Background: Type 2 diabetes mellitus (T2DM) induces endothelial dysfunction and inflammation, which are the main factors for atherosclerosis and cardiovascular disease. The present study aimed to compare the effects of rosuvastatin monotherapy and rosuvastatin/ezetimibe combination therapy on lipid profile, insulin sensitivity, and vascular inflammatory response in patients with T2DM. Methods: A total of 101 patients with T2DM and dyslipidemia were randomized to either rosuvastatin monotherapy (5 mg/day, n=47) or rosuvastatin/ezetimibe combination therapy (5 mg/10 mg/day, n=45) and treated for 12 weeks. Serum lipids, glucose, insulin, soluble intercellular adhesion molecule-1 (sICAM-1), and peroxiredoxin 4 (PRDX4) levels were determined before and after 12 weeks of treatment. Results: The reduction in low density lipoprotein cholesterol (LDL-C) by more than 50% from baseline after treatment was more in the combination therapy group. The serum sICAM-1 levels increased significantly in both groups, but there was no difference between the two groups. The significant changes in homeostasis model assessment of insulin resistance (HOMA-IR) and PRDX4 were confirmed only in the subgroup in which LDL-C was reduced by 50% or more in the combination therapy group. However, after adjusting for diabetes mellitus duration and hypertension, the changes in HOMA-IR and PRDX4 were not significant between the two groups. Conclusion Although rosuvastatin/ezetimibe combination therapy had a greater LDL-C reduction effect than rosuvastatin monotherapy, it had no additional effects on insulin sensitivity and vascular inflammatory response. Further studies are needed on the effect of long-term treatment with ezetimibe on insulin sensitivity and vascular inflammatory response.

Background and Objectives: Atrial fibrillation (AF) is associated with decreased cardiac resynchronization therapy (CRT) benefits compared to sinus rhythm (SR). Effective biventricular (BiV) pacing is a determinant of CRT success, but AF can interfere with adequate BiV pacing and affect clinical outcomes. We investigated the effect of device-detected AF on clinical outcomes and optimal BiV pacing in patients with heart failure (HF) treated with CRT. Methods: We retrospectively analyzed 174 patients who underwent CRT implantation between 2012 and 2019 at a tertiary center. The optimal BiV pacing percentage was defined as ≥98%. Device-detected AF was defined as an atrial high-rate episode ≥180 beats per minute lasting more than 6 minutes during the follow-up period. We stratified the patients without preexisting AF at pre-implantation into device-detected AF and no-AF groups. Results: A total of 120 patients did not show preexisting AF at pre-implantation, and 54 had AF. Among these 120 patients, 19 (15.8%) showed device-detected AF during a median follow-up of 25.1 months. The proportion of optimal BiV pacing was significantly lower in the device-detected AF group than in the no-AF group (42.1% vs. 75.2%, p=0.009). The devicedetected AF group had a higher incidence of HF hospitalization, cardiovascular death, and all-cause death than the no-AF group. The device-detected AF and previous AF groups showed no significant differences regarding the percentage of BiV pacing and clinical outcomes. Conclusions For HF patients implanted with CRT, device-detected AF was associated with lower optimal BiV pacing and worse clinical outcomes than no-AF.

Background: Topical recombinant human epidermal growth factor (rhEGF) is effective in the treatment of diabetic foot ulcers, surgical wounds, burns, and scars. Binding of EGF to EGF receptors results in cell proliferation and differentiation. Objective: This study aimed to evaluate the efficacy of topical rhEGF ointment compared with that of topical mupirocin in healing herpes zoster (HZ) lesions. Methods: Thirty patients diagnosed with typical HZ were recruited in August, 2018. The rats were randomly divided into two groups: topical mupirocin and topical rhEGF ointment. HZ lesions were evaluated using the Vancouver Scar Scale (VSS) at the initial visit, 1st, 2nd, and 4th weeks. Results: The total number of recruited patients (n=30) included males (n=16, 53.3%) and females (n=14, 46.7%) with a mean age of 58.2. The proportion of patients with a 50% reduction in the VSS score (VSS 50) at 2nd week was significantly higher in the rhEGF group (33.0% vs. 72.0%, respectively, p=0.035). The complete resolution rate (VSS=0, 1) at 4th week was also higher in the rhEGF group (17.5% vs. 50.0%, p=0.03). Conclusion Topical rhEGF showed a more rapid treatment response and anti-scarring effect than topical mupirocin in patients with HZ lesions.

