Background: Nilotinib is a tyrosine kinase inhibitor approved by the Ministry of Food and Drug Safety for frontline and 2nd line treatment of Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML). This study aimed to confirm the safety and efficacy of nilotinib in routine clinical practice within South Korea. Methods: An open-label, multicenter, single-arm, 12-week observational post-marketing surveillance (PMS) study was conducted on 669 Korean adult patients with Ph + CML from December 24, 2010, to December 23, 2016. The patients received nilotinib treatment in routine clinical practice settings. Safety was evaluated by all types of adverse events (AEs) during the study period, and efficacy was evaluated by the complete hematological response (CHR) and cytogenetic response. Results: During the study period, AEs occurred in 61.3% (410 patients, 973 events), adverse drug reactions (ADRs) in 40.5% (271/669 patients, 559 events), serious AEs in 4.5% (30 patients, 37 events), and serious ADRs in 0.7% (5 patients, 8 events). Furthermore, unexpected AEs occurred at a rate of 6.9% (46 patients, 55 events) and unexpected ADRs at 1.2% (8 patients, 8 events). As for the efficacy results, CHR was achieved in 89.5% (442/494 patients), and minor cytogenetic response or major cytogenetic response was achieved in 85.8% (139/162 patients). Conclusion This PMS study shows consistent results in terms of safety and efficacy compared with previous studies. Nilotinib was well tolerated and efficacious in adult Korean patients with Ph + CML in routine clinical practice settings.

To provide a nationwide representative dataset for the study on health impact of air pollution, we combined the data from the Korea National Health and Nutrition Examination Survey with the daily air quality and weather data by matching the date of examination and the residential address of the participants. The database of meteorological factors and air quality as sources of exposure data were estimated using the Community Multiscale Air Quality model. The linkage dataset was merged by three ways; administrative district, si-gun-gu (city, county, and district), and geocode (in latitude and longitude coordinate units) based on the participants’ residential address, respectively. During the study period, the exposure dataset of 85,018 individuals (38,306 men and 46,712 women) whose examination dates were recorded were obtained. According to the definition of exposure period, the dataset was combined with the data on short-term, mid-term, and long-term exposure to air pollutants and the meteorological indices. Calculation of the daily merged dataset’s average air pollution linked by si-gun-gu and geocode units showed similar results. This study generated a daily average of meteorological indices and air pollution exposure dataset for all regions including rural and remote areas in Korea for 11 years. It is expected to provide a platform for the researchers studying the health impact of air pollution and climate change on the representative population and area, which may facilitate the establishment of local health care plans by understanding the residents’ health status at the local as well as national level.

Cardiovascular disease (CVD) and its complications are the leading cause of morbidity and mortality in the world. Because of the side effects and incomplete recovery from current therapy, stem cell therapy emerges as a potential therapy for CVD treatment, and endothelial progenitor cell (EPC) is one of the key stem cells used for therapeutic applications. The effect of this therapy required the expansion of EPC function. To enhance the EPC activation, proliferation, and angiogenesis using dronedarone hydrochloride (DH) is the purpose of this study. DH received approval for atrial fibrillation treatment and its cardiovascular protective effects were already reported. In this study, DH significantly increased EPC proliferation, tube formation, migration, and maintained EPCs surface marker expression. In addition, DH treatment up-regulated the phosphorylation of AKT and reduced the reactive oxygen species production. In summary, the cell priming by DH considerably improved the functional activity of EPCs, and the use of which might be a novel strategy for CVD treatment.

Cardiovascular disease (CVD) and its complications are the leading cause of morbidity and mortality in the world. Because of the side effects and incomplete recovery from current therapy, stem cell therapy emerges as a potential therapy for CVD treatment, and endothelial progenitor cell (EPC) is one of the key stem cells used for therapeutic applications. The effect of this therapy required the expansion of EPC function. To enhance the EPC activation, proliferation, and angiogenesis using dronedarone hydrochloride (DH) is the purpose of this study. DH received approval for atrial fibrillation treatment and its cardiovascular protective effects were already reported. In this study, DH significantly increased EPC proliferation, tube formation, migration, and maintained EPCs surface marker expression. In addition, DH treatment up-regulated the phosphorylation of AKT and reduced the reactive oxygen species production. In summary, the cell priming by DH considerably improved the functional activity of EPCs, and the use of which might be a novel strategy for CVD treatment.

