We examined time trend and age-period-cohort effects on acute myocardial infarction (AMI) mortality in Korean adults from 1988 to 2007. Annual AMI mortality data and population statistics from 1988 to 2007 were obtained from the STATISTICS KOREA website. Age adjusted mortality for four 5-yr calendar periods (1988-1992 to 2003-2007) was calculated by direct standardization using the Year 2000 WHO world standard population. A log-linear Poisson regression model was used to estimate age, period, and cohort effects on AMI mortality. In both genders, age-adjusted AMI mortality increased from period one (1988-1992) to period three (1998-2002) but decreased in period four (2003-2007). An exponential age effect was noted in both genders. The rate ratio of the cohort effect increased up to the 1943 birth cohort and decreased gradually thereafter, and the rate ratio of the period effect increased up to period three (1998-2002) and decreased thereafter. Our results suggest that AMI mortality in Korean adults has decreased since the period 1998-2002 and age, period, and cohort effects have influenced on AMI mortality.
Adult ; Age Distribution ; Age Factors ; Aged ; Cohort Effect ; Female ; Humans ; Male ; Middle Aged ; Myocardial Infarction/*mortality ; Republic of Korea/epidemiology ; Time Factors

Most cases of congenital hyperthyroidism are autoimmune forms caused by maternal thyroid stimulating antibodies. Nonautoimmune forms of congenital hyperthyroidism caused by activating mutations of the thyrotropin receptor (TSHR) gene are rare. A woman gave birth to a boy during an emergency cesarean section at 33 weeks of gestation due to fetal tachycardia. On the 24th day of life, thyroid function tests were performed due to persistent tachycardia, and hyperthyroidism was confirmed. Auto-antibodies to TSHR, thyroid peroxidase, and thyroglobulin were not found. The patient was treated with propylthiouracil and propranolol, but hyperthyroidism was not well controlled. At 3 months of age, the patient had craniosynostosis and hydrocephalus, and underwent a ventriculoperitoneal shunt operation. Direct sequencing of the TSHR gene showed a heterozygous mutation of c.1899C>A (p.Asp633Glu) in exon 10. No mutations were discovered in any of the parents in a familial genetic study. We have reported a case of sporadic nonautoimmune congenital hyperthyroidism, by a missense mutation of the TSHR gene, for the first time in South Korea.
Cesarean Section ; Craniosynostoses ; Emergencies ; Exons ; Female ; Germ-Line Mutation ; Humans ; Hydrocephalus ; Hyperthyroidism* ; Immunoglobulins, Thyroid-Stimulating ; Iodide Peroxidase ; Korea ; Male ; Mutation, Missense ; Parents ; Parturition ; Pregnancy ; Propranolol ; Propylthiouracil ; Receptors, Thyrotropin ; Tachycardia ; Thyroglobulin ; Thyroid Function Tests ; Ventriculoperitoneal Shunt

Cytochrome P450 (CYP) 3A enzymes, the most important phase 1 drug-metabolizing enzymes, are responsible for 50% of the metabolism of clinically used drugs. CYP3A activity varies widely among individuals, which can affect the probability of adverse drug reactions and drug-drug interactions mediated by the induction or inhibition of the enzyme. Hence, it is important to be able to predict CYP3A activity in individuals to reduce the incidence of unexpected drug responses. To specifically and quickly measure CYP3A activity, we developed method based on gas chromatography interfaced with triple-quadrupole mass spectrometry for the quantification of cortisol, cortisone, 6β-hydroxycortisol, and 6β-hydroxycortisone simultaneously in urine and 4β-hydroxycholesterol in plasma. The results were calculated based on charcoal-stripped steroid-free urine and plasma control samples. The accuracy and precision were 93.18% to 110.0% and 1.96% to 5.34%, respectively. This method was then applied to measure endogenous steroids from urine and plasma samples of healthy Korean males and females. The calibration curves of all analytes showed good linearity with a correlation coefficient (r2) that ranged from 0.9953 to 0.9999. Therefore, this validated method can be used to measure endogenous biomarkers to predict CYP3A activity and might be applicable in the prediction of CYP3A-mediated drug interactions of new drug candidates.

