tbuckley/cabot-search huggingface dataset:
Prognostic impact of peripheral blood WT1-mRNA expression in patients with MDS
Authors: Christina Rautenberg, Ulrich Germing, Sabrina Pechtel, Marius Lamers, Carolin Fischermanns, Paul Jäger, Stefanie Geyh, Rainer Haas, Guido Kobbe, Thomas Schroeder
Journal: Blood Cancer Journal (2019)

Few reports suggested a prognostic impact of Wilms'Tumor-1 (WT1)-mRNA overexpression in MDS, but translation into clinical routine was hampered by limited patients numbers, differing sample sources, non-standardized methods/cut-offs. To evaluate whether WT1-mRNA expression yields additional prognostic information, we measured peripheral blood (PB) WT1-mRNA expression in 94 MDS using a standardized assay offering a validated cut-off to discriminate between normal and WT1-mRNA overexpression. Overall, 54 patients (57%) showed WT1-mRNA overexpression, while 40 patients (43%) had normal WT1-mRNA expression. This enabled discrimination between MDS and both healthy controls and non-MDS cytopenias. Furthermore, WT1-mRNA expression correlated with WHO 2016 subcategories and IPSS-R as indicated by mean WT1-mRNA expression and frequency of WT1-mRNA overexpressing patients within respective subgroups. Regarding the entire group, PB WT1-mRNA expression was associated with prognosis, as those patients showing WT1-mRNA overexpression had higher risk for disease progression and AML transformation and accordingly shorter progression-free, leukemia-free and overall survival in univariate analysis. In multivariate analysis, prognostic impact of PB WT1-mRNA expression status was independent of IPSS-R and enabled more precise prediction of PFS, but not OS, within IPSS-R very low/low and intermediate risk groups. Overall, measuring PB WT1-mRNA appears valuable to support diagnostics and refine prognostication provided by the IPSS-R.
Targeting Metabolic Enzyme Pyruvate Kinase M2: A Novel Strategy to Inhibit Platelet Function and Arterial Thrombosis
Authors: Manasa K Nayak, Madankumar Ghatge, Nirav Dhanesha, Gagan D Flora, Manish Jain, Omar Rodriguez, Kathleen Markan, Mathhhew Potthoff, Steven R. Lentz, Anil K Chauhan
Journal: Blood (2019)
Pro-Active Dasatinib Dose Reduction Based on Trough Levels May Minimise Toxicity and Preserve Efficacy - Interim Analysis of the ALLG CML 12 Direct Study
Authors: David T Yeung, Andrew Grigg, Naranie Shanmuganathan, Ann Christine Solterbeck, Deborah L. White, Susan Branford, Nicholas Viiala, Philip Arthur Rowlings, Anthony K Mills, Jake Shortt, Campbell Tiley, David M Ross, David Kipp, Rosemary Anne Harrup, Ilona Cunningham, John Kwan, Richard Eek, Howard Mutsando, Ken-Soon Tan, Kate Burbury, Matthew P.F. Wright, Timothy P. Hughes, On Behalf of the ALLG
Journal: Blood (2019)
Absence of Damaging Effects of Stem Cell Donation in Unrelated Donors Assessed By FISH and Gene Variance Screening
Authors: Elisabeth P. Nacheva, Trudy Ahyee, C Navarette, Juanah Addada, Rachel Pawson, Richard Syzdlo, Stephen Mackinnon, Bronwen E. Shaw, J. Alejandro Madrigal
Journal: Blood (2019)
Plasma ctDNA RAS mutation analysis by digital polymerase chain reaction in patients with inoperable pancreatic cancer
Authors: S. Gkoura, M. Kastrisiou, A. Kougioumtzi, C. Tzallas, K. Gkrepi, A. Goussia, A. Magklara, G. Pentheroudakis
Journal: Annals of Oncology (2019)
Hodgkin's Disease
Authors: Ronald Dorfman
Journal: JAMA (1969)

