Purpose: The aim of this study is to evaluate the safety and efficacy of ex vivo activated and expanded natural killer (NK) cell therapy (SNK01) plus pembrolizumab in a randomized phase I/IIa clinical trial. Materials and Methods: Overall, 18 patients with advanced non–small cell lung cancer (NSCLC) and a programmed death ligand 1 tumor proportion score of 1% or greater who had a history of failed frontline platinum-based therapy were randomized (2:1) to receive pembrolizumab every 3 weeks +/– 6 weekly infusions of SNK01 at either 2×109 or 4×109 cells per infusion (pembrolizumab monotherapy vs. SNK01 combination). The primary endpoint was safety, whereas the secondary endpoints were the objective response rate (ORR), progression-free survival (PFS), overall survival, and quality of life. Results: Since no dose-limiting toxicity was observed, the maximum tolerated dose was determined as SNK01 4×109 cells/dose. The safety data did not show any new safety signals when SNK01 was combined with pembrolizumab. The ORR and the 1-year survival rate in the NK combination group were higher than those in patients who underwent pembrolizumab monotherapy (ORR, 41.7% vs. 0%; 1-year survival rate, 66.7% vs. 50.0%). Furthermore, the median PFS was higher in the SNK01 combination group (6.2 months vs. 1.6 months, p=0.001). Conclusion Based on the findings of this study, the NK cell combination therapy may consider as a safe treatment method for stage IV NSCLC patients who had a history of failed platinum-based therapy without an increase in adverse events.

BACKGROUND: In this study, four types of effervescent vitamins marketed in Korea were analyzed for their acidity and vitamin content. For this purpose, bovine teeth were immersed in vitamin, and surface microhardness and appearance were measured before and after immersion to evaluate tooth demineralization and erosion.METHODS: Bovine permanent incisors with sound surface enamel were cut to 5×5 mm size, embedded in acrylic resin, and polished using a polishing machine with Sic-paper. The prepared samples were analyzed for pH, vitamin content, and surface hardness before and after immersion using a surface microhardness meter. Demineralization of surface dental enamel was observed using a scanning electron microscope.RESULTS: The average pH of the four effervescent vitamins was less than 5.5; the pH of the positive control Oronamin C was the lowest at 2.76, while that of the negative control Samdasoo was the highest at 6.86. The vitamin content was highest in Berocca and lowest in the DM company Multivitamin. On surface microhardness analysis, surface hardness values of all enamel samples were found to be decreased significantly after 1 and 10 minutes of immersion (p<0.05). After 10 minutes of immersion, there was a significant difference in the decrease in hardness between the experimental groups (p<0.05). Scanning electron microscopy observation showed that dental enamel demineralization after 10 minutes of immersion was the most severe in Oronamin C except for Samdasoo, followed by DM company Multivitamin and VitaHEIM. Immersion in BeroNew and Berocca resulted in similar effects.CONCLUSION: There is a risk of tooth erosion due to decreased tooth surface microhardness when using the four types of effervescent vitamins and vitamin carbonated beverages with pH below 5.5. Therefore, high pH vitamin supplements are recommended to prevent tooth erosion.
Carbonated Beverages ; Dental Enamel ; Hardness ; Hydrogen-Ion Concentration ; Immersion ; Incisor ; Korea ; Microscopy, Electron, Scanning ; Tablets ; Tooth ; Tooth Demineralization ; Tooth Erosion ; Vitamins

BACKGROUND/AIMS: We evaluated the efficacy and safety of daclatasvir (DCV) and asunaprevir (ASV) in patients with chronic hepatitis C virus (HCV) infection on hemodialysis. METHODS: We performed a single-arm, multicenter prospective study. Twenty-one chronic hemodialysis patients with HCV infection were prospectively enrolled from February 2016 to April 2017. We evaluated the virological responses at weeks 4, 12, and 24 (end of treatment [EOT]) and the sustained virological response at 12 weeks after the EOT (SVR12). The tolerability and safety of the drugs were also assessed. RESULTS: None of the 20 patients had the NS5A resistance-associated variant (NS5A RAV), and one patient was indeterminate for the NS5A RAV. Seventeen patients (80%) completed the 24 weeks of treatment with DCV and ASV. Four patients discontinued the study prior to week 12. In an intention-to-treat analysis, the SVR12 was 76.1%. In a per-protocol analysis, patients who completed DCV and ASV treatment achieved an SVR12 of 100%. DCV and ASV were well tolerated by the majority of patients. Three patients discontinued treatment due to adverse events (AEs) including dizziness, dyspnea, and neutropenia. The patient with indeterminate NS5A RAV showed viral breakthrough and discontinued treatment. CONCLUSIONS: DCV and ASV combination therapy in chronic hemodialysis patients with HCV infection achieved a high SVR12 rate with few AEs. To maximize the SVR12 rate, it is important to identify candidates by baseline RAV testing. Close monitoring of the safety and tolerability of DCV and ASV may be necessary in HCV-infected patients on hemodialysis. (ClinicalTrials.gov ID NCT02580474)
Dizziness ; Dyspnea ; Hepacivirus ; Hepatitis C ; Hepatitis C, Chronic ; Hepatitis ; Humans ; Neutropenia ; Prospective Studies ; Renal Dialysis

