The Long-Term Outcomes of Alzheimer’s Disease Patients Treated with Anti-Dementia Medications According to Baseline Dementia Severity / 생물치료정신의학

Objectives@#：To describe the differences in long-term outcomes in Alzheimer’s disease (AD) patients according to initial dementia severity. @*Methods@#：A retrospective chart review of AD patients from a dementia clinic at the University Hospital in Korea was conducted from April 2010 to March 2017. There were 168 patients enrolled, who were divided into three groups based on initial Clinical Dementing Rating (CDR). There were 55 in the very mild group (CDR=0.5 ; mean age 80.64±6.57), 93 in the mild group (CDR=1 ; mean age 80.57±7.28) and 20 in the moderate group (CDR=2 ; mean age 83.00±9.07). Participants were treated with donepezil±memantine. The observation period was 2.44±0.50 years. Cognitive function and severity of dementia were initially assessed by the Consortium to Establish a Registry for Alzheimer’s Disease Neuropsychological Assessment Battery (CERAD-NP) and were annually assessed by Mini-Mental State Exam (MMSE), CDR and CDR-Sum of boxes (CDR-SB). @*Results@#：The annual decline rate of MMSE score was -0.82 and those of very mild, mild, moderate groups were -0.63, -0.80, -1.96 respectively, while the annual change in CDR-SB score was 0.98, very mild group 0.86, mild group 1.03, moderate group 1.26. Education level, male, initial CDR were found to be significant potential factors in the annual change in MMSE, while initial CDR was a significant potential factor in the annual change in CDR-SB. @*Conclusion@#：It is meaningful that we studied long-term outcomes of anti-dementia medications in real-world clinical setting. The higher the initial severity of AD, the higher the cognitive decline rate.

APEX1 Polymorphism and Mercaptopurine-Related Early Onset Neutropenia in Pediatric Acute Lymphoblastic Leukemia / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Mercaptopurine (MP) is one of the main chemotherapeutics for acute lymphoblastic leukemia (ALL). To improve treatment outcomes, constant MP dose titration is essential to maintain steady drug exposure, while minimizing myelosuppression. We performed two-stage analyses to identify genetic determinants of MP-related neutropenia in Korean pediatric ALL patients. MATERIALS AND METHODS: Targeted sequencing of 40 patients who exhibited definite MP intolerance was conducted using a novel panel of 211 pharmacogenetic-related genes, and subsequent analysis was performed with 185 patients. RESULTS: Using bioinformatics tools and genetic data, four functionally interesting variants were selected (ABCC4, APEX1, CYP1A1, and CYP4F2). Including four variants, 23 variants in 12 genes potentially linked to MP adverse reactions were selected as final candidates for subsequent analysis in 185 patients. Ultimately, a variant allele in APEX1 rs2307486was found to be strongly associated with MP-induced neutropenia that occurred within 28 days of initiating MP (odds ratio, 3.44; p=0.02). Moreover, the cumulative incidence of MP-related neutropenia was significantly higher in patients with APEX1 rs2307486 variants, as GG genotypes were associated with the highest cumulative incidence (p < 0.01). NUDT15 rs116855232 variants were strongly associated with a higher cumulative incidence of neutropenia (p < 0.01), and a lower median dose of tolerated MP throughout maintenance treatment (p < 0.01). CONCLUSION: We have identified that APEX1 rs2307486 variants conferred an increased risk of MP-related early onset neutropenia. APEX1 and NUDT15 both contribute to cell protection from DNA damage or misincorporation, so alleles that impair the function of either gene may affect MP sensitivities, thereby inducing MP-related neutropenia.

Development of Korean Rare Disease Knowledge Base / 대한의료정보학회지

OBJECTIVES: Rare disease research requires a broad range of disease-related information for the discovery of causes of genetic disorders that are maladies caused by abnormalities in genes or chromosomes. A rarity in cases makes it difficult for researchers to elucidate definite inception. This knowledge base will be a major resource not only for clinicians, but also for the general public, who are unable to find consistent information on rare diseases in a single location. METHODS: We design a compact database schema for faster querying; its structure is optimized to store heterogeneous data sources. Then, clinicians at Seoul National University Hospital (SNUH) review and revise those resources. Additionally, we integrated other sources to capture genomic resources and clinical trials in detail on the Korean Rare Disease Knowledge base (KRDK). RESULTS: As a result, we have developed a Web-based knowledge base, KRDK, suitable for study of Mendelian diseases that commonly occur among Koreans. This knowledge base is comprised of disease summary and review, causal gene list, laboratory and clinic directory, patient registry, and so on. Furthermore, database for analyzing and giving access to human biological information and the clinical trial management system are integrated on KRDK. CONCLUSIONS: We expect that KRDK, the first rare disease knowledge base in Korea, may contribute to collaborative research and be a reliable reference for application to clinical trials. Additionally, this knowledge base is ready for querying of drug information so that visitors can search a list of rare diseases that is relative to specific drugs. Visitors can have access to KRDK via http://www.snubi.org/software/raredisease/.