tbuckley/cabot-search huggingface dataset:
ZUMA-11: A Phase 1/2 Multicenter Study of Axicabtagene Ciloleucel (Axi-Cel) + Utomilumab Patients with Refractory Large B Cell Lymphoma
Authors: Ran Reshef, David B. Miklos, John M. Timmerman, Caron A. Jacobson, Nabila N. Bennani, John M. Rossi, Marika Sherman, Lianqing Zheng, Jennifer Sun, Gabrielle Palluconi, Jenny J. Kim, Michael D. Jain
Journal: Blood (2019)
Latex Fixation in Liver Disease
Authors: J SPONAR, L PIVEC, Z SORMOVA
Journal: BMJ (1964)

no knowledge as to whether it is a widely recognized occurrence.Last year I was treating an elderly lady who suffered from congestive heart failure and severe osteoarthritis of her knees.Oral diuretics were insufficient to control the ex- tensive oedema of her legs and it seemed desirable to reinforce this with weekly injec- tion of " neptal " (o-(2-hydroxy-3-hydroxymercuripropylcarbomyl) phenoxyacetic acid and theophylline).This produced a satisfac- tory diminution in the oedema, but it became very evident that on each occasion it was accompanied by exacerbation of the pain in her knees, which improved as the oedema re- formed in the course of the next few days.Your article suggests that the lubrication of joints depends on the viscosity of the synovial fluid rather than on the quantity, but the inference I drew from my patient was that the bone surfaces were being kept separated by an increased volume of intra-articular fluid, as part of the general oedema of the leg, and that the diuretic produced a relative intra-articular dehydration and consequent friction.At all events the patient was grate- ful when I treated her oedema less diligently.-I am, etc.,
CMET-42. USE OF STEREOTACTIC RADIOSURGERY AND OUTCOMES FOLLOWING RADIOTHERAPY FOR BRAIN METASTASES IN PATIENTS WITH PRIMARY LUNG CANCER – AN AUSTRALIAN POPULATION-BASED STUDY
Authors: Wee Loon Ong, Morikatsu Wada, Farshad Foroudi
Journal: Neuro-Oncology (2019)

Abstract INTRODUCTION We aim to evaluate the use of stereotactic radiosurgery (SRS) among lung cancer (LC) patients who received radiotherapy (RT) for brain metastases (BM), and the associated outcomes. METHODS This is a population-based cohort of LC patients who received RT for BM between 2013 and 2016, as captured in the Victorian Radiotherapy Minimum Dataset. Brain RT was classified as SRS (including multi-fraction stereotactic RT) and non-SRS. Mortality data was captured through data linkage with the Victorian Cancer Registry (VCR). The primary outcomes were: proportion of patients who had SRS for BM, and overall survival (OS) following brain RT. Multivariable logistic regression was used to evaluate factors associated with SRS use. Kaplan-Meier method was used to estimate OS. Multivariable Cox regression was used to evaluate factors associated with OS. RESULTS 1,002 LC patients were included in the study. 1,395 courses of RT for BM were delivered, of which one quarter (362/1,395) were SRS. Almost all SRS were delivered in metropolitan centres (347/362), and two-third in public institutions (235/362). In multivariate logistic regressions, increasing age (OR=0.91;95%CI=0.82–0.99;P=0.04) and treatment in regional centres (OR=0.13;95%CI=0.06–0.28;P&lt; 0.001) were independently associated with lower likelihood of SRS use. Median follow-up was 3.3 months (IQR=1.3–7.8 months). 876 deaths were observed with 12-month OS of 16%. The 12-month OS for patients who had SRS were 38% vs. 12% in patient did not have SRS (P&lt; 0.001). In multivariable Cox regressions, the use of SRS (HR=0.44,95%CI=0.37–0.54;P&lt; 0.001) and female (HR=0.76;95%CI=0.67–0.87;P&lt; 0.001) were associated with improved OS, while increasing age was associated with worse OS (HR=1.02;95%CI=1.01–1.03;P&lt; 0.001). CONCLUSION This is the largest Australian study reporting on SRS use for BM in LC patients. We observed geographical variations in SRS use. We believe the impact of SRS use on OS is most likely due to patient selection for SRS.
