Background: Guidelines for switching to triple combination therapy directly after monotherapy failure are limited. This study investigated the efficacy, long-term sustainability, and safety of either mono or dual add-on therapy using alogliptin and pioglitazone for patients with type 2 diabetes mellitus (T2DM) who did not achieve their target glycemic range with metformin monotherapy. Methods: The Practical Evidence of Antidiabetic Combination Therapy in Korea (PEAK) was a multicenter, placebo-controlled, double-blind, randomized trial. A total of 214 participants were randomized to receive alogliptin+pioglitazone (Alo+Pio group, n=70), alogliptin (Alo group, n=75), or pioglitazone (Pio group, n=69). The primary outcome was the difference in glycosylated hemoglobin (HbA1c) levels between the three groups at baseline to 24 weeks. For durability, the achievement of HbA1c levels <7% and <6.5% was compared in each group. The number of adverse events was investigated for safety. Results: After 24 weeks of treatment, the change of HbA1c in the Alo+Pio, Alo, and Pio groups were –1.38%±0.08%, –1.03%±0.08%, and –0.84%±0.08%, respectively. The Alo+Pio group had significantly lower HbA1c levels than the other groups (P=0.0063, P<0.0001) and had a higher proportion of patients with target HbA1c achievement. In addition, insulin sensitivity and β-cell function, lipid profiles, and other metabolic indicators were also improved. There were no significant safety issues in patients treated with triple combination therapy. Conclusion Early combination triple therapy showed better efficacy and durability than the single add-on (dual) therapy. Therefore, combination therapy with metformin, alogliptin, and pioglitazone is a valuable early treatment option for T2DM poorly controlled with metformin monotherapy.

Background: /Aim: The Barcelona Clinic Liver Cancer (BCLC) guidelines recommend systemic therapy as the only first-line treatment for patients with BCLC stage C hepatocellular carcinoma (HCC) despite its heterogeneity of disease extent. We aimed to identify patients who might benefit from combined transarterial chemoembolization (TACE) and radiation therapy (RT) by subclassifying BCLC stage C. Methods: A total of 1,419 treatment-naïve BCLC stage C patients with macrovascular invasion (MVI) who were treated with combined TACE and RT (n=1,115) or systemic treatment (n=304) were analyzed. The primary outcome was overall survival (OS). Factors associated with OS were identified and assigned points by the Cox model. The patients were subclassified into three groups based on these points. Results: The mean age was 55.4 years, and 87.8% were male. The median OS was 8.3 months. Multivariate analysis revealed a significant association of Child-Pugh B, infiltrative-type tumor or tumor size ≥10 cm, main or bilateral portal vein invasion, and extrahepatic metastasis with poor OS. The sub-classification was categorized into low (point ≤1), intermediate (point=2), and high (point ≥3) risks based on the sum of points (range, 0–4). The OS in the low, intermediate, and high-risk groups was 22.6, 8.2, and 3.8 months, respectively. In the low and intermediate-risk groups, patients treated with combined TACE and RT exhibited significantly longer OS (24.2 and 9.5 months, respectively) than those who received systemic treatment (6.4 and 5.1 months, respectively; P<0.0001). Conclusions Combined TACE and RT may be considered as a first-line treatment option for HCC patients with MVI when classified into low- and intermediate-risk groups.

Objective: We aimed to investigate the association between statin use and the risk of major osteoporotic fractures in patients with metabolic syndrome (MetS). Methods: A nested case-control study was performed in patients with MetS (≥50 years) who had no history of osteoporotic fracture using the Korean National Health Insurance ServiceHealth Screening Cohort. This study included 17,041 patients diagnosed with new-onset osteoporotic fractures and controls matched in a 1:1 ratio by age, sex, body mass index, cohort entry date, and follow-up duration. Conditional logistic regression analysis was used to evaluate covariate-adjusted odds ratios (ORs) and 95% confidence intervals (CIs). Results: During a 4-year follow-up period, the risk of major osteoporotic fractures was significantly reduced by 9% (OR, 0.91; 95% CI, 0.85–0.97) in statin users compared with that in non-users. Among subtypes of major osteoporotic fracture, a risk reduction with statin therapy was significant for vertebral fracture (OR, 0.86; 95% CI, 0.79–0.94) but not for non-vertebral fracture (OR, 0.97; 95% CI, 0.88–1.06). Longer duration (OR, 0.97; 95% CI, 0.96–0.99, per 1-year increase) and higher cumulative dose (OR, 0.97; 95% CI, 0.95–0.99, per 365 defined daily doses) of statins were negatively associated with the risk of major osteoporotic fracture. Conclusion This study supports the hypothesis that statin therapy has a beneficial effect on major osteoporotic fractures, especially vertebral fractures, in patients with MetS.