Dr. Kent Kreisman, Junior Assistant Resident in Medicine, Jewish Hospital of St. Louis, and Assistant in Medicine, Washington University School of Medicine: A 44-year-old white woman was hospitalized on March 10, 1968, with a five-day history of fever, chills, and malaise. The past history included meningitis in childhood, recurrent asthma for 17 years, and a complete hysterectomy four years prior to admission. Physical examination revealed a middle-aged woman appearing acutely ill. Pulse rate was 120 beats per minute and regular; blood pressure, 110/60 mm Hg; respiratory rate, 20 per minute; and temperature, 104 F (40 C). Findings from examination of the head, ears, eyes, nose, throat, and thorax were unremarkable. No lymph-node enlargement was detected. The liver was palpable 6 cm below the costal margin; the spleen was not felt. Findings from examination of the extremities and the nervous system were normal. Laboratory data on admission included a hematocrit reading
Updated Study Results of CX-01, an Inhibitor of CXCL12/CXCR4, and Azacitidine for the Treatment of Hypomethylating Agent Refractory AML and MDS
Authors: Eric Huselton, Amanda F Cashen, John F. DiPersio, Meagan Jacoby, Iskra Pusic, Rizwan Romee, Mark A. Schroeder, Geoffrey L. Uy, Peter Westervelt
Journal: Blood (2019)
Shared and Distinctive Ultrastructural Abnormalities Expressed By Megakaryocytes in Bone Marrow and Spleen from Patients with Primary Myelofibrosis
Authors: Maria Zingariello, Vittorio Rosti, Alessandro M. Vannucchi, Paola Guglielmelli, Claudio Bardelli, Maria Mazzarini, Rosa Alba Rana, Giovanni Barosi, Anna Rita Rita Migliaccio
Journal: Blood (2019)
Lack of Significant Differences in Somatic Alterations between MGUS, SMM and Symptomatic Multiple Myeloma: A Result from Comprehensive Genomic Profiling Study
Authors: Anil Aktas Samur, Mariateresa Fulciniti, Raphael Szalat, Jill Corre, Niccolo Bolli, Philippe Moreau, Michel Attal, Kenneth C. Anderson, Giovanni Parmigiani, Hervé Avet-Loiseau, Mehmet Kemal Samur, Nikhil C. Munshi
Journal: Blood (2019)
Acid-Based Decalcification Methods Compromise Genomic Profiling from DNA and RNA
Authors: Ian Duncan, Natalie Danziger, Daniel Duncan, Amanda Hemmerich, Claire Edgerly, Richard Huang, Jo-Anne Vergilio, Julia A Elvin, Jie He, Nicholas Britt, Prasanth Reddy, Pratheesh Sathyan, Brian Alexander, Jeffrey S. Ross, Charlotte Brown, Shakti H. Ramkissoon, Eric A. Severson
Journal: Blood (2019)
Annals Story Slam - Signed and Spoken
Authors: Elizabeth Hendren
Journal: Annals of Internal Medicine (2019)

Web Exclusives5 November 2019Annals Story Slam - Signed and SpokenFREEElizabeth Hendren, MDElizabeth Hendren, MDSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/W19-0023 SectionsAboutVisual Abstract ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Video. Annals Story Slam - Signed and Spoken "Signed and Spoken," by Elizabeth Hendren, MD (Duration 4:27)Building on the popular Annals feature “On Being a Doctor,” storytellers share stories about the experience of doctoring on video.For more videos from and information on Annals Story Slam, visit go.annals.org/StorySlam. Comments0 CommentsSign In to Submit A Comment Author, Article, and Disclosure InformationAffiliations: PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 5 November 2019Volume 171, Issue 9Page: SS1 ePublished: 5 November 2019 Issue Published: 5 November 2019 Copyright & PermissionsCopyright © 2019 by American College of Physicians. All Rights Reserved.Loading ...
Colorectal cancer molecular classification using BRAF, KRAS, microsatellite instability, and CIMP status: Prognostic implications and response to chemotherapy.
