Revised Korean Antiviral Guideline Reduces the Hepatitis B-related Hepatocellular Carcinoma Risk in Cirrhotic Patients

BackgroundSince September 2015, the initiation of antiviral therapy (AVT) for patients with chronic hepatitis B (CHB)-related cirrhosis has been reimbursed according to the revised Korean Association for the Study of Liver (KASL) guideline, if the patient had hepatitis B virus DNA level ≥ 2,000 IU/L, regardless of aminotransferase or alanine aminotransferase levels. This study investigated whether the KASL guideline implementation reduced the risk of CHB-related hepatocellular carcinoma (HCC) in patients with cirrhosis in South Korea.MethodsA total of 429 patients with CHB-related cirrhosis who initiated AVT between 2014 and 2016 were recruited. The risk of HCC development was compared between patients who initiated AVT before and after September 2015 (pre-guideline [n = 196, 45.7%] vs. post-guideline implementation [n = 233, 54.3%]).ResultsUnivariate analysis showed that AVT initiation before guideline implementation, older age, male gender, and diabetes significantly predicted increased risk of HCC development (all P < 0.05). Subsequent multivariate analysis showed that AVT initiation before guideline implementation (HR = 1.941), older age (HR = 5.762), male gender (HR = 2.555), and diabetes (HR = 1.568) independently predicted increased risk of HCC development (all P < 0.05). Additionally, multivariate analysis showed that AVT initiation before guideline implementation (HR = 2.309), male gender (HR = 3.058), and lower platelet count (HR = 0.989) independently predicted mortality (P < 0.05). The cumulative incidences of HCC and mortality were significantly higher in patients who initiated AVT before guideline implementation than in those who initiated AVT after guideline implementation (all P < 0.05, log-rank test).ConclusionThe prognosis of patients with CHB-related cirrhosis who initiated AVT improved after guideline implementation according to the revised KASL guideline.     

Effect of Noise on Sleep and Autonomic Activity in Children according to Source

BackgroundNoise has been a major issue in children due to its effect on emotional symptoms and sleep problems. The present study investigated the effect of noise on sleep and autonomic activity in children according to three variables, namely, road traffic noise, aircraft noise, and noise sensitivity (NS).MethodsThe study is epidemiological in nature. A total of 474 subjects of four elementary schools were evaluated in conjunction with the 2014 noise map data gathered from two metropolitan regions, Seoul and Ulsan, in South Korea. Each subject completed the children''s sleep habits questionnaire, and heart rate variability (HRV) was recorded. Analysis of covariance was performed using monthly income as a covariate.ResultsAircraft noise was associated with night waking (P = 0.047), whereas no significant association was observed between sleep and road traffic noise. After stratifying by NS, no significant results were obtained for road traffic noise. However, high levels of aircraft noise in the high-NS group were associated with high degrees of bedtime resistance (P = 0.049). In terms of HRV, no significant difference was observed in the results between groups.ConclusionRoad traffic noise did not significantly alter sleep or autonomic activity in children, whereas aircraft noise exerted a negative effect on sleep. The findings suggest that the impact of noise on sleep in children varies depending on noise sources.     

How COVID-19 Affected Healthcare Workers in the Hospital Locked Down due to Early COVID-19 Cases in Korea

BackgroundThe healthcare workers (HCWs) were exposed to never-experienced psychological distress during the early stage of the coronavirus disease 2019 (COVID-19) pandemic. The aim of this study was to investigate how the COVID-19 pandemic affected the mental health of HCWs during the hospital lockdown period due to mass healthcare-associated infection during the early spread of COVID-19.MethodsA real-time online survey was conducted between April 14–18, 2020 among HCWs who worked at the university hospital where COVID-19 was confirmed in a patient, and the hospital was shut down for 3 weeks. Along with demographic variables and work-related information, psychological distress was measured using the Generalized Anxiety Disorder-7 (GAD-7), the Patient Health Questionnaire-9 (PHQ-9), the Maslach Burnout Inventory-General Survey scale, and the Stress and Anxiety to Viral Epidemics-9.ResultsThe HCWs working in the cohort ward and those who have experienced social discrimination had significantly higher level of depression (PHQ-9 score; 5.24 ± 4.48 vs. 4.15 ± 4.38; P < 0.01 and 5.89 ± 4.78 vs. 3.25 ± 3.77; P < 0.001, respectively) and anxiety (GAD-7 score; 3.69 ± 3.68 vs. 2.87 ± 3.73; P < 0.05 and 4.20 ± 4.22 vs. 2.17 ± 3.06; P < 0.001, respectively) compared to other HCWs. Worries regarding the peer relationship and the skepticism about job were associated with depression (odds ratio [OR], 1.39; 95% confidence interval [CI], 1.07–1.79; P < 0.05 and OR, 1.69; 95% CI, 1.31–2.17; P < 0.001, respectively) and anxiety (OR, 1.73; 95% CI, 1.21–2.49; P < 0.01 and OR, 1.54; 95% CI, 1.09–2.17; P < 0.05, respectively), while fear of infection or worsening of health was not. Path analysis showed that work-related stress associated with the viral epidemic rather than anxiety about the viral epidemic mainly contributed to depression.ConclusionThe present observational study indicates that mental health problems of HCWs exposed to COVID-19 are associated with distress in work and social relationship. Early intervention programs focusing on these factors are necessary.     

