14 research outputs found

    Corrigendum to ‘An international genome-wide meta-analysis of primary biliary cholangitis: Novel risk loci and candidate drugs’ [J Hepatol 2021;75(3):572–581]

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    Factors Associated with Revision Surgery after Internal Fixation of Hip Fractures

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    Background: Femoral neck fractures are associated with high rates of revision surgery after management with internal fixation. Using data from the Fixation using Alternative Implants for the Treatment of Hip fractures (FAITH) trial evaluating methods of internal fixation in patients with femoral neck fractures, we investigated associations between baseline and surgical factors and the need for revision surgery to promote healing, relieve pain, treat infection or improve function over 24 months postsurgery. Additionally, we investigated factors associated with (1) hardware removal and (2) implant exchange from cancellous screws (CS) or sliding hip screw (SHS) to total hip arthroplasty, hemiarthroplasty, or another internal fixation device. Methods: We identified 15 potential factors a priori that may be associated with revision surgery, 7 with hardware removal, and 14 with implant exchange. We used multivariable Cox proportional hazards analyses in our investigation. Results: Factors associated with increased risk of revision surgery included: female sex, [hazard ratio (HR) 1.79, 95% confidence interval (CI) 1.25-2.50; P = 0.001], higher body mass index (fo

    Staging and functional characterization of pheochromocytoma and paraganglioma by 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography.

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    Item does not contain fulltextBACKGROUND: Pheochromocytomas and paragangliomas (PPGLs) are rare tumors of the adrenal medulla and extra-adrenal sympathetic chromaffin tissues; their anatomical and functional imaging are critical to guiding treatment decisions. This study aimed to compare the sensitivity and specificity of (18)F-fluorodeoxyglucose positron emission tomography with computed tomography ((18)F-FDG PET/CT) for tumor localization and staging of PPGLs with that of conventional imaging by [(123)I]-metaiodobenzylguanidine single photon emission CT ((123)I-MIBG SPECT), CT, and magnetic resonance imaging (MRI). METHODS: A total of 216 patients (106 men, 110 women, aged 45.2 +/- 14.9 years) with suspected PPGL underwent CT or MRI, (18)F-FDG PET/CT, and (123)I-MIBG SPECT/CT. Sensitivity and specificity were measured as endpoints and compared by the McNemar test, using two-sided P values only. RESULTS: Sixty (28%) of patients had nonmetastatic PPGL, 95 (44%) had metastatic PPGL, and 61 (28%) were PPGL negative. For nonmetastatic tumors, the sensitivity of (18)F-FDG was similar to that of (123)I-MIBG but less than that of CT/MRI (sensitivity of (18)F-FDG = 76.8%; of (123)I-MIBG = 75.0%; of CT/MRI = 95.7%; (18)F-FDG vs (123)I-MIBG: difference = 1.8%, 95% confidence interval [CI] = -14.8% to 14.8%, P = .210; (18)F-FDG vs CT/MRI: difference = 18.9%, 95% CI = 9.4% to 28.3%, P < .001). The specificity was 90.2% for (18)F-FDG, 91.8% for (123)I-MIBG, and 90.2% for CT/MRI. (18)F-FDG uptake was higher in succinate dehydrogenase complex- and von Hippel-Lindau syndrome-related tumors than in multiple endocrine neoplasia type 2 (MEN2) related tumors. For metastases, sensitivity was greater for (18)F-FDG and CT/MRI than for (123)I-MIBG (sensitivity of (18)F-FDG = 82.5%; of (123)I-MIBG = 50.0%; of CT/MRI = 74.4%; (18)F-FDG vs (123)I-MIBG: difference = 32.5%, 95% CI = 22.3% to 42.5%, P < .001; CT/MRI vs (123)I-MIBG: difference = 24.4%, 95% CI = 11.3% to 31.6%, P < .001). For bone metastases, (18)F-FDG was more sensitive than CT/MRI (sensitivity of (18)F-FDG = 93.7%; of CT/MRI = 76.7%; difference = 17.0%, 95% CI = 4.9% to 28.5%, P = .013). CONCLUSIONS: Compared with (123)I-MIBG SPECT and CT/MRI, both considered gold standards for PPGL imaging, metastases were better detected by (18)F-FDG PET. (18)F-FDG PET provides a high specificity in patients with a biochemically established diagnosis of PPGL

    Corrigendum to ‘An international genome-wide meta-analysis of primary biliary cholangitis: Novel risk loci and candidate drugs’ [J Hepatol 2021;75(3):572–581] (Journal of Hepatology (2021) 75(3) (572–581), (S0168827821003342), (10.1016/j.jhep.2021.04.055))

