Background: This phase 3 study evaluated the efficacy and safety of 6-month treatment with romosozumab in Korean postmenopausal women with osteoporosis. Methods: Sixty-seven postmenopausal women with osteoporosis (bone mineral density [BMD] T-scores ≤–2.5 at the lumbar spine, total hip, or femoral neck) were randomized (1:1) to receive monthly subcutaneous injections of romosozumab (210 mg; n=34) or placebo (n=33) for 6 months. Results: At month 6, the difference in the least square (LS) mean percent change from baseline in lumbar spine BMD (primary efficacy endpoint) between the romosozumab (9.5%) and placebo (–0.1%) groups was significant (9.6%; 95% confidence interval, 7.6 to 11.5; P<0.001). The difference in the LS mean percent change from baseline was also significant for total hip and femoral neck BMD (secondary efficacy endpoints). After treatment with romosozumab, the percent change from baseline in procollagen type 1 N-terminal propeptide transiently increased at months 1 and 3, while that in C-terminal telopeptide of type 1 collagen showed a sustained decrease. No events of cancer, hypocalcemia, injection site reaction, positively adjudicated atypical femoral fracture or osteonecrosis of the jaw, or positively adjudicated serious cardiovascular adverse events were observed. At month 9, 17.6% and 2.9% of patients in the romosozumab group developed binding and neutralizing antibodies, respectively. Conclusion Treatment with romosozumab for 6 months was well tolerated and significantly increased lumbar spine, total hip, and femoral neck BMD compared with placebo in Korean postmenopausal women with osteoporosis (ClinicalTrials.gov identifier NCT02791516).

BACKGROUND: Kidney ischemia-reperfusion (IR) via laparotomy is a conventional method for kidney surgery in a mouse model. However, IR, an invasive procedure, can cause serious acute and chronic complications through apoptotic and inflammatory pathways. To avoid these adverse responses, a Non-IR and dorsal slit approach was designed for kidney surgery. METHODS: Animals were divided into three groups, 1) sham-operated control; 2) IR, Kidney IR via laparotomy; and 3) Non-IR, Non-IR and dorsal slit. The effects of Non-IR method on renal surgery outcomes were verified with respect to animal viability, renal function, apoptosis, inflammation, fibrosis, renal regeneration, and systemic response using histology, immunohistochemistry, real-time polymerase chain reaction, serum chemistry, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining, and Masson's trichrome staining. RESULTS: The Non-IR group showed 100% viability with mild elevation of serum blood urea nitrogen and creatinine values at day 1 after surgery, whereas the IR group showed 20% viability and lethal functional abnormality. Histologically, renal tubule epithelial cell injury was evident on day 1 in the IR group, and cellular apoptosis enhanced TUNEL-positive cell number and Fas/caspase-3 and KIM-1/NGAL expression. Inflammation and fibrosis were high in the IR group, with enhanced CD4/CD8-positive T cell infiltration, inflammatory cytokine secretion, and Masson's trichrome stain-positive cell numbers. The Non-IR group showed a suitable microenvironment for renal regeneration with enhanced host cell migration, reduced immune cell influx, and increased expression of renal differentiation-related genes and anti-inflammatory cytokines. The local renal IR influenced distal organ apoptosis and inflammation by releasing circulating pro-inflammatory cytokines. CONCLUSION: The Non-IR and dorsal slit method for kidney surgery in a mouse model can be an alternative surgical approach for researchers without adverse reactions such as apoptosis, inflammation, fibrosis, functional impairment, and systemic reactions.
Animals ; Apoptosis ; Blood Urea Nitrogen ; Cell Count ; Cell Movement ; Chemistry ; Creatinine ; Cytokines ; DNA Nucleotidylexotransferase ; Epithelial Cells ; Fibrosis ; Immunohistochemistry ; Inflammation ; Kidney ; Laparotomy ; Methods* ; Mice* ; Nephrectomy* ; Real-Time Polymerase Chain Reaction ; Regeneration*

