Background: In patients with coronary artery disease treated with permanent polymercoated drug-eluting stents (DES), the persistent presence of a less biocompatible polymer might delay arterial healing. Thin strut polymer-free DES have the potential to improve clinical outcomes and reduce the duration of dual antiplatelet therapy (DAPT). The purpose of this first-in-human study was to assess the safety and effectiveness of a novel polymer-free DES in patients with de novo coronary lesions. The TIGERevolutioN® stent (CG Bio Co., Ltd., Seoul, Korea) consists of a cobalt chromium platform with a strut thickness of 70 μm and a surface treated with titanium dioxide onto which everolimus-eluting stent (EES) is applied abluminally (6 µg/mm of stent length) without utilization of a polymer. Methods: A total of 20 patients were enrolled, with de novo coronary lesions (stable or unstable angina) and > 50% diameter stenosis in a vessel 2.25 to 4.00 mm in diameter and ≤ 40 mm in length for angiographic, optical coherence tomography (OCT), and clinical assessment at 8 months. All patients received DAPT after stent implantation. The primary endpoint was angiographic in-stent late lumen loss (LLL) at 8 months. Results: Twenty patients with 20 lesions were treated with TIGERevolutioN® . At 8 months, in-stent LLL was 0.7 ± 0.4 mm. On OCT, percent area stenosis was 29.2 ± 9.4% and stent strut coverage was complete in all lesions. No adverse cardiovascular event occurred at 8 months. Conclusion The new polymer-free EES was safe and effective with low LLL and excellent strut coverage at 8 months of follow-up.

BACKGROUND: Current polymer-based drug-eluting stents (DESs) have fundamental issues about inflammation and delayed re-endothelializaton of the vessel wall. Substance-P (SP), which plays an important role in inflammation and endothelial cells, has not yet been applied to coronary stents. Therefore, this study compares poly lactic-co-glycolic acid (PLGA)-based everolimus-eluting stents (PLGA-EESs) versus 2-methacryloyloxyethyl phosphorylcholine (MPC)-based SP-eluting stents (MPC-SPs) in in-vitro and in-vivo models. METHODS: The morphology of the stent surface and peptide/drug release kinetics from stents were evaluated. The invitro proliferative effect of SP released from MPC-SP is evaluated using human umbilical vein endothelial cell. Finally, the safety and efficacy of the stent are evaluated after inserting it into a pig’s coronary artery. RESULTS: Similar to PLGA-EES, MPC-SP had a uniform surface morphology with very thin coating layer thickness (2.074 lm). MPC-SP showed sustained drug release of SP for over 2 weeks. Endothelial cell proliferation was significantly increased in groups treated with SP (n = 3) compared with the control (n = 3) and those with everolimus (n = 3) (SP:118.9 ± 7.61% vs. everolimus: 64.3 ± 12.37% vs. the control: 100 ± 6.64%, p < 0.05). In the animal study, the percent stenosis was higher in MPC-SP group (n = 7) compared to PLGA-EES group (n = 7) (MPC-SP: 28.6 ± 10.7% vs. PLGAEES: 16.7 ± 6.3%, p < 0.05). MPC-SP group showed, however, lower inflammation (MPC-SP: 0.3 ± 0.26 vs. PLGAEES: 1.2 ± 0.48, p < 0.05) and fibrin deposition (MPC-SP: 1.0 ± 0.73 vs. PLGA-EES: 1.5 ± 0.59, p < 0.05) around the stent strut. MPC-SP showed more increased expression of cluster of differentiation 31, suggesting enhanced reendothelialization. CONCLUSION Compared to PLGA-EES, MPC-SP demonstrated more decreased inflammation of the vascular wall and enhanced re-endothelialization and stent coverage. Hence, MPC-SP has the potential therapeutic benefits for the treatment of coronary artery disease by solving limitations of currently available DESs.

Purpose: The treatment of male breast cancer (MBC) has been extrapolated from female breast cancer (FBC) because of its rarity despite their different clinicopathologic characteristics. We aimed to investigate the distribution of intrinsic subtypes based on immunohistochemistry, their clinical impact, and treatment pattern in clinical practice through a multicenter study in Korea. Materials and Methods: We retrospectively analyzed clinical data of 248 MBC patients from 18 institutions across the country from January 1995 to July 2016. Results: The median age of MBC patients was 63 years (range, 25 to 102 years). Among 148 intrinsic subtype classified patients, 61 (41.2%), 44 (29.7%), 29 (19.5%), and 14 (9.5%) were luminal A, luminal B, human epidermal growth factor receptor 2, and triple-negative breast cancer, respectively. Luminal A subtype showed trends for superior survival compared to other subtypes. Most hormone receptor-positive patients (166 patients, 82.6%) received adjuvant endocrine treatment. Five-year completion of adjuvant endocrine treatment was associated with superior disease-free survival (DFS) in patients classified with an intrinsic subtype (hazard ratio [HR], 0.15; 95% confidence interval [CI], 0.04 to 0.49; p=0.002) and in all patients (HR, 0.16; 95% CI, 0.05 to 0.54; p=0.003). Conclusion Distribution of subtypes of MBC was similar to FBC and luminal type A was most common. Overall survival tended to be improved for luminal A subtype, although there was no statistical significance. Completion of adjuvant endocrine treatment was associated with prolonged DFS in intrinsic subtype classified patients. MBC patients tended to receive less treatment. MBC patients should receive standard treatment according to guidelines as FBC patients.

