Background: Hearing loss (HL) is one of the most common sensory disorders, affecting over 5-8% of the world's population. Approximately half of HL cases are attributed to genetic factors. In hereditary deafness, about 75-80% is inherited through autosomal recessive inheritance, and common pathogenic genes include GJB2 and SLC26A4. Pathogenic variants in the SLC26A4gene are the leading cause of hereditary hearing loss in humans, second only to the GJB2 gene. Variants in the SLC26A4gene cause hearing loss, which can be non-syndromic autosomal recessive deafness (DFNB4, OMIM #600791) associated with enlarged vestibular aqueduct (EVA) or Pendred syndrome (Pendred, OMIM #605646). DFNB4 is characterized by sensorineural hearing loss combined with EVA or less common cochlear malformation defect. Pendred syndrome is characterized by bilateral sensorineural hearing loss with EVA and an iodine defect that can lead to thyroid goiter. Currently, it is known that EVA is associated with variants in the SLC26A4 gene and is a penetrant feature of SLC26A4-related HL. Predominant mutations in these genes differ significantly across populations. For instance, predominant SLC26A4 mutations differ among populations, including p.T416P and c.1001G>A in Caucasians, p.H723R in Japanese and Koreans, and c.919-2A>G in Han Taiwanese and Han Chinese. On the other hand, there has been no study of hearing loss related to SLC26A4 gene variants among Mongolians, which is the basis of our research. Aim: We aimed to identify the characteristics of the SLC26A4 gene variants in Mongolian people with Enlarged vestibular aqueduct and Mondini malformation. Materials and Methods: In 2022-2024, We included 13 people with hearing loss and enlarged vestibular aqueduct, incomplete cochlea (1.5 turns of the cochlea with cystic apex- incomplete partition type II- Mondini malformation) were examined by CT scan of the temporal bone in our study. WES (Whole exome sequencing) analysis was performed in the Genetics genetic-laboratory of the National Taiwan University Hospital. Results: Genetic analysis revealed 26 confirmed pathogenic variants of bi-allelic SLC26A4 gene of 8 different types in 13 cases, and c.919-2A>G variant was dominant with 46% (12/26) in allele frequency, and c.2027T>A (p.L676Q) variant 19% (5/26), c.1318A>T(p.K440X) variant 11% (3/26), c.1229C>T (p.T410M) variant 8% (2/26) ) , c.716T>A (p.V239D), c.281C>T (p.T94I), c.1546dupC, and c.1975G>C (p.V659L) variants were each 4% (1/26)- revealed. Two male children, 11 years old (SLC26A4: c.919-2A>G) and 7 years old (SLC26A4: c.919-2A>G:, SLC26A4: c.2027T>A (p.L676Q))had history of born normal hearing and progressive hearing loss. Conclusions 1. 26 variants of bi-allelic SLC26A4 gene mutation were detected in Mongolian people with EVA and Mondini malformation, and c.919-2A>G was the most dominant allele variant, and rare variants such as c.1546dupC, c.716T>A (p.V239D) were detected. 2. Our study shows that whole-exome sequencing (WES) can identify gene mutations that are not detected by polymerase chain reaction (PCR) or NGS analysis.

Metabolic dysfunction-associated fatty liver disease (MAFLD) is an increasingly common liver disease worldwide. MAFLD is diagnosed based on the presence of steatosis on images, histological findings, or serum marker levels as well as the presence of at least one of the three metabolic features: overweight/obesity, type 2 diabetes mellitus, and metabolic risk factors. MAFLD is not only a liver disease but also a factor contributing to or related to cardiovascular diseases (CVD), which is the major etiology responsible for morbidity and mortality in patients with MAFLD. Hence, understanding the association between MAFLD and CVD, surveillance and risk stratification of MAFLD in patients with CVD, and assessment of the current status of MAFLD management are urgent requirements for both hepatologists and cardiologists. This Taiwan position statement reviews the literature and provides suggestions regarding the epidemiology, etiology, risk factors, risk stratification, nonpharmacological interventions, and potential drug treatments of MAFLD, focusing on its association with CVD.

Objectives: This study aimed to present the Asia-Pacific consensus on long-term and sequential therapy for osteoporosis, offering evidence-based recommendations for the effective management of this chronic condition.The primary focus is on achieving optimal fracture prevention through a comprehensive, individualized approach. Methods: A panel of experts convened to develop consensus statements by synthesizing the current literature and leveraging clinical expertise. The review encompassed long-term anti-osteoporosis medication goals, first-line treatments for individuals at very high fracture risk, and the strategic integration of anabolic and anti resorptive agents in sequential therapy approaches. Results: The panelists reached a consensus on 12 statements. Key recommendations included advocating for anabolic agents as the first-line treatment for individuals at very high fracture risk and transitioning to anti resorptive agents following the completion of anabolic therapy. Anabolic therapy remains an option for in dividuals experiencing new fractures or persistent high fracture risk despite antiresorptive treatment. In cases of inadequate response, the consensus recommended considering a switch to more potent medications. The consensus also addressed the management of medication-related complications, proposing alternatives instead of discontinuation of treatment. Conclusions This consensus provides a comprehensive, cost-effective strategy for fracture prevention with an emphasis on shared decision-making and the incorporation of country-specific case management systems, such as fracture liaison services. It serves as a valuable guide for healthcare professionals in the Asia-Pacific region, contributing to the ongoing evolution of osteoporosis management.

