Search

The diagnosis of primary biliary cholangitis (PBC) in patients with seropositive anti‐mitochondrial antibody (AMA) but normal alkaline phosphatase (ALP) depends on a liver biopsy. We aimed to reveal potential serum biomarkers that could suggest the necessity of a liver biopsy in such patients. Retrospective analysis was performed. Subjects who were treatment naive with seropositive AMA but normal ALP and who underwent at least one liver biopsy between 2008 and 2020 were included in this study. Histologic biopsies were evaluated by two experienced pathologists blinded to the serum tests. A total of 115 patients who were treatment naive were included in this study. Of these, 77 patients (67%) exhibited histologic PBC features and nonspecific histologic features were found in the remaining 38 (33%) patients. Multivariate analysis suggested that baseline serum immunoglobulin M (IgM) >0.773 × upper limit of normal (ULN) (P < 0.001) and age >42 years (P = 0.002) were associated with the diagnosis of PBC through liver biopsies. A significant decrease in the median levels of gamma‐glutamyl transpeptidase (GGT) and IgM was found in 54 patients with PBC who received ursodeoxycholic acid (UDCA). Conclusion: For patients who were treatment naive with seropositive AMA but normal ALP, baseline serum IgM >0.773 × ULN and age >42 years were the factors that strongly suggested a diagnosis of PBC. In these patients receiving UDCA, a dynamic monitoring of GGT and IgM might be helpful in evaluating therapeutic responses. [ABSTRACT FROM AUTHOR]

Background: Cerebral venous sinus thrombosis (CVST) is a rare cause of stroke that mainly affects the young. Anticoagulation (AC) with heparin is the mainstay of treatment for CVST. Although highly anticipated, endovascular therapy (ET) including local thrombolysis and mechanical thrombectomy has been controversial., Review Summary: To compare the effectiveness and safety of ET with AC for patients with confirmed CVST, we systematically searched PubMed, Embase, and Cochrane Library from the earliest date to February 2020. Data on the total number of patients in each treatment group and the exact number of patients for each outcome were separately extracted from 10 studies with 891 patients.Our Results show that ET has a higher mortality rate compared with AC [odds ratio (OR)=1.95; 95% confidence interval (CI), 1.19-3.18; P=0.008<0.01] and has lower probability of good outcome (OR=0.48; 95% CI, 0.23-1.02; P=0.056). ET leads to a higher risk of complications than AC (OR=5.29; 95% CI, 1.17-23.95; P=0.030<0.05). No difference was found in recurrence rate between 2 treatments (OR=0.85; 95% CI, 0.31-2.35; P=0.761)., Conclusions: ET is related to a higher mortality, fewer good outcome and possibly more complications compared with AC. The risks of ET should be weighed in every individualized therapeutic decision., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: The striated muscle costamere, a multiprotein complex at the boundary between the sarcomere and the sarcolemma, plays an integral role in maintaining striated muscle structure and function. Multiple costamere-associated proteins, such as integrins and integrin-interacting proteins, have been identified and shown to play an increasingly important role in the pathogenesis of human cardiomyopathy. Kindlin-2 is an adaptor protein that binds to the integrin β cytoplasmic tail to promote integrin activation. Genetic deficiency of Kindlin-2 results in embryonic lethality, and knockdown of the Kindlin-2 homolog in Caenorhabditis elegans and Danio rerio suggests that it has an essential role in integrin function and normal muscle structure and function. The precise role of Kindlin-2 in the mammalian cardiac myocyte remains to be determined., Methods and Results: The current studies were designed to investigate the role of Kindlin-2 in the mammalian heart. We generated a series of cardiac myocyte-specific Kindlin-2 knockout mice with excision of the Kindlin-2 gene in either developing or adult cardiac myocytes. We found that mice lacking Kindlin-2 in the early developing heart are embryonic lethal. We demonstrate that deletion of Kindlin-2 at late gestation or in adult cardiac myocytes resulted in heart failure and premature death, which were associated with enlargement of the heart and extensive fibrosis. In addition, integrin β1D protein expression was significantly downregulated in the adult heart., Conclusions: Kindlin-2 is required to maintain integrin β1D protein stability. Postnatal loss of Kindlin-2 from cardiac myocytes leads to progressive heart failure, showing the importance of costameric proteins like Kindlin-2 for homeostasis of normal heart function., (© 2016 American Heart Association, Inc.)