tbuckley/cabot-search huggingface dataset:
PWE-090 Does my patient–s normal liver biopsy mean they won't develop liver disease?
Authors: B Hudson, P Thiagarajan, V Ramappa, P Kaye, G Aithal
Journal: Gut (2015)

<h3>Introduction</h3> Liver biopsy remains a commonly used investigation amongst patients with abnormal liver biochemistry and normal serology, both in the diagnosis and staging of liver disease. Although commonly considered the “gold standard” it typically samples approximately 1/50,000<sup>th</sup>of the total liver mass and as such diffuse liver disease could plausibly be missed.<sup>1</sup>It is associated with complications of pain and bleeding and has a small but appreciable mortality (0.01–0.17%).<sup>2</sup>We report follow up data from a Nottinghamshire cohort of patients with abnormal liver biochemistry and normally reported liver biopsy between 1992–2001. We aim to assess whether a normal liver biopsy in the context of abnormal liver biochemistry is protective against development of and death from chronic liver disease. <h3>Method</h3> Patients with a normally reported liver biopsy and abnormal liver chemistry from Nottingham University Hospitals between 1992–2001 were identified from retrospective scrutiny of local Histopathology databases. Patient notes and computer records as of 1<sup>st</sup>January 2015 were analysed to assess mortality, cause of death (where applicable), and development of cirrhosis. Office of National Statistics (ONS) UK population data was used to provide a comparable “control” group. <h3>Results</h3> 171 patients were identified. 32 (18.7%) were known to have died by 1<sup>st</sup>Jan 2015. Of those who had died, 2 (6.5%) had hepatocellular carcinoma secondary to cirrhosis recorded as cause of death. This figure is significantly higher than the 1.53% of deaths attributed to liver disease in the UK population in 2010.<sup>3</sup>We intend to report on the incidence of cirrhosis in the remainder of the cohort as compared to a matched control population. <h3>Conclusion</h3> Our data suggest that a normal liver biopsy in the presence of abnormal liver biochemistry does not protect against future death from complications of chronic liver disease. We question whether alternative non-invasive markers of fibrosis could potentially have comparable or superior value in predicting development of cirrhosis and death from liver disease in this patient group. <h3>Disclosure of interest</h3> None Declared. <h3>References</h3> Guido M, Rugge M. Liver biopsy sampling in chronic viral hepatitis. <i>Semin Liver Dis</i>. 2004;24(1):89–97 Grant A, Neuberger J. Guidelines on the use of liver biopsy in clinical practice. <i>BSG</i>. See comment in PubMed Commons below <i>Gut</i>. 1999;<b>45</b>(Suppl 4):IV1–IV11 Office of National Statistics – Mortality statistics – England and Wales, 2010
FRI0111 Change Over Time in the Pattern of Clinical Response to First-Line Biologic Drugs: Observational Data from a Local Registry
Authors: E.G. Favalli, M. Biggioggero, A. Becciolini, A. Marchesoni, P.L. Meroni
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> The use of biologic drugs (bDMARDs) for the treatment of rheumatoid arthritis (RA) is well established and has progressively changed over time as an effect of the increasing number of available agents and the newly proposed international recommendations. <h3>Objectives</h3> To evaluate the change over 15 years of the proportion of bDMARD treated patients achieving a 1-year remission or Low Disease Activity (LDA) in a real-life setting. <h3>Methods</h3> RA patients treated with their first bDMARD between January 2000 and December 2014 were selected from a local registry. The analysis was limited to patients with at least 1-year follow-up. The overall proportion of patients achieving a 1-year Disease Activity Score 28 (DAS28) remission (&lt;2.6) or LDA (≥2.6 and &lt;3.2) was evaluated. Sub-analyses after stratification of study population according to period of enrollment (2000-2004, 2005-2009, and 2010-2014) and disease duration (under or over 2 years) were performed by using Fisher9s and chi-squared test. <h3>Results</h3> The analysis included 676 patients (82.3% female, mean age [± SD] 54.2 [±12.1] years, mean disease duration 9.2 [±8.1]), treated with anti-TNF agents (n=637), abatacept (n=11), tocilizumab (n=22), or rituximab (n=6). In the whole study population 20.8 and 9.4% of patients achieved 1-year remission or LDA, respectively. The rate of 1-year remission or LDA was significantly higher (p&lt;0.0001) for patients enrolled in the period 2010-2014 (31 and 8%, respectively) compared with both 1999-2004 (10 and 9.6%, respectively) and 2005-2009 (24 and 10%, respectively). The relative risk of achieving 1-year remission or LDA was significantly higher in early (&lt;2 years; n=76) compared with late (&gt;2 years; n=601) RA patients (RR 1.629, 95% confidence interval 1.237-2.143; p=0.002). <h3>Conclusions</h3> In a real-life setting, about 30% of patients treated with a first-line bDMARD achieved remission or LDA after 1 year of therapy. Patients early receiving bDMARD treatment and beginning the first bDMARD after 2010 showed a significantly higher probability to achieve the therapeutic target. <h3>Disclosure of Interest</h3> None declared
Antibody Patterns in Different Human Sera Against Intracellular and Membrane-Antigen Complexes Associated With Epstein-Barr Virus&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: A Svedmyr, A Demissie, G Klein, P Clifford
Journal: JNCI Journal of the National Cancer Institute (1970)

