Background: Tenofovir disoproxil fumarate (TDF, Viread® ) had been used as a standard treatment option of chronic hepatitis B (CHB). This clinical trial was conducted to evaluate the efficacy and safety of DA-2802 (tenofovir disoproxil orotate) compared to TDF. Methods: The present study was a double blind randomized controlled trial. Patients with CHB were recruited from 25 hospitals in Korea and given DA-2802 at a dose of 319 mg once daily or Viread® at a dose of 300 mg once daily for 48 weeks from March 2017 to January 2019. Change in hepatitis B virus (HBV) DNA level at week 48 after dosing compared to baseline was the primary efficacy endpoint. Secondary efficacy endpoints were proportions of subjects with undetectable HBV DNA, those with normal alanine aminotransferase (ALT) levels, and those with loss of hepatitis B envelop antigen (HBeAg), those with loss of hepatitis B surface antigen (HBsAg). Adverse events (AEs) were also investigated. Results: A total of 122 patients (DA-2802 group: n = 61, Viread® group: n = 61) were used as full analysis set for efficacy analysis. Mean age, proportion of males, laboratory results and virologic characteristics were not different between the two groups. The change in HBV DNA level at week 48 from baseline was −5.13 ± 1.40 in the DA-2802 group and −4.97 ± 1.40 log 10 copies/mL in the Viread® group. The analysis of primary endpoint using the nonparametric analysis of covariance showed statistically significant results (P < 0.001), which confirmed non-inferiority of DA-2802 to Viread® by a prespecified noninferiority margin of 1. The proportion of undetectable HBV DNA was 78.7% in the DA-2802 group and 75.4% in the Viread® group (P = 0.698). The proportion of subjects who had normal ALT levels was 75.4% in the DA-2802 group and 73.3% in the Viread® group (P = 0.795). The proportion of those with HBeAg loss was 8.1% in the DA-2802 group and 10.8% in the Viread® group (P = 1.000). No subject showed HBsAg loss. The frequency of AEs during treatment was similar between the two groups. Most AEs were mild to moderate in severity. Conclusion DA-2802 is considered an effective and safe treatment for patients with CHB.

PURPOSE: The information committee of the Korean Society for Metabolic and Bariatric Surgery (KSMBS) performed the nationwide survey of bariatric and metabolic operations to report IFSO (International Federation for the Surgery of Obesity and Metabolic Disorders) worldwide survey annually. This study aimed to report the trends of bariatric and metabolic surgery in Korea in 2014–2017. MATERIALS AND METHODS: We analyzed the accumulated nationwide survey data conducted for annual ISFO survey from 2014 to 2017. Trends such as the number of operations by hospital type and the number of operations by surgical method were analyzed. RESULTS: The number of operations has decreased sharply in 2015 comparing to 2014 (913⇒550). The number of operations performed in private hospitals dropped sharply from 529 to 250, 198, and 103 cases. The number of revisional surgeries increased to 223 in 2015. The primary surgery number fell from 757 in 2014 to 327 in 2015. In primary surgery, sleeve gastrectomy was gradually increased from 2014 to 143 (18.9%), 105 (32.1%), 167 (47.2%) and 200 (56.3%) and became the most frequently performed surgery. On the other hand, the incidence of adjustable gastric band decreased gradually from 439 (58.0%) to 117 (35.8%), 112 (31.6%) and 59 (16.6%). CONCLUSION: The overall number of obesity metabolic operations has decreased since 2014, especially the number of adjustable gastric band, and the number of operations in private hospitals declined sharply. On the other hand, the number of operations in university hospitals did not change much, and the number of sleeve gastrectomy increased.
Bariatric Surgery ; Gastrectomy ; Hand ; Hospitals, Private ; Hospitals, University ; Incidence ; Korea ; Methods ; Obesity