Objective: aaWilson’s disease (WD) is a rare genetic disorder of copper metabolism, and longitudinal follow-up studies are limited. We performed a retrospective analysis to determine the clinical characteristics and long-term outcomes in a large WD cohort. Methods: aaMedical records of WD patients diagnosed from 2006–2021 at National Taiwan University Hospital were retrospectively evaluated for clinical presentations, neuroimages, genetic information, and follow-up outcomes. Results: aaThe present study enrolled 123 WD patients (mean follow-up: 11.12 ± 7.41 years), including 74 patients (60.2%) with hepatic features and 49 patients (39.8%) with predominantly neuropsychiatric symptoms. Compared to the hepatic group, the neuropsychiatric group exhibited more Kayser-Fleischer rings (77.6% vs. 41.9%, p < 0.01), lower serum ceruloplasmin levels (4.9 ± 3.9 vs. 6.3 ± 3.9 mg/dL, p < 0.01), smaller total brain and subcortical gray matter volumes (p < 0.0001), and worse functional outcomes during follow-up (p = 0.0003). Among patients with available DNA samples (n = 59), the most common mutations were p.R778L (allelic frequency of 22.03%) followed by p.P992L (11.86%) and p.T935M (9.32%). Patients with at least one allele of p.R778L had a younger onset age (p = 0.04), lower ceruloplasmin levels (p < 0.01), lower serum copper levels (p = 0.03), higher percentage of the hepatic form (p = 0.03), and a better functional outcome during follow-up (p = 0.0012) compared to patients with other genetic variations. Conclusion aaThe distinct clinical characteristics and long-term outcomes of patients in our cohort support the ethnic differences regarding the mutational spectrum and clinical presentations in WD.

Objective: This study aimed to evaluate the clinical outcomes and cost-effectiveness of dual-energy X-ray absorptiometry (DXA) for osteoporosis screening. Materials and Methods: Eligible patients who had and had not undergone DXA screening were identified from among those aged 50 years or older at Kaohsiung Veterans General Hospital, Taiwan. Age, sex, screening year (index year), and Charlson comorbidity index of the DXA and non-DXA groups were matched using inverse probability of treatment weighting (IPTW) for propensity score analysis. For cost-effectiveness analysis, a societal perspective, 1-year cycle length, 20-year time horizon, and discount rate of 2% per year for both effectiveness and costs were adopted in the incremental cost-effectiveness (ICER) model. Results: The outcome analysis included 10337 patients (female:male, 63.8%:36.2%) who were screened for osteoporosis in southern Taiwan between January 1, 2012, and December 31, 2021. The DXA group had significantly better outcomes than the non-DXA group in terms of fragility fractures (7.6% vs. 12.5%, P < 0.001) and mortality (0.6% vs. 4.3%, P < 0.001). The DXA screening strategy gained an ICER of US$ -2794 per quality-adjusted life year (QALY) relative to the non-DXA at the willingness-to-pay threshold of US$ 33004 (Taiwan’s per capita gross domestic product). The ICER after stratifying by ages of 50–59, 60–69, 70–79, and ≥ 80 years were US$ -17815, US$ -26862, US$ -28981, and US$ -34816 per QALY, respectively. Conclusion Using DXA to screen adults aged 50 years or older for osteoporosis resulted in a reduced incidence of fragility fractures, lower mortality rate, and reduced total costs. Screening for osteoporosis is a cost-saving strategy and its effectiveness increases with age. However, caution is needed when generalizing these cost-effectiveness results to all older populations because the study population consisted mainly of women.

Background/Aims: Obstacles exist in facilitating hepatitis C virus (HCV) care cascade. To increase timely and accurate diagnosis, disease awareness and accessibility, in-hospital HCV reflex testing followed by automatic appointments and a late call-back strategy (R.N.A. model) was applied. We aimed to compare the HCV treatment rate of patients treated with this strategy compared to those without. Methods: One hundred and twenty-five anti-HCV seropositive patients who adopted the R.N.A. model in 2020 and another 1,396 controls treated in 2019 were enrolled to compare the gaps in accurate HCV RNA diagnosis to final treatment allocation. Results: The HCV RNA testing rate was significantly higher in patients who received reflex testing than in those without reflex testing (100% vs. 84.8%, P<0.001). When patients were stratified according to the referring outpatient department, a significant improvement in the HCV RNA testing rate was particularly noted in patients from non-hepatology departments (100% vs. 23.3%, P<0.001). The treatment rate in HCV RNA seropositive patients was 83% (83/100) after the adoption of the R.N.A. model, among whom 96.1% and 73.9% of patients were from the hepatology and non-hepatology departments, respectively. Compared to subjects without R.N.A. model application, a significant improvement in the treatment rate was observed for patients from non-hepatology departments (73.9% vs. 27.8%, P=0.001). The application of the R.N.A. model significantly increased the in-hospital HCV treatment uptake from 6.4% to 73.9% for patients from non-hepatology departments (P<0.001). Conclusions The care cascade increased the treatment uptake and set up a model for enhancing in-hospital HCV elimination.

