tbuckley/cabot-search huggingface dataset:
Annals Consult Guys - Procedures With DOACs: How Long to Wait?
Authors: Geno J. Merli, Howard H. Weitz
Journal: Annals of Internal Medicine (2019)

Web Exclusives19 November 2019Annals Consult Guys - Procedures With DOACs: How Long to Wait?FREEGeno J. Merli, MD and Howard H. Weitz, MDGeno J. Merli, MDThomas Jefferson University, Philadelphia, Pennsylvania (G.J.M., H.H.W.)Search for more papers by this author and Howard H. Weitz, MDThomas Jefferson University, Philadelphia, Pennsylvania (G.J.M., H.H.W.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/W18-0050 SectionsSupplemental MaterialAboutVisual Abstract ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Annals Consult Guys brings a new perspective to the art and science of medicine with lively discussion and analysis of real-world cases and situations. They address medically relevant topics—whether they be poignant, thought-provoking, or just plain entertaining.For more videos from and information on Annals Consult Guys, visit go.annals.org/ConsultGuys. Comments0 CommentsSign In to Submit A Comment Alberto González-MárquezICPOE25 November 2019 A missing perspective Nice and instructive case. I learn't a lot.I think it could be usefull to add some insight in the indication of the epidural.Although epidural corticoids are usefull in the treatment of lumbar pain refractary to other therapies, many times the relief is transient and frequently many injections are needed. So the risk-benefit or the epidural in the present case must include the poor long term benefit offered. Author, Article, and Disclosure InformationAffiliations: Thomas Jefferson University, Philadelphia, Pennsylvania (G.J.M., H.H.W.)Disclosures: Geno J. Merli, MD, and Howard H. Weitz, MD, report that they have no financial relationships or interests to disclose.Editors' Disclosures: Christine Laine, MD, MPH, Editor in Chief, reports that her spouse has stock options/holdings with Targeted Diagnostics and Therapeutics. Darren B. Taichman, MD, PhD, Executive Editor, reports that he has no financial relationships or interests to disclose. Cynthia D. Mulrow, MD, MSc, Senior Deputy Editor, reports that she has no relationships or interests to disclose. Jaya K. Rao, MD, MHS, Deputy Editor, reports that she has stock holdings/options in Eli Lilly and Pfizer. Christina C. Wee, MD, MPH, Deputy Editor, reports employment with Beth Israel Deaconess Medical Center. Sankey V. Williams, MD, Deputy Editor, reports that he has no financial relationships or interests to disclose. Yu-Xiao Yang, MD, MSCE, Deputy Editor, reports that he has no financial relationships or interest to disclose. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byCorrection: Annals Consult Guys - Preventing Coronary Disease in Rheumatoid Arthritis: Do Guidelines Apply? 19 November 2019Volume 171, Issue 10Page: CG1KeywordsDiagnostic techniquesDisclosure ePublished: 19 November 2019 Issue Published: 19 November 2019 Copyright & PermissionsCopyright © 2019 by American College of Physicians. All Rights Reserved.Loading ...
A retrospective analysis of 66 colorectal cancer cases from Guy’s and St Thomas’ (GSTT) Molecular Tumour Board
Authors: M. Kapiris, D. Josephs, A. Kulkarni, M. Valganon, B. De Souza, J. Campbell, F. Churm, G. Nickless, P. Ross, J. De Naurois, N. Maisey, K. Thillai, J. Roca, M. George, A. Schizas, V. Datta, E. Westcott, D. Sarker
Journal: Annals of Oncology (2019)
CBMT-17. DEFECTIVE QKI-DEPENDENT LIPID METABOLISM INDUCES GENOMIC INSTABILITY AND SENSITIZES GLIOBLASTOMA TO IMMUNOTHERAPY
Authors: Takashi Shingu, Jian Hu
Journal: Neuro-Oncology (2019)