Clinical Evolution of Epithelial–Mesenchymal Transition in Human Carcinomas
Authors: Tony Navas, Robert J. Kinders, Scott M. Lawrence, Katherine V. Ferry-Galow, Suzanne Borgel, Melinda G. Hollingshead, Apurva K. Srivastava, Sergio Y. Alcoser, Hala R. Makhlouf, Rodrigo Chuaqui, Deborah F. Wilsker, Mariam M. Konaté, Sarah B. Miller, Andrea Regier Voth, Li Chen, Tomas Vilimas, Jyothi Subramanian, Lawrence Rubinstein, Shivaani Kummar, Alice P. Chen, Donald P. Bottaro, James H. Doroshow, Ralph E. Parchment
Journal: Cancer Research (2019)

The significance of the phenotypic plasticity afforded by epithelial-mesenchymal transition (EMT) for cancer progression and drug resistance remains to be fully elucidated in the clinic. We evaluated epithelial-mesenchymal phenotypic characteristics across a range of tumor histologies using a validated, high-resolution digital microscopic immunofluorescence assay (IFA) that incorporates β-catenin detection and cellular morphology to delineate carcinoma cells from stromal fibroblasts and that quantitates the individual and colocalized expression of the epithelial marker E-cadherin (E) and the mesenchymal marker vimentin (V) at subcellular resolution ("EMT-IFA"). We report the discovery of β-catenin
Efficacy of Caplacizumab in Patients with aTTP in the HERCULES Study According to Baseline Disease Severity
Authors: Paul Coppo, Spero Cataland, Flora Peyvandi, Paul Knoebl, Marie Scully, Johanna A. Kremer Hovinga, Ara Metjian, Javier De La Rubia, Katerina Pavenski, Hilde De Winter, Rui de Passos Sousa, Filip Callewaert
Journal: Blood (2019)
STEM-02. GLIOBLASTOMA CANCER STEM CELLS UTILIZE ASYMMETRIC CELL DIVISION TO PROMOTE THERAPEUTIC RESISTANCE
Authors: Masahiro Hitomi, Anastasia P Chumakova, Daniel Silver, Arnon Knudsen, Bjarne Kristensen, Justin Lathia
Journal: Neuro-Oncology (2019)

Abstract Asymmetric cell division (ACD) enables the maintenance of a stem cell population while simultaneously generating differentiated progeny. Cancer stem cells (CSCs) undergo multiple modes of cell division during tumor expansion and in response to therapy, yet the functional consequences of these division modes has yet to be determined. Using a fluorescence-based system that reports the mitotic distribution of lipid rafts enriched in cell surface receptors, we found that ACD in glioblastoma CSCs generated a daughter cell with enhanced resistance to radiation and temozolomide. Single-cell analyses using our reporter system revealed that ACD also increased the co-inheritance of epidermal growth factor receptor (EGFR) and neurotrophin receptor (p75NTR), which was validated across four additional glioblastoma CSC models. Stimulation of both receptors maintained self-renewal under differentiation conditions, and stimulation with p75NTR ligands rescued the reduction in STAT3, AKT, and ERK induced by erlotinib-mediated EGFR inhibition. Finally, knockdown of p75NTR enhanced the therapeutic efficacy of EGFR inhibition in vivo. Taken together, our data indicate that co-inheritance of p75NTR and EGFR promotes resistance to EGFR inhibition through a redundant mechanism. Overall, these findings demonstrate that ACD produces progeny with enhanced growth factor receptors, which contributes to the generation of a more therapeutically resistant CSC population, and suggest that ACD needs to be considered in the development of next-generation targeting strategies.