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.

BACKGROUND/OBJECTIVES: Dyslipidemia causes metabolic disorders such as atherosclerosis and fatty liver syndrome due to abnormally high blood lipids. Purple perilla frutescens extract (PPE) possesses various bioactive compounds such as α-asarone, chlorogenic acid and rosmarinic acid. This study examined whether PPE and α-asarone improved dyslipidemia-associated inflammation and inhibited atheroma formation in apolipoprotein E (apoE)-deficient mice, an experimental animal model of atherosclerosis.MATERIALS/METHODS: ApoE-deficient mice were fed on high cholesterol-diet (Paigen’s diet) and orally administrated with 10–20 mg/kg PPE and α-asarone for 10 wk. RESULTS: The Paigen’s diet reduced body weight gain in apoE-deficient mice, which was not restored by PPE or α-asarone. PPE or α-asarone improved the plasma lipid profiles in Paigen’s diet-fed apoE-deficient mice, and despite a small increase in high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein (LDL)-cholesterol, and very LDL were significantly reduced. Paigen’s diet-induced systemic inflammation was reduced in PPE or α-asarone-treated apoE-deficient mice. Supplying PPE or α-asarone to mice lacking apoE suppressed aorta atherogenesis induced by atherogenic diet. PPE or α-asarone diminished aorta accumulation of CD68- and/or F4/80-positive macrophages induced by atherogenic diet in apoE-deficient mice. Treatment of apoE-deficient mice with PPE and α-asarone resulted in a significant decrease in plasma cholesteryl ester transfer protein level and an increase in lecithin:cholesterol acyltransferase reduced by supply of Paigen’s diet. Supplementation of PPE and α-asarone enhanced the transcription of hepatic apoA1 and SR-B1 reduced by Paigen’s diet in apoE-deficient mice. CONCLUSIONS α-Asarone in PPE inhibited inflammation-associated atheroma formation and promoted hepatic HDL-C trafficking in dyslipidemic mice.

Purpose: This study aimed to analyze whether patients with lung cancer have a higher susceptibility of coronavirus disease 2019 (COVID-19), severe presentation, and higher mortality than those without lung cancer. Materials and Methods: A nationwide cohort of confirmed COVID-19 (n=8,070) between January 1, 2020, and May 30, 2020, and a 1:15 age-, sex-, and residence-matched cohort (n=121,050) were constructed. A nested case-control study was performed to compare the proportion of patients with lung cancer between the COVID-19 cohort and the matched cohort. Results: The proportion of patients with lung cancer was significantly higher in the COVID-19 cohort (0.5% [37/8,070]) than in the matched cohort (0.3% [325/121,050]) (p=0.002). The adjusted odds ratio [OR] of having lung cancer was significantly higher in the COVID-19 cohort than in the matched cohort (adjusted OR, 1.51; 95% confidence interval [CI], 1.05 to 2.10). Among patients in the COVID-19 cohort, compared to patients without lung cancer, those with lung cancer were more likely to have severe COVID-19 (54.1% vs. 13.2%, p < 0.001), including mortality (18.9% vs. 2.8%, p < 0.001). The adjusted OR for the occurrence of severe COVID-19 in patients with lung cancer relative to those without lung cancer was 2.24 (95% CI, 1.08 to 4.74). Conclusion The risk of COVID-19 occurrence and severe presentation, including mortality, may be higher in patients with lung cancer than in those without lung cancer.

Background: Titanium dioxide films exhibit good biocompatibility and may be effective as drug-binding matrices for drug-eluting stents. We conducted a mid-term evaluation of a novel polymer-free everolimus-eluting stent using nitrogen-doped titanium dioxide film deposition (TIGEREVOLUTION® ) in comparison with a commercial durable polymer everolimus-eluting stent (XIENCE Alpine® ) in a porcine coronary restenosis model. Methods: Twenty-eight coronary arteries from 14 mini-pigs were randomly allocated to TIGEREVOLUTION® stent and XIENCE Alpine® stent groups. The stents were implanted in the coronary artery at a 1.1–1.2:1 stent-to-artery ratio. Eleven stented coronary arteries in each group were finally analyzed using coronary angiography, optical coherence tomography, and histopathologic evaluation 6 months after stenting. Results: Quantitative coronary analysis showed no significant differences in the preprocedural, post-procedural, and 6-month lumen diameters between the groups. In the volumetric analysis of optical coherence tomography at 6 months, no significant differences were observed in stent volume, lumen volume, and percent area stenosis between the groups. There were no significant differences in injury score, inflammation score, or fibrin score between the groups, although the fibrin score was zero in the TIGEREVOLUTION® stent group (0 vs. 0.07 ± 0.11, P = 0.180). Conclusion Preclinical evaluation, including optical coherence tomographic findings 6 months after stenting, demonstrated that the TIGEREVOLUTION® stent exhibited efficacy and safety comparable with the XIENCE Alpine® stent, supporting the need for further clinical studies on the TIGEREVOLUTION® stent.