Abstract Despite transformative effects on the therapy of cancers such as melanoma and lung adenocarcinoma, blockade of the T cell immune checkpoints has generated limited impact on glioblastoma. Identifying genetic/genomic alterations that could potentially sensitize the patients to immunotherapy will significantly improve the efficacy of immunotherapy on glioblastoma patients. As part of our effort to identify novel glioma suppressors that affect the interaction of GSCs with their microenvironment, we discovered that the RNA-binding protein Quaking (QKI) is a key regulator of cellular endocytosis. QKI is mutated or deleted in ~34% of human glioblastomas. Supporting QKI’s tumor suppresser function, 92% of the Nestin-CreERT2;QkiL/L;PtenL/L;p53L/L mice developed glioblastoma with a median survival of 105 days, however, the Nestin-CreERT2;PtenL/L;p53L/L mice did not develop any glioma up to a year. Mechanistically, QKI regulates the RNA stability and alternative splicing of numerous protein and lipid components of endolysosomes, particularly the unsaturated fatty acids (UFAs). Functionally, deletion of Qki and inhibition of UFA biosynthesis both decrease endolysosome-mediated receptor degradation, thereby enriching receptors on the cytoplasmic membrane (e.g., Frizzled and Notch1) that are essential for maintaining stemness. This enrichment of receptor signaling enables GSCs to cope with the low ligand levels during their invasion. On the other hand, lower lysosomal activity induced by Qki deletion and UFA loss led to defective mitophagy. We also found that insufficient UFAs in mitochondrial membrane significantly compromised mitochondrial membrane integrity and function. These two mechanisms concomitantly led to accumulation of damaged mitochondria and higher levels of reactive oxygen species (ROS), and consequently genomic instability. Lastly, we found that the higher level of genomic instability induced by Qki loss rendered cells more sensitive to anti-CTLA4 and anti-PD1 antibodies. Taken together, our data suggest that Qki/UFA loss-induced endolysosomal and mitochondrial defects promote gliomagenesis yet render cells vulnerabilities that could be harnessed for therapeutic purposes.
RTHP-42. OUTCOMES AFTER FRACTIONATED STEREOTACTIC RADIOSURGERY FOR BRAIN METASTASES
Authors: Rebecca Anderson, Liberty Bonestroo, Christopher Spencer
Journal: Neuro-Oncology (2019)

