1,720,966 research outputs found
Recommendations on the use of magnetic resonance imaging for collaborative multicenter studies in PSC
No full textRecently, the MRI working group of the International PSC Study Group (IPSCSG) has published a position statement on the use of MRI regarding diagnosis and follow-up of PSC patients. These guidelines are intended for use by physicians in daily clinical routine. In addition, the group has outlined several areas of research, which need to be addressed in the near future. As PSC is a rare disease with the clinical outcome being determined by the development of end-stage liver disease and hepatobiliary malignancy. This article is protected by copyright. All rights reserved
Recommendations on the use of magnetic resonance imaging for collaborative multicenter studies in PSC
No full textRecently, the MRI working group of the International PSC Study Group (IPSCSG) has published a position statement on the use of MRI regarding diagnosis and follow-up of PSC patients. These guidelines are intended for use by physicians in daily clinical routine. In addition, the group has outlined several areas of research, which need to be addressed in the near future. As PSC is a rare disease with the clinical outcome being determined by the development of end-stage liver disease and hepatobiliary malignancy. This article is protected by copyright. All rights reserved
Maternal liver-related symptoms during pregnancy in primary sclerosing cholangitis
No full textBackground & Aims: Although worsening liver-related symptoms during pregnancy can occur in primary sclerosing cholangitis (PSC), there are insufficient data to effectively counsel patients on their pre-conception risk and no clear recommendations on monitoring and management during pregnancy. We aimed to describe maternal liver-related symptoms in pregnancy, both before and after PSC diagnosis, and explore factors associated with worsening symptoms and liver-related outcomes. Methods: We conducted a multicentre retrospective observational study of females with PSC and known pregnancy with live birth, via the International PSC Study Group. We included 450 patients from 12 European centres. Data included clinical variables, liver-related symptoms (pruritus and/or cholangitis) during pregnancy, and liver biochemistry. A composite primary endpoint of transplant-free survival from time of PSC diagnosis was used. Results: There were 266 pregnancies in 178 patients following PSC diagnosis. Worsening liver-related symptoms were reported in 66/228 (28.9%) pregnancies; they had a reduced transplant-free survival (p = 0.03), which retained significance on multivariate analysis (hazard ratio 3.02, 95% CI 1.24-7.35; p = 0.02). Abnormal biochemistry and/or liver-related symptoms (pruritus and/or cholangitis) were noted during pregnancy before PSC diagnosis in 21/167 (12.6%) patients. They had a reduced transplant-free survival from pregnancy (p = 0.01), which did not retain significance in a multivariable model (hazard ratio 1.10, 95% CI 0.43-2.85; p = 0.84). Conclusions: Liver-related symptoms are frequently encountered during pregnancies before the diagnosis of PSC, and pregnancy may expose the pre-clinical phase of PSC in some patients. Worsening liver-related symptoms were seen in a third of our cohort with known PSC during pregnancy; and this subgroup had a poorer prognosis, which may be related to more advanced liver disease at time of pregnancy and/or a more severe disease phenotype. Impact and implications: Patients with PSC can develop worsening of their liver-related symptoms during pregnancy; however, risk factors for this and the long-term implications are not known. We identified that there is a significant risk of these symptoms in pregnancy, both before and after PSC has been diagnosed, particularly in patients with elevated alkaline phosphatase. Furthermore, our findings suggest that worsening symptoms during pregnancy may be associated with adverse long-term clinical outcomes of liver transplantation and death in patients with known PSC. This may be related to the presence of more advanced liver disease at time of pregnancy. This information can be used to counsel patients with PSC before conception and identify patients who need close follow-up after delivery.Peer reviewe
Characterization of animal models for primary sclerosing cholangitis (PSC)
Get PDFSummaryPrimary sclerosing cholangitis (PSC) is a chronic cholangiopathy characterized by biliary fibrosis, development of cholestasis and end stage liver disease, high risk of malignancy, and frequent need for liver transplantation. The poor understanding of its pathogenesis is also reflected in the lack of effective medical treatment. Well-characterized animal models are utterly needed to develop novel pathogenetic concepts and study new treatment strategies. Currently there is no consensus on how to evaluate and characterize potential PSC models, which makes direct comparison of experimental results and effective exchange of study material between research groups difficult. The International Primary Sclerosing Cholangitis Study Group (IPSCSG) has therefore summarized these key issues in a position paper proposing standard requirements for the study of animal models of PSC