Authors: Oscar Murcia, Miriam Juárez, Eva Hernández-Illán, Maria Rodriguez-Soler, Mar Giner-Calabuig, Miren Alustiza, Cecilia Egoavil, Adela Castillejo, Cristina Alenda, Carolina Mangas, Victor Barberá, Ana Yuste, Luís Bujanda, Joan Clofent, Montserrat Andreu, Antoni Castells, Xavier Llor, Pedro Zapater, Rodrigo Jover
Journal: Journal of Clinical Oncology (2018)

668 Background: The aim of this study was to validate a molecular classification of colorectal cancer (CRC) based on microsatellite instability (MSI), CpG island methylator phenotype (CIMP) status, BRAF, and KRAS and investigate each subtype’s response to chemotherapy. Methods: This retrospective observational study included a population-based cohort of 878 CRC patients. We classified tumours into five different subtypes based on BRAF and KRAS mutation, CIMP status, and MSI. Patients with advanced stage II (T4N0M0) and stage III tumours received 5-fluoruracil (5-FU)-based chemotherapy or no adjuvant treatment based on clinical criteria. The main outcome was disease-free survival (DFS). Results: Patients with the combination of microsatellite stable (MSS) tumours, BRAF mutation and CIMP positive exhibited the worst prognosis in univariate (log rank P &lt; 0.0001) and multivariate analyses (hazard ratio 1.75, 95% CI 1.05-2.93, P = 0.03) after adjusting for age, sex, chemotherapy, and TNM stage. Treatment with 5-FU-based regimens improved prognosis in patients with the combination of MSS tumours, KRAS mutation and CIMP negative (log rank P = 0.003) as well as in patients with MSS tumours plus BRAF and KRAS wild-type and CIMP negative (log-rank P &lt; 0.001). After adjusting for age, sex, and TNM stage in the multivariate analysis, only patients with the latter molecular combination had independently improved prognosis after adjuvant chemotherapy (hazard ratio 2.06, 95% CI 1.24-3.44, P = 0.005). Conclusions: We confirmed the prognostic value of stratifying CRC according to molecular subtypes using MSI, CIMP status, and somatic KRAS and BRAF mutation. Patients with traditional chromosomally unstable tumours obtained the best benefit from adjuvant 5-FU-based chemotherapy.
Abstract O.60: Kawasaki Disease Complicated by Coronary Artery Aneurysms: Mortality and 40-year Outcomes
Authors: Cedric Manlhiot, Andrew M Crean, Nigel Fernandopulle, Brendan Lew, Tanveer H Collins, Nita Chahal, Brian W McCrindle
Journal: Circulation (2015)

Background: Long-term outcomes and life expectancy for children with a previous history of Kawasaki disease (KD), particularly those with coronary artery aneurysms (CAA), remain to be determined. Methods: An inception cohort of all patients with KD assessed at The Hospital for Sick Children in Toronto between 1978 and 2013 was assembled. Patient outcomes were obtained throughout their pediatric and adult clinical follow-up as long as available. Prevalence of outcomes over time was modelled with Kaplan-Meier survival curves. Life tables from Statistics Canada were used to obtain age/gender specific cumulative mortality for the general population. Results: The cohort included 2,623 KD patients, of whom 410 (16%) had coronary artery involvement (215 dilatation, 57 non-giant CAA and 138 giant CAA). Average follow-up for patients with coronary artery involvement was 6.7 years (13.3 years for giant CAA); 57 and 34 patients had at least 15 and 25 years of follow-up, respectively. No patients with coronary artery dilatation or non-giant CAA had revascularization or a myocardial infarct. Freedom from revascularization (14 events) for patients with giant CAA was 90±6%, 87±7% and 80±13% at 10, 20 and 40 years of follow-up. Freedom from myocardial infarct (11 events) was 94±4%, 92±5% and 89±7% at 5, 20 and 40 years. For patients without coronary artery involvement, 3 (0.1%) deaths were recorded, one secondary to complications of macrophage activation syndrome during the acute phase of KD and 2 from cancer. No deaths were noted for patients with coronary artery dilatation or non-giant CAA, although clinical follow-up was more limited. For patients with giant CAA, 3 deaths (2.2%) were noted, 2 related to CAA complications and 1 from non-medical cause. Cumulative mortality for patients with giant CAA was 1.5% at 10 years of age (expected mortality 0.7%, HR: 2.2 (0.3-11.5), p=0.08) and 3.1% at 40 years of age (expected 2.3%, HR: 1.3 (0.4-4.0), p=0.37). Conclusions: Despite risks of myocardial infarction and revascularization, patients with giant CAA had life-expectancy similar to that of the general population up to the fourth decade of life. Additional follow-up will be necessary to determine if these trends continue into later decades.
