The development of drug-resistant influenza and new pathogenic virus strains underscores the need for antiviral therapeutics. Currently, neuraminidase (NA) inhibitors are commonly used antiviral drugs approved by the US Food and Drug Administration (FDA) for the prevention and treatment of influenza. Here, we show that vitisin B (VB) inhibits NA activity and suppresses H1N1 viral replication in MDCK and A549 cells. Reactive oxygen species (ROS), which frequently occur during viral infection, increase virus replication by activating the NF-κB signaling pathway, downmodulating glucose-6-phosphate dehydrogenase (G6PD) expression, and decreasing the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) antioxidant response activity. VB decreased virus-induced ROS generation by increasing G6PD expression and Nrf2 activity, and inhibiting NF-κB translocation to the nucleus through IKK dephosphorylation. In addition, VB reduced body weight loss, increased survival, decreased viral replication and the inflammatory response in the lungs of influenza A virus (IAV)-infected mice. Taken together, our results indicate that VB is a promising therapeutic candidate against IAV infection, complements existing drug limitations targeting viral NA. It modulated the intracellular ROS by G6PD, Nrf2 antioxidant response pathway, and NF-κB signaling pathway. These results demonstrate the feasibility of a multi-targeting drug strategy, providing new approaches for drug discovery against IAV infection.

Background and Objectives: Endovascular therapy (EVT) first strategy has been widely adopted for the treatment of chronic limb threatening ischemia (CLTI) patients in realworld practice. This study aimed to investigate long-term outcomes of CLTI patients who underwent EVT and identify prognostic factors. Methods: From the retrospective cohorts of a Korean multicenter endovascular therapy registry, 1,036 patients with CLTI (792 men, 68.8 ± 9.5 years) were included. The primary endpoint was amputation-free survival (AFS) defined as the absence of major amputation or death. Secondary endpoints were major adverse limb events (MALE; a composite of major amputation, minor amputation, and reintervention). Results: Five-year AFS and freedom from MALE were 69.8% and 61%, respectively. After multivariate analysis, age (hazard ratio [HR], 1.476; p<0.001), end-stage renal disease (ESRD; HR, 2.340; p<0.001), Rutherford category (RC) 6 (HR, 1.456; p=0.036), and suboptimal EVT (HR, 1.798; p=0.005) were identified as predictors of major amputation or death, whereas smoking (HR, 0.594; p=0.007) was protective. Low body mass index (HR, 1.505; p=0.046), ESRD (HR, 1.648; p=0.001), femoropopliteal lesion (HR, 1.877; p=0.004), RC-6 (HR, 1.471;p=0.008), and suboptimal EVT (HR, 1.847; p=0.001) were predictors of MALE. The highest hazard rates were observed during the first 6 months for both major amputation or death and MALE. After that, the hazard rate decreased and rose again after 3–4 years. Conclusions In CLTI patients, long-term outcomes of EVT were acceptable. ESRD, RC-6, and suboptimal EVT were common predictors for poor clinical outcomes.

Background and Objectives: Limited data are available regarding long-term clinical outcomes of iliac artery endovascular therapy (EVT) in real-world practice. This study investigated long-term outcomes according to Trans-Atlantic Inter-Society Consensus (TASC) classifications. Methods: We analyzed data from 1,705 limbs of 1,364 patients from the retrospective cohort of the multicenter Korean Vascular Intervention Society Endovascular Therapy in Lower Limb Artery Disease registry. The primary endpoint was target lesion revascularization (TLR)-free survival. Results: TASC A, B, C, and D lesions were present in 19.4%, 26.2%, 28.7%, and 25.7% of the treated limbs, respectively. The technical success rate was 96.2% and did not differ between TASC lesion types. Complications occurred in 6.8% of cases and more occurred in TASC D (11.8%). Iliac artery EVT showed a 5-year TLR-free survival of 89.2%. The TASC D group had the lowest TLR-free rate of 79.3%. TASC D (hazard ratio [HR], 1.75; 95% confidence interval [CI], 1.12–2.73; p=0.014), plain old balloon angioplasty (HR, 4.25; 95% CI, 2.03–8.88; p<0.001), current smoker (HR, 1.89; 95% CI, 1.26–2.83; p=0.002), previous bypass surgery (HR, 3.04;95% CI, 1.28–7.19; p=0.011), combined femoropopliteal treatment (HR, 4.89; 95% CI, 3.19–7.50; p<0.001), combined below the knee treatment (HR, 2.20; 95% CI, 1.25–3.89; p=0.007), and complications (HR, 1.86; 95% CI, 1.07–3.24; p=0.028) were predictors for TLR. Conclusions Iliac artery EVT achieved excellent technical success and 5-year TLR-free survival. TASC D showed a favorable but lower 5-year TLR-free survival rate and higher complication rate compared with other TASC groups.

