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https://www.readbyqxmd.com/read/29907829/multiparametric-magnetic-resonance-imaging-for-quantitation-of-liver-disease-a-two-centre-cross-sectional-observational-study
#1
Natasha McDonald, Peter J Eddowes, James Hodson, Scott I K Semple, Nigel P Davies, Catherine J Kelly, Stella Kin, Miranda Phillips, Amy H Herlihy, Timothy J Kendall, Rachel M Brown, Desley A H Neil, Stefan G Hübscher, Gideon M Hirschfield, Jonathan A Fallowfield
LiverMultiScan is an emerging diagnostic tool using multiparametric MRI to quantify liver disease. In a two-centre prospective validation study, 161 consecutive adult patients who had clinically-indicated liver biopsies underwent contemporaneous non-contrast multiparametric MRI at 3.0 tesla (proton density fat fraction (PDFF), T1 and T2* mapping), transient elastography (TE) and Enhanced Liver Fibrosis (ELF) test. Non-invasive liver tests were correlated with gold standard histothological measures. Reproducibility of LiverMultiScan was investigated in 22 healthy volunteers...
June 15, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29619420/changes-in-natural-killer-cells-and-exhausted-memory-regulatory-t-cells-with-corticosteroid-therapy-in-acute-autoimmune-hepatitis
#2
Hannah C Jeffery, Manjit K Braitch, Chris Bagnall, James Hodson, Louisa E Jeffery, Rebecca E Wawman, Lin Lee Wong, Jane Birtwistle, Helen Bartlett, Ansgar W Lohse, Gideon M Hirschfield, Jessica Dyson, David Jones, Stefan G Hubscher, Paul Klenerman, David H Adams, Ye H Oo
Autoimmune hepatitis (AIH) is an immune-mediated liver disease currently treated by immunosuppressive medications with significant side effects. Thus, novel mechanistic treatments are greatly needed. We performed prospective deep immunophenotyping of blood immune cells in patients with acute AIH before and after corticosteroid therapy. Blood samples from 26 patients with acute AIH (United Kingdom-AIH Consortium) were phenotyped by flow cytometry at baseline and 4 months after starting corticosteroids. Pretreatment liver tissues were stained for forkhead box P3-positive (FOXP3POS ) regulatory T cells (Tregs), clusters of differentiation (CD)56POS natural killer (NK) cells, and chemokine (C-X-C motif) ligand 10...
April 2018: Hepatology communications
https://www.readbyqxmd.com/read/29593060/the-british-society-of-gastroenterology-uk-pbc-primary-biliary-cholangitis-treatment-and-management-guidelines
#3
Gideon M Hirschfield, Jessica K Dyson, Graeme J M Alexander, Michael H Chapman, Jane Collier, Stefan Hübscher, Imran Patanwala, Stephen P Pereira, Collette Thain, Douglas Thorburn, Dina Tiniakos, Martine Walmsley, George Webster, David E J Jones
Primary biliary cholangitis (formerly known as primary biliary cirrhosis, PBC) is an autoimmune liver disease in which a cycle of immune mediated biliary epithelial cell injury, cholestasis and progressive fibrosis can culminate over time in an end-stage biliary cirrhosis. Both genetic and environmental influences are presumed relevant to disease initiation. PBC is most prevalent in women and those over the age of 50, but a spectrum of disease is recognised in adult patients globally; male sex, younger age at onset (<45) and advanced disease at presentation are baseline predictors of poorer outcome...