We reviewed our leukemia database to reclassify 610 patients previously diagnosed as having acute myeloid leukemia (AML) according to the updated 2016 WHO classification. Nine patients were categorized as having myelodysplastic syndrome and myeloid neoplasms with germline predisposition. AML with recurrent genetic abnormalities accounted for 57.4% (345/601) of the patients under the 2016 WHO classification. AML with mutated NPM1 was the most common form (16.5%), with the majority associated with monocytic differentiation (63.6%). AML with double CEBPA mutations accounted for 8.3% of these cases, and the majority were previously diagnosed as AML with/without maturation (78.0%). These newly classified mutations were mutually exclusive without overlapping with other forms of AML with recurrent genetic abnormalities. AML with mutated NPM1 and AML with myelodysplasia-related changes comprised the oldest patients, whereas AML with RUNX1-RUNX1T1 included the youngest patients. The leukocyte count was highest in AML with mutated NPM1, and the percentage of peripheral blood blasts was the highest in AML with double CEBPA mutations. Our results indicate that implementation of the 2016 WHO classification of AML would not pose major difficulties in clinical practice. Hematopathologists should review and prepare genetic tests for the new classification, according to their clinical laboratory conditions.
Classification ; Humans ; Leukemia ; Leukemia, Myeloid, Acute ; Leukocyte Count ; Myelodysplastic Syndromes

BACKGROUND AND OBJECTIVES: Adequate evaluation of the upper airway is critical in the management of pediatric patients with stridor or extubation failure. For this purpose, we designed an evaluation protocol of the upper airway for these patients, in collaboration with Dept. of Pediatrics, Intensive care team and Anesthesiology. Here we present the clinical results of our evaluation protocol and provide information about the etiology and management of the upper airway problems. SUBJECTS AND METHOD: Clinical data of 380 pediatric patients (M:F=231:149) having airway evaluation for their problems (stridor or extubation failure) were retrospectively analyzed. Among them, patients of age less than 3 months ranked first (30.0%). Comorbidities of pulmonary diseases (30.8%) and cardiovascular diseases (29.5%) were found. The pre and post-evaluation diagnosis, management and prognosis were evaluated and the usefulness of an airway evaluation protocol was discussed. RESULTS: Frequent pre-evaluation diagnoses were subglottic stenosis (55.2%), laryngomalacia (12.6%) and tracheal stenosis (9.2%) and these were changed to subglottic stenosis (44.5%), laryngomalacia (9.7%), tracheal stenosis (6.6%) and no abnormality (14.5%). Particularly, 50% of pre-diagnosis laryngomalacia, 25% of subglottic stenosis and 37% of tracheal stenosis were corrected to other causes by airway evaluation. The procedures were exam only (41.6%), endoscopic dilatation (20.8%) and tracheostomy (17.9%). In 190 out of 380 (50.0%), extubation was successful, but 151 patients (39.7%) had tracheostomy tube. CONCLUSION: Adequate evaluation of the upper airway in pediatric patients with stridor or extubation failure can facilitate the diagnosis and management of their problems.
Anesthesiology ; Cardiovascular Diseases ; Comorbidity ; Constriction, Pathologic ; Cooperative Behavior ; Diagnosis ; Dilatation ; Humans ; Critical Care ; Laryngomalacia ; Lung Diseases ; Pediatrics ; Prognosis ; Respiratory Sounds* ; Retrospective Studies ; Tracheal Stenosis ; Tracheostomy