A set of sera and fluorescein-conjugated immunoglobulins derived from them were compared for anti-Epstein-Barr virus (EBV) and EBV-associated membrane-antigen reactivity by cross-blocking tests in direct immunofluorescence on fixed and viable cells, respectively. Whereas several sera showed complete cross reactivity by blocking, a number of asymmetries were found in both the membrane and anti-EBV tests, with blocking obtained in only one direction, not reciprocally. Since no experimental support was obtained to indicate that this was caused by quantitative or avidity differences, it was assumed that both the intracellular and the membrane-antigen systems consist of more than one antigenic component. Thus some EBV-positive sera would contain antibodies against a larger number of components than others. For some serum combinations, the cross-blocking patterns obtained in the anti-EBV test correlated well with the corresponding blocking patterns in the membrane test, whereas other serum combinations gave discordant results in the two tests. This can be understood from the previous demonstration that the intracellular and the membrane complexes carry different antigenic specificities, and the added assumption that a serum containing many antibody components against antigenic constituents of one system will also tend to contain many reactive components against the other, though this does not have to occur with absolute regularity. The possibility is discussed that the broadness of immunization is related to the case history, especially to the persistence of a tumor mass.
Selective Targeting of Cyclin E1-Amplified High-Grade Serous Ovarian Cancer by Cyclin-Dependent Kinase 2 and AKT Inhibition
Authors: George Au-Yeung, Franziska Lang, Walid J. Azar, Chris Mitchell, Kate E. Jarman, Kurt Lackovic, Diar Aziz, Carleen Cullinane, Richard B. Pearson, Linda Mileshkin, Danny Rischin, Alison M. Karst, Ronny Drapkin, Dariush Etemadmoghadam, David D.L. Bowtell
Journal: Clinical Cancer Research (2016)

Purpose: Cyclin E1 (CCNE1) amplification is associated with primary treatment resistance and poor outcome in high-grade serous ovarian cancer (HGSC). Here, we explore approaches to target CCNE1-amplified cancers and potential strategies to overcome resistance to targeted agents.Experimental Design: To examine dependency on CDK2 in CCNE1-amplified HGSC, we utilized siRNA and conditional shRNA gene suppression, and chemical inhibition using dinaciclib, a small-molecule CDK2 inhibitor. High-throughput compound screening was used to identify selective synergistic drug combinations, as well as combinations that may overcome drug resistance. An observed relationship between CCNE1 and the AKT pathway was further explored in genomic data from primary tumors, and functional studies in fallopian tube secretory cells.Results: We validate CDK2 as a therapeutic target by demonstrating selective sensitivity to gene suppression. However, we found that dinaciclib did not trigger amplicon-dependent sensitivity in a panel of HGSC cell lines. A high-throughput compound screen identified synergistic combinations in CCNE1-amplified HGSC, including dinaciclib and AKT inhibitors. Analysis of genomic data from TCGA demonstrated coamplification of CCNE1 and AKT2 Overexpression of Cyclin E1 and AKT isoforms, in addition to mutant TP53, imparted malignant characteristics in untransformed fallopian tube secretory cells, the dominant site of origin of HGSC.Conclusions: These findings suggest a specific dependency of CCNE1-amplified tumors for AKT activity, and point to a novel combination of dinaciclib and AKT inhibitors that may selectively target patients with CCNE1-amplified HGSC. Clin Cancer Res; 23(7); 1862-74. ©2016 AACR.
COMPLICATIONS OF DIRECT-CURRENT COUNTERSHOCK
Authors: L I GOLDBERG
Journal: JAMA (1964)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Medicaid participation by psychiatrists in private practice
Authors: J B Mitchell, J Cromwell
Journal: American Journal of Psychiatry (1982)

