Despite the availability of direct-acting antivirals (DAAs) for chronic hepatitis C virus (HCV) infection in Korea, need remains for pangenotypic regimens that can be used in the presence of hepatic impairment, comorbidities, or prior treatment failure. We investigated the efficacy and safety of sofosbuvir–velpatasvir and sofosbuvir–velpatasvir–voxilaprevir for 12 weeks in HCV-infected Korean adults. Methods: This Phase 3b, multicenter, open-label study included 2 cohorts. In Cohort 1, participants with HCV genotype 1 or 2 and who were treatment-naive or treatment-experienced with interferon-based treatments, received sofosbuvir–velpatasvir 400/100 mg/day. In Cohort 2, HCV genotype 1 infected individuals who previously received an NS5A inhibitor-containing regimen ≥ 4 weeks received sofosbuvir–velpatasvir–voxilaprevir 400/100/100 mg/day. Decompensated cirrhosis was an exclusion criterion. The primary endpoint was SVR12, defined as HCV RNA < 15 IU/mL 12 weeks following treatment. Results: Of 53 participants receiving sofosbuvir–velpatasvir, 52 (98.1%) achieved SVR12. The single participant who did not achieve SVR12 experienced an asymptomatic Grade 3 ASL/ALT elevation on day 15 and discontinued treatment. The event resolved without intervention. All 33 participants (100%) treated with sofosbuvir–velpatasvir–voxilaprevir achieved SVR 12. Overall, sofosbuvir–velpatasvir and sofosbuvir–velpatasvir–voxilaprevir were safe and well tolerated. Three participants (5.6%) in Cohort 1 and 1 participant (3.0%) in Cohort 2 had serious adverse events, but none were considered treatment-related. No deaths or grade 4 laboratory abnormalities were reported. Conclusions: Treatment with sofosbuvir–velpatasvir or sofosbuvir–velpatasvir–voxilaprevir was safe and resulted in high SVR12 rates in Korean HCV patients.

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.

For the data represented in Fig. 4B, we have generated a new figure from one of these repeat experiments.

PURPOSE: Caveolin-1 (CAV-1) expression is more associated with basal-like cancers than estrogen receptor- or ErbB-2-expressing breast cancers. However, the biological relevance of different levels of CAV-1 expression according to subtype in the epithelial compartment of breast cancer remains unclear. MATERIALS AND METHODS: We investigated whether CAV-1 functions as a tumor suppressor and/or modulator of the cytotoxic activity of docetaxel (DTX) in subtypes of breast cancer using in vitro and xenograft models. RESULTS: The levels of CAV-1 expression were closely associated with DTX sensitivity in triple-negative breast cancer cells. In addition, CAV-1 significantly inhibited cell proliferation and modulated DTX-induced apoptosis through cell cycle arrest in the G2/M phase. The mechanisms underlying DTX-induced apoptosis differed in breast cancers according to the levels of CAV-1 expression. DTX robustly enhanced Bcl-2 inactivation by CAV-1 in MDA-MB-231 cells, while p53-mediated cell cycle arrest by DTX was more pronounced in CAV-1-low but p53-functional MCF-7 cells. In parallel with the data from breast cancer cell lines, CAV-1-transfected MCF-7 cells showed higher efficacy of DTX treatment in a xenograft model. CONCLUSION: We clearly demonstrated cooperative effects between CAV-1 and DTX in mediating apoptosis, suggesting that the levels of CAV-1 expression might be an important indicator for DTX use in breast cancer.
Apoptosis ; Breast Neoplasms* ; Breast* ; Caveolin 1* ; Cell Cycle Checkpoints ; Cell Death* ; Cell Line ; Cell Proliferation ; Estrogens ; Heterografts ; MCF-7 Cells ; Negotiating ; Triple Negative Breast Neoplasms