BACKGROUND: Femoral neck fracture is common in the elderly population. Acute kidney injury (AKI) is an important risk factor for mortality in patients who have had such fracture. We evaluated the incidence of AKI in patients who had femoral neck fracture and identified risk factors for AKI and mortality. METHODS: This was an observational cohort study including 285 patients who were ≥ 65 years of age and who underwent femoral neck fracture surgery between 2013 and 2017. RESULTS: The mean age was 78.63 ± 6.75 years. A total of 67 (23.5%) patients developed AKI during the hospital stay: 57 (85.1%), 5 (7.5%), and 5 (7.5%) patients were classified as having stage 1, 2, and 3 AKI, respectively. Patients with AKI had a lower baseline estimated glomerular filtration rate and higher left atrial dimension, left ventricular mass index, pulmonary artery pressure, and the ratio of early mitral inflow velocity to early diastolic mitral annulus velocity (E/e’) and were more likely to have diabetes or hypertension (HTN) (P < 0.05). The presence of HTN (odds ratio [OR], 4.570; 95% confidence interval [CI], 1.632–12.797) higher E/e’ (OR, 1.105; 95% CI, 1.019–1.198), and lower hemoglobin (OR, 0.704; 95% CI, 0.528–0.938) were independently associated with a higher risk for developing AKI. Severe AKI (OR, 24.743; 95% CI, 2.822–212.401) was associated with a higher risk of mortality. CONCLUSION: Elderly patients with femoral neck fracture had a high incidence of AKI. Diastolic dysfunction was associated with AKI. Severe AKI was associated with in-hospital mortality.
Acute Kidney Injury ; Aged ; Cohort Studies ; Femoral Neck Fractures ; Femur Neck ; Glomerular Filtration Rate ; Heart Failure, Diastolic ; Hospital Mortality ; Humans ; Hypertension ; Incidence ; Length of Stay ; Mortality ; Pulmonary Artery ; Risk Factors

BACKGROUND: We describe the genetic profiles of Korean patients with glucose-6-phosphate dehydrogenase (G6PD) deficiencies and the effects of G6PD mutations on protein stability and enzyme activity on the basis of in silico analysis. METHODS: In parallel with a genetic analysis, the pathogenicity of G6PD mutations detected in Korean patients was predicted in silico. The simulated effects of G6PD mutations were compared to the WHO classes based on G6PD enzyme activity. Four previously reported mutations and three newly diagnosed patients with missense mutations were estimated. RESULTS: One novel mutation (p.Cys385Gly, labeled G6PD Kangnam) and two known mutations [p.Ile220Met (G6PD São Paulo) and p.Glu416Lys (G6PD Tokyo)] were identified in this study. G6PD mutations identified in Koreans were also found in Brazil (G6PD São Paulo), Poland (G6PD Seoul), United States of America (G6PD Riley), Mexico (G6PD Guadalajara), and Japan (G6PD Tokyo). Several mutations occurred at the same nucleotide, but resulted in different amino acid residue changes in different ethnic populations (p.Ile380 variant, G6PD Calvo Mackenna; p.Cys385 variants, Tomah, Madrid, Lynwood; p.Arg387 variant, Beverly Hills; p.Pro396 variant, Bari; and p.Pro396Ala in India). On the basis of the in silico analysis, Class I or II mutations were predicted to be highly deleterious, and the effects of one Class IV mutation were equivocal. CONCLUSIONS: The genetic profiles of Korean individuals with G6PD mutations indicated that the same mutations may have arisen by independent mutational events, and were not derived from shared ancestral mutations. The in silico analysis provided insight into the role of G6PD mutations in enzyme function and stability.
Asian Continental Ancestry Group/*genetics ; Child ; Child, Preschool ; DNA/chemical synthesis/genetics/metabolism ; Exons ; Glucosephosphate Dehydrogenase/chemistry/*genetics/metabolism ; Glucosephosphate Dehydrogenase Deficiency/*genetics/pathology ; Humans ; Male ; Mutation, Missense ; Polymorphism, Genetic ; Protein Structure, Tertiary ; Republic of Korea ; Sequence Analysis, DNA

