tbuckley/cabot-search huggingface dataset:
Deep vein thrombosis and anaesthetic technique in emergency hip surgery.
Authors: F M Davis, M Quince, V G Laurenson
Journal: BMJ (1980)

sent for virological examination.She described her illness, which had begun on 30 July with headache, fever, malaise, and tiredness followed by the appearance of mouth ulcers and several blisters on arms, legs, and trunk.This was clinically diagnosed as chickenpox.On admission she had several healing blisters on limbs and trunk (see figure).Her only child, a girl of .. . . . . .--, ...... ...Case-2.Appearance of healing blister at time of admission. 16months, had been unwell with a fever and papular rash on the buttocks the week before the patient's illness.Coxsackie virus A16 was isolated (in MRC5.cells) from the products of conception and identified by neutrahsation tests in suckling mice.Case 3-A third patient reported that she had had a mild attack of hand- foot-and-mouth disease in the 14th week of pregnancy after contact with infected children.She described mouth ulcers and a few skin vesicles but no systemic upset.Her pregnancy was continuing normally to mid-term.Pre-illness serum was available for these three patients, and convalescent samples obtained from each.Using an indirect immunofluorescence test for antibody to Coxsackie virus A16,1 we showed a specific response in all three patients.Some IgG antibody was detectable in all pre-illness sera (titres 16, 8, 8), but there was a significant increase' in each convalescent serum titre (128, 512, 512).The specificity of the pre-existing antibody remains to be determined.
The Result of a Phase 1 Study of Selinexor in Combination with High-Dose Melphalan and Autologous Hematopoietic Cell Transplantation for Multiple Myeloma
Authors: Taiga Nishihori, Melissa Alsina, Jose Ochoa, Omar Alexis Castaneda Puglianini, Rachid Baz, Kenneth H. Shain, Jason B. Brayer, Jongphil Kim, Michael Dumala, Joel G. Turner, Daniel M Sullivan
Journal: Blood (2019)
Sinusoidal Obstructive Syndrome Among Pediatric and Adolescent and Young Adult Patients: Analysis of Pediatric EBMT Diagnostic and Severity Criteria at MD Anderson
Authors: Francesco Tambaro, Dristhi Ragoonanan, Sajad Khazal, Demetrios Petropoulos, Priti Tewari, Partow Kebriaei, William G. Wierda, Mira A. Kohorst, Kris Michael Mahadeo
Journal: Blood (2019)
Niveau, a Phase 3 Study for Pts with B- or T-Cell Aggressive Non-Hodgkin Lymphoma in First Relapse or Progression Not Eligible for High-Dose Chemotherapy (HDT), Testing Nivolumab in Combination with Gemcitabine, Oxaliplatin (GemOx), Plus Rituximab (R) in Case of B-Cell Lymphoma
Authors: Gerhard Held, Roch Houot, Abraham Avigdor, Marc André, Anna Dabrowska-Iwanicka, Ulrich Jaeger, Sanne Tonino, Marek Trneny, Gomes da Silva Maria, Philippe Gaulard, Thierry Jo Molina, Andreas Rosenwald, Grzegorz Rymkiewicz, Thierry Fest, Karin Tarte, Markus Loeffler, Marita Ziepert, Bettina Altmann, Viola Poeschel, Corinne Haioun
Journal: Blood (2019)
Sulphamerazine Treatment of Pneumonia in Adults
Authors: R. N. Johnston
Journal: BMJ (1948)

MBRICASH 73 for insurance practitioners to put in notices of resignation from the N.H.I. service and for members of National Service and Ministry of Pensions Medical Boards to do likewise.This would serve to show this dictator-minded Minister that we are by no means disposed to walk into his parlour or to succumb to his ruthless threat of force, and that we at last realize that we can place no trust whatever in his word.Having marked our disapproval in this unmistakable fashion, we could then settle down with quieter minds to hold our plebiscite, and to get ready for the inevitable conflict.
