Purpose: We investigated the consistent efficacy and safety of eflapegrastim, a novel long-acting granulocyte-colony stimulating factor (G-CSF), in Koreans and Asians compared with the pooled population of two global phase 3 trials. Materials and Methods: Two phase 3 trials (ADVANCE and RECOVER) evaluated the efficacy and safety of fixed-dose eflapegrastim (13.2 mg/0.6 mL [3.6 mg G-CSF equivalent]) compared to pegfilgrastim (6 mg based on G-CSF) in breast cancer patients who received neoadjuvant or adjuvant docetaxel/cyclophosphamide. The primary objective was to demonstrate non-inferiority of eflapegrastim compared to pegfilgrastim in mean duration of severe neutropenia (DSN) in cycle 1, in Korean and Asian subpopulations. Results: Among a total of 643 patients randomized to eflapegrastim (n=314) or pegfilgrastim (n=329), 54 Asians (29 to eflapegrastim and 25 to pegfilgrastim) including 28 Koreans (14 to both eflapegrastim and pegfilgrastim) were enrolled. The primary endpoint, DSN in cycle 1 in the eflapegrastim arm was non-inferior to the pegfilgrastim arm in Koreans and Asians. The DSN difference between the eflapegrastim and pegfilgrastim arms was consistent across populations: –0.120 days (95% confidence interval [CI], –0.227 to –0.016), –0.288 (95% CI, –0.714 to 0.143), and –0.267 (95% CI, –0.697 to 0.110) for pooled population, Koreans and Asians, respectively. There were few treatment-related adverse events that caused discontinuation of eflapegrastim (1.9%) or pegfilgrastim (1.5%) in total and no notable trends or differences across patient populations. Conclusion This study may suggest that eflapegrastim showed non-inferior efficacy and similar safety compared to pegfilgrastim in Koreans and Asians, consistently with those of pooled population.

Background: The Baumann skin type (BST) classification provides a new approach for clinical care of dermatologic patients. Objective: To investigate the correlation of skin types with genetic factors and environmental factors that have an important influence on Korean skin by comparing and analyzing the correlation between phenotype and genotype. Methods: From July to October 2016, 774 adults who visited the one online shopping mall were subjected to skin BST questionnaire and gene single-nucleotide polymorphism (SNP) tests. Oral epithelial cells of the subjects were collected using a Genoplan DNA analysis kit, and 14 genes were analyzed by a genetic analysis agency (Genoplan Inc., Fukuoka, Japan). Results: The most abundant skin type was OSNT (oily, sensitive, non-pigmented, tight) observed in 205 participants (26.5%). Of the filaggrin (FLG) SNPs, 143 participants (18.5%) had the GG (good) SNP; 391 (50.5%), GA (normal) SNP; and 240 (31.0%), AA (poor) SNP. Among those whose FLG SNP was GG (good), 121 (84.6%) were sensitive and 22 (15.4%) were resistant. Of those whose filaggrin (FLG) SNP was GA (normal), 337 (86.2%) were sensitive and 54 (13.8%) were resistant. Of those whose FLG SNP was AA (poor), 213 (88.8%) were sensitive and 27 (11.3%) were resistant. There was also a statistically significant difference in the fruit-vegetable consumption and use of a sunbathing bed between sensitive and resistant type in the groups that classified the FLG SNP as GA. Conclusion This is the first study to investigate the association of BST with genetic factors and environmental factors.

Background/Aims: Besifovir dipivoxil maleate (BSV), an acyclic nucleotide phosphonate, shows potent antiviral activity against hepatitis B virus. Our previous 48-week trial revealed that BSV has comparable antiviral efficacy to tenofovir disoproxil fumarate (TDF) and better safety profiles in terms of improved renal and bone safety. This extension study evaluated the prolonged efficacy and safety of BSV in treatment-naive chronic hepatitis B patients. Methods: Patients continued to participate in an open-label BSV study after an initial 48-week double-blind comparison of BSV and TDF treatment. The antiviral efficacy and drug safety was evaluated up to 192 weeks in two groups: patients continuing BSV treatment (BSV-BSV) and patients switching from TDF to BSV after 48 weeks (TDF-BSV). Results: Among 197 patients receiving randomized treatments, 170 (86%) entered the open-label phase and 152 (77%) entered the 192-week extension study. Virological response rates over 192 weeks were 92.50% and 93.06% in the BSV-BSV and TDF-BSV groups, respectively (P=0.90). Hepatitis B envelop antigen seroconversion and alanine aminotransferase normalization rates were similar between the groups (P=0.75 and P=0.36, respectively). There were no drug-resistant mutations to BSV. Bone mineral density and renal function were well preserved in the BSV-BSV group, whereas these initially worsened then recovered after switching therapy in the TDF-BSV group. Conclusions BSV maintained potent antiviral efficacy after 192 weeks and showed no evidence of drug resistance. BSV was safe, well tolerated, and effective in patients who switched from TDF to BSV. Trial Registration Number: NCT01937806 (date: 10 Sep 2013).