BACKGROUND/AIMS: The diagnosis of chronic thromboembolic pulmonary hypertension (CTEPH) is difficult for numerous reasons and is related with a poor prognosis. In Korea, the incidence of CTEPH and its clinical features are unknown. Thus, in this study, we evaluated the clinical characteristics and outcomes of CTEPH in a Korean cohort. METHODS: This study included South Korean patients diagnosed with CTEPH between September 2008 and October 2011. Baseline characteristics, treatments and outcomes were analyzed. RESULTS: A total of 134 patients were included in this study with 76 females (56.7%). Their median age was 58.3 +/- 15.9 years and dyspnea (112 patients, 83.5%) was the most common presenting symptom. Sixty-three patients (47%) had a history of acute pulmonary embolism or deep vein thrombosis, and six (4.5%) had pulmonary tuberculosis. In total, 28 patients (21%) underwent pulmonary thromboendarterectomy (PTE), and 99 patients had medical therapy. During the study period, 18 patients (13.4%) died. In a multivariate analysis, higher hemoglobin (relative risk [RR], 1.516; 95% confidence interval [CI], 1.053 to 2.184; p = 0.025) and lower total cholesterol levels (RR, 0.982; 95% CI, 0.965 to 0.999; p = 0.037) were associated with increased mortality. CONCLUSIONS: This was the first national cohort study of Korean patients with CTEPH. Accurate diagnosis, characterization and distributions of CTEPH are imperative for prompt treatment in patients, particularly those undergoing PTE.
Adult ; Aged ; Antihypertensive Agents/therapeutic use ; Chi-Square Distribution ; Chronic Disease ; Drug Therapy, Combination ; Endarterectomy ; Female ; Humans ; Hypertension, Pulmonary/diagnosis/*epidemiology/mortality/therapy ; Logistic Models ; Male ; Middle Aged ; Multivariate Analysis ; Odds Ratio ; Prevalence ; Prospective Studies ; Pulmonary Embolism/diagnosis/*epidemiology/mortality/therapy ; Registries ; Republic of Korea/epidemiology ; Retrospective Studies ; Risk Factors ; Time Factors ; Treatment Outcome

BACKGROUND: Detailed profiles of acute hypothermia and electrocardiographic (ECG) manifestations of arrhythmogenicity were examined to analyze acute hypothermia and ventricular arrhythmogenic potential immediately after portal vein unclamping (PVU) in living-donor liver transplantation (LT). METHODS: We retrospectively analyzed electronically archived medical records (n = 148) of beat-to-beat ECG, arterial pressure waveforms, and blood temperature (BT) from Swan-Ganz catheters in patients undergoing living-donor LT. The ECG data analyzed were selected from the start of BT drop to the initiation of systolic hypotension after PVU. RESULTS: On reperfusion, acute hypothermia of < 34degrees C, < 33degrees C and < 32degrees C developed in 75.0%, 37.2% and 11.5% of patients, respectively. BT decreased from 35.0degrees C +/- 0.8degrees C to 33.3degrees C +/- 1.0degrees C (range 35.8degrees C-30.5degrees C). The median time to nadir of BT was 10 s after PVU. Difference in BT (DeltaBT) was weakly correlated with graft-recipient weight ratio (GRWR; r = 0.22, P = 0.008). Compared to baseline, arrhythmogenicity indices such as corrected QT (QTc), Tp-e (T wave peak to end) interval, and Tp-e/QTc ratio were prolonged (P < 0.001 each). ST height decreased and T amplitude increased (P < 0.001 each). However, no correlation was found between DeltaBT and arrhythmogenic indices. CONCLUSIONS: In living-donor LT, regardless of extent of BT drop, ventricular arrhythmogenic potential developed immediately after PVU prior to occurrence of systolic hypotension.
Arrhythmias, Cardiac ; Arterial Pressure ; Catheters ; Electrocardiography ; Humans ; Hypotension* ; Hypothermia ; Liver Transplantation* ; Liver* ; Medical Records ; Portal Vein ; Reperfusion* ; Retrospective Studies ; Transplants*

OBJECTIVES: Neuroblastoma (NBL) predominantly affects children under 5 years of age. Through multimodal therapy, including chemotherapy, radiotherapy, surgery, and peripheral blood stem cell transplantation, the survival rate in patients with NBL have improved while treatment-related complications have also increased. Treatment-related ototoxicity, mainly from cisplatin, can result in profound hearing loss requiring cochlear implantation (CI). We analyzed the effectiveness and hearing preservation of CI recipients who had treated with multimodal therapy due to NBL. METHODS: Patients who received multimodal therapy for NBL and subsequent CIs were enrolled. A detailed review of the perioperative hearing test, speech evaluation, and posttreatment complications was conducted. Speech performance was analyzed using the category of auditory performance (CAP) score and the postoperative hearing preservation of low frequencies was also compared. Patients who were candidates for electro-acoustic stimulation (EAS) used an EAS electrode for low frequency hearing preservation. RESULTS: Three patients were identified and all patients showed improvement of speech performance after CI. The average of CAP score improved from 4.3 preoperatively to 5.8 at 1 year postoperatively. Two patients who were fitted with the Flex electrode showed complete hearing preservation and the preserved hearing was maintained over 1 year. The one remaining patient was given the standard CI-512 electrode and showed partial hearing preservation. CONCLUSION: Patients with profound hearing loss resulting from NBL multimodal therapy can be good candidates for CI, especially for EAS. A soft surgical technique as well as a specifically designed electrode should be applied to this specific population during the CI operation in order to preserve residual hearing and achieve better outcomes.
Child* ; Cisplatin ; Cochlear Implantation* ; Cochlear Implants* ; Combined Modality Therapy* ; Drug Therapy ; Electrodes ; Hearing Loss* ; Hearing Tests ; Hearing* ; Humans ; Neuroblastoma* ; Peripheral Blood Stem Cell Transplantation ; Radiotherapy ; Survival Rate

