Taipei Veterans General Hospital

About: Taipei Veterans General Hospital is a healthcare organization based out in Taipei, Taiwan. It is known for research contribution in the topics: Population & Cancer. The organization has 11878 authors who have published 16478 publications receiving 363424 citations. The organization is also known as: Táiběi Róngmín Zǒngyī Yuàn.

Trans-Ethnic Fine-Mapping of Lipid Loci Identifies Population-Specific Signals and Allelic Heterogeneity That Increases the Trait Variance Explained

Abstract: Genome-wide association studies (GWAS) have identified ~100 loci associated with blood lipid levels, but much of the trait heritability remains unexplained, and at most loci the identities of the trait-influencing variants remain unknown. We conducted a trans-ethnic fine-mapping study at 18, 22, and 18 GWAS loci on the Metabochip for their association with triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C), respectively, in individuals of African American (n = 6,832), East Asian (n = 9,449), and European (n = 10,829) ancestry. We aimed to identify the variants with strongest association at each locus, identify additional and population-specific signals, refine association signals, and assess the relative significance of previously described functional variants. Among the 58 loci, 33 exhibited evidence of association at P<1 × 10(-4) in at least one ancestry group. Sequential conditional analyses revealed that ten, nine, and four loci in African Americans, Europeans, and East Asians, respectively, exhibited two or more signals. At these loci, accounting for all signals led to a 1.3- to 1.8-fold increase in the explained phenotypic variance compared to the strongest signals. Distinct signals across ancestry groups were identified at PCSK9 and APOA5. Trans-ethnic analyses narrowed the signals to smaller sets of variants at GCKR, PPP1R3B, ABO, LCAT, and ABCA1. Of 27 variants reported previously to have functional effects, 74% exhibited the strongest association at the respective signal. In conclusion, trans-ethnic high-density genotyping and analysis confirm the presence of allelic heterogeneity, allow the identification of population-specific variants, and limit the number of candidate SNPs for functional studies.

A Changing Paradigm for the Treatment of Intermediate-Stage Hepatocellular Carcinoma: Asia-Pacific Primary Liver Cancer Expert Consensus Statements

Abstract: The Asia-Pacific Primary Liver Cancer Expert (APPLE) Consensus Statement on the treatment strategy for patients with intermediate-stage hepatocellular carcinoma (HCC) was established on August 31, 2019, in Sapporo, Hokkaido during the 10th Annual APPLE Meeting. This manuscript summarizes the international consensus statements developed at APPLE 2019. Transarterial chemoembolization (TACE) is the only guideline-recommended global standard of care for intermediate-stage HCC. However, not all patients benefit from TACE because intermediate-stage HCC is a heterogeneous disease in terms of tumor burden and liver function. Ten important clinical questions regarding this stage of HCC were raised, and consensus statements were generated based on high-quality evidence. In intermediate-stage HCC, preservation of liver function is as important as achieving a high objective response (OR) because the treatment goal is to prolong overall survival. Superselective conventional TACE (cTACE) is recommended as the first choice of treatment in patients eligible for effective (curative) TACE, whereas in patients who are not eligible, systemic therapy is recommended as the first choice of treatment. TACE is not indicated as the first-line therapy in TACE-unsuitable patients. Another important statement is that TACE should not be continued in patients who develop TACE failure/refractoriness in order to preserve liver function. Targeted therapy is the recommended first-line treatment for TACE-unsuitable patients. Especially, the drug, which can have higher OR rate, is preferred. Immunotherapy, transarterial radioembolization, TACE + targeted therapy or other modalities may be considered alternative options in TACE-unsuitable patients who are not candidates for targeted therapy. Better liver function, such as albumin-bilirubin grade 1, is an important factor for maximizing the therapeutic effect of systemic therapy.

Congenital and acquired long QT syndrome. Current concepts and management.

Abstract: Congenital long QT syndrome (LQTS) is a rare but potentially lethal disease, characterized by prolongation of QT interval, recurrent syncope, and sudden death. In the pregenomic era (1959 -1991), sympathetic imbalance was thought to be responsible for this disease. Since 1991 (postgenomic era), 7 LQTS genes have been discovered and more than 300 mutations have been identified to account for approximately 70% of patients affected. Despite the advancement in molecular genetic knowledge, diagnosis of congen- ital LQTS is still based on electrocardiographic and clinical charac- teristics. Beta-blockers remain the mainstay treatment. For high-risk patients, the implantable cardioverter-defibrillator (ICD) offer an effective therapeutic option to reduce mortality. Gene-based specific therapy is still preliminary. Further studies are required to investi- gate new strategies for targeting the defective genes or mutant channels. For acquired LQTS, it is generally believed that the main issue is the blockade of the slow component of the delayed rectifier K current (IKr). These IKr blockers have a "reverse frequency- dependent" effect on the QTc interval and increase the dispersion in repolarization. In the presence of risk factors such as female gender, slow heart rate, and hypokalemia, these IKr blockers have a high propensity to induce torsades de pointes. For patients with a history of drug-induced LQTS, care must be taken to avoid further exposure to QT-prolonging drugs or conditions. Molecular genetic analysis could be useful to unravel subclinical mutations or polymorphisms. Physicians not only need to be aware of the pharmacodynamic and pharmacokinetic interactions of various important drugs, but also need to update their knowledge.