Background: Wilson’s disease (WD) is an autosomal recessive disorder in which copper (Cu) accumulates in organs, particularly in the liver and central nervous system. This study aimed to investigate the prevalence, incidence, and treatment patterns of WD patients in Korea. Methods: National Health Insurance System (NHIS) claims data from 2010 to 2020 were analyzed. patients with WD as a primary or additional diagnosis at least once were identified using the International Classification of Diseases (ICD)-10 disease code E83.0 and a record for a registration program for rare intractable diseases in Korea. Results: The average age- and sex-adjusted prevalence and incidence of WD between 2010 and 2020 were 3.06/100,000 and 0.11/100,000, respectively. The mean age of the patients with newly diagnosed WD was 21.0 ± 15.9 years. Among the 622 WD incident cases during the study period, 19.3% of the patients had liver cirrhosis and 9.2% had received liver transplantation. Psychological and neurological diseases were present in 40.7% and 48.1% of the patients, respectively. Regarding the diagnosis of WD, liver biopsy was performed in only 51.6% of new cases. D-penicillamine, trientine, or zinc were prescribed in 81.5% of the incident cases, and the treatment uptake rates decreased with increasing age. Conclusion The prevalence of WD in Korea is 3.06/100,000 and approximately 1,800 patients use medical services annually. A significant proportion of patients are diagnosed at the cirrhotic stage and not treated with Cu-chelating therapeutics, suggesting the need for early diagnosis and adequate treatment to improve prognosis.

BACKGROUND: A drug-eluting stent (DES) is a highly beneficial medical device used to widen or unblock narrowed blood vessels. However, the drugs released by the implantation of DES may hinder the re-endothelialization process, increasing the risk of late thrombosis. We have developed a tacrolimus-eluting stent (TES) that as acts as a potent antiproliferative and immunosuppressive agent, enhancing endothelial regeneration. In addition, we assessed the safety and efficacy of TES through both in vitro and in vivo tests. METHODS: Tacrolimus and Poly(lactic-co-glycolic acid) (PLGA) were applied to the metal stent using electrospinning equipment. The surface morphology of the stent was examined before and after coating using a scanning electron microscope (SEM) and energy dispersive X-rays (EDX). The drug release test was conducted through high-performance liquid chromatography (HPLC). Cell proliferation and migration assays were performed using smooth muscle cells (SMC).The stent was then inserted into the porcine coronary artery and monitored for a duration of 4 weeks. RESULTS: SEM analysis confirmed that the coating surface was uniform. Furthermore, EDX analysis showed that the surface was coated with both polymer and drug components. The HPCL analysis of TCL at a wavelength of 215 nm revealed that the drug was continuously released over a period of 4 weeks. Smooth muscle cell migration was significantly decreased in the tacrolimus group (54.1% ± 11.90%) compared to the non-treated group (90.1% ± 4.86%). In animal experiments, the stenosis rate was significantly reduced in the TES group (29.6% ± 7.93%) compared to the bare metal stent group (41.3% ± 10.18%). Additionally, the fibrin score was found to be lower in the TES group compared to the group treated with a sirolimus-eluting stent (SES). CONCLUSION Similar to SES, TES reduces neointimal proliferation in a porcine coronary artery model, specifically decreasing the fibrins score. Therefore, tacrolimus could be considered a promising drug for reducing restenosis and thrombosis.

Purpose: This study evaluated whether combination therapy is more effective than monotherapy in elderly patients with metastatic or recurrent gastric cancer (MRGC) as first-line chemotherapy. Materials and Methods: Elderly (≥ 70 years) chemo-naïve patients with MRGC were allocated to receive either combination therapy (group A: 5-fluorouracil [5-FU]/oxaliplatin, capecitabine/oxaliplatin, capecitabine/cisplatin, or S-1/cisplatin) or monotherapy (group B: 5-FU, capecitabine, or S-1). In group A, starting doses were 80% of standard doses, and they could be escalated to 100% at the discretion of the investigator. Primary endpoint was to confirm superior overall survival (OS) of combination therapy vs. monotherapy. Results: After 111 of the planned 238 patients were randomized, enrollment was terminated due to poor accrual. In the full-analysis population (group A [n=53] and group B [n=51]), median OS of combination therapy vs. monotherapy was 11.5 vs. 7.5 months (hazard ratio [HR], 0.86; 95% confidence interval [CI], 0.56 to 1.30; p=0.231). Median progression-free survival (PFS) was 5.6 vs. 3.7 months (HR, 0.53; 95% CI, 0.34 to 0.83; p=0.005). In subgroup analyses, patients aged 70-74 years tended to have superior OS with combination therapy (15.9 vs. 7.2 months, p=0.056). Treatment-related adverse events (TRAEs) occurred more frequently in group A vs. group B. However, among severe TRAEs (≥ grade 3), there were no TRAEs with a frequency difference of > 5%. Conclusion Combination therapy was associated with numerically improved OS, although statistically insignificant, and a significant PFS benefit compared with monotherapy. Although combination therapy showed more frequent TRAEs, there was no difference in the frequency of severe TRAEs.