BACKGROUND: Previous Caucasian studies have described venous thromboembolism in pregnancy; however, little is known about its incidence during pregnancy and early postpartum period in the Chinese population. We investigated the risk of venous thromboembolism in a “real-world” cohort of pregnant Chinese women with no prior history of venous thromboembolism. METHODS: In this observational study, 15,325 pregnancies were identified in 14,162 Chinese women at Queen Mary Hospital, Hong Kong between January 2004 and September 2016. Demographic data, obstetric information, and laboratory and imaging data were retrieved and reviewed. RESULTS: The mean age at pregnancy was 32.4±5.3 years, and the median age was 33 years (interquartile range, 29–36 yr). Pre-existing or newly diagnosed diabetes mellitus was present in 627 women (4.1%); 359 (0.7%) women had pre-existing or newly detected hypertension. There was a small number of women with pre-existing heart disease and/or rheumatic conditions. Most deliveries (86.0%) were normal vaginal; the remaining were Cesarean section 2,146 (14.0%). The incidence of venous thromboembolism was 0.4 per 1,000 pregnancies, of which 83.3% were deep vein thrombosis and 16.7% were pulmonary embolism. In contrast to previous studies, 66.7% of venous thrombosis occurred in the first trimester. CONCLUSION: Chinese women had a substantially lower risk of venous thromboembolism during pregnancy and the postpartum period compared to that of Caucasians. The occurrence of pregnancy-related venous thromboembolism was largely confined to the early pregnancy period, probably related to the adoption of thromboprophylaxis, a lower rate of Cesarean section, and early mobilization.
Asian Continental Ancestry Group ; Cesarean Section ; Cohort Studies ; Diabetes Mellitus ; Early Ambulation ; Female ; Heart Diseases ; Hong Kong ; Humans ; Hypertension ; Incidence ; Observational Study ; Postpartum Period ; Pregnancy ; Pregnancy Trimester, First ; Pregnant Women ; Pulmonary Embolism ; Venous Thromboembolism ; Venous Thrombosis

BACKGROUNDThe environmental sources associated with community-acquired or nosocomial legionellosis were not always detectable in the mainland of China and Hong Kong, China. The objective of this study was to illustrate the control measures implemented for nosocomial and community outbreaks of legionellosis, and to understand the environmental distribution of legionella in the water system in Hong Kong, China.

METHODSWe investigated the environmental sources of two cases of legionellosis acquired in the hospital and the community by extensive outbreak investigation and sampling of the potable water system using culture and genetic testing at the respective premises.

RESULTSThe diagnosis of nosocomial legionellosis was suspected in a patient presenting with nosocomial pneumonia not responsive to multiple beta-lactam antibiotics with subsequent confirmation by Legionella pneumophila serogroup 1 antigenuria. High counts of Legionella pneumophila were detected in the potable water supply of the 70-year-old hospital building. Another patient on continuous ambulatory peritoneal dialysis presenting with acute community-acquired pneumonia and severe diarrhoea was positive for Legionella pneumophila serogroup 1 by polymerase chain reaction (PCR) testing on both sputum and nasopharyngeal aspirate despite negative antigenuria. Paradoxically the source of the second case was traced to the water system of a newly commissioned office building complex. No further cases were detected after shock hyperchlorination with or without superheating of the water systems. Subsequent legionella counts were drastically reduced. Point-of-care infection control by off-boiled or sterile water for mouth care and installation of water filter for showers in the hospital wards for immunocompromised patients was instituted. Territory wide investigation of the community potable water supply showed that 22.1% of the household water supply was positive at a mean legionella count of 108.56 CFU/ml (range 0.10 to 639.30 CFU/ml).

CONCLUSIONSPotable water systems are open systems which are inevitably colonized by bacterial biofilms containing Legionella species. High bacterial counts related to human cases may occur with stagnation of flow in both old or newly commissioned buildings. Vigilance against legionellosis is important in healthcare settings with dense population of highly susceptible hosts.

Aged ; Aged, 80 and over ; Biofilms ; Community-Acquired Infections ; diagnosis ; epidemiology ; Female ; Hong Kong ; epidemiology ; Humans ; Legionellosis ; diagnosis ; epidemiology ; Male ; Water Microbiology

Exertional headache is one entity of Valsalva maneuver-related headache syndrome. It is usually idiopathic, but has occasionally been reported to be associated with secondary causes. However, central nervous system infection has not been mentioned before. We encountered a young man who suffered an isolated exertional headache and was found to have an active varicella-zoster virus central nervous system infection without typical intracranial hypertension or outfl ow obstruction. Intracranial vasoconstriction was detected during headache when the patient performed acute lifting or heavy exertion. The fi ndings in this patient suggest a specifi c relationship between varicella-zoster virus-related vasculopathy and exertional headache from other Valsalva maneuver-related headache syndrome