Background/Aims: Besifovir dipivoxil maleate (BSV), an acyclic nucleotide phosphonate, shows potent antiviral activity against hepatitis B virus. Our previous 48-week trial revealed that BSV has comparable antiviral efficacy to tenofovir disoproxil fumarate (TDF) and better safety profiles in terms of improved renal and bone safety. This extension study evaluated the prolonged efficacy and safety of BSV in treatment-naive chronic hepatitis B patients. Methods: Patients continued to participate in an open-label BSV study after an initial 48-week double-blind comparison of BSV and TDF treatment. The antiviral efficacy and drug safety was evaluated up to 192 weeks in two groups: patients continuing BSV treatment (BSV-BSV) and patients switching from TDF to BSV after 48 weeks (TDF-BSV). Results: Among 197 patients receiving randomized treatments, 170 (86%) entered the open-label phase and 152 (77%) entered the 192-week extension study. Virological response rates over 192 weeks were 92.50% and 93.06% in the BSV-BSV and TDF-BSV groups, respectively (P=0.90). Hepatitis B envelop antigen seroconversion and alanine aminotransferase normalization rates were similar between the groups (P=0.75 and P=0.36, respectively). There were no drug-resistant mutations to BSV. Bone mineral density and renal function were well preserved in the BSV-BSV group, whereas these initially worsened then recovered after switching therapy in the TDF-BSV group. Conclusions BSV maintained potent antiviral efficacy after 192 weeks and showed no evidence of drug resistance. BSV was safe, well tolerated, and effective in patients who switched from TDF to BSV. Trial Registration Number: NCT01937806 (date: 10 Sep 2013).

BACKGROUND: Type 2 diabetes mellitus (T2DM) is associated with an increased risk for dementia. The effects of hypoglycemia on dementia are controversial. Thus, we evaluated whether hypoglycemia increases the risk for dementia in senior patients with T2DM. METHODS: We used the Korean National Health Insurance Service Senior cohort, which includes >10% of the entire senior population of South Korea. In total, 5,966 patients who had ever experienced at least one episode of hypoglycemia were matched with those who had not, using propensity score matching. The risk of dementia was assessed through a survival analysis of matched pairs. RESULTS: Patients with underlying hypoglycemic events had an increased risk for all-cause dementia, Alzheimer's dementia (AD), and vascular dementia (VaD) compared with those who had not experienced a hypoglycemic event (hazard ratio [HR], 1.254; 95% confidence interval [CI], 1.166 to 1.349; P<0.001 for all-cause dementia; HR, 1.264; 95% CI, 1.162 to 1.375; P<0.001 for AD; HR, 1.286; 95% CI, 1.110 to 1.490; P<0.001 for VaD). According to number of hypoglycemic episodes, the HRs of dementia were 1.170, 1.201, and 1.358 in patients with one hypoglycemic episode, two or three episodes, and more than three episodes, respectively. In the subgroup analysis, hypoglycemia was associated with an increased risk for dementia in both sexes with or without T2DM microvascular or macrovascular complications. CONCLUSION Our findings suggest that patients with a history of hypoglycemia have a higher risk for dementia. This trend was similar for AD and VaD, the two most important subtypes of dementia.

