Viral load and the duration of viral shedding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are important determinants of the transmission of coronavirus disease 2019.In this study, we examined the effects of viral doses on the lung and spleen of K18-hACE2 transgenic mice by temporal histological and transcriptional analyses. Approximately, 1×105 plaque-forming units (PFU) of SARS-CoV-2 induced strong host responses in the lungs from 2 days post inoculation (dpi) which did not recover until the mice died, whereas responses to the virus were obvious at 5 days, recovering to the basal state by 14 dpi at 1×102 PFU. Further, flow cytometry showed that number of CD8+ T cells continuously increased in 1×102 PFU-virusinfected lungs from 2 dpi, but not in 1×105 PFU-virus-infected lungs. In spleens, responses to the virus were prominent from 2 dpi, and number of B cells was significantly decreased at 1×105PFU; however, 1×102 PFU of virus induced very weak responses from 2 dpi which recovered by 10 dpi. Although the defense responses returned to normal and the mice survived, lung histology showed evidence of fibrosis, suggesting sequelae of SARS-CoV-2 infection. Our findings indicate that specific effectors of the immune response in the lung and spleen were either increased or depleted in response to doses of SARS-CoV-2. This study demonstrated that the response of local and systemic immune effectors to a viral infection varies with viral dose, which either exacerbates the severity of the infection or accelerates its elimination.

BACKGROUND/AIMS: Previous studies have reported a high rate of sustained virologic response (SVR) and a low rate of serious adverse events with the use of daclatasvir (DCV) and asunaprevir (ASV) combination therapy. We evaluated the efficacy and safety of DCV and ASV combination therapy for patients with chronic hepatitis C virus (HCV) genotype 1b infection in real world. METHODS: We enrolled 278 patients (184 treatment-naïve patients) from five hospitals in Daegu and Gyeongsangbuk-do. We evaluated the rates of rapid virologic response (RVR), end-of-treatment response (ETR), and SVR at 12 weeks after completion of treatment (SVR12). Furthermore, we investigated the rate of adverse events and predictive factors of SVR12 failure. RESULTS: The mean age of patients was 59.5 ± 10.6 years, and 140 patients (50.2%) were men. Seventy-seven patients had cirrhosis. Baseline information regarding nonstructural protein 5A (NS5A) sequences was available in 268 patients. Six patients presented with pretreatment NS5A resistance-associated variants. The RVR and the ETR rates were 96.6% (258/267) and 95.2% (223/232), respectively. The overall SVR12 rate was 91.6% (197/215). Adverse events occurred in 17 patients (7.9%). Six patients discontinued treatment because of liver enzyme elevation (n = 4) and severe nausea (n = 2). Among these, four achieved SVR12. Other adverse events observed were fatigue, headache, diarrhea, dizziness, loss of appetite, skin rash, and dyspnea. Univariate analysis did not show significant predictive factors of SVR12 failure. CONCLUSIONS DCV and ASV combination therapy showed high rates of RVR, ETR, and SVR12 in chronic HCV genotype 1b-infected patients in real world and was well tolerated without serious adverse events.

BackgroundUntil now, various types of combined therapy with nucleotide analogs and pegylated interferon (Peg-INF) in patients with hepatitis B patients have been tried. However, studies regarding the benefits of de novo combination, late-add on, and sequential treatment are very limited. The objective of the current study was to identify the efficacy of sequential treatment of Peg-INF after short-term antiviral treatment.

MethodsBetween June 2010 and June 2015, hepatitis B e antigen (HBeAg)-positive patients (n = 162) received Peg-IFN for 48 weeks (mono-treatment group, n = 81) and entecavir (ETV) for 12 weeks with a 48-week course of Peg-IFN starting at week 5 of ETV therapy (sequential treatment group, n = 81). The primary endpoint was HBeAg seroconversion at the end of follow-up period after the 24-week treatment. The primary endpoint was analyzed using Chi-square test, Fisher's exact test, and regression analysis.

ResultsHBeAg seroconversion rate (18.2% vs. 18.2%, t = 0.03, P = 1.000) and seroclearance rate (19.7% vs. 19.7%, t = 0.03, P = 1.000) were same in both mono-treatment and sequential treatment groups. The rate of alanine aminotransferase (ALT) normalization (45.5% vs. 54.5%, t = 1.12, P = 0.296) and serum hepatitis B virus (HBV)-DNA <2000 U/L (28.8% vs. 28.8%, t = 0.10, P = 1.000) was not different in sequential and mono-treatment groups at 24 weeks of Peg-INF. Viral response rate (HBeAg seroconversion and serum HBV-DNA <2000 U/L) was not different in the two groups (12.1% vs. 16.7%, t = 1.83, P = 0.457). Baseline HBV-DNA level (7 logU/ml vs. 7.5 logU/ml, t = 1.70, P = 0.019) and hepatitis B surface antigen titer (3.6 logU/ml vs. 4.0 logU/ml, t = 2.19, P = 0.020) were lower and predictors of responder in mono-treatment and sequential treatment groups, respectively.

ConclusionsThe current study shows no differences in HBeAg seroconversion rate, ALT normalization, and HBV-DNA levels between mono-therapy and sequential therapy regimens.

