OBJECTIVE: To estimate the cardiovascular (CV) and gastrointestinal (GI) risks of etoricoxib in the treatment of osteoarthritis (OA) compared to a placebo and other non-steroidal anti-inflammatory drugs (NSAIDs). METHODS: A systematic review of randomized, controlled trials (RCTs) of etoricoxib were performed. Bayesian network meta-analysis was used over a duration of 12 weeks. The incidence of CV and GI events for a duration ≥26 weeks were also tabulated and presented using descriptive statistics. RESULTS: From this search, 10 studies were identified. Of these, 6 and 5 RCTs that measured the CV and GI events at 12 weeks were included in meta-analysis. They showed that etoricoxib did not increase the CV events compared to the placebo or NSAIDs during the 12 week period (odds ratio [OR]=0.59 compared to celecoxib, OR=0.89 with ibuprofen, OR=0.70 with placebo, and OR=2.16 with naproxen). The risk of GI events was comparable to that of most comparators, with the exception of naproxen, which had a significantly lower risk of GI events (OR=0.18) during the 12 week period. For a duration ≥26 weeks, the incidence of CV and GI events with etoricoxib increased with increasing duration. CONCLUSION: Etoricoxib is an alternative short-term treatment option for OA, showing comparable CV and GI complications to other NSAIDs. Nevertheless, further studies will be needed to elucidate the long-term safety of etoricoxib in the treatment of OA.
Anti-Inflammatory Agents ; Anti-Inflammatory Agents, Non-Steroidal ; Celecoxib ; Ibuprofen ; Incidence ; Naproxen ; Osteoarthritis*

A nodular density was detected on a chest radiograph taken from a 57-year-old Korean woman who was visiting a hospital for a routine check. Chest computed tomography revealed a 4.8 cm lobulated mass in the right lung and another focal nodular lesion in the left lung; biopsies of both lungs revealed adenocarcinoma. We conducted DNA sequencing and peptide nucleic acid clamping to investigate the potential double primary lung cancer. The results verified that the mass in the right lung had a mutation in the epidermal growth factor receptor, whereas the nodule in the left lung had a wild-type sequence, showing that these two were genetically different cancers from one another. Thus, we demonstrate that genetic testing is useful in determining double primary lung cancer, and we herein report on this case.
Adenocarcinoma* ; Biopsy ; Constriction ; Diagnosis, Differential ; Epidermal Growth Factor* ; Female ; Genetic Testing ; Humans ; Lung Neoplasms ; Lung* ; Middle Aged ; Radiography, Thoracic ; Receptor, Epidermal Growth Factor* ; Sequence Analysis, DNA ; Thorax

Background and Objectives: Neo-aortic root dilatation (ARD) and annular dilatation (AAD) tend to develop after arterial switch operation (ASO). However, the trend of neo-aortic growth has not been well established. This paper aims to identify this trend, its associated factors, and predictors of neo-aortic dilatation after ASO. Methods: We analyzed the growth trend of the neo-aortic root, annulus, and sinotubular junction (STJ) z-scores using random coefficients model and the risk factors affecting neoaortic dilatation in 163 patients who underwent ASO from 2006 to 2015. Results: Among 163 patients, 41 had a ventricular septal defect, and 11 had Taussig-Bing (TB) anomaly. The median follow-up duration was 6.61 years. The increased in the neo-aortic root z-score was different between the trapdoor and non-trapdoor coronary artery transfer techniques (0.149/year, p<0.001 vs. 0.311/year, p<0.001). Moreover, the neo-aortic annulus and STJ z-score significantly increased over time after ASO (0.067/year, p<0.001; 0.309/ year, p<0.001). Pulmonary artery banding (PAB) was rather a negative affecting factor. The probabilities of freedom from ARD, AAD, and neo-aortic STJ dilatation at 10 years after ASO were 33.4%, 53.9%, and 65.4%. Neo- aortic regurgitation within 1 year was the predictor of ARD, AAD, and neo-aortic STJ dilatation. TB anomaly, PAB, and native pulmonary sinus z-score were other predictors for ARD. Conclusion The growth of neo-aortic root, annulus, and STJ after ASO was greater than somatic growth during childhood. The coronary artery transfer technique affected the growth pattern of the neo-aortic root.