P2.07 Prevalence of Hypovitaminosis D in Patients with Advanced Adenocarcinoma of Smokers and Non-Smokers
Authors: I.B. Gonçalves, A. Ferreira, G. Fraga, J. Vasconcellos, T. Montella, W. Peres, C.G. Ferreira
Journal: Journal of Thoracic Oncology (2019)
Low Levels of Plasmacytoid Dendritic Cells at the Time of Engraftment Are a Valuable Severe aGVHD Indicator in Children Undergoing Allogeneic Stem Cell Transplantation
Authors: Bohan Li, Xinran Chu, Lijun Meng, Peifang Xiao, Jie Li, Jun Lu, Yi Zhang, Shaoyan Hu
Journal: Blood (2019)
Feasibility and Impact of Embedded Geriatric Consultation for Frail Older Adults with Blood Cancer: A Randomized Controlled Trial
Authors: Gregory A. Abel, Hajime Uno, Anna M. Tanasijevic, Zilu Zhang, Tammy T Hshieh, Clark T Dumontier, Richard Chen, Lee Mozessohn, Richard M. Stone, Robert J. Soiffer, Jane Driver
Journal: Blood (2019)
Potential increase in androgen sensitivity following antisense oligonucleotide suppression of Bcl-2 in a prostate cancer model.
Authors: Patrick Guinan, Marvin Rubenstein, Courtney M.P. Hollowell
Journal: Journal of Clinical Oncology (2012)

e13532 Background: Antisense oligonucleotides (oligos) have been employed against in vivo and in vitro prostate cancer models targeting growth stimulatory gene products. While most oligos have targeted growth factors or their receptors, others have been directed against inhibitors of apoptosis and mediators of androgen action. In LNCaP cells we evaluated a set of oligos which targeted and comparably suppressed the expression of the apoptosis inhibitor protein bcl-2. To evaluate the specificity of this type of gene therapy, targeted and non-targeted genes were evaluated for their expression. The purpose was to identify whether additional (non-targeted) genes altered their expression in a manner which could circumvent or compensate for the suppression of bcl-2, promoting growth through increased androgen sensitivity. Methods: LNCaP prostate cells were treated with mono- and bispecific oligos directed against bcl-2. Employing RT-PCR the expression of both targeted and non-targeted genes (androgen receptor [AR], coactivators p300 and creb binding protein [CREB]) was determined. Results: LNCaP cells adapted to the suppression of bcl-2 (an apoptosis inhibitor) with enhanced expression of both AR and p300. This suggests an increased sensitivity to androgens. Conclusions: In this model, oligo treatment directed against bcl-2, may be evaded through a compensatory increase in both AR and p300 expression. This promotion of tumor growth, and the altered expression of AR coactivators normally seen in advanced disease, suggests a tumor transition to a more aggressive phenotype following suppressive treatment directed against bcl-2.
False-negative hypoglycaemic screening test for patients in coma
Authors: P Proetzsch, H Wendel
Journal: BMJ (1978)

Further investigation has shown that the incorrect Reflomat result may have resulted from inserting the Reflomat strip into the machine upside down, which can give spurious readings up to 4 0 mmol/l.Incorrect insertion of the strip is, of course, more likely when testing for hypoglycaemia since the test surface fails to show significant colour change in this situation.This problem does not appear to be significant with the more recently available Reflotest-Hypoglycemie strips, though false results may occur.if either of the strips is not fully inserted into the machine.Although all laboratory results should be interpreted in the context of the clinical findings, we should like to alert your readers to this potential cause of error and suggest that the manufacturers alter the colour of the blank reverse side of the strip to obviate this risk.