Trial RegistrationClinicalTrials.gov, NCT01220596; https://clinicaltrials.gov/ct2/show/NCT01220596?term=NCT01220596&rank=1.

BACKGROUNDS/AIMS: Both preoperative transcatheter arterial chemoembolization (TACE) alone and portal vein embolization (PVE) alone have a detrimental prognostic effect on the post-resection outcomes in patients with hepatocellular carcinoma (HCC). The main objective of this study was to assess the prognostic impact of preoperative TACE on the long-term survival outcomes in patients undergoing preoperative PVE and right liver resection for solitary HCC. METHODS: Patients who underwent macroscopic curative right liver resection of solitary HCC that lied between 3.0 and 7.0 cm (n=113) with or without preoperative TACE and PVE were selected for the study, making these subjects were divided into three groups; the TACE-PVE group (n=27), the PVE-alone group (n=13), and the control group (n=73). The subjects in the three groups were followed up for > or =36 months or until death. RESULTS: The 1-, 3-, 5-, and 10-year overall patient survival rates of all 113 patients were 96.5%, 88.2%, 81.3% and 65.0%, respectively. The 1-, 3-, 5-, and 10-year overall patient survival rates were 96.3%, 83.4%, 83.4% and 47.6% respectively in the TACE-PVE group; 84.6%, 76.9%, 57.7% and 19.2% respectively in the PVE-alone group; and 98.6%, 91.7%, 85.1% and 81.7% respectively in the control group (p=0.047). Patients were also sub-grouped according to tumor size, and those with a tumor of up to cutoff at 5 cm showed no prognostic difference (p=0.774), but tumor size >5 cm was associated with inferior patient survival only in the TACE-PVE group (p=0.018). CONCLUSIONS: Preoperative sequential TACE and PVE appear to be compliant to the conventional oncological concept in addition to induction of the future remnant liver regeneration. Therefore, we suggest that preoperative TACE should be come first whenever preoperative PVE for major hepatectomy is planned, especially in patients with hypervascular HCC tumors.
Carcinoma, Hepatocellular* ; Hepatectomy* ; Humans ; Liver ; Liver Regeneration ; Portal Vein* ; Survival Rate

OBJECTIVE: Few studies have evaluated the personality characteristics of patients with obstructive sleep apnea (OSA) and simple snoring. We investigated the personality characteristics of OSA and simple snoring patients and compared differences in personality between the two groups using the Eysenck Personality Questionnaire (EPQ). MATERIALS AND METHODS: Two hundred and thirty-seven patients who were suspected to have OSA or simple snoring participated in this study. A self-questionnaire which included the EPQ was administered to all participants. All subjects underwent polysomnography in a sleep laboratory and those with an apnea-hypopnea index (AHI) > or =5 were included in the OSA group, while those with an AHI <5 were included in the simple snoring group. RESULTS: OSA patients had significantly lower scores for Psychoticism (F=4.563, p=0.034) than simple snorers. There were no significant differences in Extraversion (F=3.029, p=0.083), Lie (F=0.398, p=0.529), or Neuroticism (F=3.367, p=0.068) scores between the two groups. In the correlation analysis of the OSA group, AHI was positively correlated with Extraversion score (r=0.16, p=0.029) and negatively correlated with Lie score (B=-0.31, p<0.001). Using multiple stepwise linear regression analysis with the four EPQ parameter scores as dependent variables, Lie score was associated with older age (B=0.14, p<0.001) and lower AHI (B=-0.05, p<0.001), Psychoticism score was associated with higher Pittsburgh Sleep Quality Index (PSQI ; B=0.14, p<0.001), Neuroticism score was associated with higher PSQI (B=0.34, p=0.001) and female sex (B=3.15, p=0.003), and Extraversion score was associated with younger age (B=-0.08, p=0.020) and higher body mass index (B=0.26, p=0.023). CONCLUSION: This study suggests that patients with OSA are significantly less prone to psychotic personality characteristics than those with simple snoring. Among OSA patients, higher AHI was correlated with low falsehood and high extraversion tendencies.
Body Mass Index ; Extraversion (Psychology) ; Female ; Humans ; Linear Models ; Polysomnography ; Surveys and Questionnaires ; Sleep Apnea, Obstructive* ; Snoring*

Liver enzyme elevations, as an indicator of liver function, are widely associated with metabolic diseases. Genome-wide population-based association studies have identified a genetic susceptibility to liver enzyme elevations and their related traits; however, the genetic architecture in childhood remains largely unknown. We performed a genome-wide association study to identify new genetic loci for liver enzyme levels in a Korean childhood cohort (n = 484). We observed three novel loci (rs4949718, rs80311637, and rs596406) that were multiply associated with elevated levels of alanine transaminase and aspartate transaminase. Although there are some limitations, including genetic power, additional replication and functional characterization will support the clarity on the genetic contribution that the ST6GALNAC3, ADAMTS9, and CELF2 genes have in childhood liver function.
Alanine Transaminase ; Aspartate Aminotransferases ; Child ; Cohort Studies ; Genetic Loci ; Genetic Predisposition to Disease ; Genome-Wide Association Study ; Humans ; Liver ; Metabolic Diseases