Incidence of Myocardial Infarction and Cerebrovascular Accident in Patients With Hidradenitis Suppurativa
Authors: Sarah Reddy, Andrew Strunk, Gregor B. E. Jemec, Amit Garg
Journal: JAMA Dermatology (2019)

Although hidradenitis suppurativa (HS) is associated with several cardiovascular risk mediators, information on the risk of myocardial infarction (MI) and cerebrovascular accident (CVA) in this population is sparse.To compare risk of MI, CVA, and composite disease (MI or CVA) in patients with HS, stratified by use of biologic agents, with controls without HS.A retrospective cohort analysis was conducted between January 1, 1999, and April 1, 2019, using a demographically heterogeneous population-based sample of over 56 million unique patients. Individuals with HS (n = 49 862) and without HS (n = 1 421 223) were identified using electronic health records data.The primary outcome was incidence of composite MI or CVA.Of the 49 862 patients with HS, 37 981 were women (76.2%), 29 711 were white (59.6%), and mean (SD) age was 38.3 (13.3) years. Crude incidence rate of composite disease was 6.6 (95% CI, 6.3-7.0) per 1000 person-years in patients with HS compared with 6.8 (95% CI, 6.7-6.8) per 1000 person-years in controls. In patients with HS, crude incidence rates were 2.9 (95% CI, 2.6-3.1) per 1000 person-years for MI alone and 4.1 (95% CI, 3.9-4.4) per 1000 person-years for CVA alone compared with 3.2 (95% CI, 3.18-3.25) per 1000 person-years for MI alone in control patients and 4.1 (95% CI, 4.0-4.1) per 1000 person-years for CVA alone in control patients. In adjusted analysis, patients with HS had a 23% increased risk of composite disease (hazard ratio [HR], 1.23; 95% CI, 1.17-1.30; P < .001) and a similar increase in the risk of MI alone (HR, 1.21; 95% CI, 1.12-1.32; P < .001) and CVA alone (HR, 1.22; 95% CI, 1.14-1.31; P < .001) compared with control patients. The relative difference in composite MI or CVA risk between patients with HS and controls was highest among younger patients HR in subgroup aged 18-29 years: 1.67; 95% CI, 1.37-2.03).Patients with HS appear to have an increased risk of MI and CVA. Early management of modifiable cardiovascular risk mediators may be warranted in patients with HS.
Toward healthier abortion and drug laws
Authors: Richard Hurley
Journal: BMJ (2019)

Since Northern Ireland’s law was amended last month, women who want an abortion can be treated as patients rather than criminals, as one doctor puts it in a feature this week (p 224). Previously, abortion in Northern Ireland was permitted only when a woman faced permanent harm, with no exceptions for severe fetal abnormality or after rape or incest. Many women had to travel overseas to receive care considered routine in the rest of the UK. Doctors also risked criminalisation if they did not report a suspected illicit abortion. The law change removes this …
IMMU-17. TARGETING GLIOBLASTOMA WITH DNAM-1-BASED CHIMERIC ANTIGEN RECEPTOR (CAR) T CELLS
Authors: Tobias Weiss, Hanna Meister, Michael Weller, Charles Sentman, Patrick Roth
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND Genetically engineered T cells that express a chimeric antigen receptor (CAR) have shown powerful anti-tumor activity in extracranial malignancies. This concept is now also being explored against glioblastoma. However, many single target antigens used for CAR cell therapy are non-homogeneously expressed. We assessed the therapeutic potential of CAR T cells targeting 2 antigens which are homogeneously expressed by glioma cells which reduces the probability of tumor immune escape due to antigen loss. METHODS We analyzed the expression of CD112 and CD155, which are ligands to the activating immune cell receptor DNAX Accessory Molecule-1 (DNAM-1), in a panel of mouse and human glioma cell lines as well as in human glioblastoma samples and generated glioma cells with a CD112 or CD155 knock-out. To exploit the specific binding properties of DNAM-1, we generated first or second-generation CAR T cells that use DNAM-1 as an antigen-binding domain and investigated their anti-tumor activity in vitro and in vivo using syngeneic orthotopic mouse glioma models. RESULTS CD112 and CD155 are homogeneously expressed in mouse and human glioma cell lines as well as human glioblastoma tissue specimens. CRISPR/Cas9-mediated knock-out of CD112 or CD155 affected the migration of glioma cells, but had no impact on the proliferation or susceptibility to irradiation or temozolomide. DNAM-1-based CAR T cells exerted high cytolytic activity and secretion of various effector cytokines in vitro. Upon intravenous administration, DNAM-1-based CAR T cells did not exert significant toxicity, homed to the tumor site in the brain and prolonged the survival of orthotopic glioma-bearing mice with durable anti-tumor responses in a fraction of mice. CONCLUSION CD112 and CD155 represent attractive targets for glioma immunotherapy using genetically engineered immune cells. Based on the data obtained from our preclincal assessment of DNAM-1-based CAR T cells, this immunotherapeutic strategy might also be explored in human glioma patients.