Background and Objectives: Neo-aortic root dilatation (ARD) and annular dilatation (AAD) tend to develop after arterial switch operation (ASO). However, the trend of neo-aortic growth has not been well established. This paper aims to identify this trend, its associated factors, and predictors of neo-aortic dilatation after ASO. Methods: We analyzed the growth trend of the neo-aortic root, annulus, and sinotubular junction (STJ) z-scores using random coefficients model and the risk factors affecting neoaortic dilatation in 163 patients who underwent ASO from 2006 to 2015. Results: Among 163 patients, 41 had a ventricular septal defect, and 11 had Taussig-Bing (TB) anomaly. The median follow-up duration was 6.61 years. The increased in the neo-aortic root z-score was different between the trapdoor and non-trapdoor coronary artery transfer techniques (0.149/year, p<0.001 vs. 0.311/year, p<0.001). Moreover, the neo-aortic annulus and STJ z-score significantly increased over time after ASO (0.067/year, p<0.001; 0.309/ year, p<0.001). Pulmonary artery banding (PAB) was rather a negative affecting factor. The probabilities of freedom from ARD, AAD, and neo-aortic STJ dilatation at 10 years after ASO were 33.4%, 53.9%, and 65.4%. Neo- aortic regurgitation within 1 year was the predictor of ARD, AAD, and neo-aortic STJ dilatation. TB anomaly, PAB, and native pulmonary sinus z-score were other predictors for ARD. Conclusion The growth of neo-aortic root, annulus, and STJ after ASO was greater than somatic growth during childhood. The coronary artery transfer technique affected the growth pattern of the neo-aortic root.

BACKGROUND: A latent cytomegalovirus (CMV) cause chronic inflammation through undesirable inflation of cell-mediated immune response. CMV immunoglobulin G has been associated with cardiovascular disease and type 1 diabetes mellitus. We evaluated impact of CMV diseases on new-onset type 2 diabetes mellitus (T2DM).METHODS: From the Korean Health Insurance Review and Assessment Service claim database of entire population with 50 million, we retrieved 576 adult case group with CMV diseases diagnosed with International Statistical Classification of Diseases and Related-Health Problems 10th Revision (ICD-10) B25 code between 2010 and 2014 after exclusion of patients with T2DM to 2006. The 2,880 control patients without T2DM from 2006 to cohort entry point were selected between 2010 and 2014 by age, sex matching with case group. The subjects without new-onset T2DM were followed until 2015. T2DM, hypertension (HTN), dyslipidemia (DYS), and end-stage renal disease (ESRD) were coded as ICD-10.RESULTS: The frequency of new-onset T2DM in case group was significantly higher than that in control (5.6% vs. 2.2%, P<0.001). The group with T2DM (n=95) had higher incidence of CMV diseases than the group without T2DM (n=3,361) (33.7% vs. 16.2%, P<0.001). In multivariate regression model adjusted by age, sex, lower income, HTN, and DYS, the incidence rate (IR) of T2DM in case group was significantly higher than that in the control group (IR per 1,000, 19.0 vs. 7.3; odds ratio, 2.1; 95% confidence interval, 1.3 to 3.2). The co-existence of HTN, DYS, and ESRD with CMV diseases did not influence the IR of T2DM.CONCLUSION: CMV diseases increase the patients' risk of developing T2DM.
Adult ; Cardiovascular Diseases ; Case-Control Studies ; Classification ; Cohort Studies ; Cytomegalovirus ; Diabetes Mellitus, Type 1 ; Diabetes Mellitus, Type 2 ; Dyslipidemias ; Humans ; Hypertension ; Immunoglobulin G ; Incidence ; Inflammation ; Inflation, Economic ; Insurance, Health ; International Classification of Diseases ; Kidney Failure, Chronic ; Odds Ratio

A nodular density was detected on a chest radiograph taken from a 57-year-old Korean woman who was visiting a hospital for a routine check. Chest computed tomography revealed a 4.8 cm lobulated mass in the right lung and another focal nodular lesion in the left lung; biopsies of both lungs revealed adenocarcinoma. We conducted DNA sequencing and peptide nucleic acid clamping to investigate the potential double primary lung cancer. The results verified that the mass in the right lung had a mutation in the epidermal growth factor receptor, whereas the nodule in the left lung had a wild-type sequence, showing that these two were genetically different cancers from one another. Thus, we demonstrate that genetic testing is useful in determining double primary lung cancer, and we herein report on this case.
Adenocarcinoma ; Biopsy ; Constriction ; Diagnosis, Differential ; Epidermal Growth Factor ; Female ; Genetic Testing ; Humans ; Lung Neoplasms ; Lung ; Middle Aged ; Radiography, Thoracic ; Receptor, Epidermal Growth Factor ; Sequence Analysis, DNA ; Thorax