Background and Objectives: Human induced pluripotent stem cell (hiPSC)-derived cardiomyocyte (CM) hold greatpromise as a cellular source of CM for cardiac function restoration in ischemic heart disease. However, the use of animal-derived xenogeneic substances during the biomanufacturing of hiPSC-CM can induce inadvertent immune responses or chronic inflammation, followed by tumorigenicity. In this study, we aimed to reveal the effects of xenogeneic substances on the functional properties and potential immunogenicity of hiPSC-CM during differentiation, demonstrating the quality and safety of hiPSC-based cell therapy. Methods: and Results: We successfully generated hiPSC-CM in the presence and absence of xenogeneic substances(xeno-containing (XC) and xeno-free (XF) conditions, respectively), and compared their characteristics, including the contractile functions and glycan profiles. Compared to XC-hiPSC-CM, XF-hiPSC-CM showed early onset of myocyte contractile beating and maturation, with a high expression of cardiac lineage-specific genes (ACTC1, TNNT2, and RYR2) by using MEA and RT-qPCR. We quantified N-glycolylneuraminic acid (Neu5Gc), a xenogeneic sialic acid, in hiPSC-CM using an indirect enzyme-linked immunosorbent assay and liquid chromatography-multiple reaction monitoring-mass spectrometry. Neu5Gc was incorporated into the glycans of hiPSC-CM during xeno-containing differentiation, whereas it was barely detected in XF-hiPSC-CM. Conclusions To the best of our knowledge, this is the first study to show that the electrophysiological function andglycan profiles of hiPSC-CM can be affected by the presence of xenogeneic substances during their differentiation and maturation. To ensure quality control and safety in hiPSC-based cell therapy, xenogeneic substances should be excluded from the biomanufacturing process.

BACKGROUND: Biodegradable poly (l-lactic acid) (PLLA), a bio safe polymer with a large elastic modulus, is widely used in biodegradable medical devices. However, because of its poor mechanical properties, a PLLA strut must be made twice as thick as a metal strut for adequate blood vessel support. Therefore, the mechanical properties of a drug-eluting metal-based stents (MBS) and a bioresorbable vascular scaffolds (BVS) were evaluated and their safety and efficacy were examined via a long-term rabbit iliac artery model. METHODS: The surface morphologies of the MBSs and BVSs were investigated via optical and scanning electron microscopy. An everolimus-eluting (EE) BVS or an EE-MBS was implanted into rabbit iliac arteries at a 1.1:1 stent-toartery ratio. Twelve months afterward, stented iliac arteries from each group were analyzed via X-ray angiography, optical coherence tomography (OCT), and histopathologic evaluation. RESULTS: Surface morphology analysis of the EE coating on the MBS confirmed that it was uniform and very thin (4.7 lm). Comparison of the mechanical properties of the EE-MBS and EE-BVS showed that the latter outperformed the former in all aspects (radial force (2.75 vs. 0.162 N/mm), foreshortening (0.24% vs. 1.9%), flexibility (0.52 vs. 0.19 N), and recoil (3.2% vs. 6.3%). At all time points, the percent area restenosis was increased in the EE-BVS group compared to the EE-MBS group. The OCT and histopathological analyses indicate no significant changes in strut thickness. CONCLUSION BVSs with thinner struts and shorter resorption times should be developed. A comparable long-term safety/efficacy evaluation after complete absorption of BVSs should be conducted.

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.

Eurotiales is a relatively large order of Ascomycetes, well-known for their ability to produce secondary metabolites with potential beneficial applications. To understand their diversity and distribution, different environmental sources including soil, freshwater, insect, and indoor air were investigated. Eight strains of Eurotiales were isolated and identified based on their morphological characters and a multi-gene phylogenetic analysis of the ITS, BenA, CaM, and RPB2 regions. We identified eight taxa that were previously not reported from Korea: Aspergillus baeticus, A. griseoaurantiacus, A. spinulosporus, Penicillium anthracinoglaciei, P. labradorum, P.nalgiovense, Talaromyces atroroseus, and T. georgiensis. Detailed descriptions, illustrations, and phylogenetic tree for the eight new records species are presented, and information regarding the records is also discussed.