Using national survey data, the authors examined the characteristics of psychiatrists in private practice who treat Medicaid patients. They found that the average Medicaid participation rate was 8%; 39.9% of psychiatrists did not see any Medicaid patients. Participating psychiatrists were more likely to be foreign medical graduates and to have a hospital-oriented practice. Psychiatrists with large Medicaid practices saw significantly more patients per week but spent less time with them. These psychiatrists were also disproportionately located in the West. The authors conclude that these variations are a result of state program differences in Medicaid reimbursement and eligibility policies.
Spoken on the Occasion ot the Director's Award to Dr. Wilhelm on Friday, September 1, 1978
Authors: H L Stewart
Journal: JNCI Journal of the National Cancer Institute (1979)

Journal Article Spoken on the Occasion ot the Director's Award to Dr. Wilhelm on Friday, September 1, 1978 Get access Harold L. Stewart, M.D. Harold L. Stewart, M.D. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 62, Issue 4, April 1979, Pages 719–721, https://doi.org/10.1093/jnci/62.4.719 Published: 01 April 1979 Article history Received: 21 September 1978 Published: 01 April 1979
Use of 18F-FDG PET-CT for Detection of Active Disease in Acute Myeloid Leukemia
Authors: Saeed Elojeimy, A. Luana Stanescu, Marguerite T. Parisi
Journal: Clinical Nuclear Medicine (2015)

A 4-year-old girl with history of acute myeloid leukemia post chemotherapy and stem cell transplant presented with pancytopenia. F-FDG PET-CT (PET-CT) showed multiple metastatic bone and extra medullary soft tissue lesions. Bone marrow biopsy after additional chemotherapy was negative. Concurrent FDG PET-CT demonstrated hypermetabolic foci in the left thigh and hand consistent with residual soft tissue disease. These lesions resolved after further treatment, but a subsequent PET-CT identified a new site of biopsy-proven chloroma. This case illustrates the important role of FDG PET-CT in identifying clinically undetectable extramedullary sites of disease, which may impact subsequent clinical management.
AB0407 Dermatologic Adverse Events in A Cohort of Patients with Rheumatoid Arthritis Using Anti-TNFs in A Real-Life Setting
Authors: A. Palomino, V. Giraldo, P. Santos-Moreno, G. Saavedra-Martinez, L. Villarreal, D. Gomez, J. Bello-Gualtero, A. Tique, F. Salas
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Biological therapy is a major therapeutic tool to prevent clinical and radiological progression of rheumatoid arthritis (RA). On the other hand, adverse effects of these medications are a problem in clinical practice. <h3>Objectives</h3> The aim of this study was to describe and compare the most frequent dermatologic adverse events with the use of biologic anti-TNF therapy in patients with RA in a real-life ambulatory setting. <h3>Methods</h3> A descriptive study was done. A review of dermatological adverse event reports presented in pharmacovigilance committee was completed monthly during last 36 months in a specialized in RA center in Colombia. Descriptive epidemiology was used, percentages and averages were calculated. <h3>Results</h3> 570 patients were using biological therapy in a cohort of 2214 RA patients last 36 months. Were 490 women (85.9%) and 80 (14.0%) men. Mean age 60.7 years old. In 163 (28.5% of all) patients were reported adverse events (AE). In 77 (46.9% of all AE) patients were reported dermatologic adverse events (AE); AE were categorized according WHO classification in mild, moderate and severe; between them 27 (35.0%) were mild, 47 (61.0%) were moderate and 3 (3.9%) were severe. From 77 events reported, only 6 (7.7%) needed biopsied to clarified what type of dermatologic reaction presented. Regarding therapeutic approach in 36 patients (46.7%) biologics were suspended, in 29 (37.6%) was permanently withdrawn and patients were switched to another biological, and 12 (15.5%) patients were followed for drug and reactions surveillance. From 77 events reported, 22 (28.6%) were acute dermatitis, 26 (33.7%) were dermatologic symptoms due to allergic skin rashes, 8 (10.3%) infection by Herpes zoster, and the other 21 cases (27.2%) were due to other causes. Concerning to type of biologic in 64 patients (83.1%), dermatologic adverse events were with anti-TNF therapies. <h3>Conclusions</h3> Dermatological adverse events using biologics founded in patients of a specialized RA center are similar to those reported in literature; Biological therapy is considered a safe and recommended treatment for management of RA. Dermatologic AE were more mostly common with anti-TNFs therapies. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.5422
An FGFR3 Autocrine Loop Sustains Acquired Resistance to Trastuzumab in Gastric Cancer Patients
Authors: Geny Piro, Carmine Carbone, Ivana Cataldo, Federica Di Nicolantonio, Simone Giacopuzzi, Giuseppe Aprile, Francesca Simionato, Federico Boschi, Marco Zanotto, Maria Mihaela Mina, Raffaela Santoro, Valeria Merz, Andrea Sbarbati, Giovanni de Manzoni, Aldo Scarpa, Giampaolo Tortora, Davide Melisi
Journal: Clinical Cancer Research (2016)