A therapeutic confirmatory study to assess the safety and efficacy of Zydena (udenafil) for the treatment of erectile dysfunction in male patients with diabetes mellitus

IntroductionPatients with diabetes mellitus (DM) are reported to experience more severe erectile dysfunction (ED) symptoms and respond less to ED treatments compared with patients with ED of other etiologies.AimThis study was undertaken to evaluate the safety and efficacy of udenafil for the treatment of ED in a larger number of patients with DM.MethodsA placebo‐controlled, randomized, double‐blind, double‐dummy, parallel‐group design multicenter study, fixed‐dose trial was conducted. The trial involved seven study sites in Korea, with 174 ED patients with DM. The subjects, treated with placebo, 100 mg, or 200 mg of udenafil for 12 weeks, were asked to complete the International Index of Erectile Function (IIEF), the Sexual Encounter Profile (SEP) diary, and the Global Assessment Question (GAQ) during the study period.Main Outcome MeasuresThe primary efficacy parameter was the change in the erectile function domain (EFD) score of IIEF from baseline. Secondary parameters were IIEF questions 3 (Q3) and Q4, SEP Q2 and Q3, rate of achieving normal erectile function (EFD ≥ 26), and the response to GAQ.ResultsCompared with the placebo, patients receiving both doses of udenafil showed statistically significant improvements in the IIEF‐EFD score, respectively. However, statistically significant difference was not observed between the udenafil 100 mg and the udenafil 200 mg groups. Similar results were observed in the comparison of Q3 and Q4 of IIEF, SEP diary, and GAQ. The percentages of subjects experiencing at least one adverse event related to the study drugs were 3.6%, 15.8%, and 22.4% for the placebo, udenafil 100 mg, and udenafil 200 mg groups, respectively. However, these events were all mild in severity. Major adverse events were flushing, headache, nausea, and conjunctival hyperemia.ConclusionUdenafil was significantly effective for the treatment of ED, demonstrating statistically significant improvement in erectile function in patients with DM. The incidence of adverse events was relatively low and well tolerated in patients with DM. Moon DG, Yang DY, Lee CH, Ahn TY, Min KS, Park K, Park CK, and Kim JJ. A therapeutic confirmatory study to assess the safety and efficacy of Zydena^® (udenafil) for the treatment of erectile dysfunction in male patients with diabetes mellitus. J Sex Med 2011;8:2048–2061.     

Prognostic factors of the long-term survival after transjugular intrahepatic portosystemic shunt in the treatment of gastric and esophageal variceal bleeding

Transjugular intrahepatic portosystemic shunt (TIPSS) is a promising method of treatment for gastric or esophageal variceal bleeding. This study was performed to determine the prognostic factors contributing to the survival of patients after TIPSS for gastric or esophageal variceal bleeding. One hundred and fifty-five patients who underwent TIPSS between September 1991 and March 2001 were followed up by clinical examination, upper gastrointestinal endoscopy, and Duplex sonography. The mean portohepatic pressure gradient prior to TIPSS was 20.5+/-9.93 mmHg and dropped to 10.7+/-6.62 mmHg after TIPSS (p<0.001). The cumulative survival rate was 75.1% at 6 months, 66.6% at 1 yr, 58.4% at 2 yr, and 38.1% at 5 yr. Survival after TIPSS was inversely related to the Child-Pugh classification (p<0.05). The rebleeding rate was 18.3% at 6 months, 21.0% at 1 yr, 32.8% at 2 yr, and 53.1% at 5 yr. The causes of deaths were hepatic failure (53.5%), recurrent variceal bleeding (11.6%), pneumonia (4.6%), sepsis (3.5%), hepatic encephalopathy (2.3%), and unknown (17.4%). Multivariate analysis (Cox proportional hazard model) revealed that the Child-Pugh classification and age were statistically significant independent prognostic factors. In conclusion, TIPSS is an effective method of treatment for variceal bleeding in cases where other treatment modalities including endoscopic therapy are unsuccessful and the most important prognostic factors are preprocedural hepatic reserve (Child-Pugh class) and age.     