Abstract PURPOSE To examine outcomes in patients undergoing linear accelerator (LINAC) based fractionated stereotactic radiosurgery (fSRS) to 30 Gy in 5 fractions. METHODS We completed a retrospective review of patients with brain metastases treated with 5-fraction LINAC fSRS at Phelps Health. All patients with CNS metastatic disease treated with fSRS were included in the study. Incidence of symptomatic radionecrosis (sRN), local brain failure (LBF), time to death, target volume and dose, prior whole brain radiotherapy (WBRT), prior surgical resection, and concurrent immunotherapy were assessed. sRN was defined as grade 2 or higher per CTCAE v4.0. RESULTS From 2016–2019, 28 patients and 60 lesions were treated. The most common metastasis histology was non-small cell lung cancer (n = 22), renal cell carcinoma (n = 12), and melanoma (n = 11). Median follow-up time was 6.49 months (range 0.33 – 23.96). Of 60 lesions, three lesions developed sRN and one asymptomatic patient developed radiographic evidence of radiation necrosis. Mean GTV was 1.03cm3 in patients with sRN. Of 57 lesions without sRN, median GTV was 1.45cm3 (range 0.11 - 20.1). Mean time to sRN was 3.17 months. Two symptomatic patients received prior WBRT. One symptomatic patient received concurrent immunotherapy. No symptomatic patients had surgical resection prior to fSRS. Among 24 lesions without prior radiation, 1 (4.2%) developed sRN. 10 lesions underwent surgical resection prior to fSRS with none developing sRN. 34 lesions were treated with concurrent immunotherapy and one developed sRN (2.9%). Local failure occurred in 9 lesions (15%). Median time to death for all patients was 4.50 months (range 1.02 - 19.40). CONCLUSIONS fSRS to 30 Gy in 5 fractions has promising efficacy with low incidence of sRN in treatment of CNS metastatic disease. Further investigation is required to determine predictors in patient outcome.
Development and Performance of Risk Stratification Models for AML Patients Utilizing ELN-2017 Guidelines and Additional Prognostic Factors: A SWOG Report
Authors: Era L Pogosova-Agadjanyan, Anna Moseley, Megan Othus, Frederick R. Appelbaum, Thomas R. Chauncey, I-Ming L. Chen, Harry P. Erba, John E. Godwin, Isaac C. Jenkins, Min Fang, Mike Huynh, Kenneth J Kopecky, Alan F. List, Jasmine Naru, Jerald P. Radich, Emily Stevens, Brooke E Willborg, Cheryl L. Willman, Brent L Wood, Qing Zhang, Soheil Meshinchi, Derek Stirewalt
Journal: Blood (2019)
Real-World Clinical Burden of Sickle Cell Disease in the US Community-Practice Setting: A Single-Center Experience from the Foundation for Sickle Cell Disease Research
Authors: Lanetta Bronté-Hall, Matthew Parkin, Courtney Green, Elsa Tchouambou, Lynn Huynh, Charu Puri-Sharma, Rose Chang, Anjulika Chawla, James Signorovitch, Gershwin Theophilus Blyden
Journal: Blood (2019)
Review of The American Society of Colon and Rectal Surgeons Clinical Practice Guidelines for the Use of Bowel Preparation in Elective Colon and Rectal Surgery
Authors: Donald E. Fry
Journal: JAMA Surgery (2019)

This Clinical Guideline Synopsis reviews the Clinical Practice Guidelines Committee of the American Society of Colon and Rectal Surgery guidelines on the use of bowel preparation in elective colon and rectal surgery.
Pressure Ulcer Treatment Strategies
Authors: M.E. Beth Smith, Annette Totten, David H. Hickam, Rongwei Fu, Ngoc Wasson, Basmah Rahman, Makalapua Motu’apuaka, Somnath Saha
Journal: Annals of Internal Medicine (2013)

Pressure ulcers are major sources of morbidity, mortality, and health care costs. This systematic review examined the comparative effectiveness and harms of strategies for treating pressure ulcers....
COMP-17. LARGE-SCALE TRANSCRIPTOMIC CHARACTERIZATION OF PRIMARY AND RECURRENT GLIOBLASTOMA IDENTIFIES GENE EXPRESSION SIGNATURE OF TUMOR RESPONSE TO STANDARD THERAPY
Authors: Andrew Dhawan, Justin Lathia, David Peereboom, Gene Barnett, Gabrielle Yeaney, Manmeet Ahluwalia
Journal: Neuro-Oncology (2019)