BACKGROUND: The adductor canal block (ACB) is an effective intervention for postoperative analgesia following total knee arthroplasty (TKA). However, the ideal ACB regimen has not yet been established. We compared the analgesic effects between a continuous ACB group and fentanyl-based intravenous patient-controlled analgesia (IV-PCA) with a single-shot ACB group. METHODS: Patients who underwent TKA were randomly allocated to either a continuous ACB group (Group CACB) or IV-PCA with a single-shot ACB group (Group IVACB). Before the surgery, ultrasound guided ACB with 0.5% ropivacaine 20 cc was provided to all patients. Before skin incision, the infusion system (0.2% ropivacaine through an adductor canal catheter in group CACB vs. intravenous fentanyl in group IVACB) was connected. The postoperative pain severity; the side effects of local anesthetics and opioids; administration of rescue analgesics and anti-emetics; and sensorimotor deficits were measured. RESULTS: Postoperative pain severity was significantly higher in the IVACB group at 30 min, 4 h, 24 h, and 48 h after surgery. The averages and standard deviations (SD) of the NRS score of postoperative pain were 0.14 ± 0.37, 4.57 ± 2.37, 6.00 ± 1.63, and 4.28 ± 1.49, respectively in the IVACB group. Rescue analgesic requirements and quadriceps muscle strength were not statistically different between the groups throughout the postoperative period. Moreover, rescue antiemetic requirements were higher in group IVACB than group CACB. CONCLUSIONS: In this study, the continuous ACB provided superior analgesia and fewer side effects without any significant motor deficit than the IV-PCA with a single-shot ACB.
Analgesia ; Analgesia, Patient-Controlled ; Analgesics ; Analgesics, Opioid ; Anesthetics, Local ; Antiemetics ; Arthroplasty, Replacement, Knee ; Catheters ; Fentanyl ; Humans ; Nausea ; Pain Management ; Pain, Postoperative ; Postoperative Period ; Quadriceps Muscle ; Skin ; Ultrasonography ; Vomiting

OBJECTIVE: To evaluate the clinical features that could serve as predictive factors for improvement in gait speed after robotic treatment. METHODS: A total of 29 patients with motor incomplete spinal cord injury received 4-week robot-assisted gait training (RAGT) on the Lokomat (Hocoma AG, Volketswil, Switzerland) for 30 minutes, once a day, 5 times a week, for a total of 20 sessions. All subjects were evaluated for general characteristics, the 10-Meter Walk Test (10MWT), the Lower Extremity Motor Score (LEMS), the Functional Ambulatory Category (FAC), the Walking Index for Spinal Cord Injury version II (WISCI-II), the Berg Balance Scale (BBS), and the Spinal Cord Independence Measure version III (SCIM-III) every 0, and 4 weeks. After all the interventions, subjects were stratified using the 10MWT score at 4 weeks into improved group and non-improved group for statistical analysis. RESULTS: The improved group had younger age and shorter disease duration than the non-improved group. All subjects with the American Spinal Injury Association Impairment Scale level C (AIS-C) tetraplegia belonged to the non-improved group, while most subjects with AIS-C paraplegia, AIS-D tetraplegia, and AIS-D paraplegia belonged to the improved group. The improved group showed greater baseline lower extremity strength, balance, and daily living function than the non-improved group. CONCLUSION: Assessment of SCIM-III, BBS, and trunk control, in addition to LEMS, have potential for predicting the effects of robotic treatment in patients with motor incomplete spinal cord injury.
Gait* ; Humans ; Locomotion ; Lower Extremity ; Paraplegia ; Quadriplegia ; Rehabilitation ; Robotics ; Spinal Cord Injuries* ; Spinal Cord* ; Spinal Injuries ; Walking

PURPOSE: The roles of circulating tumor cells (CTCs) as predictive and prognostic factors, as well as key mediators in the metastatic cascade, have been investigated. This study aimed to validate a method to quantify CTCs in peripheral blood using a real-time reverse transcriptase polymerase chain reaction (RT-PCR) assay for cytokeratin (CK)-19 and to evaluate the utility of this assay in detecting CTCs in breast cancer patients. MATERIALS AND METHODS: Real-time monitoring PCR of fluorescently labeled specific hybridization probes for CK-19 mRNA was established. Peripheral blood samples from 30 healthy donors, 69 patients with early breast cancer, 47 patients with locally advanced breast cancer, and 126 patients with metastatic breast cancer were prospectively obtained and analyzed for CTC detection. RESULTS: CK-19 mRNA was not detectable in healthy subjects using the real-time RT-PCR method. The detection rates of CK-19 mRNA in breast cancer patients were 47.8% for early breast cancer (33/69), 46.8% for locally advanced breast cancer (22/47), and 61.1% for metastatic breast cancer (77/129). The detection rate of CK-19-positive CTCs in metastatic disease was slightly higher than early or locally advanced breast cancer; however, the detection rate according to disease burden was not statistically different (p=0.097). The detection rate was higher in patients with pleural metastasis (p=0.045). CTC detection was associated with poor survival (p=0.014). CONCLUSION: A highly specific and sensitive CK-19 mRNA-based method to detect CTCs in peripheral blood in breast cancer patients can be used in further prospective studies to evaluate the predictive and prognostic importance of CTCs.
Biomarkers, Tumor/*blood ; Breast Neoplasms/blood/*pathology ; Female ; Humans ; Keratin-19/*blood/genetics ; *Neoplastic Cells, Circulating ; Prognosis ; Prospective Studies ; RNA, Messenger/*blood ; Real-Time Polymerase Chain Reaction ; *Reverse Transcriptase Polymerase Chain Reaction/methods