PURPOSE: We aim to identify what potential bias factors affected students' overall course evaluation, and to observe what factors should be considered in the curriculum evaluation system of medical schools. METHODS: This study analyzed students' ratings of preclinical instructions at the Ajou University School of Medicine. The ratings of instructions involved 41 first-year and 45 second-year medical students. RESULTS: There was a statistically significant difference between years of study and ratings' scoring. Learning difficulty, learning amount, student assessment, and teacher preparation from second-year students were significantly higher than first-year students (p<0.05). The analysis results revealed that student assessment was the predictor of ratings from first-year students, while teacher preparation was the predictor of ratings from second-year students. CONCLUSION: We found significant interactions between year of study and the students' rating results. We were able to confirm that satisfaction of instructions factors perceived by medical students were different for the characteristics of courses. Our results may be an important resource for evaluating preclinical curriculums.
Bias (Epidemiology)* ; Curriculum ; Humans ; Learning ; Schools, Medical ; Students, Medical

Eradication of Helicobacter pylori using first-line therapy is becoming less effective. Subjects who had been treated for H. pylori infection were prospectively enrolled through an on-line database registry from October 2010 to December 2012. Demographic data, detection methods, treatment indication, regimens, durations, compliance, adverse events, and eradication results for H. pylori infection were collected. Data of 3,700 patients from 34 hospitals were analyzed. The overall eradication rate of the first-line therapy was 73.0%. Eradication failure was significantly associated with old age, concomitant medication, and comorbidity. Regional differences in eradication rates were observed. The most common first-line therapy was proton pump inhibitor-based triple therapy (standard triple therapy, STT) for 7 days (86.8%). The eradication rates varied with regimens, being 73% in STT, 81.8% in bismuth-based quadruple therapy, 100% in sequential therapy, and 90.3% in concomitant therapy. The eradication rate in treatment-naïve patients was higher than that in patients previously treated for H. pylori infection (73.8% vs. 58.5%, P < 0.001). The overall eradication rate for second-line therapy was 84.3%. There was no statistical difference in eradication rates among various regimens. H. pylori eradication rate using STT is decreasing in Korea and has become sub-optimal, suggesting the need for alternative regimens to improve the efficacy of first-line therapy for H. pylori infection.
Adult ; Age Factors ; Aged ; Anti-Bacterial Agents/*therapeutic use ; Databases, Factual ; Drug Therapy, Combination ; Female ; Helicobacter Infections/*drug therapy/microbiology ; Helicobacter pylori/isolation & purification ; Humans ; Internet ; Logistic Models ; Male ; Middle Aged ; Prospective Studies ; Proton Pump Inhibitors/*therapeutic use ; Registries ; Republic of Korea ; Treatment Outcome

Eradication of Helicobacter pylori using first-line therapy is becoming less effective. Subjects who had been treated for H. pylori infection were prospectively enrolled through an on-line database registry from October 2010 to December 2012. Demographic data, detection methods, treatment indication, regimens, durations, compliance, adverse events, and eradication results for H. pylori infection were collected. Data of 3,700 patients from 34 hospitals were analyzed. The overall eradication rate of the first-line therapy was 73.0%. Eradication failure was significantly associated with old age, concomitant medication, and comorbidity. Regional differences in eradication rates were observed. The most common first-line therapy was proton pump inhibitor-based triple therapy (standard triple therapy, STT) for 7 days (86.8%). The eradication rates varied with regimens, being 73% in STT, 81.8% in bismuth-based quadruple therapy, 100% in sequential therapy, and 90.3% in concomitant therapy. The eradication rate in treatment-naïve patients was higher than that in patients previously treated for H. pylori infection (73.8% vs. 58.5%, P < 0.001). The overall eradication rate for second-line therapy was 84.3%. There was no statistical difference in eradication rates among various regimens. H. pylori eradication rate using STT is decreasing in Korea and has become sub-optimal, suggesting the need for alternative regimens to improve the efficacy of first-line therapy for H. pylori infection.
Adult ; Age Factors ; Aged ; Anti-Bacterial Agents/*therapeutic use ; Databases, Factual ; Drug Therapy, Combination ; Female ; Helicobacter Infections/*drug therapy/microbiology ; Helicobacter pylori/isolation & purification ; Humans ; Internet ; Logistic Models ; Male ; Middle Aged ; Prospective Studies ; Proton Pump Inhibitors/*therapeutic use ; Registries ; Republic of Korea ; Treatment Outcome

In this article, a part of fund and grant supports was omitted unintentionally.