Abstract A near-universal phenomenon in glioblastoma is disease recurrence following surgical resection and chemoradiotherapy. Development of biomarkers predictive of therapeutic response to better guide care and inform future targeted therapies is crucial. In this work, a total of 84 glioblastoma surgical specimens involving 44 primary tumors and 40 matched samples at time of re-resection, were characterized utilizing RNA-sequencing. Transcriptomic analysis was carried out with the goal of identifying underlying differences between those patients with prolonged response to standard therapy and delayed time to re-resection. We examined individual gene expression, gene coexpression networks, and well-known gene pathways in this dataset that showed consistent association with time to re-resection in both primary and progressed specimens, independent of tumor molecular subtype. Leveraging this large, well-characterized dataset, and using a novel computational methodology based on a seed-gene approach, we identified a predictive gene signature for therapeutic response. Our analyses revealed a striking degree of heterogeneity among gene expression associated with response to standard therapy and time to re-resection, adding to the complexity of signature derivation. The novel signature we obtained for response showed components involving genes such as those in the IGF pathway (IGF2BP2, IGF2BP3) and PDGF-signalling pathway (MYC, FLI1, ARHGAP4, JAK3) predictive of poor response to therapy. Likewise, predictors of positive response to therapy included genes involved in the apoptosis and RAS pathways (RAB4A, CHUK) and DNA replication pathways (SSBP2). In sum, this is among the largest cohorts of well-characterized clinical tumor samples for which there is transcriptomic information from primary and re-resected samples from matched patients. Our results not only highlight an innovative computational method for gene signature derivation in the setting of significant underlying heterogeneity, but also result in a predictive gene signature, offering the potential to give therapy to those who stand to benefit most.
Interim Analysis of the Extension Study with rVIII-SingleChain in Previously Untreated Patients (PUPs) with Severe Hemophilia A (CSL627-3001)
Authors: Elena Santagostino, Kathelijn Fischer, Christoph Koenigs, Claudia Djambas Khayat, Samantha Lucas, Blanca Salazar, Andres Brainsky, Thomas Chung, Brahm Goldstein, Johnny Mahlangu
Journal: Blood (2019)
Dangers of Steroids for Rheumatoid Arthritis
Authors: F. D. Hart
Journal: BMJ (1964)

SIR,-We wish to support Dr. R. E. Smith's plea (14 March, p. 695) for a full adoption of the metric system as soon as possible, and especially his suggestion that we must abandon the past and not use the system in terms of more or less exact equivalents of the Imperial system.The 1963 editions of the British Pharmacopocia and British Pharmaceutical Codex 'both include notices stating that up to 30 June 1965 preparations in the old system may be supplied when metric or Imperial prescriptions or those without strengths are -presented.This is to allow timne for the disposal of old stocks.The time limit has now been extended to 31 July 1965 for manufacturers or wholesalers and 31 January 1966 for retailers.The General Notices of the Codex state that the Codex Revision Committee intended to reformulate all the preparations of the -Codex in rational metric terms, but it was found impossible to carry out all the necessary experimental work before the volume had to go to press.It was therefore decided that the 1963 Codex reformulation should confine this to certain solid unit dosage forms, such as lozenges, pastilles, pessaries, suppositories, and tablets.The remaining preparations will be altered in the next edition (due in 1968).Liquid formulae containing new products have, however, been formulated in rational metric quantities.This results in some linctuses, for example, being made up to a 5 ml.dose and others to a 60 minim (4 ml.) dose.The anomalies will be removed in the -next edition.This delay is unfortunate since it will prolong the confusion.As we pointed out in this journal in 1953,1 the change means a certain amount of hard- ship to those who have to alter their prescribing habits, but the eventual result will justify it.This hospital changed completely to the metric system on 1 January 1957 after two years' notice had been given, and the change -went smoothly with no serious difficulties.2A U.C.H. sister stated that " getting accustomed to the metric system was like learning a new language, and learning to think in this new language took time and effort," but she concluded that once the effort had been made " the advantage of the metric system as far as the nursing staff is con- cerned is that it is more simple and, therefore, safer."' We consider it is best to change as soon as possible to rational quantities based on 50 mg.instead of 60.As one of us has
Association Between Prescribed Opioids and Infections in Patients With Neutropenia and Cancer
Authors: Carolin E. M. Jakob, Melanie Stecher, Annika Y. Claßen, Axel Hamprecht, Oliver A. Cornely, Jörg J. Vehreschild
Journal: JAMA Internal Medicine (2019)