March 28, 2018: Gut
https://www.readbyqxmd.com/read/29231188/major-hepatic-complications-in-ursodeoxycholic-acid-treated-patients-with-primary-biliary-cholangitis-risk-factors-and-time-trends-in-incidence-and-outcome
#4
Maren H Harms, Willem J Lammers, Douglas Thorburn, Christophe Corpechot, Pietro Invernizzi, Harry L A Janssen, Pier M Battezzati, Frederik Nevens, Keith D Lindor, Annarosa Floreani, Cyriel Y Ponsioen, Marlyn J Mayo, George N Dalekos, Tony Bruns, Albert Parés, Andrew L Mason, Xavier Verhelst, Kris V Kowdley, Jorn C Goet, Gideon M Hirschfield, Bettina E Hansen, Henk R van Buuren
OBJECTIVES: In this era of near universal ursodeoxycholic acid (UDCA) treatment for primary biliary cholangitis (PBC), progression to cirrhosis still occurs in an important proportion of patients. The aim of this study was to describe the incidence of cirrhosis-associated complications in patients with PBC and assess risk factors and impact on survival. METHODS: Cohorts of UDCA-treated patients from 16 European and North-American liver centers were included. We used Cox proportional hazards assumptions and Kaplan-Meier estimates...
February 2018: American Journal of Gastroenterology
https://www.readbyqxmd.com/read/29220537/milder-disease-stage-in-patients-with-primary-biliary-cholangitis-over-a-44-year-period-a-changing-natural-history
#5
Carla F Murillo Perez, Jorn C Goet, Willem J Lammers, Aliya Gulamhusein, Henk R van Buuren, Cyriel Y Ponsioen, Marco Carbone, Andrew Mason, Christophe Corpechot, Pietro Invernizzi, Marlyn J Mayo, Pier Maria Battezzati, Annarosa Floreani, Albert Pares, Frederik Nevens, Kris V Kowdley, Tony Bruns, George N Dalekos, Douglas Thorburn, Gideon Hirschfield, Nicholas F LaRusso, Keith D Lindor, Kalliopi Zachou, Raoul Poupon, Palak J Trivedi, Xavier Verhelst, Harry L A Janssen, Bettina E Hansen
Changes over time in the presenting features and clinical course of patients with primary biliary cholangitis are poorly described. We sought to describe temporal trends in patient and disease characteristics over a 44-year period across a large international primary biliary cholangitis cohort of 4,805 patients diagnosed between 1970 and 2014, from 17 centers across Europe and North America. Patients were divided into five cohorts according to their year of diagnosis: 1970-1979 (n = 143), 1980-1989 (n = 858), 1990-1999 (n = 1,754), 2000-2009 (n = 1,815), and ≥2010 (n = 235)...
May 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29195081/corrigendum-to-klinefelter-s-syndrome-47-xxy-is-in-excess-among-men-with-sj%C3%A3-gren-s-syndrome-clin-immunol-168-2016-25-29
#6
Valerie M Harris, Rohan Sharma, Joshua Cavett, Biji T Kurien, Ke Liu, Kristi A Koelsch, Astrid Rasmussen, Lida Radfar, David Lewis, Donald U Stone, C Erick Kaufman, Shibo Li, Barbara Segal, Daniel J Wallace, Michael H Weisman, Swamy Venuturupalli, Jennifer A Kelly, Marta E Alarcon-Riquelme, Bernardo Pons-Estel, Roland Jonsson, Xianglan Lu, Jacques-Eric Gottenberg, Juan-Manuel Anaya, Deborah S Cunninghame-Graham, Andrew J W Huang, Michael T Brennan, Pamela Hughes, Ilias Alevizos, Corinne Miceli-Richard, Edward C Keystone, Vivian P Bykerk, Gideon Hirschfield, Gang Xie, Katherine A Siminovitch, Wan-Fai Ng, Gunnel Nordmark, Sara Magnusson Bucher, Per Eriksson, Roald Omdal, Nelson L Rhodus, Maureen Rischmueller, Michael Rohrer, Marie Wahren-Herlenius, Torsten Witte, Xavier Mariette, Christopher J Lessard, John B Harley, Kathy L Sivils, R Hal Scofield
No abstract text is available yet for this article.
February 2018: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/29147139/insights-into-the-management-of-wilson-s-disease
#7
REVIEW
Mohmadshakil Kathawala, Gideon M Hirschfield
Wilson's disease is a rare, inherited autosomal recessive disease of copper metabolism, in which the causative gene, ATP7B , results in absent or reduced function of the ATP7B transporter important for biliary excretion of copper and incorporation of copper into caeruloplasmin. Affected patients accumulate excessive copper within the liver, brain and other tissues. A disease mainly of children, adolescents and young adults; clinical features vary from the asymptomatic state to chronic liver disease, acute liver failure, and neuropsychiatric manifestations...