The majority of gastric cancer patients who achieve an initial response to trastuzumab-based regimens develop resistance within 1 year of treatment. This study was aimed at identifying the molecular mechanisms responsible for resistance.A HER2+-trastuzumab sensitive NCI-N87 gastric cancer orthotopic nude mouse model was treated with trastuzumab until resistance emerged. Differentially expressed transcripts between trastuzumab-resistant and sensitive gastric cancer cell lines were annotated for functional interrelatedness by Ingenuity Pathway Analysis software. Immunohistochemical analyses were performed in pretreatment versus posttreatment biopsies from gastric cancer patients receiving trastuzumab-based treatments. All statistical tests were two-sided.Four NCI-N87 trastuzumab-resistant (N87-TR) cell lines were established. Microarray analysis showed HER2 downregulation, induction of epithelial-to-mesenchymal transition, and indicated fibroblast growth factor receptor 3 (FGFR3) as one of the top upregulated genes in N87-TR cell lines. In vitro, N87-TR cell lines demonstrated a higher sensitivity than did trastuzumab-sensitive parental cells to the FGFR3 inhibitor dovitinib, which reduced expression of pAKT, ZEB1, and cell migration. Oral dovitinib significantly (P = 0.0006) reduced tumor burden and prolonged mice survival duration in N87-TR mouse models. A higher expression of FGFR3, phosphorylated AKT, and ZEB1 were observed in biopsies from patients progressing under trastuzumab-based therapies if compared with matched pretreatment biopsies.This study identified the FGFR3/AKT axis as an escape pathway responsible for trastuzumab resistance in gastric cancer, thus indicating the inhibition of FGFR3 as a potential strategy to modulate this resistance. Clin Cancer Res; 22(24); 6164-75. ©2016 AACR.
Vulnerability to sodium lactate in panic disorder patients given cognitive-behavioral therapy
Authors: M K Shear, A J Fyer, G Ball, S Josephson, M Fitzpatrick, B Gitlin, A Frances, J Gorman, M Liebowitz, D F Klein
Journal: American Journal of Psychiatry (1991)

Six patients with panic disorder who had panicked during sodium lactate infusion were given cognitive-behavioral treatment for 12-24 weeks. After treatment they underwent another lactate infusion, and four patients were rates as having no panic, suggesting that reduced vulnerability to lactate accompanies remission of panic. Controlled trials of cognitive-behavioral therapy and use of lactate infusion as a measure of remission are recommended.
Diagnosis and Treatment Algorithm for Blood Flow Obstructions in Patients With Left Ventricular Assist Device
Authors: Anna Mara Scandroglio, Friedrich Kaufmann, Marina Pieri, Alexandra Kretzschmar, Marcus Müller, Panagiotis Pergantis, Stephan Dreysse, Volkmar Falk, Thomas Krabatsch, Evgenij V. Potapov
Journal: Journal of the American College of Cardiology (2016)
Vancomycin-Resistant<i>Staphylococcus aureus</i>— Delaware, 2015
Authors: Maroya Spalding Walters, Paula Eggers, Valerie Albrecht, Tatiana Travis, David Lonsway, Greg Hovan, Debra Taylor, Kamile Rasheed, Brandi Limbago, Alexander Kallen
Journal: MMWR Morbidity and Mortality Weekly Report (2015)