BACKGROUND: Low levels of serum vitamin D is associated with several lung diseases. The production and activation of matrix metalloproteinases (MMPs) may play an important role in the pathogenesis of emphysema. The aim of the current study therefore is to investigate if vitamin D modulates the expression and activation of MMP-2 and MMP-9 in human lung fibroblasts (HFL-1) cells. METHODS: HFL-1 cells were cast into three-dimensional collagen gels and stimulated with or without interleukin-1beta (IL-1beta) in the presence or absence of 100 nM 25-hydroxyvitamin D (25(OH)D) or 1,25-dihydroxyvitamin D (1,25(OH)2D) for 48 hours. Trypsin was then added into the culture medium in order to activate MMPs. To investigate the activity of MMP-2 and MMP-9, gelatin zymography was performed. The expression of the tissue inhibitor of metalloproteinase (TIMP-1, TIMP-2) was measured by enzyme-linked immunosorbent assay. Expression of MMP-9 mRNA and TIMP-1, TIMP-2 mRNA was quantified by real time reverse transcription polymerase chain reaction. RESULTS: IL-1beta significantly stimulated MMP-9 production and mRNA expression. Trypsin converted latent MMP-2 and MMP-9 into their active forms of MMP-2 (66 kDa) and MMP-9 (82 kDa) within 24 hours. This conversion was significantly inhibited by 25(OH)D (100 nM) and 1,25(OH)2D (100 nM). The expression of MMP-9 mRNA was also significantly inhibited by 25(OH)D and 1,25(OH)2D. CONCLUSION: Vitamin D, 25(OH)D, and 1,25(OH)2D play a role in regulating human lung fibroblast functions in wound repair and tissue remodeling through not only inhibiting IL-1beta stimulated MMP-9 production and conversion to its active form but also inhibiting IL-1beta inhibition on TIMP-1 and TIMP-2 production.
Collagen ; Emphysema ; Enzyme-Linked Immunosorbent Assay ; Fibroblasts* ; Gelatin ; Gels ; Humans ; Interleukin-1beta ; Lung Diseases ; Lung* ; Matrix Metalloproteinase 9 ; Matrix Metalloproteinases ; Polymerase Chain Reaction ; Reverse Transcription ; RNA, Messenger ; Tissue Inhibitor of Metalloproteinase-1 ; Tissue Inhibitor of Metalloproteinase-2 ; Trypsin ; Vitamin D* ; Wounds and Injuries

BACKGROUND: Early oral intake (EOI) associated with early recovery of normal bowel function has been shown to be an important determinant for improving patients' satisfaction. We investigated the tolerability of EOI and its effects on the recovery of bowel function after epidural anesthesia. METHODS: A prospective randomized trial of patients undergoing lower extremities surgery under epidural anesthesia was performed. A liquid drink was given to 150 patients in the EOI group 1 hours after surgery, and to 150 patients in the delayed oral intake (DOI) group 8 hours after surgery. We recorded presence of bowel sounds immediately after operation, symptoms of ileus, time to the first flatus, time to the first defecation, degree of appetite before the first meal, and patients' satisfaction. RESULTS: There was no significant difference in the presence of immediate postoperative bowel sounds, the degree of appetite before the first meal, mild ileus, and severe ileus between groups. Time to the first flatus and time to the first defecation in the EOI group were shorter than those of the DOI group. The patients' satisfaction in the EOI group was higher than that of the DOI group. CONCLUSIONS: For uncomplicated patients undergoing lower extremities under epidural anesthesia, beginning oral hydration as early as 1 hour after the operation is safe and well tolerated and resulting in faster recovery of bowel function and higher patients' satisfaction.
Anesthesia, Epidural ; Appetite ; Defecation ; Flatulence ; Humans ; Ileus ; Lower Extremity ; Meals ; Prospective Studies

