Background/Aims: We used next-generation sequencing (NGS) to analyze resistance-associated substitutions (RASs) and retreatment outcomes in patients with chronic hepatitis C virus (HCV) infection who failed direct-acting antiviral agent (DAA) treatment in South Korea. Methods: Using prospectively collected data from the Korean HCV cohort study, we recruited 36 patients who failed DAA treatment in 10 centers between 2007 and 2020; 29 blood samples were available from 24 patients. RASs were analyzed using NGS. Results: RASs were analyzed for 13 patients with genotype 1b, 10 with genotype 2, and one with genotype 3a. The unsuccessful DAA regimens were daclatasvir+asunaprevir (n=11), sofosbuvir+ribavirin (n=9), ledipasvir/sofosbuvir (n=3), and glecaprevir/pibrentasvir (n=1). In the patients with genotype 1b, NS3, NS5A, and NS5B RASs were detected in eight, seven, and seven of 10 patients at baseline and in four, six, and two of six patients after DAA failure, respectively. Among the 10 patients with genotype 2, the only baseline RAS was NS3 Y56F, which was detected in one patient. NS5A F28C was detected after DAA failure in a patient with genotype 2 infection who was erroneously treated with daclatasvir+asunaprevir. After retreatment, 16 patients had a 100% sustained virological response rate. Conclusions NS3 and NS5A RASs were commonly present at baseline, and there was an increasing trend of NS5A RASs after failed DAA treatment in genotype 1b. However, RASs were rarely present in patients with genotype 2 who were treated with sofosbuvir+ribavirin. Despite baseline or treatment-emergent RASs, retreatment with pan-genotypic DAA was highly successful in Korea, so we encourage active retreatment after unsuccessful DAA treatment.

Purpose: To evaluate the reliability and validity of the Cataract-related Visual Function Questionnaire (CVFQ). Methods: A prospective cross-sectional study of 141 cataract patients was conducted from March 2022 to June 2022. The questionnaire was created based on a literature review and advice from an expert panel. This study determined its construct validity, criterion validity, internal consistency, and test-retest reliability. Results: The CVFQ consists of 15 items distributed among five categories: overall visual quality, overall visual function, distance vision, near vision, and glare. In the exploratory factor analysis of validity, the first three principal components explained 77.8% of the variance. The p-values in the Spearman correlation test comparing the pre- and postoperative total CVFQ score and best-corrected visual acuity (BCVA) were 0.006 and 0.004, respectively. In the reliability analysis, Cronbach’s alpha was > 0.9 for internal consistency and the p-values of each subcategory were all significant in the analysis of test-retest reliability. Conclusions Our results indicate that the CVFQ is useful for measuring the visual quality and visual function of cataract patients in Korea.

Purpose: This study aimed to evaluate the clinical infrastructure and utilization of radiotherapy (RT) services in Korea between 2017 and 2019. Materials and Methods: We extracted the data of patients who underwent RT between 2017 and 2019 from the Health Insurance Review and Assessment Service. We further analyzed this data according to the diagnosis and treatment modalities of patients diagnosed with International Classification of Disease 10 (ICD-10) diagnostic codes C00–C97 and D00–D48. In addition, we collected statistics on RT facilities in Korea using a nationwide survey. Results: The total number of patients who received RT in 2017, 2018, and 2019 were 77,901, 81,849, and 87,460, respectively. The number of patients diagnosed with ICD 10 C- and D-codes in 2019 was 86,339, of whom 39,467 were men and 46,872 women. The rate of utilization of RT among cancer patients was 30.4% in 2017 and 2018 and 30.9% in 2019. In 2019, the most common types of cancers treated with RT were breast, lung, prostate, colorectal, and liver cancers. Regarding the RT infrastructure in Korea, there were 95 radiation oncology centers, 237 megavoltage (MV) teletherapy units, 35 brachytherapy units, and two proton accelerators in 2019. There were 4.5 MV teletherapy machines per million. Conclusion The number of patients treated with RT has increased consistently from 2017 to 2019. As the number of patients with cancer increases, it is expected that the RT infrastructure will be further expanded in Korea.

