This study aimed to compare the pharmacokinetic (PK) and safety profiles of 2 fenofibric acid formulations under fasting and fed conditions. The reference was a 135 mg capsule, while the test was a 110 mg enteric-coated tablet. This randomized, open-label, two-sequence, two-period crossover phase 1 clinical trial was conducted in healthy Korean men. Sixty participants were enrolled in each of the fasting and feeding groups. Blood samples were collected 72 hours after drug administration. PK parameters were calculated using a noncompartmental method with Phoenix WinNonlin ® . A total of 53 and 51 participants from the fasting and feeding groups, respectively, completed the study. The geometric mean ratio and 90% confidence intervals of the maximum concentration (C max ) and area under the concentration-time curve to the last measurable plasma concentration were 0.9195 (0.8795–0.9614) and 0.8630 (0.8472–0.8791) in the fasting study and 1.0926 (1.0102–1.1818) and 0.9998 (0.9675–1.0332) in the fed study, respectively. The time to reach C max of the enteric-coated tablet compared to that of the capsule was extended by 1 and 3 hours under fasting and fed conditions, respectively. In conclusion, enteric-coated tablets have a higher bioavailability than capsules. In addition, the enteric-coated tablet was smaller than the capsule, making it easier for patients to swallow.

Background: For acute ischemic stroke (AIS) patients with history of prior stroke (PS) and diabetes mellitus (DM), intravenous recombinant tissue plasminogen activator (IV-tPA) therapy in the 3- to 4.5-hour window is off-label in Korea. This study aimed to assess the safety and efficacy of IV-tPA in these patients. Methods: Using data from a prospective multicenter stroke registry between January 2009 and March 2021, we identified AIS patients who received IV-tPA in the 3- to 4.5-hour window, and compared the outcomes of symptomatic intracranial hemorrhage (SICH), 3-month mortality, 3-month modified Rankin Scale (mRS) score 0-1 and 3-month mRS distribution between patients with both PS and DM (PS/DM, n=56) versus those with neither PS nor DM, or with only one (non-PS/DM, n=927). Results: The PS/DM group versus the non-PS/DM group was more likely to have a prior disability, hypertension, hyperlipidemia, coronary heart disease and less likely to have atrial fibrillation. The PS/DM and the non-PS/DM groups had comparable rates of SICH (0% vs. 1.7%; p>0.999) and 3-month mortality (10.7% vs. 10.2%; p=0.9112). The rate of 3-month mRS 0-1 was non-significantly lower in the PS/DM group than in the non-PS/DM group (30.4% vs. 40.7%; adjusted odds ratio [95% confidence interval], 0.81 [0.41-1.59]). Conclusions In the 3- to 4.5-hour window, AIS patients with PS/DM, as compared to those with non-PS/DM, might benefit less from IV-tPA. However, given the similar risks of SICH and mortality, IV-tPA in the late time window could be considered in patients with both PS and DM.

Background and Objectives: Smoking is well-established as a risk factor for coronary artery disease. However, recent studies demonstrated favorable results, including reduced mortality, among smokers, which are referred to as the “smoker's paradox”. This study examined the impact of smoking on clinical outcomes in patients with acute myocardial infarction (AMI) undergoing percutaneous coronary intervention (PCI). Methods: Patients with AMI undergoing PCI between 2004 and 2014 were enrolled and classified according to smoking status. The primary endpoint was a composite of major adverse cardiovascular events (MACE) including cardiac death, myocardial infarction, stroke, and revascularization. Results: Among the 10,683 patients, 4,352 (40.7%) were current smokers. Smokers were 10.7 years younger and less likely to have comorbidities such as hypertension, diabetes mellitus, chronic kidney disease, stroke, and prior PCI. Smokers had less MACE (hazard ratio [HR], 0.644; 95% confidence interval [CI], 0.594–0.698; p<0.001) and cardiac death (HR, 0.494; 95% CI, 0.443–0.551; p<0.001) compared to nonsmokers during the 5 years in an unadjusted model. However, after propensity-score matching, smokers showed higher risk of MACE (HR, 1.125; 95% CI, 1.009–1.254; p=0.034) and cardiac death (HR, 1.190; 95% CI, 1.026–1.381; p=0.022). Smoking was a strong independent predictor of lung cancer (propensityscore matched HR, 2.749; 95% CI, 1.416–5.338; p=0.003). Conclusions In contrast to the unadjusted model, smoking is associated with worse cardiovascular outcome and higher incidence of lung cancer after adjustment of various confounding factors. This result can be explained by the characteristics of smokers, which were young and had fewer comorbidities.