The answer to these 2 questions invariably leads to others.Will AMCs and other sponsors be shamed into doing a better job once their results are posted with indications of their flaws?Will the US Food and Drug Administration and NIH be prompted to use their enforcement authorities, thus incentivizing trial sponsors to provide higher quality information?Or will the public come to distrust the ClinicalTrials.govresults database when so many posted entries display notices of errors?Both the NIH and trial sponsors have a role to play in ensuring that accurate results are publicly available within the legally mandated time frame, but only the sponsor can provide the meaningful information.ClinicalTrials.govcontinually works to improve the data entry system, increase realtime alerts to problematic entries, and increase staffing levels.These steps are likely to reduce frustration and burden of data entry but are unlikely to reduce most identified errors, which reflect difficulties understanding fundamental principles of trial methods or lack of access to the required data.These problems reflect deficiencies in the research enterprise that demand attention independent of ClinicalTrials.govreporting.If the data in ClinicalTrials.govcannot be trusted, then how can one trust journal publications that rely on the same information?Although external pressure might incentivize improved reporting, in the end, the practices of individual investigators will continue to reflect the culture established by their leaders and the support of their organizations.
Clinical Outcomes Following Bone Marrow Transplant in Patients with Sickle Cell Disease: A Cohort Study of US Medicaid Enrollees
Authors: Mufaddal Mahesri, Sebastian Schneeweiss, Raisa Levin, Denise Globe, Krista McKerracher, Alex Mutebi, Rhonda Bohn, Maureen Achebe, Rishi J Desai
Journal: Blood (2019)
Unusual Urinary Contaminants
Authors: J. J. Taylor
Journal: BMJ (1965)

JOURNAII agree with Dr. Todd that aspirin may well have been a proper drug to prescribe for the " subjects " that he questioned.He tells us that, as a profession, our fault is not the failure to give treatment, but the giving of too much treatment." Steroids, chloroquine, gold, and phenylbutazone are all dangerous drugs which should be reserved for the severely afflicted but which are too often given to patients with minor diseases who 'demand' that something be done."If treatment means just the prescription of drugs he has a case, but every experienced family doctor and many consultants know that proper advice is advice proper to the individual patient, and that the prescription of drugs forms only a small part of the manage- ment of the patient.When we see an out- patient for the first time, we do not know if this patient is suffering from " a minor disease," or will in five years' time be " severely afflicted " and be suitable for treat-
CBMT-04. MOLECULAR MECHANISM OF OLIG2-CDK2 INTERACTION IN GLIOMA CELLS
Authors: Norihiko Saito, Nozomi Hirai, Kazuya Aoki, Sho Sato, Ryo Suzuki, Yu Hiramoto, Haruo Nakayama, Morito hayashi, Takatoshi Sakurai, Satoshi Iwabuchi
Journal: Neuro-Oncology (2019)