A French Multicentric Prospective Cohort of 6000 Patients with Integrative Epidemiological, Clinical, Biological and Treatment Data to Improve Knowledge on Outcome of Lymphoma Patients: Pilot Phase Results of the Real World Data in Lymphoma and Survival in Adults (REALYSA) Study
Authors: Herve Ghesquieres, Cedric Rossi, Fanny Cherblanc, Sandra Le Guyader, Fontanet Bijou, Pierre Sujobert, Pascale Fabbro-Peray, Luc Mathieu Fornecker, Adeline Bernier, Isabelle Baldi, Krimo Bouabdallah, Camille Laurent, Lucie Oberic, Nadine Morineau, Gilles A. Salles, Loic Ysebaert, Alain Monnereau
Journal: Blood (2019)
Myocardial dysfunction in long‐term breast cancer survivors treated at ages 40–50 years
Authors: Judy N. Jacobse, Lars C. Steggink, Gabe S. Sonke, Michael Schaapveld, Yoran M. Hummel, Tessa G. Steenbruggen, Joop D. Lefrandt, Janine Nuver, Anne P.G. Crijns, Berthe M.P. Aleman, Peter van der Meer, Jourik A. Gietema, Flora E. van Leeuwen
Journal: European Journal of Heart Failure (2019)

Anthracyclines increase heart failure (HF) risk, but the long-term prevalence of myocardial dysfunction in young breast cancer (BC) survivors is unknown. Early measures of left ventricular myocardial dysfunction are needed to identify BC patients at risk of symptomatic HF.Within an established cohort, we studied markers for myocardial dysfunction among 569 women, who were 5-7 years (n = 277) or 10-12 years (n = 292) after BC treatment at ages 40-50 years. Left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS) were assessed by echocardiography. N-terminal pro-brain natriuretic peptide (NT-proBNP) was measured in serum. Associations between patient-related and treatment-related risk factors and myocardial dysfunction were evaluated using linear and logistic regression. Median ages at BC diagnosis and cardiac assessment were 46.7 and 55.5 years, respectively. Anthracycline-treated patients (n = 313), compared to the no-anthracycline group (n = 256), more often had decreased LVEF (10% vs. 4%), impaired GLS (34% vs. 27%) and elevated NT-proBNP (23% vs. 8%). GLS and LVEF declined in a linear fashion with increasing cumulative anthracycline dose (GLS: +0.23 and LVEF: -0.40 per cycle of 60 mg/m2 ; P < 0.001) and GLS was worse for patients with left breast irradiation. The risk of NT-proBNP >125 ng/L was highest for patients who received 241-300 mg/m2 anthracycline dose compared to the no-anthracycline group (odds ratio: 3.30, 95% confidence interval: 1.83-5.96).Impaired GLS and increased NT-proBNP levels are present in a substantial proportion of young BC survivors treated with anthracyclines. Whether this will lead to future cardiac disease needs to be evaluated by longitudinal assessment.
MNGI-09. MENINGIOMA WITH MULTIPLE DRIVERS: GENOMIC LANDSCAPE AND CLINICAL CORRELATIONS
Authors: Chang Li, Evgeniya Tyrtova, Mark Youngblood, Danielle Miyagishima, Daniel Duran, Julio Montejo, Koray Özduman, Amar Sheth, Amy Zhao, Elena Fomchenko, Victoria Clark, Sadaf Sohrabi, Sarah Koljaka, Xuejun Li, M Necmettiin Pamir, Timuçin Avşar, Türker Kilic, Hongda Zhu, Ye Gong, Yasar Bayri, Nduka Amankulor, Kaya Bilgüvar, Sacit Omay, Anita Huttner, Matthias Simon, Boris Krischek, Michel Kalamarides, Jennifer Moliterno, E Zeynep Erson-Omay, Murat Günel
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND Previous studies have established several meningioma genomic subgroups, defined by the mutually exclusive genomic drivers. However, we distinguished a small subset of meningiomas simultaneously harboring multiple drivers from different genomic subgroups, thus referred to as “multiple-driver meningiomas”, that has not been previously investigated. We aimed to characterize the genomic landscape and clinical features of multiple-driver meningiomas. METHODS We identified 42 cases of multiple-driver meningiomas from a cohort of 3,016 cases screened for genomic drivers via molecular inversion probe sequencing (MIPS) and/or whole-exome sequencing (WES) previously in