Background and Objectives: Smoking is well-established as a risk factor for coronary artery disease. However, recent studies demonstrated favorable results, including reduced mortality, among smokers, which are referred to as the “smoker's paradox”. This study examined the impact of smoking on clinical outcomes in patients with acute myocardial infarction (AMI) undergoing percutaneous coronary intervention (PCI). Methods: Patients with AMI undergoing PCI between 2004 and 2014 were enrolled and classified according to smoking status. The primary endpoint was a composite of major adverse cardiovascular events (MACE) including cardiac death, myocardial infarction, stroke, and revascularization. Results: Among the 10,683 patients, 4,352 (40.7%) were current smokers. Smokers were 10.7 years younger and less likely to have comorbidities such as hypertension, diabetes mellitus, chronic kidney disease, stroke, and prior PCI. Smokers had less MACE (hazard ratio [HR], 0.644; 95% confidence interval [CI], 0.594–0.698; p<0.001) and cardiac death (HR, 0.494; 95% CI, 0.443–0.551; p<0.001) compared to nonsmokers during the 5 years in an unadjusted model. However, after propensity-score matching, smokers showed higher risk of MACE (HR, 1.125; 95% CI, 1.009–1.254; p=0.034) and cardiac death (HR, 1.190; 95% CI, 1.026–1.381; p=0.022). Smoking was a strong independent predictor of lung cancer (propensityscore matched HR, 2.749; 95% CI, 1.416–5.338; p=0.003). Conclusions In contrast to the unadjusted model, smoking is associated with worse cardiovascular outcome and higher incidence of lung cancer after adjustment of various confounding factors. This result can be explained by the characteristics of smokers, which were young and had fewer comorbidities.

Background/Aims: Enzymatic analysis of aspartate/alanine aminotransferase (AST/ALT) does not exactly represent the progression of liver fibrosis or inflammation. Immunoassay for AST (cytoplasmic [c] AST/mitochondrial [m] AST) and ALT (ALT1/ALT2) has been suggested as one alternatives for enzymatic analysis. The objective of this study was to evaluate the efficacy of immunoassay in predicting liver fibrosis and inflammation. Methods: A total of 219 patients with chronic hepatitis B (CHB) who underwent hepatic venous pressure gradient (HVPG) and liver biopsy before antiviral therapy were recruited. Serum samples were prepared from blood during HVPG. Results of biochemical parameters including enzymatic AST/ALT and immunological assays of cAST, mAST, ALT1, and ALT2 through sandwich enzyme-linked immunosorbent assay (ELISA) immunoassay with fluorescence labeled monoclonal antibodies were compared with the results of METAVIR stage of live fibrosis and the Knodell grade of inflammation. Results: METAVIR fibrosis stages were as follows: F0, six (3%); F1, 52 (24%); F2, 88 (40%); F3, 45 (20%); and F4, 28 patients (13%). Mean levels of AST and ALT were 121 ± 157 and 210 ± 279 IU/L, respectively. Mean HVPG score of all patients was 4.7 ± 2.5 mmHg. According to the stage of liver fibrosis, HVPG score (p < 0.001, r = 0.439) and ALT1 level (p < 0.001, r = 0.283) were significantly increased in all samples from patients with CHB. ALT (p < 0.001, r = 0.310), ALT1 (p < 0.001, r = 0.369), and AST (p < 0.001, r = 0.374) levels were positively correlated with Knodell grade of inflammation. Conclusions ALT1 measurement by utilizing sandwich ELISA immunoassay can be useful method for predicting inf lammation grade and fibrosis stage in patients with CHB.