Background/Aims: This study aimed to evaluate the cost-effectiveness of hepatitis C virus (HCV) screening compared to no screening in the Korean population from societal and healthcare system perspectives. Methods: A published decision-tree plus Markov model was used to compare the expected costs and quality-adjusted life years (QALY) between one-time universal HCV screening and no screening in the population aged 40–65 years using the National Health Examination (NHE) program. Input parameters were obtained from analyses of the National Health Insurance claims data, Korean HCV cohort data, or from the literature review. The population aged 40–65 years was simulated in a model spanning a lifetime from both the healthcare system and societal perspectives, which included the cost of productivity loss due to HCV-related deaths. The incremental cost-effectiveness ratio (ICER) between universal screening and no screening was estimated. Results: The HCV screening strategy had an ICER of $2,666/QALY and $431/QALY from the healthcare system and societal perspectives, respectively. Both ICERs were far less than the willingness-to-pay threshold of $25,000/QALY, showing that universal screening was highly cost-effective compared to no screening. In various sensitivity analyses, the most influential parameters on cost-effectiveness were the antibodies to HCV (anti-HCV) prevalence, screening costs, and treatment acceptance; however, all ICERs were consistently less than the threshold. If the anti-HCV prevalence was over 0.18%, screening could be cost-effective. Conclusions One-time universal HCV screening in the Korean population aged 40–65 years using NHE program would be highly cost-effective from both healthcare system and societal perspectives.

Purpose: To compare the clinical outcomes of penetrating keratoplasty (PKP) and Descemet stripping automated endothelial keratoplasty (DSAEK) in eyes with Glaucoma Ahmed Valve implants. Methods: The charts of 11 patients who underwent PKP and 11 who underwent DSAEK between February 2016 and June 2018 were retrospectively reviewed; all patients previously underwent Ahmed valve implant surgery. The best corrected visual acuity, intraocular pressure, and endothelial cell count were compared 1, 3, and 6 months after surgery. Graft rejection and graft failure were also evaluated during follow-up. The survival rates were compared using Kaplan–Meier survival analysis. Results: The difference in graft survival rates of the PKP and DSAEK groups was not significant (p = 0.295); however, graft failure occurred earlier in the PKP group (12.9 ± 10.1 vs. 18.8 ± 5.3 months). The postoperative best corrected visual acuity of the PKP group had improved at 1 (p = 0.027) and 3 (p = 0.017) months, while the DSAEK group showed significant improvement at 1, 3, and 6 months (all p = 0.005). Intergroup analysis showed better visual prognosis of the DSAEK group at 1, 3, and 6 months after surgery (p = 0.023, p = 0.007, and p = 0.004, respectively). Conclusions In our study, the two corneal transplantation methods did not have significantly different graft survival rates; however, graft failure occured later in the DSAEK group and the postoperative visual acuity was better than in the PKP group. Although further study is needed, performing DSAEK in patients with an Ahmed valve implant seems to be a good alternative to PKP.

Background and Objectives: This study aimed to investigate the association between cardiovascular events and 2 different levels of elevated on-treatment diastolic blood pressures (DBP) in the presence of achieved systolic blood pressure targets (SBP). Methods: A nation-wide population-based cohort study comprised 237,592 patients with hypertension treated. The primary endpoint was a composite of cardiovascular death, myocardial infarction, and stroke. Elevated DBP was defined according to the Seventh Report of Joint National Committee (JNC7; SBP <140 mmHg, DBP ≥90 mmHg) or to the 2017 American College of Cardiology/American Heart Association (ACC/AHA) definitions (SBP <130 mmHg, DBP ≥80 mmHg). Results: During a median follow-up of 9 years, elevated on-treatment DBP by the JNC7 definition was associated with an increased risk of the occurrence of primary endpoint compared with achieved both SBP and DBP (adjusted hazard ratio [aHR], 1.14; 95% confidence interval [CI], 1.05–1.24) but not in those by the 2017 ACC/AHA definition. Elevated ontreatment DBP by the JNC7 definition was associated with a higher risk of cardiovascular mortality (aHR, 1.42; 95% CI, 1.18–1.70) and stroke (aHR, 1.19; 95% CI, 1.08–1.30). Elevated on-treatment DBP by the 2017 ACC/AHA definition was only associated with stroke (aHR, 1.10;95% CI, 1.04–1.16). Similar results were seen in the propensity-score-matched cohort. Conclusion Elevated on-treatment DBP by the JNC7 definition was associated a high risk of major cardiovascular events, while elevated DBP by the 2017 ACC/AHA definition was only associated with a higher risk of stroke. The result of study can provide evidence of DBP targets in subjects who achieved SBP targets.