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    It has come to our attention that the name of one of the authors in our manuscript was incorrectly spelled ‘Jinyoung Byan’; the correct spelling is ‘Jinyoung Byun’ as in the author list above. In addition, the excel files of the supplementary tables were not included during the online publication of our article. These have now been made available online. We apologize for any inconvenience caused

    Corrigendum to \u2018An international genome-wide meta-analysis of primary biliary cholangitis: Novel risk loci and candidate drugs\u2019 [J Hepatol 2021;75(3):572\u2013581] (Journal of Hepatology (2021) 75(3) (572\u2013581), (S0168827821003342), (10.1016/j.jhep.2021.04.055))

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    It has come to our attention that the name of one of the authors in our manuscript was incorrectly spelled \u2018Jinyoung Byan\u2019; the correct spelling is \u2018Jinyoung Byun\u2019 as in the author list above. In addition, the excel files of the supplementary tables were not included during the online publication of our article. These have now been made available online. We apologize for any inconvenience caused

    Corrigendum to ‘An international genome-wide meta-analysis of primary biliary cholangitis: Novel risk loci and candidate drugs’ [J Hepatol 2021;75(3):572–581] (Journal of Hepatology (2021) 75(3) (572–581), (S0168827821003342), (10.1016/j.jhep.2021.04.055))

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    Governance of Steel and Kryptonite Politics in Contemporary Public Education Reform

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    An international genome-wide meta-analysis of primary biliary cholangitis: Novel risk loci and candidate drugs.

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    BACKGROUNDS & AIMS Primary biliary cholangitis (PBC) is a chronic liver disease in which autoimmune destruction of the small intrahepatic bile ducts eventually leads to cirrhosis. Many patients have inadequate response to licensed medications, motivating the search for novel therapies. Previous genome-wide association studies (GWAS) and meta-analyses (GWMA) of PBC have identified numerous risk loci for this condition, providing insight into its aetiology. We undertook the largest GWMA of PBC to date, aiming to identify additional risk loci and prioritise candidate genes for in silico drug efficacy screening. METHODS We combined new and existing genotype data for 10,516 cases and 20,772 controls from 5 European and 2 East Asian cohorts. RESULTS We identified 56 genome-wide significant loci (20 novel) including 46 in European, 13 in Asian, and 41 in combined cohorts; and a 57 genome-wide significant locus (also novel) in conditional analysis of the European cohorts. Candidate genes at newly identified loci include FCRL3, INAVA, PRDM1, IRF7, CCR6, CD226, and IL12RB1, which each play key roles in immunity. Pathway analysis reiterated the likely importance of pattern recognition receptor and TNF signalling, JAK-STAT signalling, and differentiation of T helper (T)1 and T17 cells in the pathogenesis of this disease. Drug efficacy screening identified several medications predicted to be therapeutic in PBC, some of which are well-established in the treatment of other autoimmune disorders. CONCLUSIONS This study has identified additional risk loci for PBC, provided a hierarchy of agents that could be trialled in this condition, and emphasised the value of genetic and genomic approaches to drug discovery in complex disorders. LAY SUMMARY Primary biliary cholangitis (PBC) is a chronic liver disease that eventually leads to cirrhosis. In this study, we analysed genetic information from 10,516 people with PBC and 20,772 healthy individuals recruited in Canada, China, Italy, Japan, the UK, or the USA. We identified several genetic regions associated with PBC. Each of these regions contains several genes. For each region, we used diverse sources of evidence to help us choose the gene most likely to be involved in causing PBC. We used these 'candidate genes' to help us identify medications that are currently used for treatment of other conditions, which might also be useful for treatment of PBC

    Fracture fixation in the operative management of hip fractures (FAITH): an international, multicentre, randomised controlled trial

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    Background Reoperation rates are high after surgery for hip fractures. We investigated the effect of a sliding hip screw versus cancellous screws on the risk of reoperation and other key outcomes. Methods For this international, multicentre, allocation concealed randomised controlled trial, we enrolled patients aged 50 years or older with a low-energy hip fracture requiring fracture fixation from 81 clinical centres in eight countries. Patients were assigned by minimisation with a centralised computer system to receive a single large-diameter screw with a side-plate (sliding hip screw) or the present standard of care, multiple small-diameter cancellous screws. Surgeons and patients were not blinded but the data analyst, while doing the analyses, remained blinded to treatment groups. The primary outcome was hip reoperation within 24 months after initial surgery to promote fracture healing, relieve pain, treat infection, or improve function. Analyses followed the intention-to-treat principle. This study was registered with ClinicalTrials.gov, number NCT00761813. Findings Between Mar
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