BACKGROUND: Bronchopulmonary dysplasia (BPD) may result in chronic pulmonary artery hypertension and right ventricular (RV) dysfunction. Various echocardiographic assessments of RV dysfunction have been used to determine whether echocardiographic measurements of premature infants with BPD could provide sensitive measures of RV function that correlates with BPD severity. METHODS: Twenty-eight control subjects without BPD (non BPD group), 28 patients with mild BPD, 11 patients with moderate BPD, and six patients with severe BPD underwent echocardiograms with standard measurement such as ejection fraction by M-mode, tricuspid regurgitation pressure gradient, myocardial performance index (MPI) derived from pulse Doppler, and tissue Doppler imaging (TDI) measurements. BPD severity was classified by the NICHD/NHLBI/ORD workshop rating scale. Twenty-eight control subjects without BPD (non BPD group), 28 patients with mild BPD, 11 patients with moderate BPD, and six patients with severe BPD underwent echocardiograms with standard measurement such as ejection fraction by M-mode, tricuspid regurgitation pressure gradient, myocardial performance index (MPI) derived from pulse Doppler, and TDI measurements. BPD severity was classified by the NICHD/NHLBI/ORD workshop rating scale. RESULTS: None of the standard echocardiographic findings was significantly different between the control group and BPD groups. However, mean septal TDI-MPI of the severe BPD group (0.68 ± 0.06) was significantly (p < 0.01) higher than that of the non-BPD (0.58 ± 0.10) or the mild BPD group (0.59 ± 0.12). In addition, mean RV TDI-MPI of the severe BPD group (0.71 ± 0.13) was significantly (p < 0.05) higher than that of the non-BPD group (0.56 ± 0.08) or the mild BPD group (0.60 ± 0.125). Linear regression showed a good correlation between the severity of BPD and RV TDI-MPI (p = 0.01, R = 0.30) or septal TDI-MPI (p = 0.04, R = 0.24). CONCLUSION: Echocardiographic evaluation of RV function based on an assessment of RV TDI-MPI can provide RV dysfunction parameter in premature infants with BPD.
Bronchopulmonary Dysplasia ; Child* ; Diagnosis* ; Echocardiography* ; Education ; Humans ; Hypertension ; Infant, Newborn ; Infant, Premature ; Linear Models ; Prognosis* ; Pulmonary Artery ; Tricuspid Valve Insufficiency ; Ventricular Function, Right

Pregnant women with antiphospholipid syndrome (APS) carry a high risk of arterial or venous thrombosis. Such thrombotic conditions occur more frequently in patients with triple positivity to antiphospholipid antibodies or with high antibody titers. Hepatic infarction is a rare complication in pregnant women with APS, and it sometimes mimics HELLP syndrome. This report describes a preeclamptic pregnant woman with APS who had high titers of three antiphospholipid antibodies. She experienced severe epigastric pain with elevated liver enzymes; in addition, she had tachycardia and tachypnea. The clinical findings suggested hepatic infarction and pulmonary thromboembolism, a partial manifestation of catastrophic APS. Therefore, she underwent emergent cesarean section at 25+2 weeks of gestation. After the delivery, her laboratory test indicated HELLP-like features, and computed tomography confirmed hepatic infarction and pulmonary micro-thromboembolism. Here, we report a case of a partial manifestation of catastrophic APS in a pregnant woman with triple antibody positivity, including a brief literature review.
Antibodies, Antiphospholipid ; Antiphospholipid Syndrome* ; Cesarean Section ; Female ; HELLP Syndrome ; Humans ; Infarction* ; Liver ; Pregnancy ; Pregnant Women* ; Pulmonary Embolism ; Tachycardia ; Tachypnea ; Venous Thrombosis

Pregnant women with antiphospholipid syndrome (APS) carry a high risk of arterial or venous thrombosis. Such thrombotic conditions occur more frequently in patients with triple positivity to antiphospholipid antibodies or with high antibody titers. Hepatic infarction is a rare complication in pregnant women with APS, and it sometimes mimics HELLP syndrome. This report describes a preeclamptic pregnant woman with APS who had high titers of three antiphospholipid antibodies. She experienced severe epigastric pain with elevated liver enzymes; in addition, she had tachycardia and tachypnea. The clinical findings suggested hepatic infarction and pulmonary thromboembolism, a partial manifestation of catastrophic APS. Therefore, she underwent emergent cesarean section at 25+2 weeks of gestation. After the delivery, her laboratory test indicated HELLP-like features, and computed tomography confirmed hepatic infarction and pulmonary micro-thromboembolism. Here, we report a case of a partial manifestation of catastrophic APS in a pregnant woman with triple antibody positivity, including a brief literature review.
Antibodies, Antiphospholipid ; Antiphospholipid Syndrome* ; Cesarean Section ; Female ; HELLP Syndrome ; Humans ; Infarction* ; Liver ; Pregnancy ; Pregnant Women* ; Pulmonary Embolism ; Tachycardia ; Tachypnea ; Venous Thrombosis