PURPOSE: Previously, we reported the presence of virus-encoded microRNAs (miRNAs) in the urine of prostate cancer (CaP) patients. In this study, we investigated the expression of two herpes virus-encoded miRNAs in prostate tissue. METHODS: A total of 175 tissue samples from noncancerous benign prostatic hyperplasia (BPH), 248 tissue samples from patients with CaP and BPH, and 50 samples from noncancerous surrounding tissues from these same patients were analyzed for the expression of two herpes virus-encoded miRNAs by real-time polymerase chain reaction (PCR) and immunocytochemistry using nanoparticles as molecular beacons. RESULTS: Real-time reverse transcription-PCR results revealed significantly higher expression of hsv1-miR-H18 and hsv2-miRH9- 5p in surrounding noncancerous and CaP tissues than that in BPH tissue (each comparison, P<0.001). Of note, these miRNA were expressed equivalently in the CaP tissues and surrounding noncancerous tissues. Moreover, immunocytochemistry clearly demonstrated a significant enrichment of both hsv1-miR-H18 and hsv2-miR-H9 beacon-labeled cells in CaP and surrounding noncancerous tissue compared to that in BPH tissue (each comparison, P<0.05 for hsv1-miR-H18 and hsv2- miR-H9). CONCLUSIONS: These results suggest that increased expression of hsv1-miR-H18 and hsv2-miR-H95p might be associated with tumorigenesis in the prostate. Further studies will be required to elucidate the role of these miRNAs with respect to CaP and herpes viral infections.
Carcinogenesis ; Herpesviridae ; Humans ; Hyperplasia* ; Immunohistochemistry ; MicroRNAs ; Nanoparticles ; Prostate* ; Prostatic Hyperplasia ; Prostatic Neoplasms ; Real-Time Polymerase Chain Reaction

PURPOSE: Up to 71% of South Korean postmenopausal women have vitamin D deficiency {serum 25-hydroxyvitamin D [25(OH) D] level <50 nmol/L}. Data on vitamin D supplementation was collected during the screening phase of an efficacy/safety study of denosumab in Korean postmenopausal women with osteoporosis. This report describes the effect of vitamin D supplementation on repletion to 25(OH)D levels ≥50 nmol/L in Korean postmenopausal women with osteoporosis. MATERIALS AND METHODS: Vitamin D levels of Korean postmenopausal women (60-90 years old) were measured by extracting 25(OH)D2 and 25(OH)D3 from serum samples via protein precipitation and using liquid chromatography with tandem mass spectrometry detection. Calibration curves were constructed from the mass chromatograms to obtain total vitamin D levels. Subjects with serum 25(OH)D levels <50 nmol/L were supplemented with 1000 IU of vitamin D tablets during the 2.5-month-long screening period. Dose, frequency, and duration were determined by the investigator. If repletion was achieved (≥50 nmol/L) on retest, subjects were eligible to be rescreened for study entry. RESULTS: Of 371 subjects screened, 191 (52%) required vitamin D supplementation, and 88% (168 of 191) were successfully repleted. More than half of the subjects (58%) who were successfully repleted received doses of 2000 IU daily. The mean time to successful repletion was 31 days (standard deviation 8.4 days; range 11-48 days). CONCLUSION: Supplementation with daily median doses of 2000 IU vitamin D successfully repleted 88% of Korean postmenopausal women with osteoporosis within 48 days to a serum vitamin D level of 50 nmol/L.
Aged ; Aged, 80 and over ; *Asian Continental Ancestry Group ; Bone Density Conservation Agents/*therapeutic use ; *Dietary Supplements ; Double-Blind Method ; Female ; Humans ; Middle Aged ; Osteoporosis, Postmenopausal/*complications/drug therapy/ethnology ; Postmenopause/blood ; Republic of Korea ; Vitamin D/analogs & derivatives/blood/*therapeutic use ; Vitamin D Deficiency/diagnosis/*drug therapy/ethnology