Evolution in Practice Patterns and Differences Among Experts and Community Healthcare Providers in the Treatment of Patients with Chronic Lymphocytic Leukemia
Authors: Bing-E Xu, Kristen M Rosenthal, Krista Marcello, Farrukh T. Awan, Steven Coutre, Nicole Lamanna, Jeff P. Sharman, Timothy A Quill, Kevin L Obholz, Andrew D. Zelenetz
Journal: Blood (2019)
NIMG-15. DEUTERIUM METABOLIC IMAGING (DMI) MEASURES THE WARBURG EFFECT IN BRAIN TUMORS
Authors: Zachary Corbin, Isabel Prado, Robert Fulbright, Douglas Rothman, Robin de Graaf, Henk De Feyter
Journal: Neuro-Oncology (2019)

Abstract INTRODUCTION Metabolic changes in cancer have gained renewed interest as potential diagnostic and prognostic markers. The tendency to favor glycolysis in the presence of oxygen has been coined the Warburg Effect. We developed a magnetic resonance-based method that illustrates this metabolic shift. Deuterium Metabolic Imaging (DMI) observes glucose metabolism by tracing deuterium-labeled downstream metabolites, effectively representing the Warburg Effect. This pilot study uses DMI to visualize in vivo the Warburg Effect in subjects with brain tumors. METHODS We screened Yale Neuro-Oncology patients, excluding those with diabetes and MRI contraindications. Recruited subjects orally consumed 0.75g/kg of [6,6’-2H2]-glucose dissolved in water. Imaging studies were performed using a 4T magnet interfaced to a Bruker spectrometer. All data were analyzed in Matlab 8.3. Deuterium-labeled metabolite levels were overlaid on MRI to generate amplitude color maps for glucose, glutamate+glutamine (Glx), lactate, and the lactate/Glx ratio, representing the Warburg Effect. RESULTS Six brain tumor subjects were imaged. Age ranged from 53 to 72 years, and five subjects were men. Diagnoses included 4 glioblastomas (GBMs), 1 anaplastic oligodendroglioma (AO), and 1 meningioma. DMI mapping revealed regional differences between tumor sites and contralateral areas. All GBMs showed the Warburg Effect, while the AO and meningioma did not. CONCLUSION The Warburg Effect was not evident in DMI of every high-grade brain tumor, as it was not observed in the WHO grade III AO. While this tumor has a lower WHO grade than GBM, we speculate that this discrepancy relates to its molecular characterization, including an IDH1 R132H mutation, MGMT methylation, and 1p/19q codeletion. The brain tumor treatment paradigm is shifting from one based upon WHO grade to one centered around molecular features. We believe DMI provides detailed metabolic information about tumor aggressiveness, which may be linked to molecular characteristics, underscoring its clinical relevance for brain tumor diagnosis and management.