Background and Objectives: Few studies have investigated the obesity paradox in clinical outcomes of peripheral artery disease (PAD). We investigated the association between body massindex (BMI) and clinical outcomes in PAD patients undergoing endovascular therapy (EVT). Methods: Patients (n=2,914) from the retrospective Korean Vascular Intervention Society Endovascular Therapy in Lower Limb Artery Disease registry were categorized according to BMI: underweight (<18.5 kg/m2 , n=204), normal weight (18.5–25 kg/m2 , n=1,818), overweight (25–30 kg/m2 , n=766), or obese (≥30 kg/m2 , n=126). Groups were compared for major adverse cardiovascular events (MACE) and major adverse limb events (MALE). Results: The underweight and obese groups were older and had more frequent critical limb ischemia and infrapopliteal artery disease than the normal or overweight groups (all p<0.001). Hypertension and diabetes were more frequent and current smoking was less frequent in the overweight and obese groups than the underweight or normal weight groups (all p <0.001). The underweight group showed the higher rates of MACE and MALE at 3 years (17.2%, 15.7%) compared with the normal weight (10.8%, 11.7%), overweight (8.4%, 10.7%), or obese groups (8.7%, 14.3%) (log-rank p<0.001, p=0.015). In contrast, the risk of MACE was lower in the overweight than the normal weight group (adjusted hazard ratio, 0.706; 95% CI, 0.537–0.928). Conclusions In PAD patients undergoing EVT, underweight was an independent predictor for MACE and MALE, whereas MACE risk was lower for overweight than normal weight patients.

Background and Objectives: The EPIC™ stent is a self-expanding, nitinol stent that has been designed to enhance flexibility and provide expansion within vessels. The aim of the present study was to investigate the clinical efficacy and safety of the EPIC™ stent when used to treat iliac artery diseases in a prospective Korean multicenter registry. Methods: A total of 138 patients with iliac artery diseases who received endovascular treatment with EPIC™ stents at 9 Korean sites were enrolled in a prospective cohort and followed for 1 year. The primary endpoint was the 1-year freedom from target lesion revascularization (TLR). The secondary endpoints were 1-year clinical patency and freedom from major adverse events (MAEs). Results: The mean age of the study subjects was 66.8±8.5 years and most subjects were male (86.2%). The most frequent lesion type was Trans-Atlantic Inter-Society Consensus B (43.5%) and the majority (56.5%) of the target lesions were located in the common iliac artery. Procedural success was obtained in 99.3% of patients. The freedom from TLR and the clinical patency at 1-year follow-up were 94.9% and 92.3%, respectively. The 1-year rate of MAEs was 5.1%. Combined coronary artery disease (hazard ratio [HR], 5.91; 95% confidence interval [CI], 1.13–30.89; p=0.035) and smaller stent diameter (HR, 0.38; 95% CI, 0.17–0.88;p=0.023) were identified as independent risk factors of TLR after EPIC™ stent implantation. Conclusions The EPIC™ stents demonstrated excellent immediate and 1-year efficacy and safety outcomes in iliac artery lesions in this multicenter, prospective, registry-based study.

Tumor localization is challenging in the context of ductal carcinoma in situ (DCIS) treated with breast-conserving surgery. Conventional localization methods are generally performed under the guidance of ultrasonography or mammography and are rarely performed with magnetic resonance imaging (MRI), which is more sensitive than the aforementioned modalities in detecting DCIS. Here, we report the application of MRI-based individualized 3-dimensional (3D)-printed breast surgical guides (BSGs) for patients with breast cancer.We successfully resected indeterminate and suspicious lesions that were only detected using preoperative MRI, and the final histopathologic results confirmed DCIS with clear resection margins. MRI guidance combined with 3D-printed BSGs can be used for DCIS localization, especially for lesions easily detectable using MRI only.