November 2017: Therapeutic Advances in Gastroenterology
https://www.readbyqxmd.com/read/29111807/book-reviews-fundamentals-of-anaesthesia-4th-edn-edited-by-ted-lin-tim-smith-colin-pinnock-cambridge-university-press-2017-price-%C3%A2-84-99-pp-983-isbn-9781107612389-aging-and-development-social-and-emotional-perspectives-2nd-edn-peter-f-coleman-ann-o-hanlon-routledge
#8
https://www.readbyqxmd.com/read/29101259/deciphering-the-biology-of-igg4-related-disease-specific-antigens-and-disease
#9
Debashis Haldar, Gideon M Hirschfield
No abstract text is available yet for this article.
April 2018: Gut
https://www.readbyqxmd.com/read/29067151/primary-sclerosing-cholangitis-and-the-management-of-uncertainty-and-complexity
#10
REVIEW
Katherine Arndtz, Gideon M Hirschfield
Primary sclerosing cholangitis (PSC) is a rare chronic autoimmune disease with no effective therapy and a large unmet need for new treatments. Patients require significant healthcare resources over their lifetime with high rates of hospital admission, malignancy, liver transplantation and death. As a rare disease, expertise in management can be limited to large referral liver transplant programmes, and even then there is frequently variation in practice. In this case-based review, we aim to discuss common clinical dilemmas encountered by clinicians managing patients with PSC and address related competencies in the 2010 Gastroenterology Curriculum...
October 2017: Frontline Gastroenterology
https://www.readbyqxmd.com/read/29063616/genetic-association-studies-and-the-risk-factors-for-developing-the-immuno-bile-logic-disease-primary-biliary-cholangitis
#11
Evaggelia Liaskou, Gideon M Hirschfield
No abstract text is available yet for this article.
April 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29023915/a-randomized-trial-of-obeticholic-acid-monotherapy-in-patients-with-primary-biliary-cholangitis
#12
Kris V Kowdley, Velimir Luketic, Roger Chapman, Gideon M Hirschfield, Raoul Poupon, Christoph Schramm, Catherine Vincent, Christian Rust, Albert Parés, Andrew Mason, Hanns-Ulrich Marschall, David Shapiro, Luciano Adorini, Cathi Sciacca, Tessa Beecher-Jones, Olaf Böhm, Richard Pencek, David Jones
Obeticholic acid (OCA), a potent farnesoid X receptor agonist, was studied as monotherapy in an international, randomized, double-blind, placebo-controlled phase 2 study in patients with primary biliary cholangitis who were then followed for up to 6 years. The goals of the study were to assess the benefit of OCA in the absence of ursodeoxycholic acid, which is relevant for patients who are intolerant of ursodeoxycholic acid and at higher risk of disease progression. Patients were randomized and dosed with placebo (n = 23), OCA 10 mg (n = 20), or OCA 50 mg (n = 16) given as monotherapy once daily for 3 months (1 randomized patient withdrew prior to dosing)...
May 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28844936/toronto-hcc-risk-index-a-validated-scoring-system-to-predict-10-year-risk-of-hcc-in-patients-with-cirrhosis
#13
Suraj A Sharma, Matthew Kowgier, Bettina E Hansen, Willem Pieter Brouwer, Raoel Maan, David Wong, Hemant Shah, Korosh Khalili, Colina Yim, E Jenny Heathcote, Harry L A Janssen, Morris Sherman, Gideon M Hirschfield, Jordan J Feld
BACKGROUND & AIMS: Current guidelines recommend biannual surveillance for hepatocellular carcinoma (HCC) in all patients with cirrhosis, regardless of etiology. However, HCC incidence is not well established for many causes of cirrhosis. We aimed to assess the disease-specific incidence of HCC in a large cohort of patients with cirrhosis and to develop a scoring system to predict HCC risk. METHODS: A derivation cohort of patients with cirrhosis diagnosed by biopsy or non-invasive measures was identified through retrospective chart review...