To provide a nationwide representative dataset for the study on health impact of air pollution, we combined the data from the Korea National Health and Nutrition Examination Survey with the daily air quality and weather data by matching the date of examination and the residential address of the participants. The database of meteorological factors and air quality as sources of exposure data were estimated using the Community Multiscale Air Quality model. The linkage dataset was merged by three ways; administrative district, si-gun-gu (city, county, and district), and geocode (in latitude and longitude coordinate units) based on the participants’ residential address, respectively. During the study period, the exposure dataset of 85,018 individuals (38,306 men and 46,712 women) whose examination dates were recorded were obtained. According to the definition of exposure period, the dataset was combined with the data on short-term, mid-term, and long-term exposure to air pollutants and the meteorological indices. Calculation of the daily merged dataset’s average air pollution linked by si-gun-gu and geocode units showed similar results. This study generated a daily average of meteorological indices and air pollution exposure dataset for all regions including rural and remote areas in Korea for 11 years. It is expected to provide a platform for the researchers studying the health impact of air pollution and climate change on the representative population and area, which may facilitate the establishment of local health care plans by understanding the residents’ health status at the local as well as national level.

Purpose: Alpha-fetoprotein (AFP) is a prognostic marker for hepatocellular carcinoma (HCC). We investigated the prognostic value of AFP levels in patients who achieved complete response (CR) to transarterial chemoembolization (TACE) for HCC. Materials and Methods: Between 2005 and 2018, 890 patients with HCC who achieved a CR to TACE were recruited. An AFP responder was defined as a patient who showed elevated levels of AFP (>10 ng/mL) during TACE, but showed normalization or a >50% reduction in AFP levels after achieving a CR. Results: Among the recruited patients, 569 (63.9%) with naïve HCC and 321 (36.1%) with recurrent HCC after complete resection were treated. Before TACE, 305 (34.3%) patients had multiple tumors, 219 (24.6%) had a maximal tumor size >3 cm, and 22 (2.5%) had portal vein tumor thrombosis. The median AFP level after achieving a CR was 6.36 ng/mL. After a CR, 473 (53.1%) patients experienced recurrence, and 417 (46.9%) died [median progression-free survival (PFS) and overall survival (OS) of 16.3 and 62.8 months, respectively]. High AFP levels at CR (>20 ng/mL) were independently associated with a shorter PFS [hazard ratio (HR)=1.403] and OS (HR=1.284), together with tumor multiplicity at TACE (HR=1.518 and 1.666, respectively). AFP non-responders at CR (76.2%, n=359 of 471) showed a shorter PFS (median 10.5 months vs. 15.5 months, HR=1.375) and OS (median 41.4 months vs. 61.8 months, HR=1.424) than AFP responders (all p=0.001). Conclusion High AFP levels and AFP non-responders were independently associated with poor outcomes after TACE. AFP holds clinical implications for detailed risk stratification upon achieving a CR after TACE.

BACKGROUND: Menkes disease (MD) is a rare X-linked hereditary multisystemic disorder that is caused by dysfunction of copper metabolism. Patients with MD typically present with progressive neurodegeneration, some connective tissue abnormalities, and characteristic “kinky” hair. In addition, various types of urological complications are frequent in MD because of underlying connective tissue abnormalities. In this study, we studied the clinical features and outcomes of MD, focusing on urological complications. METHODS: A total of 14 unrelated Korean pediatric patients (13 boys and 1 girl) with MD were recruited, and their phenotypes and genotypes were analyzed by retrospective review of their medical records. RESULTS: All the patients had early-onset neurological deficit, including developmental delay, seizures, and hypotonia. The girl patient showed normal serum copper and ceruloplasmin levels as well as milder symptoms. Mutational analysis of the ATP7A gene revealed 11 different mutations in 12 patients. Bladder diverticula was the most frequent urological complication: 8 (57.1%) in the 14 patients or 8 (72.7%) in the 11 patients who underwent urological evaluation. Urological imaging studies were performed essentially for the evaluation of accompanying urinary tract infections. Four patients had stage II chronic kidney disease at the last follow-up. CONCLUSION: Urologic problems occurred frequently in MD, with bladder diverticula being the most common. Therefore, urological imaging studies and appropriate management of urological complications, which may prevent or reduce the development of urinary tract infections and renal parenchymal damage, are required in all patients with MD.
Ceruloplasmin ; Connective Tissue ; Copper ; Diverticulum ; Female ; Follow-Up Studies ; Genotype ; Hair ; Humans ; Medical Records ; Menkes Kinky Hair Syndrome* ; Metabolism ; Muscle Hypotonia ; Phenotype ; Renal Insufficiency, Chronic ; Retrospective Studies ; Seizures ; Urinary Bladder ; Urinary Tract Infections