Background: Gestational diabetes mellitus (GDM) is the most common metabolic complication of pregnancy. To define the altered pathway in GDM placenta, we investigated the transcriptomic profiles from human placenta between GDM and controls. Methods: Clinical parameters and postpartum complications were reviewed in all participants.Differentially expressed canonical pathways were analyzed between the GDM and control groups based on transcriptomic analysis. CD4 + T, CD8 + T, and senescent T cell subsets were determined by flow cytometry based on staining for specific intracellular cytokines. Results: Gene ontology analysis revealed that the placenta of GDM revealed upregulation of diverse mitochondria or DNA replication related pathways and downregulation of T-cell immunity related pathways. The maternal placenta of the GDM group had a higher proportion of CD4 + T and CD8 + T cells than the control group. Interestingly, senescent CD4 + T cells tended to increase and CD8 + T cells were significantly increased in GDM compared to controls, along with increased programmed cell death-1 (CD274 + ) expression. Programmed death-ligand 1 expression in syncytotrophoblasts was also significantly increased in patients with GDM. Conclusion This study demonstrated increased proinflammatory T cells, senescent T cells and immune-check point molecules in GDM placentas, suggesting that changes in senescent T cells and immune-escape signaling might be related to the pathophysiology of GDM.

Background: There has been no comparison of the determinants of admission route between acute ischemic stroke (AIS) and acute myocardial infarction (AMI). We examined whether factors associated with direct versus transferred-in admission to regional cardiocerebrovascular centers (RCVCs) differed between AIS and AMI. Methods: Using a nationwide RCVC registry, we identified consecutive patients presenting with AMI and AIS between July 2016 and December 2018. We explored factors associated with direct admission to RCVCs in patients with AIS and AMI and examined whether those associations differed between AIS and AMI, including interaction terms between each factor and disease type in multivariable models. To explore the influence of emergency medical service (EMS) paramedics on hospital selection, stratified analyses according to use of EMS were also performed. Results: Among the 17,897 and 8,927 AIS and AMI patients, 66.6% and 48.2% were directly admitted to RCVCs, respectively. Multivariable analysis showed that previous coronary heart disease, prehospital awareness, higher education level, and EMS use increased the odds of direct admission to RCVCs, but the odds ratio (OR) was different between AIS and AMI (for the first 3 factors, AMI > AIS; for EMS use, AMI < AIS). EMS use was the single most important factor for both AIS and AMI (OR, 4.72 vs. 3.90). Hypertension and hyperlipidemia increased, while living alone decreased the odds of direct admission only in AMI;additionally, age (65–74 years), previous stroke, and presentation during non-working hours increased the odds only in AIS. EMS use weakened the associations between direct admission and most factors in both AIS and AMI. Conclusions Various patient factors were differentially associated with direct admission to RCVCs between AIS and AMI. Public education for symptom awareness and use of EMS is essential in optimizing the transportation and hospitalization of patients with AMI and AIS.

Background: Cardiac resynchronization therapy (CRT) is an effective treatment option for patients with heart failure (HF) and left ventricular (LV) dyssynchrony. However, the problem of some patients not responding to CRT remains unresolved. This study aimed to propose a novel in silico method for CRT simulation. Methods: Three-dimensional heart geometry was constructed from computed tomography images. The finite ele‑ ment method was used to elucidate the electric wave propagation in the heart. The electric excitation and mechani‑ cal contraction were coupled with vascular hemodynamics by the lumped parameter model. The model parameters for three-dimensional (3D) heart and vascular mechanics were estimated by matching computed variables with measured physiological parameters. CRT effects were simulated in a patient with HF and left bundle branch block (LBBB). LV end-diastolic (LVEDV) and end-systolic volumes (LVESV), LV ejection fraction (LVEF), and CRT responsiveness measured from the in silico simulation model were compared with those from clinical observation. A CRT responder was defined as absolute increase in LVEF ≥ 5% or relative increase in LVEF ≥ 15%. Results: A 68-year-old female with nonischemic HF and LBBB was retrospectively included. The in silico CRT simu‑ lation modeling revealed that changes in LVEDV, LVESV, and LVEF by CRT were from 174 to 173 mL, 116 to 104 mL, and 33 to 40%, respectively. Absolute and relative ΔLVEF were 7% and 18%, respectively, signifying a CRT responder.In clinical observation, echocardiography showed that changes in LVEDV, LVESV, and LVEF by CRT were from 162 to 119 mL, 114 to 69 mL, and 29 to 42%, respectively. Absolute and relative ΔLVESV were 13% and 31%, respectively, also signifying a CRT responder. CRT responsiveness from the in silico CRT simulation model was concordant with that in the clinical observation. Conclusion This in silico CRT simulation method is a feasible technique to screen for CRT non-responders in patients with HF and LBBB.

Background and Objectives: Ambient particulate matter (PM) in real urban air pollution (RUA) is an environmental health risk factor associated with increased cardiac events. This study investigated the threshold level to induce arrhythmia, as well as arrhythmogenic mechanism of RUA that mainly consisted of PM <2.5 μm in aerodynamic diameter close to ultrafine particles. Methods: RUA was artificially produced by a lately developed pyrolysis based RUA generator.C57BL/6 mice were divided into 4 groups: a control group (control, n=12) and three groups with exposure to RUA with the concentration of 200 µg/㎥ (n=12), 400 µg/㎥ (n=12), and 800 µg/㎥ (n=12). Mice were exposed to RUA at each concentration for 8 hr/day and 5 day/week to mimic ordinary human activity during 3 weeks. Results: The QRS and QTc intervals, as well as intracellular Ca2+ duration, apicobasal action potential duration (APD) gradient, fibrosis, and inflammation of left ventricle of mouse hearts were increased dose-dependently with the increase of RUA concentration, and significantly increased at RUA concentration of 400 µg/㎥ compared to control (all p<0.001). In mice exposed to RUA concentration of 800 µg/㎥ , spontaneous ventricular arrhythmia was observed in 42%, with significant increase of inflammatory markers, phosphorylated Ca2+ /calmodulindependent protein kinase II (CaMKII), and phospholamban (PLB) compared to control. Conclusions RUA could induce electrophysiological changes such as APD and QT prolongation, fibrosis, and inflammation dose-dependently, with significant increase of ventricular arrhythmia at the concentration of 400 µg/㎥ . RUA concentration of 800 µg/㎥ increased phosphorylation of CaMKII and PLB.