August 24, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/28839868/evolving-strategies-to-reduce-colectomy-rates-in-primary-sclerosing-cholangitis-inflammatory-bowel-disease-clinical-remission-of-corticosteroid-refractory-colitis-post-liver-transplant-with-vedolizumab
#14
Saqib Mumtaz, Jason Goh, Gideon M Hirschfield, James Ferguson, Sheldon C Cooper
Primary sclerosing cholangitis (PSC) is associated with inflammatory bowel disease (IBD) in approximately 70% of patients, with ulcerative colitis (UC) being the most common subtype of IBD identified. There is a paucity of data on the optimum management strategy for IBD flares in the post-liver transplant patient, particularly when refractory to conventional treatments. Vedolizumab is a novel gut-specific monoclonal antibody, which has recently been approved for use by National Institute for Health and Care Excellence for moderate-to-severe UC...
October 2016: Frontline Gastroenterology
https://www.readbyqxmd.com/read/28839864/autoimmune-liver-disease-evaluating-overlapping-and-cross-over-presentations-a-case-based-discussion
#15
Margaret Corrigan, Gideon M Hirschfield
The three classic autoimmune liver diseases are recognised based on identifying varying clinical, laboratory, histological and radiological features that collectively classify patients. In the absence of defined aetiological factors, it is recognised that disease spectrum is broad, and, in this context, it is not infrequent for disease boundaries to be blurred, leading to overlapping features that may be present at the time of diagnosis or may appear later in the course of disease. Given the absence of accepted diagnostic criteria for overlap/cross-over syndromes, alongside weak data for intervention, it is recommended that a multidisciplinary, patient-specific approach be used to establish individual treatment pathways...
October 2016: Frontline Gastroenterology
https://www.readbyqxmd.com/read/28818518/seladelpar-mbx-8025-a-selective-ppar-%C3%AE-agonist-in-patients-with-primary-biliary-cholangitis-with-an-inadequate-response-to-ursodeoxycholic-acid-a-double-blind-randomised-placebo-controlled-phase-2-proof-of-concept-study
#16
David Jones, Pol F Boudes, Mark G Swain, Christopher L Bowlus, Michael R Galambos, Bruce R Bacon, Yvonne Doerffel, Norman Gitlin, Stuart C Gordon, Joseph A Odin, David Sheridan, Markus-Alexander Wörns, Virginia Clark, Linsey Corless, Heinz Hartmann, Mark E Jonas, Andreas E Kremer, George F Mells, Peter Buggisch, Bradley L Freilich, Cynthia Levy, John M Vierling, David E Bernstein, Marek Hartleb, Ewa Janczewska, Fedja Rochling, Hemant Shah, Mitchell L Shiffman, John H Smith, Yun-Jung Choi, Alexandra Steinberg, Monika Varga, Harinder Chera, Robert Martin, Charles A McWherter, Gideon M Hirschfield
BACKGROUND: Many patients with primary biliary cholangitis have an inadequate response to first-line therapy with ursodeoxycholic acid. Seladelpar is a potent, selective agonist for the peroxisome proliferator-activated receptor-delta (PPAR-δ), which is implicated in bile acid homoeostasis. This first-in-class study evaluated the anti-cholestatic effects and safety of seladelpar in patients with an inadequate response to ursodeoxycholic acid. METHODS: The study was a 12-week, double-blind, placebo-controlled, phase 2 trial of patients with alkaline phosphatase of at least 1·67 times the upper limit of normal (ULN) despite treatment with ursodeoxycholic acid...