Somatic Mutations Potentiating RAS-MAPK Signaling Confer Resistant Potential Against FLT3-Inhibitors to Acute Myelogenous Leukemia
Authors: Masayasu Hayashi, Yoshikane Kikushige, Takuya Harada, Toshihiro Miyamoto, Takahiro Maeda, Koichi Akashi
Journal: Blood (2019)
TMIC-29. METABOLIC INTERACTIONS BETWEEN TREATMENT-RESISTANT SLOW-CYCLING CELLS AND THE IMMUNE SYSTEM IN HIGH-GRADE GLIOMA
Authors: Elias Sayour, Changlin Yang, Guimei Tian, Adam Grippin, Mariana Dajac, Brian Nazareth, Michael Andrews, Aida Karachi, Hector Mendez-Gomez, Brian Stover, Ginger Moore, Joseph Flores-Toro, Bayli Divita, Jesse Kresak, Maryam Rahman, Catherine Flores, Jianping Huang, Jeffrey Harrison, Duane Mitchell, Loic Deleyrolle
Journal: Neuro-Oncology (2019)

Abstract INTRODUCTION Intratumoral heterogeneity is increasingly recognized as a determinant of therapy resistance and disease recurrence; this is exemplified by glioblastoma (GBM), one of the most lethal malignancies. We recently revealed that GBM contain cell subpopulations with distinct metabolic requirements, with fast-cycling cells (FCCs) harnessing aerobic glycolysis, and treatment-resistant slow-cycling cells (SCCs) preferentially engaging lipid metabolism. How the different tumor cell populations interact with immune cells and how this metabolic heterogeneity shapes the immune landscape in GBM has yet to be understood. OBJECTIVES: The objectives of this study are to understand the mechanisms of communication in the tumor microenvironment, specifically to characterize the metabolic interactions between SCCs (a therapeutically resistant population of cancer cells that drive disease progression and recurrence) and the immune compartment. METHODS The murine glioma cell line KR158 (derived from a Nf1;Trp53 mutant mouse) was used to establish the slow-cycling cell paradigm and metabolic heterogeneity in an immune-competent model of glioma. RESULTS Similar to what we observed in patient-derived specimens, mouse KR158-derived SCCs demonstrate tumorigenicity, treatment resistance and up-regulation of stemness programs and lipid metabolic pathways. We determined that tumor progression is regulated by the interaction of SCCs with the immune system and established that these cells are driving a pro-tumorigenic microenvironment via the recruitment of immune suppressive myeloid cells. Importantly, the immune microenvironment shaped by SCCs is marked by specific metabolic features showing enhanced lipid exchange capacities that we propose are exploited by SCCs to support their survival and functions. CONCLUSION Our study indicates that SCCs play a pivotal role in shifting the GBM milieu toward an immune regulatory phenotype but importantly reveals an unprecedented metabolic cooperation, which represents a novel therapeutic target to antagonize GBM.
Stimulatory effect on the transport mediated by organic anion transporting polypeptide 2B1
Authors: Jiro Ogura, Hiroaki Yamaguchi, Nariyasu Mano
Journal: Asian Journal of Pharmaceutical Sciences (2019)

Drug-drug interaction (DDI) is one of causes of adverse drug events and can result in life-threatening consequences. Organic anion-transporting polypeptide (OATP) 2B1 is a major uptake transporter in the intestine and contributes to transport various clinically used therapeutic agents. The intestine has a high risk of DDI, because it has a special propensity to be exposed to a high concentration of drugs. Thus, understanding drug interaction mediated by OATP2B1 in the absorption process is important for the prevention of adverse drug events, including decrease in the therapeutic effect of co-administered drugs. Acute drug interaction occurs through the direct inhibitory effect on transporters, including OATP2B1. Moreover, some compounds such as clinically used drugs and food components have an acute stimulatory effect on transport of co-administered drugs by OATP2B1. This review summarizes the acute stimulatory effect on the transport mediated by OATP2B1 and discusses the mechanisms of the acute stimulatory effects of compounds. There are two types of acute stimulatory effects, substrate-independent and -dependent interactions on OATP2B1 function. The facilitating translocation of OATP2B1 to the plasma membrane is one of causes for the substrate-independent acute stimulatory effect. On the contrary, the substrate-dependent effect is based on the direct binding to the substrate-binding site or allosteric progesterone-binding site of OATP2B1.