Abstract Oligodendrocyte transcription factor 2 (OLIG2) promotes proliferation of normal neural stem/progenitor cells and glioma cells. However, the mechanisms underlying the regulation of OLIG2 remain largely unknown. Here we identified OLIG2 as a critical phosphorylation target for cyclin-dependent kinase 2 (CDK2). CDK2-mediated OLIG2 phosphorylation stabilizes OLIG2 protein from proteasomal degradation. Phosphorylated OLIG2 binds to the E-Box regions of p27 promoter and represses p27 transcription, which in turn activates CDK2 in positive feedback manner. CDK2-mediated OLIG2 phosphorylation promotes cell cycle progression, cell proliferation, and tumorigenesis. OLIG2 inhibition disrupted cell cycle control mechanism by decreasing CDK2 and elevating apoptosis-related molecules. Inhibition of CDK2 activity disrupted OLIG2-CDK2 interactions and attenuated OLIG2 protein stability. In addition, OLIG2-high glioma initiating cells are highly sensitive to CDK2 inhibitor treatment, indicating that OLIG2 can be a biomarker for personalized treatment for glioblastoma patients with CDK2 inhibitors. Further investigation on these mechanisms may lead to novel targeted therapy on GBMs with high OLIG2 expression.
Outpatient BEAM Using Daily Etoposide and Cytarabine with Autologous Hematopoietic Stem Cell Transplantation for Lymphoma Is Feasible and Decreases Inpatient Length of Stay
Authors: Naomi Cazeau, Kathleen Cavalier, Valkal Bhatt, Courtney McElrath, Nicole Lestrange, Margot Lachaud-Richard, Faye Inumerables, Marci Andrejko, Jason Batalha, Abigail Cohen, Melissa Cortes, Christina Kiss, Dayna Palumbo, Heather J Landau, Oscar B Lahoud, Parastoo B. Dahi, Michael Scordo, Craig S. Sauter, Sergio A. Giralt, Gunjan L. Shah
Journal: Blood (2019)
Efficacy of Phosphatidylinositol 3-Kinase (PI3K) Inhibitors in Patients with Relapsed and Refractory Chronic Lymphocytic Leukemia/ Small Lymphocytic Lymphoma
Authors: Anita Sultan, Bradley J. Grant, Donald P. Quick, Chandler Graf, Sriman Swarup, Sriman Swarup, Jonathan Kopel, Thura Win Htut, Somedeb Ball, Ei Moe Phyu, Myat Min Han, Yin Mon Myat, Nicholas D'Cunha, Myint Aung Win, Kyaw Zin Thein
Journal: Blood (2019)
O.01 Challenges of Interpreting NGS Liquid Biopsy (LB) Results in Advanced NSCLC: Are ESCAT and OncoKB Scales Reliable?
Authors: A. Russo, M. Mccusker, J. Chen, K.A. Scilla, R. Mehra, A. Gittens, C.D. Rolfo
Journal: Journal of Thoracic Oncology (2019)
NanoSatellite: accurate characterization of expanded tandem repeat length and sequence through whole genome long-read sequencing on PromethION
Authors: Arne De Roeck, Wouter De Coster, Liene Bossaerts, Rita Cacace, Tim De Pooter, Jasper Van Dongen, Svenn D’Hert, Peter De Rijk, Mojca Strazisar, Christine Van Broeckhoven, Kristel Sleegers
Journal: Genome biology (2019)

Technological limitations have hindered the large-scale genetic investigation of tandem repeats in disease. We show that long-read sequencing with a single Oxford Nanopore Technologies PromethION flow cell per individual achieves 30× human genome coverage and enables accurate assessment of tandem repeats including the 10,000-bp Alzheimer's disease-associated ABCA7 VNTR. The Guppy "flip-flop" base caller and tandem-genotypes tandem repeat caller are efficient for large-scale tandem repeat assessment, but base calling and alignment challenges persist. We present NanoSatellite, which analyzes tandem repeats directly on electric current data and improves calling of GC-rich tandem repeats, expanded alleles, and motif interruptions.
Molecular characterization of a second myeloid neoplasm developing after treatment for acute myeloid leukemia
Authors: Luise Hartmann, Niroshan Nadarajah, Manja Meggendorfer, Alexander Höllein, Calogero Vetro, Wolfgang Kern, Torsten Haferlach, Claudia Haferlach, Anna Stengel
Journal: Leukemia (2019)
Inherited transmission of the CSF3R T618I mutational hotspot in familial chronic neutrophilic leukemia
Authors: Nicolas Duployez, Christophe Willekens, Isabelle Plo, Alice Marceau-Renaut, Stéphane de Botton, Laurène Fenwarth, Thomas Boyer, Guillemette Huet, Olivier Nibourel, Christian Rose, Brigitte Nelken, Bruno Quesnel, Claude Preudhomme
Journal: Blood (2019)
Biomarkers of Hemostatic Dysregulation and Inflammation in Lymphoma: Potential Relevance to Thrombogenesis
Authors: Darko Antic, Natasa Milic, Emily Bontekoe, Debra Hoppensteadt, Vladislava Djurasinovic, Vojin Vukovic, Vladimir Otasevic, Kristina Tomic, Biljana Mihaljevic, Jawed Fareed
Journal: Blood (2019)