Exposure-Response Relationship of the SMART-Ig Anti-hC5 Antibody Crovalimab (SKY59): Results from the Umbrella Phase 1/2 Composer Trial in Healthy Volunteers and PNH Patients
Authors: Alexandre Sostelly, Simon Buatois, Antoine Soubret, Erica Winter, Barbara Klughammer, Joy C. Hsu, Gregor Jordan, Christoph Bucher, Jean-Eric Charoin, Keisuke Gotanda, Kenji Shinomiya, Zsolt Nagy, Jens P. Panse, Sung-Soo Yoon, Régis Peffault de Latour, Junichi Nishimura, Alexander Röth
Journal: Blood (2019)
ATIM-05. A PHASE I STUDY TARGETING NEWLY DIAGNOSED GLIOBLASTOMA WITH ANTI-CD3 × ANTI-EGFR BISPECIFIC ANTIBODY ARMED T CELLS (EGFR BATS) IN COMBINATION WITH RADIATION AND TEMOZOLOMIDE
Authors: Camilo Fadul, Jungeun Kim, Archana Thakur, Benjamin Purow, Maria-Beatriz Lopes, David Schiff, Jessica Kassay-McAllister, Joseph Donahue, Qin Liu, Lawrence Lum
Journal: Neuro-Oncology (2019)

Abstract Overcoming the highly immunosuppressive glioblastoma (GBM) microenvironment is critical to successful immunotherapy. In a recently-launched phase I trial we are examining the safety and feasibility of a novel adoptive cell immunotherapy platform, activated T cells (ATC) with anti-CD3 X anti-EGFR bispecific antibody (EGFR BATs), for patients with newly-diagnosed GBM. Autologous T cells obtained before radiation and chemotherapy are expanded and activated, becoming cytotoxic T lymphocytes. We postulate that these activated T cells armed with bispecific antibody will enhance the response to radiation/temozolomide and potentially increase trafficking to the GBM microenvironment. In a 3 + 3 design dose-escalation trial, we will determine the maximum tolerated dose (MTD) of three dose tiers of EGFR BATs (80, 120 and 160 billion cells divided in eight infusions) in combination with radiation/temozolomide in patients with newly-diagnosed GBM. Patients undergo leukapheresis prior to initiating radiation/temozolomide. Patients receive EGFR BATs on days 14 and 21 after finishing concurrent RT/ temozolomide and on day 21 of six cycles of adjuvant temozolomide. We are measuring peripheral blood immune response before and after immunotherapy and correlating the results with patient characteristics and clinical outcomes. The first four patients have been treated at the first dose tier (80 billion cells) without any dose-limiting toxicity. Updated safety and feasibility results on the patients in the first two dose tiers will be presented, as well as immune monitoring studies, imaging studies, and clinical outcomes.
Overcoming Adaptive Therapy Resistance in AML By Targeting Immune Response Pathways
Authors: Katelyn M. Melgar, LaQuita M Jones, Mackenzie Walker, Lyndsey C Bolanos, Kathleen Hueneman, Mark Wunderlich, Jiang-Kang Jiang, Kelli Wilson, Xiaohu Zhang, Patrick Sutter, Xin Xu, Kwangmin Choi, Gregory Tawa, Donald Lorimer, Jan Abendroth, Eric O'Brien, Scott Hoyt, Ellin Berman, Christopher Famulare, James C Mulloy, Ross L. Levine, Jan S Rosenbaum, John P Perentesis, Craig J Thomas, Daniel T. Starczynowski
Journal: Blood (2019)
Pharmacological Inhibition of the RNA m6a Writer METTL3 As a Novel Therapeutic Strategy for Acute Myeloid Leukemia
Authors: Konstantinos Tzelepis, Etienne De Braekeleer, Eliza Yankova, Justyna Rak, Demetrios Aspris, Ana Filipa Domingues, Richard Fosbeary, Alan Hendrick, Dan Leggate, Yaara Ofir-Rosenfeld, Alexandra Sapetschnig, Cristina Pina, Mark Albertella, Wesley Blackaby, Oliver Rausch, George S. Vassiliou, Tony Kouzarides
Journal: Blood (2019)
DDEL-15. NANOTHERAPEUTIC TARGETING OF TUMOR ENDOTHELIUM FOR ENHANCING DRUG DELIVERY PAST THE BLOOD-BRAIN BARRIER
Authors: Hiro Kiguchi, Daniel Tylawsky, Jake Vaynshteyn, Jeffrey Gerwin, Mandana Manzari, Janki Shah, Na Li, Yosi Shamay, Matthew Greenblatt, Daniel Heller, Praveen Raju