OBJECTIVES: The purpose of this study is to find the influential clinical and physical characteristics which affect apnea-hypopnea index (AHI) in suspected obstructive sleep apnea (OSA) patients. METHODS: We evaluated the comprehensive factors including sleep related symptoms, clinical scales, medical history, substance use, and anthropometric data of the 119 participants who complained of the symptoms of OSA. All the participants underwent attended-full night laboratory polysomnography. The correlation and multiple regression analysis were conducted to find the influential and predictive factors of AHI. RESULTS: A multiple linear regression model 1 showed that higher AHI was associated with higher body mass index (BMI)(p < 0.001) and higher frequency of observed apnea (p = 0.002). In multiple linear regression model 2, AHI was associated with higher BMI (p < 0.001) and loudness of snoring (p = 0.018). CONCLUSIONS: The present preliminary results suggest that BMI and observed apnea are most influential factors that affect AHI in suspected OSA patients. In the future study we will design the prediction formula for the OSA and AHI, which is useful in the clinical medical field.
Apnea ; Body Mass Index ; Humans ; Linear Models ; Polysomnography ; Sleep Apnea, Obstructive ; Snoring ; Weights and Measures

Isolated tubal torsion is a rare disease that causes acute lower abdominal pain. In most of cases, the ovary and the fallopian tube are together twisted due to an ovarian tumor, but the fallopian tube alone is rarely twisted. Tubal torsion mainly occurs in fertile women, and it rarely occurs prior to menarche and during menopause. We experienced a case where isolated tubal torsion occurred in a perimenopausal female with total abdominal hysterectomy, while the findings showed a normal ovary. We report this case with a brief review of related literature.
Abdominal Pain ; Fallopian Tubes ; Female ; Humans ; Hysterectomy ; Menarche ; Menopause ; Ovary ; Rare Diseases

BACKGROUND: The presence of porcine endogenous retrovirus (PERV) has been considered as one of the main hurdles to transplant pig's organs or tissues to human beings. There has been no report that PERV infection is associated with human diseases. Because pigs have their own characteristics of PERV according to pig strain, it is necessary to analyze the infectivity of PERV from SNU miniature pig to human cells for future utilization as a transplantation donor. MATERIALS AND METHODS: Human cell lines were infected with culture supernatant from porcine cell line or immunomodulator-stimulated peripheral blood mononuclear cells (PBMC) of SNU miniature pigs. They were also co-cultured with PBMC or islet cells of SNU miniature pigs. The presence of PERV genes and general pig marker gene in cells was determined by nested PCR with primer set for PERV pol and pig mitochondrial cytochrome oxidase II (COII), respectively. RESULTS: Infection test with the culture supernatant from PBMC of SNU miniature pigs showed that PERV pol but not COII was detected only in a few cases, but there was no uniform infection pattern in scope of stimulators and cell types. PERV pol was not demonstrated in co-cultures of human cell line with PBMC or islet cells from SNU miniature pigs after 80 days of co-cultures. CONCLUSIONS: In vitro infectivity test suggests that PERV from SNU miniature pig might not replicate productively in human cell lines although it could infect human cells and integrate into chromosome.
Cell Line ; Coculture Techniques ; Electron Transport Complex IV ; Endogenous Retroviruses ; Humans ; Islets of Langerhans ; Polymerase Chain Reaction ; Sprains and Strains ; Swine ; Tissue Donors ; Transplantation, Heterologous ; Transplants

BACKGROUND/AIMS: The incidence and prevalence of Crohn's disease are increasing in Korea. However, the guidelines for the management of Crohn's disease have not been established in Korea. In the current study we determined the difference in the treatment methods between physicians in Korea for Crohn's disease. METHODS: We retrospectively analyzed the use of medical and surgical treatment modalities in 92 patients with newly diagnosed Crohn's disease. We compared the treatment strategies among 4 physicians at 3 different institutions. RESULTS: Prednisone, 5-aminosalicylates, antibiotics, immunomodulators, infliximab, and surgery were prescribed or preformed in 64%, 92%, 24%, 35%, 9%, and 22% of the patients, respectively. The surgical procedures included 12 bowel resections and 8 fistulectomies. The prescription rates for 5-aminosalicylates, prednisone, antibiotics, and infliximab did not differ, but of the use of immunomodulators was significantly different between physicians (p=0.012). The mean interval between diagnosis and the start of immunomodulators was 14 months, and was not different between physicians. The median dosage of immunomodulators was 50 mg per day, and was not different between physicians. CONCLUSIONS: A difference in medical treatment strategies for Crohn's disease between physicians exists in Korea. Specifically, there was a significant difference in the use of immunodulators between physicians. The development of treatment guidelines for Crohn's disease, together with efforts to decrease the inter-physician difference for treating Crohn's disease are needed.
Anti-Bacterial Agents ; Antibodies, Monoclonal ; Crohn Disease ; Humans ; Immunologic Factors ; Incidence ; Infliximab ; Korea ; Prednisone ; Prescriptions ; Prevalence ; Retrospective Studies