BACKGROUND/AIMS: Sofosbuvir plus ribavirin is a standard treatment for patients infected with chronic hepatitis C virus (HCV) genotype 2 in Korea. The purpose of this study was to examine the efficacy and safety of this treatment in Korean patients with chronic HCV genotype 2 infection. METHODS: We retrospectively analyzed clinical data of patients treated with sofosbuvir plus ribavirin for chronic HCV genotype 2 from May 2016 to December 2017 at eight hospitals located in the Daejeon-Chungcheong area. RESULTS: A total of 172 patients were treated with sofosbuvir plus ribavirin. Of them, 163 patients completed the treatment, and 162 patients were tested for sustained virologic response 12 weeks after treatment discontinuation (SVR12). Mean age was 59.6±12.3 years (27–96), and 105 (64.4%) patients were female. Of the total patients, 49 (30.1%) were diagnosed with cirrhosis, and 31 of them were treated for 16 weeks. Sofosbuvir plus ribavirin was the first-line treatment for 144 (88.3%) patients. Eleven (6.7%) patients were intolerant to previous interferon-based treatment. Eight (5.0%) patients relapsed after interferon-based treatment. HCV RNA non-detection rate at 4, 8, and 12 weeks was 97.5%, 99.1%, and 99.3%, respectively, and SVR12 was 98.8% (161/163). During treatment, 18 (11.0%) patients had to reduce their administrated dose of ribavirin because of anemia. One patient stopped the treatment because of severe anemia. Other adverse events, including dizziness, indigestion, and headache, were found in 26 (16.0%) patients. CONCLUSIONS: A 12-16 week treatment with sofosbuvir plus ribavirin is remarkably effective and well tolerated in Korean patients with chronic HCV genotype 2 infection.
Anemia ; Dizziness ; Dyspepsia ; Female ; Fibrosis ; Genotype ; Headache ; Hepacivirus* ; Hepatitis C* ; Hepatitis C, Chronic ; Hepatitis* ; Humans ; Korea ; Retrospective Studies* ; Ribavirin* ; RNA ; Sofosbuvir*

PURPOSE: The present study aimed to evaluate the efficacy and safety of polymer-free drug-coated BioFreedom stent implantation in comparison to coronary artery bypass graft (CABG) before major noncardiac surgery. MATERIALS AND METHODS: In a multicenter registry, 55 patients required revascularization before major noncardiac surgery that should not be delayed >6 months. Of them, 27 underwent BioFreedom stent implantation and 28 underwent CABG. Primary outcomes included rate of noncardiac surgery, time from revascularization to noncardiac surgery, and occurrence of composite outcomes (all-cause death, myocardial infarction, stent thrombosis, stroke, repeat revascularization, or major bleeding). RESULTS: The rate of major noncardiac surgery was significantly higher in the BioFreedom group (92.6%) than in the CABG group (64.3%; p=0.027). Time from revascularization to noncardiac surgery was significantly shorter in the BioFreedom group (38.0 days) than in the CABG group (73.0 days; p=0.042). During the hospitalization for revascularization period, the occurrence of primary outcomes did not differ between the groups. However, the BioFreedom group showed a shorter hospitalization period and lower total treatment cost than the CABG group. During the hospital stay for noncardiac surgery, the occurrence of composite outcome was not significantly different between groups (4% vs. 0%; p>0.999): stroke occurred in only 1 case, and there were no cases of death or stent thrombosis in the BioFreedom group. CONCLUSION: This study demonstrated that BioFreedom stenting as a revascularization strategy before major noncardiac surgery might be feasible and safe in selected patients with less severe coronary artery diseases.
Coronary Artery Bypass ; Coronary Artery Disease ; Coronary Vessels* ; Drug-Eluting Stents ; Health Care Costs ; Hospitalization ; Humans ; Length of Stay ; Myocardial Infarction ; Percutaneous Coronary Intervention ; Preoperative Care ; Stents* ; Stroke ; Thrombosis ; Transplants

Transcatheter aortic valve implantation (TAVI) is an alternative treatment modality for surgical aortic valve replacement in patients at high surgical risk. Transfemoral access is not feasible in many cases with unfavorable iliofemoral anatomy or severe peripheral arterial disease (PAD). Elderly patients with severe aortic valve stenosis have a higher prevalence of PAD due to atherosclerotic degenerative changes in the large and small vessels. Transsubclavian, transapical, and direct access to the ascending aorta by thoracotomy are alternative routes for the TAVI procedure. In this case, we describe a patient with a previous coronary artery bypass graft and bilateral iliac artery stenosis who successfully underwent TAVI using a CoreValve(R) by transfemoral approach after balloon angioplasty of iliac artery stenosis.
Aged ; Angioplasty, Balloon ; Aorta ; Aortic Valve ; Aortic Valve Stenosis ; Constriction, Pathologic ; Coronary Artery Bypass ; Heart Valve Prosthesis ; Humans ; Iliac Artery ; Peripheral Arterial Disease ; Prevalence ; Thoracotomy ; Transplants