Osteoclasts originated from hematopoietic stem cells are multi-nucleated cells that can resorb the bone matrix. Receptor activator of nuclear factor kappa-B (RANK)/RANK ligand (RANKL) signaling pathway is crucial for the differentiation and activation of osteoclasts. In this study, we investigated for the first time whether or not RANKL induced mitogen- and stress-activated kinase 1 (MSK1) phosphorylation at Ser 376. Activation of MSK1 was detected as soon as 5 min after RANKL stimulation and sparsely detected at 30 min after stimulation. RANKL-induced MSK1 phosphorylation occurred in a dose-dependent manner. MSK1 is known as a downstream signaling molecule of cAMP-dependent protein kinase (PKA). Treatment with the PKA inhibitor H89 significantly suppressed c-Fos and nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1) induction upon RANKL stimulation. In addition, cAMP response element-binding protein (CREB) phosphorylation was extremely inhibited by H89 treatment. Mitogen-activated protein kinases (MAPKs) have been investigated for induction of MSK1 phosphorylation. Specific signaling pathway inhibitors for p38 and extracellular signal-regulated kinases (ERKs) significantly blocked RANKL-induced MSK1 activation. Finally, as a downstream effector of the p38-MSK1 pathway, c-Fos transcriptional activity was determined. RANKL-mediated elevation of c-Fos transcriptional activity was significantly suppressed by p38 inhibitor. Moreover, a dominant negative form of CREB suppressed activation of NFATc1. In conclusion, RANKL-stimulated MSK1 phosphorylation could play a role in induction of NFATc1 through CREB and c-Fos activation as a downstream molecule of p38, ERK MAPKs, and PKA. Our results support basic information for the development of osteoclast specific inhibitors.
Bone Matrix ; Cyclic AMP Response Element-Binding Protein ; Cyclic AMP-Dependent Protein Kinases ; Extracellular Signal-Regulated MAP Kinases ; Hematopoietic Stem Cells ; Mitogen-Activated Protein Kinases ; NFATC Transcription Factors ; Osteoclasts ; Phosphorylation ; Phosphotransferases

OBJECTIVE: To evaluate the differences in subjective calcification detection rates and objective calcium volumes in lung nodules according to different reconstruction methods using hybrid kernel (FC13-H) and iterative reconstruction (IR). MATERIALS AND METHODS: Overall, 35 patients with small (< 4 mm) calcified pulmonary nodules on chest CT were included. Raw data were reconstructed using filtered back projection (FBP) or IR algorithm (AIDR-3D; Canon Medical Systems Corporation), with three types of reconstruction kernel: conventional lung kernel (FC55), FC13-H and conventional soft tissue kernel (FC13). The calcium volumes of pulmonary nodules were quantified using the modified Agatston scoring method. Two radiologists independently interpreted the role of each nodule calcification on the six types of reconstructed images (FC55/FBP, FC55/AIDR-3D, FC13-H/FBP, FC13-H/AIDR-3D, FC13/FBP, and FC13/AIDR-3D). RESULTS: Seventy-eight calcified nodules detected on FC55/FBP images were regarded as reference standards. The calcium detection rates of FC55/AIDR-3D, FC13-H/FBP, FC13-H/AIDR-3D, FC13/FBP, and FC13/AIDR-3D protocols were 80.7%, 15.4%, 6.4%, 52.6%, and 28.2%, respectively, and FC13-H/AIDR-3D showed the smallest calcium detection rate. The calcium volume varied significantly with reconstruction protocols and FC13/AIDR-3D showed the smallest calcium volume (0.04 ± 0.22 mm³), followed by FC13-H/AIDR-3D. CONCLUSION: Hybrid kernel and IR influence subjective detection and objective measurement of calcium in lung nodules, particularly when both techniques (FC13-H/AIDR-3D) are combined.
Calcium ; Humans ; Lung* ; Research Design ; Thorax* ; Tomography, X-Ray Computed*

BACKGROUND: Lead (Pb), mercury (Hg), and cadmium (Cd) are well-known environmental pollutants. They are unnecessary in the biological processes of humans. This study was performed to estimate the representative background exposure levels to the metals by measuring concentrations in whole blood of the Korean general population. METHODS: This population-based cross-sectional study included 4,000 subjects (1,886 males and 2,114 females) 0–83 years of age in 2010 and 2011. Adult subjects (≥ 19 years of age) were collected by sex- and age-stratified probability method, and preschool- and school-aged subjects were recruited by a cluster sampling method. Written consent was provided prior to blood sampling. Pb and Cd blood concentrations were determined by a flameless atomic absorption spectrophotometry, and blood Hg was analyzed by a direct Hg analyzer. RESULTS: The geometric mean, median and 95th percentile of blood Pb was 1.82 µg/dL, 1.83 µg/dL, and 3.78 µg/dL, respectively. The respective values were 2.92 µg/L, 2.87 µg/L, 9.12 µg/L for Hg, and 0.56 µg/L, 0.59 µg/L, 2.20 µg/L for Cd. Blood Pb and Hg were higher in males than in females, but no sex difference was observed, respectively, in subjects 0–4 years of age for Pb and in subjects less than 20 years for Hg. However, blood Cd was higher in females than in males and no sex difference was observed in subjects < 30 years of age. CONCLUSION: This study provides representative data of human exposure to Pb, Hg, and Cd covering whole age groups of the general population in Korea.
Adult ; Biological Processes ; Cadmium ; Cross-Sectional Studies ; Environmental Pollutants ; Female ; Humans ; Korea ; Male ; Metals ; Methods ; Sex Characteristics ; Spectrophotometry, Atomic