Background and Objectives: Few studies have investigated the obesity paradox in clinical outcomes of peripheral artery disease (PAD). We investigated the association between body massindex (BMI) and clinical outcomes in PAD patients undergoing endovascular therapy (EVT). Methods: Patients (n=2,914) from the retrospective Korean Vascular Intervention Society Endovascular Therapy in Lower Limb Artery Disease registry were categorized according to BMI: underweight (<18.5 kg/m2 , n=204), normal weight (18.5–25 kg/m2 , n=1,818), overweight (25–30 kg/m2 , n=766), or obese (≥30 kg/m2 , n=126). Groups were compared for major adverse cardiovascular events (MACE) and major adverse limb events (MALE). Results: The underweight and obese groups were older and had more frequent critical limb ischemia and infrapopliteal artery disease than the normal or overweight groups (all p<0.001). Hypertension and diabetes were more frequent and current smoking was less frequent in the overweight and obese groups than the underweight or normal weight groups (all p <0.001). The underweight group showed the higher rates of MACE and MALE at 3 years (17.2%, 15.7%) compared with the normal weight (10.8%, 11.7%), overweight (8.4%, 10.7%), or obese groups (8.7%, 14.3%) (log-rank p<0.001, p=0.015). In contrast, the risk of MACE was lower in the overweight than the normal weight group (adjusted hazard ratio, 0.706; 95% CI, 0.537–0.928). Conclusions In PAD patients undergoing EVT, underweight was an independent predictor for MACE and MALE, whereas MACE risk was lower for overweight than normal weight patients.

Background and Objectives: The EPIC™ stent is a self-expanding, nitinol stent that has been designed to enhance flexibility and provide expansion within vessels. The aim of the present study was to investigate the clinical efficacy and safety of the EPIC™ stent when used to treat iliac artery diseases in a prospective Korean multicenter registry. Methods: A total of 138 patients with iliac artery diseases who received endovascular treatment with EPIC™ stents at 9 Korean sites were enrolled in a prospective cohort and followed for 1 year. The primary endpoint was the 1-year freedom from target lesion revascularization (TLR). The secondary endpoints were 1-year clinical patency and freedom from major adverse events (MAEs). Results: The mean age of the study subjects was 66.8±8.5 years and most subjects were male (86.2%). The most frequent lesion type was Trans-Atlantic Inter-Society Consensus B (43.5%) and the majority (56.5%) of the target lesions were located in the common iliac artery. Procedural success was obtained in 99.3% of patients. The freedom from TLR and the clinical patency at 1-year follow-up were 94.9% and 92.3%, respectively. The 1-year rate of MAEs was 5.1%. Combined coronary artery disease (hazard ratio [HR], 5.91; 95% confidence interval [CI], 1.13–30.89; p=0.035) and smaller stent diameter (HR, 0.38; 95% CI, 0.17–0.88;p=0.023) were identified as independent risk factors of TLR after EPIC™ stent implantation. Conclusions The EPIC™ stents demonstrated excellent immediate and 1-year efficacy and safety outcomes in iliac artery lesions in this multicenter, prospective, registry-based study.

Tumor localization is challenging in the context of ductal carcinoma in situ (DCIS) treated with breast-conserving surgery. Conventional localization methods are generally performed under the guidance of ultrasonography or mammography and are rarely performed with magnetic resonance imaging (MRI), which is more sensitive than the aforementioned modalities in detecting DCIS. Here, we report the application of MRI-based individualized 3-dimensional (3D)-printed breast surgical guides (BSGs) for patients with breast cancer.We successfully resected indeterminate and suspicious lesions that were only detected using preoperative MRI, and the final histopathologic results confirmed DCIS with clear resection margins. MRI guidance combined with 3D-printed BSGs can be used for DCIS localization, especially for lesions easily detectable using MRI only.

Background: and PurposeImpulse-control disorder is an important nonmotor symptom of Parkinson's disease (PD) that can lead to financial and social problems, and be related to a poor quality of life. A nationwide multicenter prospective study was performed with the aim of validating the Korean Version of the Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease Rating Scale (K-QUIP-RS). Methods: The K-QUIP-RS was constructed using forward and backward translation, and pretesting of the prefinal version. PD patients on stable medical condition were recruited from 27 movement-disorder clinics. Participants were assessed using the K-QUIP-RS and evaluated for parkinsonian motor and nonmotor statuses and for PD-related quality of life using a predefined evaluation battery. The test–retest reliability of the K-QUIP-RS was assessed over an interval of 10–14 days, and correlations between the KQUIP-RS and other clinical scales were analyzed. Results: This study enrolled 136 patients. The internal consistency of the K-QUIP-RS was indicated by a Cronbach's α coefficient of 0.846, as was the test–retest reliability by a Guttman split-half coefficient of 0.808. The total K-QUIP-RS score was positively correlated with the scores for depression and motivation items on the Unified PD Rating Scale (UPDRS), Montgomery-Asberg Depression Scale, and Rapid-Eye-Movement Sleep-Behavior-Disorders Questionnaire. The total K-QUIP-RS score was also correlated with the scores on part II of the UPDRS and the PD Quality of Life-39 questionnaire, and the dopaminergic medication dose. Conclusions The K-QUIP-RS appears to be a reliable assessment tool for impulse-control and related behavioral disturbances in the Korean PD population.