October 2017: Lancet. Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/28794437/genetic-variation-at-the-cd28-locus-and-its-impact-on-expansion-of-pro-inflammatory-cd28-negative-t-cells-in-healthy-individuals
#17
Evaggelia Liaskou, Louisa Jeffery, Dimitrios Chanouzas, Blagoje Soskic, Michael F Seldin, Lorraine Harper, David Sansom, Gideon M Hirschfield
The CD28 locus is associated with susceptibility to a variety of autoimmune and immune-mediated inflammatory diseases including primary sclerosing cholangitis (PSC). Previously, we linked the CD28 pathway in PSC disease pathology and found that vitamin D could maintain CD28 expression. Here, we assessed whether the PSC-associated CD28 risk variant A (rs7426056) affects CD28 expression and T cell function in healthy individuals (n = 14 AA, n = 14 AG, n = 14 GG). Homozygotes for the PSC disease risk allele (AA) showed significantly lower CD28 mRNA expression ex-vivo than either GG or AG (p < 0...
August 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28701337/should-we-screen-for-cirrhosis
#18
Mark Hudson, Nick Sheron, Ian A Rowe, Gideon M Hirschfield
No abstract text is available yet for this article.
July 12, 2017: BMJ: British Medical Journal
https://www.readbyqxmd.com/read/28692793/rare-x-chromosome-abnormalities-in-systemic-lupus-erythematosus-and-sj%C3%A3-gren-s-syndrome
#19
Rohan Sharma, Valerie M Harris, Joshua Cavett, Biji T Kurien, Ke Liu, Kristi A Koelsch, Anum Fayaaz, Kaustubh S Chaudhari, Lida Radfar, David Lewis, Donald U Stone, C Erick Kaufman, Shibo Li, Barbara Segal, Daniel J Wallace, Michael H Weisman, Swamy Venuturupalli, Jennifer A Kelly, Bernardo Pons-Estel, Roland Jonsson, Xianglan Lu, Jacques-Eric Gottenberg, Juan-Manuel Anaya, Deborah S Cunninghame-Graham, Andrew J W Huang, Michael T Brennan, Pamela Hughes, Ilias Alevizos, Corinne Miceli-Richard, Edward C Keystone, Vivian P Bykerk, Gideon Hirschfield, Gunnel Nordmark, Sara Magnusson Bucher, Per Eriksson, Roald Omdal, Nelson L Rhodus, Maureen Rischmueller, Michael Rohrer, Marie Wahren-Herlenius, Torsten Witte, Marta Alarcón-Riquelme, Xavier Mariette, Christopher J Lessard, John B Harley, Wan-Fai Ng, Astrid Rasmussen, Kathy L Sivils, R Hal Scofield
OBJECTIVE: Sjögren's syndrome (SS) and systemic lupus erythematosus (SLE) are related by clinical and serologic manifestations as well as genetic risks. Both diseases are more commonly found in women than in men, at a ratio of ~10 to 1. Common X chromosome aneuploidies, 47,XXY and 47,XXX, are enriched among men and women, respectively, in either disease, suggesting a dose effect on the X chromosome. METHODS: We examined cohorts of SS and SLE patients by constructing intensity plots of X chromosome single-nucleotide polymorphism alleles, along with determining the karyotype of selected patients...
November 2017: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/28690174/clinical-outcomes-of-donation-after-circulatory-death-liver-transplantation-in-primary-sclerosing-cholangitis
#20
Palak J Trivedi, Irene Scalera, Emma Slaney, Richard W Laing, Bridget Gunson, Gideon M Hirschfield, Andrea Schlegel, James Ferguson, Paolo Muiesan
BACKGROUND & AIM: Primary sclerosing cholangitis (PSC) is a progressive fibro-inflammatory cholangiopathy for which liver transplantation is the only life-extending intervention. These patients may benefit from accepting liver donation after circulatory death (DCD), however their subsequent outcome is unknown. The aim of this study was to determine the clinical impact of using DCD liver grafts in patients specifically undergoing transplantation for PSC. METHODS: Clinical outcomes were prospectively evaluated in PSC patients undergoing transplantation from 2006 to 2016 stratified by donor type (DCD, n=35 vs...
November 2017: Journal of Hepatology
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