OBJECTIVE: Black raspberry (Rubus occidentalis) has been known for its anti-inflammatory and anti-oxidant effects and for improving vascular endothelial function in patients at high-risk for cardiovascular disease. We investigated short-term effects of black raspberry on lipid profiles, vascular endothelial function and circulating endothelial progenitor cells in statin naïve participants with metabolic syndrome. METHODS: Patients with metabolic syndrome (n=51) without lipid lowering medications were prospectively randomized into the black raspberry group (n=26, 750 mg/day) and placebo group (n=25) during the 12-week follow-up. Lipid profiles, brachial artery flow-mediated dilatation (baFMD) and inflammatory cytokines such as IL-6, TNF-α, C-reactive protein, adiponectin, sICAM-1, sVCAM-1 were measured at baseline and at 12-week follow-up. Central blood pressure and augmentation index were also measured at baseline and at 12-week follow-up. RESULTS: Decreases from baseline in total cholesterol levels (-22.7±34.3 mg/dL vs. 0.0±34.7mg/dL, p<0.05, respectively) and total cholesterol/HDL ratio (-0.34±0.68 vs. 0.17±0.56, p<0.05, respectively) were significantly greater in the black raspberry group when compared to the placebo group. Decreases from baseline in IL-6 (-0.5±1.4 pg/mL vs. -0.1±1.1 pg/mL, p<0.05, respectively) and TNF-α levels (-5.4±4.5 pg/mL vs. -0.8±4.0 pg/mL, p<0.05, respectively) were significantly greater in the black raspberry group. Increases from the baseline in adiponectin levels (2.9±2.1 µg/mL vs. -0.2±2.5 µg/mL, p<.05) were significant in the black raspberry group. Increases in baFMD at 12-week follow-up were significantly greater in the black raspberry group when compared to the placebo group (2.9±3.6 mm vs. 1.0±3.9 mm, p<0.05, respectively). Radial augmentation indexes were significantly decreased in the black raspberry group when compared to the placebo group (-2±10% vs. 4±13%, p<0.05). CONCLUSION: The use of black raspberry significantly decreased serum total cholesterol levels, inflammatory cytokines, and augmentation index, thereby improving vascular endothelial function in statin naïve participants with metabolic syndrome during the 12-week follow-up.
Adiponectin ; Antioxidants ; Blood Pressure ; Brachial Artery ; C-Reactive Protein ; Cardiovascular Diseases ; Cholesterol ; Cytokines ; Dilatation ; Endothelial Progenitor Cells ; Follow-Up Studies ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors* ; Interleukin-6 ; Prospective Studies ; Rubus*

Pseudohypoparathyroidism (PHP) is a rare disorder caused by genetic and epigenetic aberrations in the GNAS complex locus resulting in impaired expression of stimulatory G protein (Gsα). PHP type Ib (PHP-Ib) is characterized by hypocalcemia and hyperphosphatemia due to renal resistance to the parathyroid hormone, and is distinguished from PHP-Ia by the absence of osteodystrophic features. An 11-yr-old boy presented with poor oral intake and cramping lower limb pain after physical activity. Laboratory studies revealed hypocalcemia, hyperphosphatemia, and increased parathyroid hormone levels. The GNAS complex locus was evaluated using the methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) assay. Gain of methylation in the NESP55 domain and loss of methylation in the antisense (AS) transcript, XL, and A/B domains in the maternal allele were observed. Consequently, we present a case of PHP-Ib diagnosed using MS-MLPA.
Alleles ; Epigenomics ; GTP-Binding Proteins ; Humans ; Hyperphosphatemia ; Hypocalcemia ; Lower Extremity ; Male ; Methylation* ; Motor Activity ; Multiplex Polymerase Chain Reaction ; Muscle Cramp ; Parathyroid Hormone ; Pseudohypoparathyroidism*

Hereditary spherocytosis (HS) is caused by mutations in the SPTA1, SPTB, ANK1, SLC4A1, and EPB42 genes, all of which encode erythrocyte membrane proteins. Mutations in SLC4A1, which encodes band 3 protein, have rarely been reported as the causative factor among Korean patients with HS. Here, we report two Korean patients with HS carrying mutations in SLC4A1. Patient 1 was a 3-year-old girl with unremarkable past and family histories and was evaluated for anemia that was detected after a complete blood count. She was suspected of having HS considering the spherocytosis of her peripheral blood smear, increased osmotic fragility, hemolytic features in blood chemistry tests, and splenomegaly. Sequence analysis revealed that the patient harbored a single heterozygous missense mutation, c.2278C>T (p.Arg760Trp) in exon 17 of SLC4A1. Patient 2 was a 23-year-old man who had a prior history of intermittent jaundice. Although the patient did not have anemia, a genetic test for HS was performed due to evidence of hemolytic features in the blood chemistry test, splenomegaly, and a family history of HS. The test confirmed a single heterozygous missense mutation, c.2423G>T (p.Arg808Leu) in exon 18 of SLC4A1.
Anemia ; Anion Exchange Protein 1, Erythrocyte ; Blood Cell Count ; Chemistry ; Child, Preschool ; Erythrocyte Membrane ; Exons ; Female ; Humans ; Jaundice ; Mutation, Missense ; Osmotic Fragility ; Sequence Analysis ; Splenomegaly ; Young Adult