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 prevalence of asthma in the elderly is rapidly increasing. However, we do not fully understand the pathogenesis of elderly asthma, especially for the roles of micronutrients. This study aimed to evaluate the associations between serum levels of micronutrients, including several vitamins and minerals, and clinical features of the elderly asthmatics. METHODS: A total of 317 asthmatics aged 65 or older were enrolled. Serum levels of vitamin D, vitamin B₁₂, folate, Mg, and Se were measured and then the associations between serum micronutrient levels and clinical features of elderly asthmatics were evaluated. RESULTS: Positive correlations with significance among serum levels of vitamin B₁₂, vitamin D, and folate were found. Serum micronutrients levels showed no difference according to the atopic status and symptom severity. The serum folate level was significantly associated with forced expiratory volume in 1 second, and serum vitamin B₁₂ and folate levels were significantly associated with serum total IgE level. Interestingly, elderly asthmatics with exacerbation history showed significantly lower serum levels of vitamin D and Mg, but significantly higher serum levels of Se. CONCLUSION: Serum levels of micronutrients, such as vitamin D, vitamin B₁₂, Mg, folate, and Se, were significantly associated with some clinical features of elderly asthmatics. Clinical meanings of these associations need to be investigated further.
Aged* ; Asthma ; Folic Acid ; Forced Expiratory Volume ; Humans ; Immunoglobulin E ; Micronutrients* ; Minerals ; Miners ; Prevalence ; Vitamin D ; Vitamins

PURPOSE: Patient-derived tumor xenografts (PDXs) can provide more reliable information about tumor biology than cell line models. We developed PDXs for epithelial ovarian cancer (EOC) that have histopathologic and genetic similarities to the primary patient tissues and evaluated their potential for use as a platform for translational EOC research. MATERIALS AND METHODS: We successfully established PDXs by subrenal capsule implantation of primary EOC tissues into female BALB/C-nude mice. The rate of successful PDX engraftment was 48.8% (22/45 cases). Hematoxylin and eosin staining and short tandem repeat analysis showed histopathological and genetic similarity between the PDX and primary patient tissues. RESULTS: Patients whose tumors were successfully engrafted in mice had significantly inferior overall survival when compared with those whose tumors failed to engraft (p=0.040). In preclinical tests of this model, we found that paclitaxel-carboplatin combination chemotherapy significantly deceased tumor weight in PDXs compared with the control treatment (p=0.013). Moreover, erlotinib treatment significantly decreased tumor weight in epidermal growth factor receptor–overexpressing PDX with clear cell histology (p=0.023). CONCLUSION: PDXs for EOC with histopathological and genetic stability can be efficiently developed by subrenal capsule implantation and have the potential to provide a promising platform for future translational research and precision medicine for EOC.
Animals ; Biology ; Cell Line ; Drug Therapy, Combination ; Eosine Yellowish-(YS) ; Epidermal Growth Factor ; Erlotinib Hydrochloride ; Female ; Hematoxylin ; Heterografts* ; Humans ; Mice ; Microsatellite Repeats ; Molecular Targeted Therapy ; Ovarian Neoplasms* ; Precision Medicine ; Translational Medical Research ; Tumor Burden

PURPOSE: We aimed to translate the Test for Respiratory and Asthma Control in Kids (TRACK) instrument into Korean, with subsequent linguistic validation. METHODS: The multistep process of forward translation, reconciliation, back-translation, cognitive debriefing, and proofreading of the Korean version of the TRACK was completed. RESULTS: Two bilingual medical personnel independently translated the original English version of the TRACK into Korean one. After moderating the translation into a single reconciled one, 4 other bilingual persons were invited to translate the Korean draft back into an English one. Discrepancies between the original English version and the back-translated one were reviewed, and the need to modify the reconciled Korean draft was discussed. Twenty caregivers of asthmatic children took part in interviews that examine the appropriateness of the Korean version of the TRACK. The feedback from caregivers were then reviewed by a panel of pediatric allergists and reflected in the final Korean version. The document was finally proofread to check the spelling, grammar, layout and formatting. CONCLUSION: Translation and linguistic validation of the Korean version of the TRACK instrument were completed.
Asthma* ; Caregivers ; Child ; Humans ; Linguistics* ; Translations

PURPOSE: Although home renovation exposure during childhood has been identified as a risk factor for the development of allergy, there is limited information on the association between prenatal exposure to home renovation and cord blood (CB) IgE response. The aims of this study were to identify the effect of prenatal exposure to home renovation on CB IgE levels, and to investigate whether this exposure interacts with neonatal genes and whether the effect can be modified by maternal atopy. METHODS: This study included 1,002 mother-neonate pairs from the COhort for Childhood Origin of Asthma and allergic diseases (COCOA). Prenatal environmental factors were collected using a questionnaire. The levels of CB IgE were measured by the ImmunoCAP system, and DNA was extracted from CB. RESULTS: Exposure to home renovation during the prenatal period was associated with significantly higher levels of CB IgE only in neonates from atopic mothers, and the effect of renovation exposure on CB IgE levels persisted from 31 months before birth. Furthermore, prenatal exposure to home renovation increased the risk of CB IgE response interacting with polymorphisms of NRF2 and GSTP1 genes only in neonates from atopic mothers. CONCLUSIONS: Maternal atopy modified the effect of prenatal exposure to home renovation on CB serum IgE response as well as the interaction between the exposure and neonatal genes involved in the oxidative stress pathway. These findings suggest that the genetically susceptible offspring of atopic mothers may be more vulnerable to the effect of prenatal exposure to home renovation on the development of allergy.
Asthma ; Cohort Studies ; DNA ; Fetal Blood* ; Gene-Environment Interaction ; Humans ; Hypersensitivity ; Immunoglobulin E* ; Infant, Newborn ; Mothers ; Oxidative Stress ; Parturition ; Polymorphism, Single Nucleotide ; Reactive Oxygen Species* ; Risk Factors