Journal: Neuro-Oncology (2020)

Abstract OBJECTIVE The Sonic Hedgehog (SHH) medulloblastoma subgroup accounts for ~25% of all cases and has an intermediate prognosis. Current therapies result in devastating morbidities including intellectual disability and secondary malignancies. Although molecularly targeted agents against the SHH pathway have demonstrated efficacy, on-target bone toxicities suggest new therapeutic approaches are needed. METHODS We investigated the SHH pathway inhibitor, vismodegib, packaged in a fucoidan-based nanoparticle (Fi-Vis) that targets P-selectin expressed on endothelial cells and induced by low-dose ionizing radiation (XRT) in a time- and dose-dependent manner. This P-selectin targeting nanoparticle shows selectivity toward tumor and not normal brain vasculature in a GEM SHH medulloblastoma model as assessed by ex vivo infrared imaging and molecular studies. RESULTS Quantitative RT-PCR analysis of SHH medulloblastoma following single dose XRT and Fi-Vis treatment (10mg/kg) showed synergistic reduction of Gli1 expression (&amp;gt;90% target inhibition). We demonstrate that low-dose XRT (0.25Gy) can induce P-selectin expression specifically on medulloblastoma tumor endothelium and synergize with low-dose Fi-Vis (10mg/kg) to significantly enhance mouse survival (p&amp;lt;0.01) compared to radiation or Fi-Vis alone. Assessment of bone toxicity using micro-CT and histological analysis following Fi-Vis administration in postnatal (P10) mice shows no bone toxicity when compared to free vismodegib. Finally, in vitro studies using bEnd.3 brain endothelial cells and in vivo studies using Cav1 knockout mice suggest a caveolin-1 mediated transcytosis mechanism for nanoparticle entry across the blood-brain barrier. CONCLUSIONS These data suggest applicability of combined XRT and tumor vasculature-targeted nanotherapeutic dose de-escalation strategies for SHH medulloblastoma with implications for other pediatric brain tumors.
CBMT-46. MICRORNA-206 ATTENUATES GLIOMA CELL PROLIFERATION, MIGRATION, AND INVASION BY BLOCKING THE WNT/β-CATENIN PATHWAY VIA DIRECT TARGETING OF FRIZZLED 7
Authors: Yingyi Wang, Fengqi Zhou, Chunsheng Zhao
Journal: Neuro-Oncology (2019)

Abstract Glioma is one of the most frequent primary malignant brain tumours in adults and accumulating evidence has shown that microRNAs (miRNAs) are associated with various types of tumours, including glioma. It is essential to acquire a better understanding of the roles and mechanisms of miRNAs in WNT-driven glioblastoma (GBM). Here, we report that miR-206 inhibited the WNT/β-catenin pathway by directly targeting Frizzled 7 (FZD7) and functioned as a tumour-suppressor in glioma. The expression of miR-206 in human samples and glioma cells was assessed by real-time quantitative PCR (RT-qPCR), fluorescence in situ hybridization (FISH), and histological analysis. Cell Counting Kit-8 (CCK-8), colony formation, EdU, flow cytometry, wound healing, transwell invasion, and three-dimensional migration were performed to observe cellular proliferation, migration, and invasion in vitro. The effects of miR-206 in vivo were investigated using a xenograft nude mouse model. miR-206 expression was significantly downregulated in glioma specimens. FZD7 was confirmed as a direct target of miR-206. GBM cell proliferation, migration, and invasion were blocked by restoring the expression of miR-206. Moreover, intracranial glioma models demonstrated an inhibitory effect of miR-206 on intracranial glioma tumour growth. Our results suggested that miR-206 plays a key role in blocking the WNT/β-catenin signalling pathway by suppressing FZD7 and provides a prospective therapeutic strategy for the treatment of malignant glioma and other WNT-driven tumours.