Background and Objectives: Atrial high-rate episodes (AHREs) can be continuously detected by cardiovascular implantable electronic devices (CIEDs); however, the predictors of clinically relevant AHREs are unclear. Methods: This prospective multicenter study monitored 816 patients (median age 73 years, 40.4% male) without atrial fibrillation (AF) from September 2017 to July 2020. AHREs was defined as a programmed atrial detection rate >220 beats/min. The reference values of 6 minutes and 6 hours were set to analyze clinical implication of AHREs based on previously published data that the 6 minutes excluded most episodes of oversensing. Results: During a median follow-up of 18 months (interquartile interval 9–26 months), AHREs with the longest durations of >15 seconds, >6 minutes, and >6 hours and clinically documented AF by electrocardiography were noted in 246 (30.1%), 112 (13.7%), 49 (6.0%), and 24 (2.9%) patients, respectively. Among patients developing AHREs >6 minutes, 102 (91.1%) of 112 patients were identified at the 6-month visit. Patients with AHREs >6 minutes had higher proportions of sick sinus syndrome, subjects with atrial premature beat >1% on Holter monitoring, and larger left atrium (LA) size than patients with AHREs ≤6 minutes.Multivariable logistic regression analysis showed that LA diameter >41 mm (odds ratio [OR], 2.08; 95% confidence interval [95% CI], 1.25–3.45), and sick sinus syndrome (OR, 3.22; 95% CI, 1.91–5.43) were associated with AHREs >6 minutes. Conclusions In patients with LA diameter >41 mm, and sick sinus syndrome before CIEDs implantation is associated with risk of developing AHREs >6 minutes.

Objective: Anosognosia is a common phenomenon in individuals with dementia. Anosognosia Questionnaire for dementia (AQ-D) is a well-known scale for evaluating anosognosia. This study aimed to establish a Korean version of the AQ-D (AQ-D-K) and to evaluate the reliability and validity of the AQ-D-K in patients with Alzheimer’s disease (AD) dementia. Methods: We translated the original English version of AQ-D into Korean (AQ-D-K). Eighty-four subjects with very mild or mild AD dementia and their caregivers participated. Reliability of AQ-D-K was assessed by internal consistency and one-month test-retest reliability. Construct validity and concurrent validity were also evaluated. Results: Internal consistencies of the AQ-D-K patient form and caregiver form were high (Cronbach alpha 0.95 and 0.93, respectively). The test-retest reliability of AQ-D-K measured by intra-class correlation coefficient was 0.84. Three factors were identified: 1) anosognosia of instrumental activity of daily living; 2) anosognosia basic activity of daily living; and 3) anosognosia of depression and disinhibition. AQ-D-K score was significantly correlated with the clinician-rated anosognosia rating scale (ARS), center for epidemiological studies-depression scale (CES-D) and state-trait anxiety inventory (STAI). Conclusion The findings suggest that the AQ-D-K is a reliable and valid scale for evaluating anosognosia for AD dementia patients using Korean language.

In 2017, Korean Society of Medical Oncology (KSMO) published the Korean management guideline of metastatic prostate cancer. This paper is the 2nd edition of the Korean management guideline of metastatic prostate cancer. We updated recent many changes of management in metastatic prostate cancer in this 2nd edition guideline. The present guideline consists of the three categories: management of metastatic hormone sensitive prostate cancer; management of metastatic castration resistant prostate cancer; and clinical consideration for treating patients with metastatic prostate cancer. In category 1 and 2, levels of evidence (LEs) have been mentioned according to the general principles of evidence-based medicine. And grades of recommendation (GR) was taken into account the quality of evidence, the balance between desirable and undesirable effects, the values and preferences, and the use of resources and GR were divided into strong recommendations (SR) and weak recommendations (WR). A total of 16 key questions are selected. And we proposed recommendations and described key evidence for each recommendation. The treatment landscape of metastatic prostate cancer is changing very rapid and many trials are ongoing. To verify the results of the future trials is necessary and should be applied to the treatment for metastatic prostate cancer patients in the clinical practice. Especially, many prostate cancer patients are old age, have multiple underlying medical comorbidities, clinicians should be aware of the significance of medical management as well as clinical efficacy of systemic treatment.