PURPOSE: We investigated the changes in serum 25-hydroxyvitamin D (25[OH]D) levels before and after neoadjuvant chemotherapy (NCT) and the associations with pathologic complete response (pCR) and survival in patients with breast cancer. METHODS: Serum 25(OH)D concentrations were measured pre- and post-NCT in 374 patients between 2010 and 2013. Based on a cutoff of 20 ng/mL, patients were categorized into “either sufficient” or “both deficient” groups. The associations with clinicopathological data, including pCR and survival, were analyzed using multivariable analyses. RESULTS: Patients with either pre- or post-NCT sufficient 25(OH)D levels accounted for 23.8%, and the overall pCR rate was 25.9%. Most patients showed 25(OH)D deficiency at diagnosis and 65.8% showed decreased serum levels after NCT. Changes in 25(OH)D status were associated with postmenopause status, rural residence, baseline summer examination, and molecular phenotype, but not pCR. No association between survival and 25(OH)D status was found, including in the subgroup analyses based on molecular phenotypes. CONCLUSION: Most Korean patients with breast cancer showed vitamin D deficiency at diagnosis and a significant decrease in the serum concentration after NCT. No association with oncologic outcomes was found. Therefore, although optimal management for vitamin D deficiency is urgent for skeletal health, further research is warranted to clearly determine the prognostic role of vitamin D in patients with breast cancer who are candidates for NCT.
Breast Neoplasms* ; Breast* ; Diagnosis ; Drug Therapy* ; Humans ; Neoadjuvant Therapy ; Phenotype ; Polymerase Chain Reaction ; Postmenopause ; Treatment Outcome ; Vitamin D ; Vitamin D Deficiency

OBJECTIVE: To assess the clinical outcome of chemical synovectomy with rifampicin in hemophilic arthropathy by using the World Federation of Hemophilia (WFH) scoring system and plain radiograph. METHODS: We performed rifampicin synovectomy (RS) on 30 joints of 28 hemophilic patients diagnosed as hemophilic arthropathy stage I–III (based on Fernandez-Palazzi clinical classification). Clinical status (bleeding frequency, pain, joint physical status) and radiological staging were evaluated as parts of the WFH scoring system before and 1 year after RS. The patients were divided into two groups by the Arnold-Hilgartner scale of the initial X-ray as stage 3 or less for the low-stage group (n=17) and over 3 for the high-stage group (n=13). RESULTS: Total WFH joint physical scores were reduced after injection, and the number of bleeding episodes and pain showed especially significant improvement. For other subscores of the WFH joint physical score, only swelling, range of motion, and crepitus showed statistically significant improvement. According to the severity of the radiologic finding, the WFH joint physical score of both the low-stage and high-stage groups showed significant improvement. In the radiological aspect, the low-stage group, without joint space narrowing at the initial plain radiograph, showed no further aggravation after injection. However, in the high-stage group, radiology found aggravation regardless of the procedure. CONCLUSION: It is suggested that chemical synovectomy with rifampicin may prevent hemarthrosis and improve clinical symptoms. Especially in the early stage of arthropathy without joint-space narrowing, it seems to have an additional benefit that delays radiological aggravation and preserves joint status.
Arthralgia ; Hemarthrosis ; Hemophilia A ; Hemorrhage ; Humans ; Joints ; Range of Motion, Articular ; Rifampin*