Vancomycin-resistant Staphylococcus aureus (VRSA) is a rare, multidrug-resistant bacterium of public health concern that emerged in the United States in 2002. VRSA (S. aureus with vancomycin minimum inhibitory concentration [MIC] ≥16 μg/mL) arises when vancomycin resistance genes (e.g., the vanA operon, which codes for enzymes that result in modification or elimination of the vancomycin binding site) from vancomycin-resistant enterococci (VRE) are transferred to S. aureus (1). To date, all VRSA strains have arisen from methicillin-resistant S. aureus (MRSA). The fourteenth VRSA isolate (VRSA 14) identified in the United States was reported to CDC in February 2015.
AB0287 High Levels of 25(OH)D Are Associated with Lower Disease Activity in Patients with Newly Diagnosed Rheumatoid Arthritis: Table 1.
Authors: L.A. Rasch, N.P.C. Konijn, Y.H.M. Krul-Poel, L.H.D. van Tuyl, H.G. Raterman, M.M. Ter Wee, D. den Uyl, S. Simsek, M. Nurmohamed, W.F. Lems
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> Vitamin D deficiency is highly common in patients with rheumatoid arthritis (RA) (1). In vitro, vitamin D has anti-inflammatory effects and vitamin D has been linked to disease activity in RA due to its immuno-modulatory properties (1,2). <h3>Objectives</h3> To investigate the association between vitamin D status and disease activity in newly diagnosed RA patients before start of therapy. <h3>Methods</h3> Consecutive patients with active, newly diagnosed RA (symptom duration &lt;2 years), were randomized for treatment with COBRA or COBRA-light therapy (3). Before start of therapy, baseline values were determined, including Disease Activity Score (44 joint; DAS) and serum 25-hydroxy vitamin D (25(OH)D) levels. Based on the widely used cut-off values, patients were stratified into three groups based on baseline serum 25(OH)D levels: &lt;50 nmol/l, 50-74 nmol/l, and ≥75 nmol/l. <h3>Results</h3> Baseline serum 25(OH)D levels were determined in 147 of 164 included RA patients in the COBRA-light trial (90% of trial population). Serum 25(OH)D levels of the different groups are presented in Table 1. Patients with a baseline serum 25(OH)D level ≥75 nmol/l had a significant lower mean DAS compared to patients with a baseline serum 25(OH)D &lt;75 nmol/l (p=0.001). Vitamin D deficient patients (&lt;50 nmol/l) had a significant shorter symptom duration (p=0.003), and were more often rheumatoid factor positive (p=0.015) compared to patients with sufficient serum 25(OH)D levels. <h3>Conclusions</h3> Newly diagnosed RA patients with serum 25(OH)D levels ≥75 nmol/l demonstrate a significant lower disease activity than patients with a serum 25(OH)D level &lt;75 nmol/l before start of therapy. This study cannot distinguish whether a lower DAS at baseline is caused by immuno-modulatory properties due to higher serum 25(OH)D levels, or that higher serum 25(OH)D levels are caused by more frequent outdoor activities related to a lower DAS. Since 75% of the newly diagnosed RA patients have insufficient serum 25(OH)D levels (&lt;75 nmol/l), vitamin D supplementation should be considered in every newly diagnosed RA patient. <h3>References</h3> Grazio S, et al. Am J Med Sci 2014. Baker JF, et al. Clin Exp Rheumatol 2012. Den Uyl D, et al. Ann Rheum Dis 2013. <h3>Disclosure of Interest</h3> L. Rasch: None declared, N. Konijn: None declared, Y. Krul-Poel: None declared, L. van Tuyl: None declared, H. Raterman: None declared, M. ter Wee: None declared, D. den Uyl: None declared, S. Simsek: None declared, M. Nurmohamed: None declared, W. Lems Grant/research support from: This research was performed within the framework of project T1-106 of the Dutch Top Institute Pharma, and was additionally funded by an unrestricted grant from Pfizer.