Autophagic lipid metabolism sustains mTORC1 activity in TSC-deficient neural stem cells
Authors: Chenran Wang, Michael A. Haas, Fuchun Yang, Syn Yeo, Takako Okamoto, Song Chen, Jian Wen, Pranjal Sarma, David R. Plas, Jun-Lin Guan
Journal: Nature Metabolism (2019)
Phase 3, Multi-Center, International, Randomized, Double-Blind, Placebo Controlled Study of Oral Rigosertib + Injectable Azacitidine (AZA) Versus Injectable Azacitidine in Treatment-Naive Patients with Higher-Risk Myelodysplastic Syndrome (HR-MDS)
Authors: Guillermo Garcia-Manero, Shyamala C. Navada, Pierre Fenaux, Patrick S. Zbyszewski, Afoluso Ronnee Adesanya, Nozar Azarnia, Steven M. Fruchtman, Lewis R. Silverman
Journal: Blood (2019)
Renal Pathology in Patients with Monoclonal Gammopathy or Multiple Myeloma: Monoclonal Immunoglobulins Are Not Always the Cause
Authors: Eftathios Kastritis, Nikolaos Kanellias, Foteini Theodorakakou, Erasmia Psimenou, Charikleia Gakiopoulou, Smaragdi Marinaki, Maria Roussou, Maria Gavriatopoulou, Magdalini Migkou, Evangelos Eleutherakis-Papaiakovou, Panagiotis Malandrakis, Evangelos Terpos, Meletios A. Dimopoulos
Journal: Blood (2019)
A Phase II Clinical Trial of Post-Transplant Cyclophosphamide for Graft Versus Host Disease Prevention Following Myeloablative Peripheral Blood Stem Cell Matched Unrelated Donor Hematopoietic Stem Cell Transplantation
Authors: Omer Jamy, Racquel Innis-Shelton, Susan Bal, Ravi K. Paluri, Samina Karim, Joseph H. Chewning, Donna Salzman, Luciano J. Costa, Antonio Di Stasi, Lawrence S. Lamb, Shin Mineishi, Ayman Saad
Journal: Blood (2019)
Clinical Trial Accrual at Initial Course of Therapy for Cancer and Its Impact on Survival
Authors: Nicholas G. Zaorsky, Ying Zhang, Vonn Walter, Leila T. Tchelebi, Vernon M. Chinchilli, Niraj J. Gusani
Journal: Journal of the National Comprehensive Cancer Network (2019)

This retrospective cohort study sought to characterize the accrual of patients with cancer into clinical trials at the time of diagnosis and analyze the impact of accrual on survival.The National Cancer Database (NCDB) was queried for patients enrolled in clinical trials at their initial course of treatment for 46 cancers from 2004 through 2015. Descriptive statistics were used to characterize the accrual of patients with cancer in clinical trials at diagnosis, and Kaplan-Meier graphical displays, log-rank tests, odds ratios, and stratified Cox proportional hazards models were used to analyze the impact of accrual on overall survival (OS). Strata were defined using 10 variables. Model-based adjusted survival curves of 2 groups were reverse-generated based on a Weibull distribution.Of 12,097,681 patients in the NCDB, 11,576 (0.1%) were enrolled in trials. Patients in clinical trials typically had metastatic disease (30.9% vs 16.4%; P<.0001), were white (88.0% vs 84.8%; P<.0001), had private/managed care insurance (56.4% vs 41.8%; P<.0001), had fewer comorbidities (Charlson-Deyo score 0: 81.9% vs 75.7%; P<.0001, and Charlson-Deyo scores 1-3: 18.1% vs 24.3%; P<.0001) compared with those not in trials. At a median follow-up of 64 months, enrollment in a clinical trial was associated with improved OS in univariate and stratified analyses, with a median survival of 60.0 versus 52.5 months (hazard ratio, 0.876; 95% CI, 0.845-0.907; P<.0001). Stratified analysis with matched baseline characteristics between patients enrolled and not enrolled in a clinical trial showed superior OS at 5 years (95.0% vs 90.2%; P<.0001).Enrollment in clinical trials at first line of therapy in the United States is exceedingly low and favors young, healthy, white patients with metastatic disease and private insurance who are treated at academic medical centers. Patients with cancer treated in clinical trials live longer than those not treated in trials.