OBJECTIVES: A clinical data warehouse (CDW) is part of our hospital information system, and it provides user-friendly ‘data search and extraction’ interfaces for query composition. We carried out a risk factor analysis for the extended use of opioids after coronary artery bypass grafting (CABG), taking advantage of the CDW system. METHODS: From 2015 to 2017, clinical data from 461 patients who had undergone either isolated or concomitant CABG were extracted using the CDW; the extracted data included baseline patient characteristics, various examination results, and opioid prescription information. Supplementary data that could not be extracted with the CDW were collected via manual review of the electronic medical records. RESULTS: Data from a total of 447 patients were analyzed finally. The mean patient age was 66.8 ± 10.9 years, 332 patients (74%) were male, and 235 patients (53%) had diabetes. Among the 447 patients, 90 patients (20.1%) took some type of opioid at the 15th postoperative day. An oral rapid-acting agent was the most frequently used opioid (83%). In the risk factor analysis for extended opioid use, duration of operation was the only significant risk factor (odds ratio = 1.004; 95% confidence interval, 1.001–1.007; p = 0.008). CONCLUSIONS: Longer operation time was associated with the risk of extended opioid use after CABG. CDW was a helpful tool for extracting mass clinical data rapidly, but to maximize its utility, the data should be checked carefully as they are entered in the system so that post-processing can be minimized. Further refinement of the clinical data input and output interface is warranted.
Analgesics, Opioid ; Coronary Artery Bypass ; Coronary Vessels ; Database Management Systems ; Electronic Health Records ; Hospital Information Systems ; Humans ; Male ; Prescriptions ; Risk Factors

The authors regret that there was an important error in the results in Table 1; the ATP7A mutations detected in Patients 2 and 14 were incorrectly noted.

OBJECTIVES: Air pollution causes various disease in exposed populations, and can lead to premorbid health effects manifested as both physical and psychological functional impairment. The present study investigated the subjective stress level in daily life in relation to the level of air pollution. METHODS: Data from the Community Health Survey (2013), comprising 99,162 men, and 121,273 women residing in 253 healthcare administrative districts, were combined with air pollutant concentration modelling data from the Korean Air Quality Forecasting System, and were stratified by subjective stress levels into five strata for multiple logistic regression. Levels of exposure were divided into five quintiles according to the annual concentration of nitrogen dioxide (NO2), and were analyzed using a single-pollutant model using NO2 concentration only, and a multi-pollutant model adjusted for the concentration of particulate matter < 10 µm in diameter. RESULTS: Analysis of men and women in various age groups showed the highest odds ratio (OR) for subjective stress level at the highest NO2 concentration quintile in men and women aged 30–64 years (men: 2.91; 95% confidence interval [CI], 2.12 to 4.01; women: 1.82; 95% CI, 1.32 to 2.51). As the NO2 concentration quintile increased, the OR increased. Men showed higher ORs than women in all strata. CONCLUSIONS: In the present study, annual NO2 concentrations were found to be associated with subjective stress levels. This association was especially clear among socioeconomically active men and women aged 30–64 years.
Air Pollution ; Delivery of Health Care ; Female ; Forecasting ; Health Surveys* ; Humans ; Korea* ; Logistic Models ; Male ; Nitrogen Dioxide ; Odds Ratio ; Particulate Matter ; Quality of Life