Purpose: Microinvasive breast cancer (MIBC) is an invasive carcinoma with a tumor dimension not exceeding 1 mm. Owing to its low incidence, the rate of axillary node metastasis and its management are not well established. The aim of this study was to assess the incidence of lymph node metastasis (LNM) and identify variables associated with LNM, as well as to evaluate the need for axillary staging in MIBC patients by analyzing nationwide data. Methods: The Korean Breast Cancer Society registry was searched to identify MIBC patients diagnosed between January 1996 and April 2020. Patients without neoadjuvant chemotherapy experiences, systemic metastasis, and missing or discordant data were eligible for the analysis. The incidence rate of LNM was determined, and variables associated with LNM were identified by multivariable regression analysis. Results: Of 2,427 MIBC patients identified, 98 (4.0%) had LNM and 12 (0.5%) had N2/3 disease. Type of breast operation (odds ratio [OR], 2.093; 95% confidence interval [CI], 1.332–3.290; P = 0.001), age (OR, 2.091; 95% CI, 1.326–3.298; P = 0.002), hormone receptor status (OR, 2.220; 95% CI, 1.372–3.594; P = 0.001), and lymphovascular invasion (OR, 11.143; 95% CI, 6.354–19.540; P < 0.001) were significantly related to LNM. Conclusion The incidence of LNM in MIBC patients was only 4.0% in our study, suggesting that de-escalation of axillary surgical interventions could be carefully considered. The indications for axillary staging should be individualized considering tumor volume, age, hormone receptor status, and lymphovascular invasion to improve the quality of life of MIBC survivors.

Purpose: This study was performed to identify the risk of mortality in patients diagnosed with human epidermal growth factor receptor 2 (HER2)-positive ductal carcinoma in situ (DCIS). Methods: We selected 2,592 patients with HER2-positive DCIS from Korean Breast Cancer Society (KBCS) database between January 1997 and December 2019. Patients who received neoadjuvant chemotherapy were excluded. Logistic regression analysis was used to determine the association between clinical factors and overall death after adjusting for tumor and clinical characteristics. Mortality data were modified using the Statistics Korea data. Results: Thirty deaths (1.2%) were identified out of 2,592 patients in the KBCS database. In the univariate logistic regression analysis, older age, higher body mass index (BMI), type of breast surgery (mastectomy), estrogen receptornegative, progesterone receptor-negative, and exposure to endocrine therapy were significant clinical factors associated with death. In the multivariate analysis, age (hazard ratio [HR], 1.062; 95% confidence interval [CI], 1.015–1.111; P = 0.006), BMI (HR, 1.179; 95% CI, 1.032–1.347, P = 0.016), breast surgery type (mastectomy vs. lumpectomy; HR, 0.285; 95% CI, 0.096–0.844; P = 0.024), and endocrine therapy (HR, 0.314; 95% CI, 0.099–0.995; P = 0.049) were significant risk factors for mortality. Conclusion Advanced age, higher BMI, mastectomy, and the absence of endocrine therapy were factors associated with poor survival of patients with HER2-positive DCIS. This finding requires further validation combined with additional analysis of large databases.