Background: This study aimed to describe the current status of acute stroke care in Korea and explore disparities among hospitals and regions. Methods: The 2013 and 2014 national stroke audit data and the national health insurance claims data were linked and used for this study. Stroke patients hospitalized via emergency rooms within 7 days of stroke onset were selected. Results: A total of 19,608 patients treated in 216 hospitals were analyzed. Among them 76% had ischemic stroke; 15%, intracerebral hemorrhage (ICH); and 9%, subarachnoid hemorrhage (SAH). Of the hospitals, 31% provided inpatient stroke unit care. Ambulances were used in 56% of cases, and the median interval from onset to arrival was 4.5 hours. One-quarter of patients were referred from other hospitals. Intravenous thrombolysis (IVT) and endovascular treatment (EVT) rates were 11% and 4%, respectively. Three-quarters of the analyzed hospitals provided IVT and/or EVT, whereas 47% of hospitals providing IVT and 67% of hospitals providing EVT had less than one case per month. Decompressive surgery was performed on 28% of ICH patients, and clipping and coiling were performed in 17.2% and 14.3% of SAH patients, respectively. There were noticeable regional disparities between the various interventions, ambulance use, arrival time, and stroke unit availability. Conclusion This study describes the current status of acute stroke care in Korea. Despite quite acceptable quality of stroke care, it suggests regional and hospital disparities. Expansion of stroke units, stroke center certification or accreditation, and connections between stroke centers and emergency medical services are highly recommended.

Background: To track triage, routing, and treatment status regarding access to endovascular treatment (EVT) after acute ischemic stroke (AIS) at a national level. Methods: From national stroke audit data, potential candidates for EVT arriving within 6 hours with National Institute of Health Stroke Scale score of ≥ 7 were identified. Acute care hospitals were classified as thrombectomy-capable hospitals (TCHs, ≥ 15 EVT cases/year) or primary stroke hospital (PSH, < 15 cases/year), and patients' initial routes and subsequent inter-hospital transfer were described. Impact of initial routing to TCHs vs. PSHs on EVT and clinical outcomes were analyzed using multilevel generalized mixed effect models. Results: Out of 14,902 AIS patients, 2,180 (14.6%) were EVT candidates. Eighty-one percent of EVT candidates were transported by ambulance, but only one-third were taken initially to TCHs. Initial routing to TCHs was associated with greater chances of receiving EVT compared to initial routing to PSHs (33.3% vs 12.1%, P < 0.001; adjusted odds ratio [aOR], 2.21; 95% confidence interval [CI], 1.59–2.92) and favorable outcome (38.5% vs. 28.2%, P < 0.001; aOR, 1.52; 95% CI, 1.16–2.00). Inter-hospital transfers to TCHs occurred in 17.4% of those initially routed to a PSH and was associated with the greater chance of EVT compared to remaining at PSHs (34.8% vs. 7.5%, P < 0.001), but not with better outcomes. Conclusion Two-thirds of EVT candidates were initially routed to PSHs despite greater chance of receiving EVT and having favorable outcomes if routed to a TCH in Korea. Process improvement is needed to direct appropriate patients to TCHs.

Background: This study aimed to determine the magnitude of volume reduction of the latissimus dorsi (LD) muscle after treatment using only postoperative radiotherapy (PORTx) in patients who underwent immediate breast reconstruction using an extended LD musculocutaneous (eLDMC) flap after partial mastectomy. Methods: We retrospectively reviewed 28 patients who underwent partial mastectomy and an eLDMC flap, received only PORTx, and underwent chest computed tomography (CT) 7 to 10 days after surgery and 18±4 months after the end of radiotherapy, from March 2011 to June 2016. The motor nerve to the LD was resected in all patients. One plastic surgeon performed the procedures, and the follow-up period was at least 36 months (mean, 46.6 months). The author obtained LD measurements from axial CT views, and the measurements were verified by an experienced radiologist. The threshold for statistical significance was set at P<0.05. Results: A statistically significant decrease in the LD volume was found after the end of PORTx (range, 61.19%–80.82%; mean, 69.04%) in comparison to the measurements obtained 7 to 10 days postoperatively (P<0.05). All cases were observed clinically for over 3 years. Conclusions The size of an eLDMC flap should be determined considering an average LD reduction of 69% after PORTx. Particular care should be taken in determining the size of an eLDMC flap if the LD is thick or if it occupies a large portion of the flap.