Background: Titanium dioxide films exhibit good biocompatibility and may be effective as drug-binding matrices for drug-eluting stents. We conducted a mid-term evaluation of a novel polymer-free everolimus-eluting stent using nitrogen-doped titanium dioxide film deposition (TIGEREVOLUTION® ) in comparison with a commercial durable polymer everolimus-eluting stent (XIENCE Alpine® ) in a porcine coronary restenosis model. Methods: Twenty-eight coronary arteries from 14 mini-pigs were randomly allocated to TIGEREVOLUTION® stent and XIENCE Alpine® stent groups. The stents were implanted in the coronary artery at a 1.1–1.2:1 stent-to-artery ratio. Eleven stented coronary arteries in each group were finally analyzed using coronary angiography, optical coherence tomography, and histopathologic evaluation 6 months after stenting. Results: Quantitative coronary analysis showed no significant differences in the preprocedural, post-procedural, and 6-month lumen diameters between the groups. In the volumetric analysis of optical coherence tomography at 6 months, no significant differences were observed in stent volume, lumen volume, and percent area stenosis between the groups. There were no significant differences in injury score, inflammation score, or fibrin score between the groups, although the fibrin score was zero in the TIGEREVOLUTION® stent group (0 vs. 0.07 ± 0.11, P = 0.180). Conclusion Preclinical evaluation, including optical coherence tomographic findings 6 months after stenting, demonstrated that the TIGEREVOLUTION® stent exhibited efficacy and safety comparable with the XIENCE Alpine® stent, supporting the need for further clinical studies on the TIGEREVOLUTION® stent.

Purpose: This study aimed to analyze whether patients with lung cancer have a higher susceptibility of coronavirus disease 2019 (COVID-19), severe presentation, and higher mortality than those without lung cancer. Materials and Methods: A nationwide cohort of confirmed COVID-19 (n=8,070) between January 1, 2020, and May 30, 2020, and a 1:15 age-, sex-, and residence-matched cohort (n=121,050) were constructed. A nested case-control study was performed to compare the proportion of patients with lung cancer between the COVID-19 cohort and the matched cohort. Results: The proportion of patients with lung cancer was significantly higher in the COVID-19 cohort (0.5% [37/8,070]) than in the matched cohort (0.3% [325/121,050]) (p=0.002). The adjusted odds ratio [OR] of having lung cancer was significantly higher in the COVID-19 cohort than in the matched cohort (adjusted OR, 1.51; 95% confidence interval [CI], 1.05 to 2.10). Among patients in the COVID-19 cohort, compared to patients without lung cancer, those with lung cancer were more likely to have severe COVID-19 (54.1% vs. 13.2%, p < 0.001), including mortality (18.9% vs. 2.8%, p < 0.001). The adjusted OR for the occurrence of severe COVID-19 in patients with lung cancer relative to those without lung cancer was 2.24 (95% CI, 1.08 to 4.74). Conclusion The risk of COVID-19 occurrence and severe presentation, including mortality, may be higher in patients with lung cancer than in those without lung cancer.

BACKGROUND/AIMS: Although eosinophilic liver infiltration (ELI) is not rare, few data exist regarding its clinical characteristics and etiology. Therefore, we evaluated these aspects to better understand the clinical implications of this lesion type, which is reasonably common in Korea. METHODS: Patients suspected of having ELI, based on abdominal computed tomography results obtained between January 2010 and September 2017, were enrolled in this retrospective study. The presumptive etiologies of ELI were categorized as parasite infections, hypereosinophilic syndrome (HES), eosinophilic granulomatosis with polyangiitis (EGPA), malignancies, and unidentified. Clinical courses and treatment responses were also evaluated. RESULTS: The mean age of the enrolled patients (male, 237/328) was 62 years. Most patients (63%) were diagnosed incidentally and had peripheral eosinophilia (90%). Only 38% of the enrolled patients (n=126) underwent further evaluations to elucidate the etiology of the suspected ELI; 82 (25%) had parasite infections, 31 (9%) had HES, five (2%) had EGPA, and five (2%) had drug reactions in conjunction with eosinophilia and systemic symptoms. Almost half of the other enrolled patients had cancer. Radiologic resolution was achieved in 191 patients (61%; median time to radiologic resolution, 185 days). Resolution of peripheral eosinophilia was achieved in 220 patients (79%). In most cases, the course of ELI was benign. CONCLUSIONS: This large ELI study is unique in that the incidence rate, underlying diseases, and clinical courses were comprehensively evaluated. Clinicians should investigate the etiology of ELI, as several of the underlying diseases require intervention rather than observation.
Eosinophilia ; Eosinophils ; Granulomatosis with Polyangiitis ; Humans ; Hypereosinophilic Syndrome ; Incidence ; Korea ; Liver ; Parasites ; Retrospective Studies