BACKGROUND: Human skin is exposed to various environmental stresses, such as heat, cold, and ultraviolet (UV) radiation. Heat shock proteins (HSPs) induced by temperature elevations, as a physiologic response to mediate repair mechanisms and reduce cellular damage. OBJECTIVE: The purpose of this study was to investigate the induction of HSPs in human skin cells after UV exposure. METHODS: We performed immunoblotting using a specific monoclonal antibody to the HSP70 family, one of the best-conserved stress proteins in humans, with cultured normal human keratinocytes, A431 cells, human melanocytes, SK30 cells, and human dermal fibroblasts (HDF). RESULTS: Our results indicated that high expression of HSP70 in the unstressed state was noted in epidermal cells, including normal human keratinocytes, A431 cells, human melanocytes, and SK30 cells, but epidermal cells showed no additional up-regulation of HSP70 after UV irradiation. On the other hand, HDF expressed very small amounts of HSP70 at baseline, but significantly higher amounts of HSP70 after UV exposure. CONCLUSION: These findings suggest that constitutive expression of HSP70 in epidermal cells may be an important mechanism for protection of the human epidermis from environmental stresses, such as sunlight exposure.
Cold Temperature ; Epidermis ; Fibroblasts ; Hand ; Heat-Shock Proteins ; Hot Temperature ; HSP70 Heat-Shock Proteins ; Humans ; Immunoblotting ; Keratinocytes ; Melanocytes ; Skin ; Sunlight ; Up-Regulation

Hobnail hemangioma is a benign vascular tumor that typically presents as a small, single lesion on the skin of the trunk or limb. It occurs mainly in young or middle-aged adults (mean age: 30 years) but rarely in childhood. Histologically, hobnail hemangioma is characterized by a biphasic growth pattern, with dilated vascular spaces lined by hobnail endothelial cells in the superficial dermis, and collagen dissection narrow vascular channels in the deeper dermal parts, as well as inflammatory aggregates, fibrosis, and hemosiderin deposits. We report a case of hobnail hemangioma in a 10-year-old girl who had a violaceous papule surrounded by an ecchymotic halo on the left thigh. She underwent treatment with surgical excision with primary closure. To the best of our knowledge, our case is the first reported case of childhood hobnail hemangioma in Korean dermatological literatures.
Adult ; Child ; Collagen ; Dermis ; Endothelial Cells ; Extremities ; Female ; Fibrosis ; Hemangioma* ; Hemosiderin ; Humans ; Skin ; Thigh

BACKGROUND: Pemphigus vulgaris is an autoimmune bullous dermatoses of skin and mucosa characterized by loss of adhesion between keratinocytes, a process known as acantholysis. Apoptosis, programmed cell death, may participate in pathogenesis of intercellular detachment and loss of cell-matrix interaction. OBJECTIVE: This study was designed to investigate the induction of apoptosis in the pemphigus lesional epidermis and to elucidate the mechanism of apoptosis induced by pemphigus sera. METHODS: Hoechst 33342 staining was performed to determine the induction of apoptosis in the pemphigus lesional epidermis. In addition, we used HaCaT cells treated with pemphigus sera and analyzed the expression of caspase-3, caspase-8, caspase-9 and bcl-2, bcl-xL, bax, bak by the RT-PCR method. RESULTS: In Hoechst 33342 staining, typical findings of apoptosis were observed in the pemphigus lesional epidermis showing acantholysis. RT-PCR showed the upregulation of caspase group (caspase-3, caspase-8, caspase-9), the downregulation of antiapoptotic bcl-2 family (bcl-2, bcl-xL) and the upregulation of proapoptotic bcl-2 family (bax, bak). CONCLUSION: These results suggest that apoptosis may be associated with acantholysis of pemphigus lesional epidermis and may play an important role in the pathogenesis of pemphigus.
Acantholysis ; Apoptosis* ; Caspase 3 ; Caspase 8 ; Caspase 9 ; Cell Death ; Down-Regulation ; Epidermis ; Humans ; Keratinocytes ; Mucous Membrane ; Pemphigus* ; Skin ; Skin Diseases, Vesiculobullous ; Up-Regulation