our laboratory. All driver mutations were validated via Sanger sequencing and chromosome 22 loss was accessed with qPCR. Clinical information was collected and genome-to-clinical correlations were statistically analyzed. We selected 10 multiple-driver meningioma cases for tumor-normal WES for further characterization of genomic architecture. RESULTS Multiple-driver meningiomas were significantly enriched for NF2 alteration (p&lt; 0.001), had significantly higher WHO grade (p= 0.005) and proportion of recurrent tumors (p= 0.007) when compared with “single-driver meningiomas”, i.e. harboring driver alterations from a single genomic subgroup. Among female cases, those with multiple drivers were nearly four times more likely to be high-grade (II or III) compared to single-driver female samples (48.6% vs. 12.6%, p&lt; 0.001). Among tumors harboring NF2 alteration, multiple-driver meningiomas demonstrated skull base predilection compared with single-driver meningiomas (50.0% vs. 27.9%, p= 0.005). WES analysis of 10 multiple-driver meningiomas identified 1p and/or 14q loss in 60% of cases. Clonality analysis revealed the presence of sub-clonal cell populations in 9 cases with all driver mutations clustered into the founding clone in 7 cases, suggesting their acquisition in the early phase of tumor development. CONCLUSION Multiple-driver meningiomas demonstrate distinct genomic and clinical features that distinguish them as clinically aggressive. They frequently occur in surgically challenging skull base locations, and are more prevalent among high-grade and recurrent cases.
Prediction of Cardiac Complications in SCD
Authors: Alessia Pepe, Laura Pistoia, Maria Rita Gamberini, Silvia Macchi, Francesca Valeria Commendatore, Elena Facchini, Lorella Pitrolo, Mauro Celli, Aurelio Maggio, Paolo Preziosi, Vincenzo Positano, Antonella Meloni
Journal: Blood (2019)
Ultra-Accurate Assessment of Pretreatment ABL1 Kinase Domain (KD) Mutations in Patients (pts) with Newly Diagnosed Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia (Ph+ ALL) Using Duplex Sequencing (DS)
Authors: Nicholas J. Short, Hagop M. Kantarjian, Rashmi Kanagal-Shamanna, Koji Sasaki, Farhad Ravandi, Jorge E. Cortes, Marina Y Konopleva, Ghayas C. Issa, Steven M. Kornblau, Guillermo Garcia-Manero, Victor Rivera, Rebecca Garris, Jacob Higgins, Gabriel Pratt, Lindsey N. Williams, Charles C. Valentine, Jesse J. Salk, Justin Prichard, Jerald P. Radich, Elias Jabbour
Journal: Blood (2019)
Strategy for Overcoming Crebbp and EP300 Mutations in Lymphoma: Development of First-in-Class HAT Activators
Authors: Yuxuan Liu, Jole Fiorito, Yulissa Gonzalez, Brian Estrella, Elisa Calcagno, Elisa Zuccarello, Howook Hwang, Barry Honig, Shixian Deng, Donald Landry, Owen A. O'Connor, Ottavio Arancio, Jennifer E Amengual
Journal: Blood (2019)
Impact of p53 Knock-Down on T-Cell Proliferation and T-Cell Mediated Cytotoxicity Against AML Cell Lines Mediated By a CD33 Specific BiTE® Antibody Construct
Authors: Lea Pawlowsky, Bettina Brauchle, Maryam Kazerani Pasikhani, Ana Ogrinc Wagner, Veit Bücklein, Felix S. Lichtenegger, Roman Kischel, Klaus H. Metzeler, Karsten Spiekermann, Michael Andreeff, Naval G. Daver, Michael von Bergwelt, Marion Subklewe
Journal: Blood (2019)
The Role of Imaging in Predicting Time to First Treatment and Overall Survival in Individuals with CLL-like High Count Monoclonal B-Cell Lymphocytosis
Authors: William J Archibald, Timothy G. Call, Sara J. Achenbach, Kari G Rabe, Curtis A. Hanson, Wei Ding, Amber Koehler, Eli Muchtar, Suzanne R. Hayman, Saad S. Kenderian, Jose F. Leis, Yucai Wang, Amie Fonder, Min Shi, Daniel L. Van Dyke, Susan M. Schwager, Susan L. Slager, Neil E. Kay, Sameer A. Parikh
Journal: Blood (2019)
Genome-Scale CRISPR-Cas9 Synthetic Lethal Screening of AML Cell Line Identified Functional Modulators of Etoposide Resistance Predictive of Clinical Outcome in AML Patients
Authors: Roya Rafiee, Amin Sobh, Abdelrahman H. Elsayed, Abderrahmane Tagmount, Chris D Vulpe, Jatinder K Lamba
