be related to Dicer1 syndrome.
Pre-Clinical Evaluation of the PI3K-p110β/δ Inhibitor KA2237 in Mantle Cell Lymphoma
Authors: Shengjian Huang, Loretta J. Nastoupil, Hui Guo, Taylor Bell, Makhdum Ahmed, Carrie J Li, Jack Wang, Yang Liu, Victoria Zhang, Caroline R Kim, Jordan N Boyle, Elizabeth A Lorence, Laura T Lam, Zhihong Chen, Hui Zhang, Stephen Joseph Shuttleworth, Krystle Nomie, Michael Wang, Liang Zhang
Journal: Blood (2016)