OBJECTIVE: Miniscrew-assisted rapid palatal expansion (MARPE) is a means for expanding the basal bone without surgical intervention in young adults. Here, we assessed the differences in dental, alveolar, and skeletal measurements taken before (T0), immediately after (T1), and 1 year after (T2) MARPE. METHODS: Twenty-four patients (mean age, 21.6 years) who had undergone MARPE and cone-beam computed tomography at T0, T1, and T2 were included. Changes in the following parameters were compared using paired t-tests: intercusp, interapex, alveolar, nasal floor, and nasal cavity widths; inclination of the first molar (M1) and its alveolus; and thickness and height of the alveolar bone. A linear mixed-effects model was used to determine variables that affected periodontal changes in the M1. RESULTS: MARPE produced significant increases in most measurements during T0–T2, despite relapse of some measurements during T1–T2. The alveolar thickness decreased on the buccal side, but increased on the palatal side. The alveolar crest level at the first premolar moved apically. Changes in the thickness and height of the alveolar bone were affected by the corresponding initial values. CONCLUSIONS: MARPE can be used as an effective tool for correcting maxillomandibular transverse discrepancy, showing stable outcomes 1 year after expansion.
Bicuspid ; Cone-Beam Computed Tomography ; Humans ; Molar ; Nasal Cavity ; Recurrence ; Young Adult

BACKGROUND/AIMS: This study compared the outcomes of patients with small hepatocellular carcinomas (HCCs) who were treated using transarterial chemoembolization (TACE) or radiofrequency ablation (RFA). METHODS: This was a post-hoc analysis of a prospective study that evaluated the diagnostic efficacy of magnetic resonance imaging (MRI) and computed tomography (CT). We analyzed 41 small hepatic nodules in 32 patients that showed typical radiologic hallmarks on both CT and gadoxate-enhanced MRI (typical nodules) and 25 small hepatic nodules from 22 patients that showed atypical radiologic hallmarks on CT and typical radiologic hallmarks on MRI (discrepant nodules). RESULTS: There were no significant differences in the baseline characteristics of the patients with typical and discrepant nodules. Complete response rates 1 month after TACE or RFA were 75.0% (18/24) and 94.1% (16/17; P=0.20), respectively, for the patients with typical nodules and 58.8% (10/17) and 100% (8/8; P=0.05), respectively, for the patients with discrepant nodules. Treatment failure rates after TACE or RFA were 33.3% (8/24) and 5.8% (1/17; P=0.15), respectively, for the patients with typical nodules and 47.0% (8/17) and 0.0% (0/8; P=0.02), respectively, for the patients with discrepant nodules. Among patients achieving complete response, there were no significant differences in the risk of marginal recurrence. CONCLUSIONS: RFA provided higher complete response rates and significantly lower treatment failure rates than TACE for patients with discrepant nodules of HCC. Therefore, a treatment modality such as RFA may be preferable for small HCCs which show discrepancy on two imaging modalities.
Carcinoma, Hepatocellular* ; Catheter Ablation* ; Humans ; Magnetic Resonance Imaging* ; Multidetector Computed Tomography ; Prospective Studies ; Recurrence ; Treatment Failure

BACKGROUND/AIMS: The aim of this study was to examine the distribution of range of liver enzymes according to age and BMI in each gender using large-scale data. METHODS: Data were gathered from 65,715 subjects who underwent a routine health check-up and did not have HBsAg and anti-HCV. Boxplot analysis was used to examine the distribution of range of liver enzymes according to age and BMI in each gender. Multivariate linear regression analysis was performed for assessment of the association of liver enzymes with age and BMI, and to determine whether the range of liver enzymes was affected by risk factors for metabolic syndrome in each gender. RESULTS: ALT, AST, and GGT levels showed significant association with BMI in both male and female after adjusting for age. The range of ALT, AST, and GGT levels varied more widely according to the increase in BMI in males than in females, and this finding was more prominent in younger subjects than in older subjects. All risk factors for metabolic syndrome were shown to affect liver enzyme levels in male subjects. However, although most risk factors for metabolic syndrome affected liver enzyme levels, there might be weak or no effect of fasting hyperglycemia on AST, and low serum HDL-cholesterol level on GGT in female subjects. CONCLUSIONS: Age, BMI, and other risk factors for metabolic syndrome had a significant effect on the distribution of range of liver enzymes in each gender, even in this study conducted from Korean health checkup subjects.
Alanine Transaminase ; Aspartate Aminotransferases ; Body Mass Index* ; Fasting ; Female ; Hepatitis B Surface Antigens ; Humans ; Hyperglycemia ; Linear Models ; Liver* ; Male ; Metabolic Syndrome X ; Risk Factors