Journal: Blood (2019)
The association of pretreatment patient characteristics on the allocation of treatment in stage II ovarian cancer
Authors: W. R. Brewster, D. M. Chase, S. Fedewa, A. Chen, E. Ward
Journal: Journal of Clinical Oncology (2009)

e17508 Background: In high-risk early stage ovarian cancer, surgery followed by adjuvant chemotherapy demonstrates improved survival in prospective trials. The objective of this research was to document patterns of care in the treatment of stage II epithelial ovarian cancer and those factors associated with less than optimal treatment. Methods: The study population was selected from patients diagnosed with ovarian cancer in 2003 to 2005 and reported to the National Cancer Database, a hospital-based cancer registry. 2,252 (93.8%) patients had sufficient information for analysis. Demographics, health insurance, Charlson co-morbidity score, area-level income, and facility characteristics were analyzed as factors potentially associated with treatment. Multivariate logistic regression was performed to assess factors associated with optimal treatment versus suboptimal treatment. Results: Among the women 2,252 women included in the study 1,533 (68.0%) received surgery and chemotherapy and 719 (32.0%) received surgery alone. In multivariate analysis, Black and Hispanic patients were significantly less like likely to receive optimal treatment as compared to white patients (OR = 0.54, 95% CI 0.36–0.82; OR = 0.51, 95% CI = 0.34–0.79, respectively). Women 75 years of age or more were significantly less likely to receive optimal treatment (OR = 0.43 95% CI 0.28–0.67) compared to women less than 53 years. Treatment in a comprehensive cancer facility or teaching hospital compared to community cancer hospitals was positively associated with optimal treatment (OR = 1.40 95% CI 1.02–1.92; OR = 1.89 95% CI 1.38–2.59). Among the 719 patients not receiving chemotherapy, 205 had no reason recorded, and the majority with information (456/514) stated that chemotherapy was not part of planned therapy. Only 33 patients (6.4%) were recorded as refusing recommended chemotherapy. Conclusions: Although only a small proportion of newly diagnosed cases, Stage II ovarian cancer patients have a high probability of benefiting from adjuvant chemotherapy, which improves the likelihood of long-term survival and cure. Further studies are needed to address the patient, clinician and health system factors associated with suboptimal treatment. No significant financial relationships to disclose.
Paics Inhibition Is a Potential Therapeutic Strategy for MYC-Positive DLBCL
Authors: Kohta Miyawaki, Takuji Yamauchi, Takeshi Sugio, Kensuke Sasaki, Hiroaki Miyoshi, Simon Osborne, Deborah Taylor, Koichi Ohshima, Koji Kato, Takahiro Maeda, Koichi Akashi
Journal: Blood (2019)
A Longitudinal Evaluation of Euroflow and Combined Quantitative Immunoprecipitation (QIP) and Free Light Chain (FLC) Mass Spectometry (MS) in Functional High Risk Multiple Myeloma
Authors: Andrew Spencer, Tiffany Khong, Flora Yuen, Hannah Victoria Giles, Malgorzata Gorniak, Hang Quach, Noemi Horvath, Ian H. Kerridge, Edwin Sze-Hung Lee, Krystal Bergin, Shreerang Sridesai, Anna Kalff, John Reynolds
Journal: Blood (2019)
Annals Graphic Medicine - Cicely Saunders: The Woman Who Changed How We Die
Authors: Nathan A. Gray
Journal: Annals of Internal Medicine (2019)