Pathogenicity and vaccine efficacy of a thymidine kinase gene deleted infectious laryngotracheitis virus expressing the green fluorescent protein gene

Summary.  The deletion of the thymidine kinase (TK) gene of herpesviruses causes a reduction in their virulence. However, the effects of the TK gene in infectious laryngotracheitis virus (ILTV) have not been clearly elucidated. In the present study, we constructed a TK gene-deleted recombinant ILTV expressing the green fluorescent protein (GFP) gene as a marker. The GFP gene was inserted in place of the TK gene in both virulent and low virulence strains of ILTV. The GFP gene in the recombinants was expressed in chicken kidney cells, LMH cells and in the chorioallantoic membrane of embryonated chicken eggs. The recombinants produced cytopathic effects in chicken kidney cells and LMH cells and formed pocks in the chorioallantoic membrane of embryonated chicken eggs. The growth rate of the recombinant in chicken kidney cells was similar to that of wild type viruses. The recombinants showed a reduction of virulence compared to that of parental viruses and induced protection against virulent ILTV in specific pathogen free chickens. The recombinant expressing GFP gene may be a candidate for a genetically engineered vaccine and provide a means to study growth kinetics and mechanism of latent infection and reactivation of ILTV. In this study, we confirmed that the TK gene is directly related to virulence of ILTV. This is the first report to show the evidence that the TK gene is a major gene related to virulence of ILTV. Received May 1, 2001; accepted November 14, 2001     

Psychometric Properties of the Korean Version of Stanford Acute Stress Reaction Questionnaire

The present study aimed to examine the psychometric properties of the Korean version of Stanford Acute Stress Reaction Questionnaire (SASRQ). A Korean version of the SASRQ was produced through forward translation, reconciliation, and back translation. A total of 100 healthy, non-clinical participants were selected through screening and clinical interview, and they each were given a set of questionnaires including SASRQ. Psychometric properties of SASRQ were then examined through statistical analyses. Full-scale and subscales of SASRQ yielded excellent internal consistency (Cronbach''s alpha=0.98 and 0.78-0.95, respectively). Test-retest reliability at 2-week intervals was satisfactory, with coefficient r ranging between 0.47 and 0.71. Convergent validity was also demonstrated by strong correlations between SASRQ and other trauma-related questionnaires. Correlation with Social Desirability Scale, however, was not found to be significant; thus evidenced divergent validity. The Korean version of SASRQ appears to be a reliable and valid measurement tool for assessing symptoms of acute stress disorder. Including clinical samples for comparison with controls would be necessary in future studies.     

A T cell/B cell/epithelial cell internet for mucosal inflammation and immunity

Conclusions Mucosal immune responses are strongly regulated by CD4⁺ T cells and their derived cytokines. In this regard, IFN-^–/– mice (i.e., which lack Th1 and have elevated Th2 cells) showed strong mucosal Th2-type responses together with S-IgA production, while IL-4^–/– (e.g., dominant Th1 and lack of Th2 cells) mice had impaired mucosal Th2 and IgA responses following oral delivery of TT and CT. However, when rSalmonella or radenovirus were used for antigen delivery, significant levels of mucosal IgA responses were induced in both IFN-^–/^– and IL-4^–/^– mice. The choice of the antigen delivery system which leads to optimal Th and B cell interactions are important for the induction of effective IgA responses, even in situations where the immune system is compromised. It is clear that Th2-type cytokines are important in mucosal IgA responses; however, other cytokine combinations can compensate for mucosal immunity in situations in which Th2 cell responses are absent. Mucosally induced tolerance may be one approach to prevent several systemic immune disorders; however, the mechanism of this phenomenon still needs to be elucidated. Our recent findings have suggested that IFN- may play an important role in induction of systemic unresponsiveness since oral tolerance was not induced in IFN-^–/^– mice.Our studies as well as those of others indicated that at least two phases of a triad of cell interactions are important for the mucosal immune system. First, it has been shown that epithelial cell-produced IL-7 and SCF and T cell-derived IL-2 are essential activation and growth signals for intestinal T cells. Second, our studies with TCR knockout mice have suggested that mucosal T cells also play a critical role in the regulation of mucosal IgA responses. Thus, a mucosal internet among T cells, T cells, and IgA B cells appear critical for mucosal homeostasis and for regulation of specific mucosal immune responses.     

A bacterial flagellin, Vibrio vulnificus FlaB, has a strong mucosal adjuvant activity to induce protective immunity

Flagellin, the structural component of flagellar filament in various locomotive bacteria, is the ligand for Toll-like receptor 5 (TLR5) of host cells. TLR stimulation by various pathogen-associated molecular patterns leads to activation of innate and subsequent adaptive immune responses. Therefore, TLR ligands are considered attractive adjuvant candidates in vaccine development. In this study, we show the highly potent mucosal adjuvant activity of a Vibrio vulnificus major flagellin (FlaB). Using an intranasal immunization mouse model, we observed that coadministration of the flagellin with tetanus toxoid (TT) induced significantly enhanced TT-specific immunoglobulin A (IgA) responses in both mucosal and systemic compartments and IgG responses in the systemic compartment. The mice immunized with TT plus FlaB were completely protected from systemic challenge with a 200x minimum lethal dose of tetanus toxin. Radiolabeled FlaB administered into the nasal cavity readily reached the cervical lymph nodes and systemic circulation. FlaB bound directly to human TLR5 expressed on cultured epithelial cells and consequently induced NF-kappaB and interleukin-8 activation. Intranasally administered FlaB colocalized with CD11c as patches in putative dendritic cells and caused an increase in the number of TLR5-expressing cells in cervical lymph nodes. These results indicate that flagellin would serve as an efficacious mucosal adjuvant inducing protective immune responses through TLR5 activation.