HLA-DPA1*02:01~B1*01:01 is a risk haplotype for primary sclerosing cholangitis mediating activation of NKp44+ NK cells
Get PDFObjective Primary sclerosing cholangitis (PSC) is characterised by bile duct strictures and progressive liver disease, eventually requiring liver transplantation. Although the pathogenesis of PSC remains incompletely understood, strong associations with HLA-class II haplotypes have been described. As specific HLA-DP molecules can bind the activating NK-cell receptor NKp44, we investigated the role of HLA-DP/ NKp44-interactions in PSC.Design Liver tissue, intrahepatic and peripheral blood lymphocytes of individuals with PSC and control individuals were characterised using flow cytometry, immunohistochemical and immunofluorescence analyses. HLA-DPA1 and HLA-DPB1 imputation and association analyses were performed in 3408 individuals with PSC and 34 213 controls. NK cell activation on NKp44/HLA-DP interactions was assessed in vitro using plate-bound HLA-DP molecules and HLA-DPB wildtype versus knock-out human cholangiocyte organoids.Results NKp44+NK cells were enriched in livers, and intrahepatic bile ducts of individuals with PSC showed higher expression of HLA-DP. HLA-DP haplotype analysis revealed a highly elevated PSC risk for HLA-DPA1* 02:01 similar to B1*01:01 (OR 1.99, p=6.7x10-50). Primary NKp44+NK cells exhibited significantly higher degranulation in response to plate-bound HLA-DPA1* 02:01-DPB1* 01:01 compared with control HLA-DP molecules, which were inhibited by anti-NKp44-blocking. Human cholangiocyte organoids expressing HLA-DPA1* 02:01-DPB1* 01:01 after IFN-gamma-exposure demonstrated significantly increased binding to NKp44-Fc constructs compared with unstimulated controls. Importantly, HLA-DPA1* 02:01-DPB1* 01:01-expressing organoids increased degranulation of NKp44+NK cells compared with HLA-DPB1- KO organoids.Conclusion Our studies identify a novel PSC risk haplotype HLA-DP A1*02:01 similar to DPB1*01:01 and provide clinical and functional data implicating NKp44+NK cells that recognise HLA-DPA1* 02:01-DPB1* 01:01 expressed on cholangiocytes in PSC pathogenesis
Follow-up magnetic resonance imaging/3D-magnetic resonance cholangiopancreatography in patients with primary sclerosing cholangitis: challenging for experts to interpret
No full textBackground: In patients with primary sclerosing cholangitis follow‐up magnetic resonance imaging (MRI) with magnetic resonance cholangiopancreatography (MRCP) is performed by many centres, particularly for the early detection of biliary malignancies and strictures. Clinically meaningful MRI‐based definitions of primary sclerosing cholangitis related complications are, however, lacking.Aim: To investigate how primary sclerosing cholangitis experts interpret follow‐up MRI/MRCP with a focus on conclusions that may impact clinical decision‐making in primary sclerosing cholangitis.Methods: Within the International Primary Sclerosing Cholangitis Study Group, an online survey on 16 real‐life primary sclerosing cholangitis cases including clinical and biochemical information as well as a T2‐weighted liver MRI/3D‐MRCP was conducted. The interpretation of images and subsequent recommendations were assessed using a multiple‐choice questionnaire. An inter‐rater reliability calculation (Fleiss′ kappa) was performed and factors potentially affecting the interpretation of magnetic resonance images were analysed using generalised linear mixed‐effect models.Results: Forty‐four members/associates of the International Primary Sclerosing Cholangitis Study Group (median experience in the care of primary sclerosing cholangitis patients: 14 years) completed the survey. The MRI interpretation significantly varied among the participants. The lowest agreement was found with respect to the indication to perform subsequent endoscopic retrograde cholangiopancreatography (ERCP; Κ = 0.12, 95%CI 0.11‐0.14). Elevated total bilirubin was the variable with the strongest effect on the rate of suspected dominant strictures, cholangiocarcinoma or ERCP recommendations. Liver cirrhosis did not prevent participants from recommending ERCP. Overall, the survey participants′ recommendations contrasted the real‐life management and outcome.Conclusions: In primary sclerosing cholangitis, the interpretation of follow‐up MRI/3D‐MRCP significantly varies even among experts and seems to be primarily affected by bilirubin levels. Generally accepted MRI‐based definitions of primary sclerosing cholangitis‐related complications are urgently needed
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Get PDF“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
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