Development of Genome-Derived Tumor Type Prediction to Inform Clinical Cancer Care
Authors: Alexander Penson, Niedzica Camacho, Youyun Zheng, Anna M. Varghese, Hikmat Al-Ahmadie, Pedram Razavi, Sarat Chandarlapaty, Christina E. Vallejo, Efsevia Vakiani, Teresa Gilewski, Jonathan E. Rosenberg, Maha Shady, Dana W. Y. Tsui, Dalicia N. Reales, Adam Abeshouse, Aijazuddin Syed, Ahmet Zehir, Nikolaus Schultz, Marc Ladanyi, David B. Solit, David S. Klimstra, David M. Hyman, Barry S. Taylor, Michael F. Berger
Journal: JAMA Oncology (2019)

Diagnosing the site of origin for cancer is a pillar of disease classification that has directed clinical care for more than a century. Even in an era of precision oncologic practice, in which treatment is increasingly informed by the presence or absence of mutant genes responsible for cancer growth and progression, tumor origin remains a critical factor in tumor biologic characteristics and therapeutic sensitivity.To evaluate whether data derived from routine clinical DNA sequencing of tumors could complement conventional approaches to enable improved diagnostic accuracy.A machine learning approach was developed to predict tumor type from targeted panel DNA sequence data obtained at the point of care, incorporating both discrete molecular alterations and inferred features such as mutational signatures. This algorithm was trained on 7791 tumors representing 22 cancer types selected from a prospectively sequenced cohort of patients with advanced cancer.The correct tumor type was predicted for 5748 of the 7791 patients (73.8%) in the training set as well as 8623 of 11 644 patients (74.1%) in an independent cohort. Predictions were assigned probabilities that reflected empirical accuracy, with 3388 cases (43.5%) representing high-confidence predictions (>95% probability). Informative molecular features and feature categories varied widely by tumor type. Genomic analysis of plasma cell-free DNA yielded accurate predictions in 45 of 60 cases (75.0%), suggesting that this approach may be applied in diverse clinical settings including as an adjunct to cancer screening. Likely tissues of origin were predicted from targeted tumor sequencing in 95 of 141 patients (67.4%) with cancers of unknown primary site. Applying this method prospectively to patients under active care enabled genome-directed reassessment of diagnosis in 2 patients initially presumed to have metastatic breast cancer, leading to the selection of more appropriate treatments, which elicited clinical responses.These results suggest that the application of artificial intelligence to predict tissue of origin in oncologic practice can act as a useful complement to conventional histologic review to provide integrated pathologic diagnoses, often with important therapeutic implications.
Pre-Clinical Efficacy of Co-Treatment with KDM1A (LSD1) Inhibitor and Ruxolitinib or BET Inhibitor Against Post-MPN-sAML Blast Progenitor Cells
Authors: Warren Fiskus, Christopher Peter Mill, Vrajesh Karkhanis, Bernardo H Lara, Prithviraj Bose, Lucia Masarova, Tapan M. Kadia, Nancy Shao, Isean Bhalla, James V Maher, Joseph D. Khoury, Sunil Sharma, Taghi Manshouri, Srdan Verstovsek, Kapil N. Bhalla
Journal: Blood (2019)
Oxphos Inhibition Induces Formation of Tunneling Nanotubes in AML Cells and Facilitates Mitochondrial Transfer from BM Stroma to AML That Contributes to Microenvironment-Mediated Drug-Resistance of AML
Authors: Haeun Yang, Yoko Tabe, Kaori Saito, Kotoko Yamatani, Rodrigo Jacamo, Helen Ma, Vivian Ruvolo, Qi Zhang, Vinitha Mary Kuruvilla, Natalia Baran, Junichi Imoto, Kazuho Ikeo, Kaori Moriya, Yuko Murakami-Tonami, Koya Suzuki, Takashi Miida, Michael Andreeff, Christopher P Vellano, Joseph Marszalek, Marina Y Konopleva
Journal: Blood (2019)