BACKGROUND/AIMS: In Korea, the nationwide gastric cancer screening program recommends biennial screening for individuals aged 40 years or older by way of either an upper gastrointestinal series or endoscopy. The national endoscopic quality assessment (QA) program began recommending endoscopy in medical institutions in 2009. We aimed to assess the effect, burden, and cost of the QA program from the viewpoint of medical institutions. METHODS: We surveyed the staff of institutional endoscopic units via e-mail. RESULTS: Staff members from 67 institutions replied. Most doctors were endoscopic specialists. They responded as to whether the QA program raised awareness for endoscopic quality (93%) or improved endoscopic practice (40%). The percentages of responders who reported improvements in the diagnosis of gastric cancer, the qualifications of endoscopists, the quality of facilities and equipment, endoscopic procedure, and endoscopic reprocessing were 69%, 60%, 66%, 82%, and 75%, respectively. Regarding reprocessing, many staff members reported that they had bought new automated endoscopic preprocessors (3%), used more disinfectants (34%), washed endoscopes longer (28%), reduced the number of endoscopies performed to adhere to reprocessing guidelines (9%), and created their own quality education programs (59%). Many responders said they felt that QA was associated with some degree of burden (48%), especially financial burden caused by purchasing new equipment. Reasonable quality standards (45%) and incentives (38%) were considered important to the success of the QA program. CONCLUSIONS: Endoscopic quality has improved after 5 years of the mandatory endoscopic QA program.
Diagnosis ; Disinfectants ; Education ; Electronic Mail ; Endoscopes ; Endoscopy ; Korea* ; Mass Screening ; Motivation ; Specialization ; Stomach Neoplasms

BACKGROUND/OBJECTIVES: We investigated the effects of a combination of grape pomace (Vitis labrusca, Campbell Early) and Omija fruit (Schizandra chinensis, Baillon) ethanol extracts on lipid metabolism and antioxidant defense system in diet-induced obese mice. MATERIALS/METHODS: Forty male C57BL/6J mice were divided into four groups and fed high-fat diet (control group, CON) or high-fat diet added 0.5% grape pomace extract (GPE), 0.05% Omija fruit extract (OFE) or 0.5% GPE plus 0.05% OFE (GPE+OFE) for 12 weeks. RESULTS: In contrast to the GPE- or OFE-supplemented groups, the GPE+OFE group showed significantly lower body weight and white adipose tissue weights than the CON group. Moreover, GPE+OFE supplementation significantly decreased plasma total cholesterol and increased the plasma HDL-cholesterol/total-cholesterol ratio (HTR) compared to the control diet. The hepatic triglyceride level was significantly lower in the GPE+OFE and GPE groups by increasing beta-oxidation and decreasing lipogenic enzyme compared to the CON group. Furthermore, GPE+OFE supplementation significantly increased antioxidant enzyme activities with a simultaneous decrease in liver H2O2 content compared to the control diet. CONCLUSIONS: Together our results suggest that supplementation with the GPE+OFE mixture may be more effective in improving adiposity, lipid metabolism and oxidative stress in high-fat diet-fed mice than those with GPE and OFE alone.
Adipose Tissue, White ; Adiposity ; Animals ; Body Weight ; Cholesterol ; Diet ; Diet, High-Fat ; Ethanol* ; Fruit* ; Humans ; Lipid Metabolism* ; Liver ; Male ; Mice ; Mice, Obese* ; Oxidative Stress ; Plasma ; Triglycerides ; Vitis* ; Weights and Measures