PURPOSE: The efficacy and safety of denosumab was compared with placebo in Korean postmenopausal women with osteoporosis in this phase III study. MATERIALS AND METHODS: Women aged 60 to 90 years with a T-score of <-2.5 and ≥-4.0 at the lumbar spine or total hip were randomized to a single 60 mg subcutaneous dose of denosumab or placebo for the 6-month double-blind phase. Eligible subjects entered the 6-month open-label extension phase and received a single dose of denosumab 60 mg. RESULTS: Baseline demographics were similar in the 62 denosumab- and 64 placebo-treated subjects who completed the double-blind phase. Treatment favored denosumab over placebo for the primary endpoint {mean percent change from baseline in lumbar spine bone mineral density (BMD) at Month 6 [3.2% (95% confidence interval 2.1%, 4.4%; p<0.0001)]}; and secondary endpoints (mean percent change from baseline in lumbar spine BMD at Month 1, total hip, femoral neck, and trochanter BMD at Months 1 and 6, and median percent change from baseline in bone turnover markers at Months 1, 3, and 6). Endpoint improvements were sustained over 12 months in the open-label extension (n=119). There were no new or unexpected safety signals. CONCLUSION: Denosumab was well tolerated and effective in increasing BMD and decreasing bone turnover markers over a 12-month period in Korean postmenopausal women. The findings of this study demonstrate that denosumab has beneficial effects on the measures of osteoporosis in Korean postmenopausal women.
Aged ; Aged, 80 and over ; *Asian Continental Ancestry Group ; Bone Density ; Bone Density Conservation Agents/*therapeutic use ; Denosumab/*therapeutic use ; Double-Blind Method ; Female ; Femur ; Femur Neck ; Humans ; Lumbar Vertebrae ; Middle Aged ; Osteoporosis, Postmenopausal/*drug therapy/*ethnology ; Postmenopause ; Republic of Korea

BACKGROUND: The present study evaluated the efficacy of a combination of ibandronate and cholecalciferol on the restoration of the levels of 25-hydroxyvitamin D (25[OH]D) and various bone markers in postmenopausal women with osteoporosis. METHODS: This was a randomized, double-blind, active-controlled, prospective 16-week clinical trial conducted in 20 different hospitals. A total of 201 postmenopausal women with osteoporosis were assigned randomly to one of two groups: the IBN group, which received a once-monthly pill containing 150 mg ibandronate (n=99), or the IBN+ group, which received a once-monthly pill containing 150 mg ibandronate and 24,000 IU cholecalciferol (n=102). Serum levels of 25(OH)D, parathyroid hormone (PTH), and various bone markers were assessed at baseline and at the end of a 16-week treatment period. RESULTS: After 16 weeks of treatment, the mean serum levels of 25(OH)D significantly increased from 21.0 to 25.3 ng/mL in the IBN+ group but significantly decreased from 20.6 to 17.4 ng/mL in the IBN group. Additionally, both groups exhibited significant increases in mean serum levels of PTH but significant decreases in serum levels of bone-specific alkaline phosphatase and C-telopeptide of type 1 collagen (CTX) at 16 weeks; no significant differences were observed between the groups. However, in subjects with a vitamin D deficiency, IBN+ treatment resulted in a significant decrease in serum CTX levels compared with IBN treatment. CONCLUSION: The present findings demonstrate that a once-monthly pill containing ibandronate and cholecalciferol may be useful for the amelioration of vitamin D deficiency in patients with postmenopausal osteoporosis. Moreover, this treatment combination effectively decreased serum levels of resorption markers, especially in subjects with a vitamin D deficiency, over the 16-week treatment period.
Alkaline Phosphatase ; Cholecalciferol* ; Collagen Type I ; Female ; Humans ; Osteoporosis* ; Osteoporosis, Postmenopausal ; Parathyroid Hormone ; Prospective Studies ; Vitamin D Deficiency