Microbial colonization of the infant gut is unstable and shows a wide range of diversity between individuals. Gut microbiota play an important role in the development of the immune system, and an imbalance in these organisms can affect health, including an increased risk of allergic diseases. Microbial colonization of young infants is affected by the delivery mode at birth and the consequent alterations of gut microbiota in early life affect the development of allergic diseases. We investigated the effects of the delivery mode on the temporal dynamics of gut microbiota in healthy Korean infants. Fecal samples were collected at 1-3 days, 1 month, and 6 months after birth in six healthy infants. Microbiota were characterized by 16S rRNA shotgun sequencing. At the first and third days of life, infants born by vaginal delivery showed a higher richness and diversity of gut microbiota compared with those born by cesarean section. However, these differences disappeared with age. The Bacteroides genus and Bacteroidetes phylum were abundant in infants born by vaginal delivery, whereas Bacilli and Clostridium g4 were increased in infants born by cesarean section. The Firmicutes phylum and Bacteroides genus showed convergent dynamics with age. This study demonstrated the effect of delivery mode on the dynamics of gut microbiota profiles in healthy Korean infants.
Bacteroides ; Bacteroidetes ; Cesarean Section ; Clostridium ; Colon ; Female ; Firmicutes ; Gastrointestinal Microbiome* ; Humans ; Immune System ; Infant* ; Microbiota ; Parturition ; Pregnancy

OBJECTIVE: This multi-center, randomized, double-blind, phase 3 trial was conducted to compare the safety and efficacy of contrast agents iohexol-380 and iohexol-350 for coronary CT angiography in healthy subjects. MATERIALS AND METHODS: Volunteers were randomized to receive 420 mgI/kg of either iohexol-350 or iohexol-380 using a flow rate of 4 mL/sec. All adverse events were recorded. Two blinded readers independently reviewed the CT images and conflicting results were resolved by a third reader. Luminal attenuations (ascending aorta, left main coronary artery, and left ventricle) in Hounsfield units (HUs) and image quality on a 4-point scale were calculated. RESULTS: A total of 225 subjects were given contrast media (115 with iohexol-380 and 110 with iohexol-350). There was no difference in number of adverse drug reactions between groups: 75 events in 56 (48.7%) of 115 subjects in the iohexol-380 group vs. 74 events in 51 (46.4%) of 110 subjects in the iohexol-350 group (p = 0.690). No severe adverse drug reactions were recorded. Neither group showed an increase in serum creatinine. Significant differences in mean density between the groups was found in the ascending aorta: 375.8 ± 71.4 HU with iohexol-380 vs. 356.3 ± 61.5 HU with iohexol-350 (p = 0.030). No significant differences in image quality scores between both groups were observed for all three anatomic evaluations (all, p > 0.05). CONCLUSION: Iohexol-380 provides improved enhancement of the ascending aorta and similar attenuation of the coronary arteries without any increase in adverse drug reactions, as compared with iohexol-350 using an identical amount of total iodine.
Angiography* ; Aorta ; Contrast Media ; Coronary Vessels ; Creatinine ; Drug-Related Side Effects and Adverse Reactions ; Image Enhancement ; Iodine ; Phenobarbital ; Volunteers

PURPOSE: To investigate whether prenatal exposure to indoor fine particulate matter (PM2.5) and environmental tobacco smoke (ETS) affects susceptibility to respiratory tract infections (RTIs) in infancy, to compare their effects between prenatal and postnatal exposure, and to determine whether genetic factors modify these environmental effects. METHODS: The study population consisted of 307 birth cohort infants. A diagnosis of RTIs was based on parental report of a physician's diagnosis. Indoor PM2.5 and ETS levels were measured during pregnancy and infancy. TaqMan was used for genotyping of nuclear factor erythroid 2-related factor (Nrf2) (rs6726395), glutathione-S-transferase-pi (GSTP) 1 (rs1695), and glutathione-S-transferase-mu (GSTM) 1. Microarrays were used for genome-wide methylation analysis. RESULTS: Prenatal exposure to indoor PM2.5 increased the susceptibility of lower RTIs (LRTIs) in infancy (adjusted odds ratio [aOR]=2.11). In terms of combined exposure to both indoor PM2.5 and ETS, prenatal exposure to both pollutants increased susceptibility to LRTIs (aOR=6.56); however, this association was not found for postnatal exposure. The Nrf2 GG (aOR=23.69), GSTM1 null (aOR=8.18), and GSTP1 AG or GG (aOR=7.37) genotypes increased the combined LRTIs-promoting effects of prenatal exposure to the 2 indoor pollutants. Such effects of prenatal indoor PM2.5 and ETS exposure were not found for upper RTIs. CONCLUSIONS: Prenatal exposure to both indoor PM2.5 and ETS may increase susceptibility to LRTIs. This effect can be modified by polymorphisms in reactive oxygen species-related genes.
Cacao* ; Cohort Studies ; Diagnosis ; Genotype ; Humans ; Infant ; Methylation ; Odds Ratio ; Oxygen ; Parents ; Particulate Matter ; Parturition ; Pregnancy ; Respiratory Tract Infections* ; Smoke* ; Tobacco