Background/Aims: The risk factors for the development of primary biliary cholangitis (PBC) is unclear. This study aimed to investigate the risk factors associated with PBC in Korea through a questionnaire survey. Methods: Consecutively enrolled 103 PBC patients from six referral hospitals and 100 age- and sex-matched community controls participated in this study. A standardized questionnaire survey including demographics, lifestyle, individual and familial medical history and reproductive history was prospectively collected and analyzed. Results: The PBC patients had a mean age of 58.3 years and a female proportion of 86.4%. The age- and sex-matched controls had a similar educational level and economic status to the PBC patients. Among the lifestyle factors, the multivariable analysis showed smoking including both first-hand and second-hand (odds ratio [OR], 2.03; 95% confidence interval [CI], 1.06 to 3.93), history of autoimmune diseases (OR, 2.46; 95% CI, 1.06 to 6.35), and family history of PBC (OR, 17.76; 95% CI, 1.77 to 2,418.74) were significantly associated with PBC, whereas alcohol intake was negatively associated with PBC. Among reproductive factors, the number of induced abortions was significantly associated with PBC, while the number of full-term deliveries was negatively associated with PBC. Conclusions A family history of PBC, accompanying autoimmune diseases, and smoking were significantly associated with PBC. More induced abortions and less full-term deliveries were associated with PBC in women. In contrast, mild to moderate alcohol intake was negatively associated with PBC. Further studies are warranted to validate the results of this study and to search for clues about the pathogenesis of PBC.

Background: Observational studies of the ongoing coronavirus disease 2019 (COVID-19) outbreak suggest that a ‘cytokine storm’ is involved in the pathogenesis of severe illness.However, the molecular mechanisms underlying the altered pathological inflammation in COVID-19 are largely unknown. We report here that toll-like receptor (TLR) 4-mediated inflammatory signaling molecules are upregulated in peripheral blood mononuclear cells (PBMCs) from COVID-19 patients, compared with healthy controls (HC). Methods: A total of 48 subjects including 28 COVID-19 patients (8 severe/critical vs. 20 mild/ moderate cases) admitted to Chungnam National University Hospital, and age/sex-matched 20 HC were enrolled in this study. PBMCs from the subjects were processed for nCounter Human Immunology gene expression assay to analyze the immune related transcriptome profiles. Recombinant proteins of severe acute respiratory syndrome coronavirus-2 (SARSCoV-2) were used to stimulate the PBMCs and monocyte-derived macrophages, and real-time polymerase chain reaction was performed to quantify the mRNA expressions of the proinflammatory cytokines/chemokines. Results: Among the most highly increased inflammatory mediators in severe/critically ill patients, S100A9, an alarmin and TLR4 ligand, was found as a noteworthy biomarker, because it inversely correlated with the serum albumin levels. We also observed that recombinant S2 and nucleocapsid proteins of SARS-CoV2 significantly increased proinflammatory cytokines/chemokines and S100A9 in human primary PBMCs. Conclusion These data support a link between TLR4 signaling and pathological inflammation during COVID-19 and contribute to develop therapeutic approaches through targeting TLR4-mediated inflammation.

PURPOSE: To evaluate the efficacy and safety of BOTULAX® in subjects with essential blepharospasm.METHODS: In this study, a total of 250 subjects with essential blepharospasm were enrolled at 15 investigational sites and a total of 220 subjects completed the study. The efficacy and safety were evaluated at weeks 4 and 16 after treatment compared with baseline. In total, 240 subjects were enrolled, treated with the investigational product, and evaluable for the primary efficacy assessment at week 4 after treatment; these subjects were included in the intention-to-treat (ITT) population. With the ITT set as the main efficacy set, efficacy assessment included Jankovic rating scale (JRS), functional disability score, investigator evaluation of global response and quality of life. Safety assessment including the incidence of adverse events was also performed.RESULTS: In terms of the primary efficacy endpoint (i.e., change in JRS total score at week 4 after treatment from baseline [ITT set]), mean change indicated a statistically significant reduction (p < 0.0001) and demonstrated the non-inferiority of the test drug to similar drugs. In terms of the secondary efficacy endpoints, mean change in JRS total score at week 16 after treatment and mean change in functional disability score at weeks 4 and 16 after treatment both exhibited a statistically significant reduction compared with baseline (p < 0.0001 for all). Among the 249 subjects treated with the investigational product in this study, 44 (17.67%) experienced 76 treatment emergent adverse events but no serious adverse events were observed.CONCLUSIONS: Based on the study results, BOTULAX® is considered to be an effective and safe treatment for essential blepharospasm.