BACKGROUND: Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) agonist has a wide-ranging influence on multiple components of metabolic syndrome. The Otsuka Long-Evans Tokushima Fatty (OLETF) rat is a useful animal model of metabolic syndrome. To determine genes related to metabolic syndrome, we examined overlapping genes that are simultaneously decreased by PPAR-gamma agonists and increased in OLETF rats using microarrays in two different models. METHODS: In the first microarray analysis, PPAR-gamma agonist-treated db/db mice were compared to standard diet-fed db/db mice. In the second microarray analysis, OLETF rats were compared to Long-Evans Tokushima Otsuka (LETO) rats (control of OLETF rats). RESULTS: Among the overlapping genes, in the present study, we validated that lipocalin-2 expression was significantly decreased in the visceral adipose tissue of PPAR-gamma agonist-treated db/db mice compared to standard diet-fed db/db mice and increased in OLETF rats compared to LETO rats using real time reverse transcription polymerase chain reaction. Furthermore, we showed for the first time that lipocalin-2 expression was significantly increased in the visceral adipose tissues of obese humans compared with nonobese humans. In addition, the expression level of lipocalin-2 in human visceral adipose tissue had a significant positive correlation with body mass index, serum interleukin-6, adipocyte fatty acid binding protein levels, and white blood cell count. CONCLUSION: Lipocalin-2 was confirmed to be a significant adipokine affected by PPAR-gamma agonist and obesity in the present study. Also, for the first time in human visceral adipose tissue, it was determined that the expression of lipocalin-2 from obese humans was significantly increased and correlated with circulating inflammatory markers.
Adipocytes ; Adipokines ; Animals ; Body Mass Index ; Carrier Proteins ; Genes, Overlapping ; Humans ; Interleukin-6 ; Intra-Abdominal Fat ; Leukocyte Count ; Mice ; Microarray Analysis ; Models, Animal ; Obesity ; Peroxisomes ; Polymerase Chain Reaction ; PPAR gamma ; Rats ; Rats, Inbred OLETF ; Reverse Transcription ; Transcriptome*

BACKGROUND/AIMS: Primary aldosteronism (PA) is now widely recognized to have a higher prevalence than was once thought. In view of its increasing prevalence, we compared chronological changes in clinical manifestations of PA according to different times of diagnosis. METHODS: In total, 85 patients diagnosed with PA from January 1986 through March 2012 were reviewed retrospectively, based on their medical records. During two periods-1986 to 2005 and 2006 to 2012-41 and 44 patients, respectively, were diagnosed with PA. We compared the clinical and biological characteristics of PA between these periods. RESULTS: The results demonstrate an increasing trend in the prevalence of idiopathic hyperaldosteronism (IHA; p = 0.19). In the 2006 to 2012 period, patients with PA presented with higher serum potassium levels at the time of diagnosis than in the 1986 to 2005 period (p < 0.0002). Adrenal vein sampling (AVS) was performed mostly in the latter period (82.3%) and the diagnostic accuracy of adrenal computed tomography, compared with AVS, was only 56.2%. About 78.0% versus 86.3% of patients had at least one target organ damage (TOD) in the 1986 to 2005 and 2006 to 2012 periods, respectively (p = 0.39). However, patients with TOD were older and had longer durations of hypertension than patients without, in both periods. CONCLUSIONS: PA is becoming more prevalent. There was an increasing tendency for IHA, and more PA patients presented with normokalemia than in the earlier period. Early and accurate diagnosis of PA with AVS and proper treatment should have substantial prognostic value.
Adrenal Cortex Neoplasms/diagnosis/epidemiology ; Adrenal Glands/radiography ; Adrenocortical Adenoma/diagnosis/epidemiology ; Adult ; Biological Markers/blood ; Female ; Humans ; Hyperaldosteronism/blood/*diagnosis/epidemiology/therapy ; Hyperkalemia/diagnosis/epidemiology ; Hyperplasia ; Hypertension/diagnosis/epidemiology ; Male ; Middle Aged ; Potassium/blood ; Predictive Value of Tests ; Prevalence ; Republic of Korea/epidemiology ; Retrospective Studies ; Risk Factors ; Time Factors ; Tomography, X-Ray Computed ; Treatment Outcome