BACKGROUND: Oral isotretinoin is an effective treatment modality for acne, but this agent may cause dryness of the skin and mucous membrane. Gamma-linolenic acid (GLA) has been known to improve skin moisture and reduce transepidermal water loss (TEWL). It is also known to have anti-inflammatory effects and to inhibit 5-alpha reductase. OBJECTIVE: This study was performed to evaluate the clinical efficacy of GLA in the prevention of xerosis and improvement of acne lesions after concomitant administration of isotretinoin. METHODS: In this prospective study, 102 Korean acne patients were enrolled and randomized to receive isotretinoin either with or without GLA for 12 weeks. Comparing evaluations included skin hydration, TEWL, visual analogue scale (VAS) score for dryness of the lips and skin, number of acne lesions such as comedos, papules, and pustules, Korean acne grading system (KAGS) grade, and patient satisfaction regarding treatment. RESULTS: The decrease of skin hydration and increase of the TEWL of the lips and cheek were less definite in the experimental group than those of the control group. VAS score for dryness of the lips and skin was significantly lower in the experimental group compared with the control group. The number of acne lesions decreased in both groups; only the numbers of papules were different between the two groups. The decrease of the KAGS grade was more definite in the experimental group than that in the control group. CONCLUSION: This study suggests that GLA could be used effectively for the improvement of acne lesions as well as for the prevention of xerosis.
Acne Vulgaris* ; Cheek ; gamma-Linolenic Acid* ; Humans ; Isotretinoin* ; Lip ; Mucous Membrane ; Oxidoreductases ; Patient Satisfaction ; Prospective Studies ; Skin

INTRODUCTION: Transcatheter aortic valve implantation (TAVI) is now considered as an alternative treatment option for severe aortic stenosis (AS) patients who cannot undergo surgical aortic valve replacement (AVR). CASE REPORT: We describe the first Korean case of transaortic TAVI with mini-sternotomy using CoreValve. A 83-year-old woman with severe AS and recent history of non-ST elevation myocardial infarction was referred to our institution for TAVI intervention. There was no amenable peripheral vascular access for transfemoral or trans-subclavian approach. Considering the relatively high procedural risk of transapical approach in this patient, we performed transaortic TAVI with mini-sternotomy. CONCLUSION: The present case suggests transaortic approach may be an effective and safe strategy for TAVI in high risk severe AS patients without eligible femoral or subclavian access routes.
Aged, 80 and over ; Aortic Valve Stenosis ; Aortic Valve* ; Female ; Heart Valve Prosthesis Implantation ; Humans ; Myocardial Infarction ; Vascular Access Devices

Transcatheter aortic valve implantation (TAVI) is indicated as an alternative treatment modality to surgical aortic valve replacement for high risk patients. The standard retrograde approach through the femoral artery is not feasible in the case of unfavorable iliofemoral anatomy or severe peripheral arterial disease (PAD). However, patients with aortic stenosis (AS) have a higher prevalence of for PAD because both diseases are consequences of atherosclerotic degenerative changes. Transsubclavian, transapical, and direct access to the ascending aorta by thoracotomy are alternative routes for the TAVI procedure. In this report, we present the first Korean patient with symptomatic severe AS and bilateral iliofemoral artery disease who was successfully treated with TAVI using a CoreValve (Medtronic, Minneapolis, MN, USA) by transsubclavian approach.
Aorta ; Aortic Valve ; Aortic Valve Stenosis ; Arteries ; Catheters ; Femoral Artery ; Heart Valve Prosthesis ; Humans ; Peripheral Arterial Disease ; Prevalence ; Prosthesis Implantation ; Thoracotomy

Surgical replacement of the aortic valve is the standard therapy for severe aortic valve stenosis. However, it is generally associated with increased mortality and morbidities in older individuals. Transcatheter aortic valve implantation (TAVI) is a less invasive procedure and has shown similar clinical outcomes as surgical treatment in elderly patients at high risk for conventional surgery. In this report, we describe the first case of TAVI using a CoreValve in Korea. An 84-year-old man with symptomatic severe aortic valve stenosis was successfully treated by transfemoral TAVI. The patient was discharged without any significant complications and remained free of adverse clinical event for a follow-up duration of 6 months.
Aged ; Aged, 80 and over ; Aortic Valve ; Aortic Valve Stenosis ; Catheters ; Follow-Up Studies ; Heart Valve Prosthesis ; Humans ; Korea ; Prosthesis Implantation