PURPOSE: To reduce lung cancer mortality, lung cancer screening was recommended using low-dose computed tomography (LDCT) to high-risk population. A protocol for multicenter lung cancer screening pilot project was developed to evaluate the effectiveness and feasibility of lung cancer screening to implement National Cancer Screening Program in Korea. MATERIALS AND METHODS: Multidisciplinary expert committee was comprised to develop a standardized protocol for Korean Lung Cancer Screening Project (K-LUCAS). K-LUCAS is a population-based single arm trial that targets high-risk population aged 55-74 years with at least 30 pack-year smoking history. LDCT results are reported by Lung-RADS suggested by American Radiology Society. Network-based system using computer-aided detection program is prepared to assist reducing diagnostic errors. Smoking cessation counselling is provided to all currently smoking participants. A small pilot test was conducted to check the feasibility and compliance of the protocols for K-LUCAS. RESULTS: In pilot test, 256 were participated. The average age of participants was 63.2 years and only three participants (1.2%) were female. The participants had a smoking history of 40.5 pack-year on average and 53.9% were current smokers. Among them, 86.3% had willing to participate in lung cancer screening again. The average willingness to quit smoking among current smokers was 12.7% higher than before screening. In Lung-RADS reports, 10 (3.9%) were grade 3 and nine (3.5%) were grade 4. One participant was diagnosed as lung cancer. CONCLUSION: The protocol developed by this study is assessed to be feasible to perform K-LUCAS in multicenter nationwide scale.
Arm ; Compliance ; Diagnostic Errors ; Early Detection of Cancer ; Female ; Humans ; Korea ; Lung Neoplasms ; Lung ; Mass Screening ; Mortality ; Pilot Projects ; Smoke ; Smoking ; Smoking Cessation

BACKGROUND: Angiotensin-converting enzyme inhibitors (ACEIs) are the first choice for the treatment of acute myocardial infarction (AMI), and angiotensin receptor blockers (ARBs) should be considered in patients intolerant to ACEIs. Although previous studies support the use of ARBs as an alternative to ACEIs, these studies showed inconsistent results. The objective of this study was to demonstrate the clinical impact of ARBs as an alternative to ACEIs in patients with AMI undergoing percutaneous coronary intervention (PCI). METHODS: The CardiOvascular Risk and idEntificAtion of potential high-risk population in AMI (COREA-AMI) registry enrolled all consecutive patients with AMI undergoing PCI. The primary endpoint was the composite of cardiovascular death, myocardial infarction, stroke, or hospitalization due to heart failure. RESULTS: Of the 3,328 eligible patients, ARBs replaced ACEIs in 816 patients, while 824 patients continued to use ACEIs and 826 patients continued to use ARBs. The remaining 862 patients did not receive ACEIs/ARBs. After the adjustment with inverse probability weighting, the primary endpoints in the first groups were similar (7.5% vs. 8.0%, hazard ratio [HR], 0.89; 95% confidence interval [CI], 0.75–1.05; P = 0.164). Composite events were less frequent in the ACEI to ARB group than no ACEI/ARB group (7.5% vs. 11.8%, HR, 0.76; 95% CI, 0.64–0.90; P = 0.002). CONCLUSION: The alternative use of ARBs following initial treatment with ACEIs demonstrates comparable clinical outcomes to those with continued use of ACEIs and is associated with an improved rate of composite events compared to no ACEI/ARB use in patients with AMI undergoing PCI. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02385682
Angiotensin Receptor Antagonists ; Angiotensin-Converting Enzyme Inhibitors ; Angiotensins ; Heart Failure ; Hospitalization ; Humans ; Myocardial Infarction ; Percutaneous Coronary Intervention ; Stroke