Web Exclusives19 November 2019Annals Graphic Medicine - Cicely Saunders: The Woman Who Changed How We DieFREENathan A. Gray, MDNathan A. Gray, MDSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/G18-0035 SectionsAboutVisual AbstractPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Download figure Download PowerPoint Download figure Download PowerPoint Download figure Download PowerPoint Download figure Download PowerPoint Download figure Download PowerPoint Download figure Download PowerPoint Download figure Download PowerPoint Download figure Download PowerPoint Download figure Download PowerPoint Download figure Download PowerPoint Download figure Download PowerPoint Download figure Download PowerPoint Comments0 CommentsSign In to Submit A Comment Adam KortowskiSolo internist30 January 2020 Touch of an angel Another angel like the one before in Your journal. Had no idea about Saunders until now.Thanks for this heartwarming graphic. Author, Article, and Disclosure InformationAffiliations: Disclosures: The author has disclosed no conflicts of interest. The form can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=G18-0035.Author/Illustrator Information: Nathan A. Gray, MD, is an Assistant Professor at Duke University Medical Center, Department of Medicine (e-mail, nathan.[email protected]duke.edu).This article was published at Annals.org on 12 November 2019. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 19 November 2019Volume 171, Issue 10Page: W64-W75KeywordsConflicts of interestDisclosureHealth care ePublished: 12 November 2019 Issue Published: 19 November 2019 Copyright & PermissionsCopyright © 2019 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Surgical Treatment of Hepatocholangiocarcinoma: A Systematic Review
Authors: Damiano Gentile, Matteo Donadon, Ana Lleo, Alessio Aghemo, Massimo Roncalli, Luca di Tommaso, Guido Torzilli
Journal: Liver Cancer (2019)

&lt;b&gt;&lt;i&gt;Background:&lt;/i&gt;&lt;/b&gt; Hepatocholangiocarcinoma (HCC-CC) is a rare liver malignancy that contains features of both hepatocellular carcinoma (HCC) and mass-forming cholangiocarcinoma (MFCCC). Three classification systems for HCC-CC are described in literature and the majority of these tumors appear to be of the transitional type. The aim of this study is to evaluate the characteristics of transitional HCC-CC and to compare long-term oncological outcomes with HCC and MFCCC in surgically treated patients. &lt;b&gt;&lt;i&gt;Summary:&lt;/i&gt;&lt;/b&gt; A systematic literature search was conducted to identify relevant studies analyzing demographic and clinical characteristics of patients with transitional HCC-CC and evaluating treatments and outcomes associated with this neoplasm. Only comparative, retrospective analyses were included. A total of 14 studies, involving 13,613 patients with primary liver malignancy, were analyzed. All patients underwent surgery, either liver resection or transplantation. Four hundred and thirty-seven patients were affected by transitional HCC-CC (3.2%). For further analysis, patients with transitional HCC-CC were divided into 2 groups, the resection group and the transplantation group. Disease-free survival (DFS) and overall survival (OS) of these patients were analyzed and compared to long-term oncological outcomes of patients with HCC and/or MFCCC, who underwent the same treatment. In the resection group, DFS rate at 5-year was 15, 31.6, and 20.3% for patients with transitional HCC-CC, HCC, and MFCCC, respectively; OS rate at 5-year was 32.7, 47.5, and 30.3% for patients with transitional HCC-CC, HCC, and MFCCC, respectively. In the transplantation group, DFS rate at 5-year was 40.9 and 87.4% for patients with transitional HCC-CC and HCC, respectively; OS rate at 5-year was 49.4 and 80.3% for patients with transitional HCC-CC and HCC, respectively. &lt;b&gt;&lt;i&gt;Key Messages:&lt;/i&gt;&lt;/b&gt; Transitional HCC-CC patients have significantly worse DFS and OS rates compared to HCC patients in both the resection group and the transplantation group. However, in the resection group, both DFS and OS rates of transitional HCC-CC patients are not statistically different from those of MFCCC patients.
Lineage Tracing in Chronic Lymphocytic Leukemia Reveals Clones with Stable Gene Expression States That Differentially Respond to Therapy
Authors: Catherine Gutierrez, Aziz Al'Khafaji, Eric Brenner, Russell Durrett, Kaitlyn Johnson, Wandi Zhang, Shuqiang Li, Kenneth J. Livak, Donna S Neuberg, Amy Brock, Catherine J. Wu
Journal: Blood (2019)