Total anomalous pulmonary venous return (TAPVR) is a rare and critical congenital vascular anomaly that requires an early operation. However, initial symptoms of TAPVR may be non-specific, and cardiovascular findings may be minimal. The heart may not be enlarged and there is often no cardiac murmur. Without cardiac murmur, these symptoms are similar to those of respiratory distress syndrome in newborns. Therefore, a high degree of suspicion and an early diagnosis of TAPVR are important. This condition generally occurs without a family history and has a low recurrence rate, but several familial cases, including siblings, have been reported worldwide. Additionally, several chromosomal or gene abnormalities associated with TAPVR have been reported. In the case presented here, two brothers with a 6-year age gap were diagnosed with TAPVR. Surgery was performed without cardiac or neurological complications. This is the first report on TAPVR in siblings in Korea.
Early Diagnosis ; Heart ; Heart Murmurs ; Humans ; Infant, Newborn ; Korea ; Recurrence ; Scimitar Syndrome* ; Siblings*

PURPOSE: Indomethacin has been reported as the prophylaxis and initial treatment of preterm infants with patent ductus arteriosus (PDA). However, there was controversy over indomethacin treatment in full-term infants with symptomatic PDA. Therefore, we evaluate the effect of indomethacin as a treatment of full-term infants with symptomatic PDA. METHODS: A retrospective study was performed to evaluate the effectiveness of indomethacin in full-term infants who had birth weight > or =2,500 g and a gestational age > or =37 weeks with symptomatic PDA at Chonnam National University Hospital between January 2007 and December 2009. According to responsiveness of indomethacin, we classified them into three groups: 1) complete responder which were completely closed after indomethacin treatment, 2) partial responder which were incompletely closed but symptoms were improved, 3) non responder which were conducted surgical ligation because did not respond. RESULTS: Among the total 29 full-term infants treated with indomethacin, 13 (44.8%) were complete responder, 8 (27.6%) were partial responder, and 8 (27.6%) were non responder. There were no significant differences in birth weight, narrow diameter of PDA, and dose of indomethacin between three groups. However, the age at initiation of treatment using indomethacin of complete (4.8+/-4.5 days, P=0.03) and partial responder (6.3+/-2.0 days, P=0.04) were earlier than those of non responder (13.8+/-8.1 days). CONCLUSION: Indomethacin can expect an effective treatment of PDA in full-term infants prior to surgical ligation.
Birth Weight ; Ductus Arteriosus, Patent* ; Gestational Age ; Humans ; Indomethacin* ; Infant* ; Infant, Newborn ; Infant, Premature ; Jeollanam-do ; Ligation ; Retrospective Studies

PURPOSE: To re-evaluate additional clinical significance of the apparent diffusion coefficient (ADC) map in the inference of infarction stage, authors studied the evolution patterns of the DWI and the ADC map of the brain infarction. MATERIALS AND METHODS: In 127 patients with cerebral infarctions, including follow-up checks, 199 studies were performed. They were classified as hourly (117 studies)-, daily (108 studies)-, weekly (62 studies)-based groups. The signal intensity (SI) was measured at the core of the infarction and contralateral area with ROI of 0.3 cm2 or more on the images of the DWI and the ADC map, and calculated the ratios of SI and ADC value of the infarction area / contralateral normal area, and compared the patterns of the change according to the evolution. RESULTS: Infarction was detected as early as 1 hour after the attack, and the ratio of SI in the DWI became over than 2 after 12 hours, which showed a plateau until the 6th day. Thereafter, it decreased slowly to 1 on the 30th day, and changed to lower SI than the surrounding brain. The ratio in the ADC map became 0.46 in 24 hours after the attack, and increased slowly to 1 in the 15th day. Thereafter, it became a higher value than the surrounding brain. Overall, the ratio in the ADC map changed earlier than in the DWI, and the ratio curves showed inverse pattern each other according to the evolution of the infarction. CONCLUSION: The evolution patterns of infarction on the ADC map showed an inverse curve of DWI curve, which means that the ADC value is accurately predictable from DWI, and the ADC map joined with the DWI seems helpful in the determination of subacute infarction between 15 to 30 days.
Brain Infarction* ; Brain* ; Cerebral Infarction ; Diffusion ; Follow-Up Studies ; Humans ; Infarction