The growing burden of generalized myasthenia gravis: a population-based retrospective cohort study in Taiwan

BackgroundThe prevalence of myasthenia gravis is increasing in many countries, including Asia. As treatment options expand, population-based information about the disease burden can inform health technology assessments.MethodsWe conducted a population-based retrospective cohort study using the Taiwan National Healthcare Insurance Research database and Death Registry to describe the epidemiology, disease burden and treatment patterns of generalized myasthenia gravis (gMG) from 2009 to 2019. Episodes of hepatitis B virus (HBV) infection or reactivation were explored.ResultsThe number of patients with gMG increased from 1,576 in 2009 to 2,638 in 2019 and the mean (standard deviation) age from 51.63 (17.32) to 55.38 (16.29) years. The female:male ratio was 1.3:1. Frequently reported co-morbidities were hypertension (32–34% of patients), diabetes mellitus (16–21%) and malignancies (12–17%). The prevalence of patients with gMG increased annually from 6.83/100,000 population in 2009 to 11.18/100,000 population in 2019 (p < 0.0001). There was no temporal trend in all-cause fatality rates (range 2.76–3.79/100 patients annually) or gMG incidence rates (2.4–3.17/100,000 population annually). First-line treatment was with pyridostigmine (82%), steroids (58%), and azathioprine (11%). There was minimal change in treatment patterns over time. Among 147 new HBV infections, 32 (22%) received ≥4 weeks of antiviral therapy suggesting chronic infection. The HBV reactivation rate was 7.2%.ConclusionThe epidemiology of gMG in Taiwan is evolving rapidly, with higher prevalence rates and increasing involvement of older age-groups suggesting a growing burden of disease and associated healthcare costs. HBV infection or reactivation may pose a previously unrecognized recognized risk for patients with gMG receiving immunosuppressants

Loss of α-catenin elicits a cholestatic response and impairs liver regeneration

The liver is unique in its capacity to regenerate after injury, during which hepatocytes actively divide and establish cell-cell contacts through cell adhesion complexes. Here, we demonstrate that the loss of α-catenin, a well-established adhesion component, dramatically disrupts liver regeneration. Using a partial hepatectomy model, we show that regenerated livers from α-catenin knockdown mice are grossly larger than control regenerated livers, with an increase in cell size and proliferation. This increased proliferation correlated with increased YAP activation, implicating α-catenin in the Hippo/YAP pathway. Additionally, α-catenin knockdown mice exhibited a phenotype reminiscent of clinical cholestasis, with drastically altered bile canaliculi, elevated levels of bile components and signs of jaundice and inflammation. The disrupted regenerative capacity is a result of actin cytoskeletal disorganisation, leading to a loss of apical microvilli, dilated lumens in the bile canaliculi, and leaky tight junctions. This study illuminates a novel, essential role for α-catenin in liver regeneration

Cognitive dysfunction in Malaysian patients with major depressive disorder: A subgroup analysis of a multicountry, cross‐sectional study

Introduction: Cognitive dysfunction has been significantly associated with functional impairment in patients with major depressive disorder (MDD). Methods: This is a subgroup analysis of 211 Malaysian patients recruited from the multicountry, multicenter, cross-sectional Cognitive Dysfunction in Asian patients with Depression (CogDAD) study. Depression severity, cognitive dysfunction, and functional disability were assessed and compared with the overall CogDAD study population. Factors associated with functional disability were also evaluated in this Malaysian patient population. Results: Approximately half of the Malaysian patients were in their first depressive episode, with the majority being treated for mild-to-moderate depression. Furthermore, Malaysian patients experienced cognitive dysfunction, with self-reported Perceived Deficits Questionnaire (PDQ-D) scores falling within the third quartile of PDQ-D severity. Malaysian patients also reported functional disability evidenced by a mean total Sheehan Disability Scale (SDS) score of 11.47 ± 6.68, with the highest SDS score reported in the “Social Life/Leisure Activities” domain. Compared with the overall CogDAD study population, the Malaysian patient population had comparable patient demographics in terms of marital and working status; outcome scores for PHQ-9 (9-item Patient Health Questionnaire for self-reported depression severity), PDQ-D and SDS; and worst perceived cognitive dysfunction reported in the “Attention/Concentration” domain. Factors found to be significantly associated with functional disability were PDQ-D score, sick leave taken, and antidepressant treatment (P < 0.05). Discussion: Findings from this subgroup analysis highlight the significance of treating cognitive dysfunction in patients with MDD and its correlation to functional disability