1.Study Design and Protocol for a Randomized Controlled Trial to Assess Long-Term Efficacy and Safety of a Triple Combination of Ezetimibe, Fenofibrate, and Moderate-Intensity Statin in Patients with Type 2 Diabetes and Modifiable Cardiovascular Risk Factors (ENSEMBLE)
Nam Hoon KIM ; Juneyoung LEE ; Suk CHON ; Jae Myung YU ; In-Kyung JEONG ; Soo LIM ; Won Jun KIM ; Keeho SONG ; Ho Chan CHO ; Hea Min YU ; Kyoung-Ah KIM ; Sang Soo KIM ; Soon Hee LEE ; Chong Hwa KIM ; Soo Heon KWAK ; Yong‐ho LEE ; Choon Hee CHUNG ; Sihoon LEE ; Heung Yong JIN ; Jae Hyuk LEE ; Gwanpyo KOH ; Sang-Yong KIM ; Jaetaek KIM ; Ju Hee LEE ; Tae Nyun KIM ; Hyun Jeong JEON ; Ji Hyun LEE ; Jae-Han JEON ; Hye Jin YOO ; Hee Kyung KIM ; Hyeong-Kyu PARK ; Il Seong NAM-GOONG ; Seongbin HONG ; Chul Woo AHN ; Ji Hee YU ; Jong Heon PARK ; Keun-Gyu PARK ; Chan Ho PARK ; Kyong Hye JOUNG ; Ohk-Hyun RYU ; Keun Yong PARK ; Eun-Gyoung HONG ; Bong-Soo CHA ; Kyu Chang WON ; Yoon-Sok CHUNG ; Sin Gon KIM
Endocrinology and Metabolism 2024;39(5):722-731
Background:
Atherogenic dyslipidemia, which is frequently associated with type 2 diabetes (T2D) and insulin resistance, contributes to the development of vascular complications. Statin therapy is the primary approach to dyslipidemia management in T2D, however, the role of non-statin therapy remains unclear. Ezetimibe reduces cholesterol burden by inhibiting intestinal cholesterol absorption. Fibrates lower triglyceride levels and increase high-density lipoprotein cholesterol (HDL-C) levels via peroxisome proliferator- activated receptor alpha agonism. Therefore, when combined, these drugs effectively lower non-HDL-C levels. Despite this, few clinical trials have specifically targeted non-HDL-C, and the efficacy of triple combination therapies, including statins, ezetimibe, and fibrates, has yet to be determined.
Methods:
This is a multicenter, prospective, randomized, open-label, active-comparator controlled trial involving 3,958 eligible participants with T2D, cardiovascular risk factors, and elevated non-HDL-C (≥100 mg/dL). Participants, already on moderate-intensity statins, will be randomly assigned to either Ezefeno (ezetimibe/fenofibrate) addition or statin dose-escalation. The primary end point is the development of a composite of major adverse cardiovascular and diabetic microvascular events over 48 months.
Conclusion
This trial aims to assess whether combining statins, ezetimibe, and fenofibrate is as effective as, or possibly superior to, statin monotherapy intensification in lowering cardiovascular and microvascular disease risk for patients with T2D. This could propose a novel therapeutic approach for managing dyslipidemia in T2D.
2.Prediction of Decompensation and Death in Advanced Chronic Liver Disease Using Deep Learning Analysis of Gadoxetic Acid-Enhanced MRI
Subin HEO ; Seung Soo LEE ; So Yeon KIM ; Young-Suk LIM ; Hyo Jung PARK ; Jee Seok YOON ; Heung-Il SUK ; Yu Sub SUNG ; Bumwoo PARK ; Ji Sung LEE
Korean Journal of Radiology 2022;23(12):1269-1280
Objective:
This study aimed to evaluate the usefulness of quantitative indices obtained from deep learning analysis of gadoxetic acid-enhanced hepatobiliary phase (HBP) MRI and their longitudinal changes in predicting decompensation and death in patients with advanced chronic liver disease (ACLD).
Materials and Methods:
We included patients who underwent baseline and 1-year follow-up MRI from a prospective cohort that underwent gadoxetic acid-enhanced MRI for hepatocellular carcinoma surveillance between November 2011 and August 2012 at a tertiary medical center. Baseline liver condition was categorized as non-ACLD, compensated ACLD, and decompensated ACLD. The liver-to-spleen signal intensity ratio (LS-SIR) and liver-to-spleen volume ratio (LS-VR) were automatically measured on the HBP images using a deep learning algorithm, and their percentage changes at the 1-year follow-up (ΔLS-SIR and ΔLS-VR) were calculated. The associations of the MRI indices with hepatic decompensation and a composite endpoint of liver-related death or transplantation were evaluated using a competing risk analysis with multivariable Fine and Gray regression models, including baseline parameters alone and both baseline and follow-up parameters.
Results:
Our study included 280 patients (153 male; mean age ± standard deviation, 57 ± 7.95 years) with non-ACLD, compensated ACLD, and decompensated ACLD in 32, 186, and 62 patients, respectively. Patients were followed for 11–117 months (median, 104 months). In patients with compensated ACLD, baseline LS-SIR (sub-distribution hazard ratio [sHR], 0.81; p = 0.034) and LS-VR (sHR, 0.71; p = 0.01) were independently associated with hepatic decompensation. The ∆LS-VR (sHR, 0.54; p = 0.002) was predictive of hepatic decompensation after adjusting for baseline variables. ∆LS-VR was an independent predictor of liver-related death or transplantation in patients with compensated ACLD (sHR, 0.46; p = 0.026) and decompensated ACLD (sHR, 0.61; p = 0.023).
Conclusion
MRI indices automatically derived from the deep learning analysis of gadoxetic acid-enhanced HBP MRI can be used as prognostic markers in patients with ACLD.
3.Deep Learning-Based Assessment of Functional Liver Capacity Using Gadoxetic Acid-Enhanced Hepatobiliary Phase MRI
Hyo Jung PARK ; Jee Seok YOON ; Seung Soo LEE ; Heung-Il SUK ; Bumwoo PARK ; Yu Sub SUNG ; Seung Baek HONG ; Hwaseong RYU
Korean Journal of Radiology 2022;23(7):720-731
Objective:
We aimed to develop and test a deep learning algorithm (DLA) for fully automated measurement of the volume and signal intensity (SI) of the liver and spleen using gadoxetic acid-enhanced hepatobiliary phase (HBP)-magnetic resonance imaging (MRI) and to evaluate the clinical utility of DLA-assisted assessment of functional liver capacity.
Materials and Methods:
The DLA was developed using HBP-MRI data from 1014 patients. Using an independent test dataset (110 internal and 90 external MRI data), the segmentation performance of the DLA was measured using the Dice similarity score (DSS), and the agreement between the DLA and the ground truth for the volume and SI measurements was assessed with a Bland-Altman 95% limit of agreement (LOA). In 276 separate patients (male:female, 191:85; mean age ± standard deviation, 40 ± 15 years) who underwent hepatic resection, we evaluated the correlations between various DLA-based MRI indices, including liver volume normalized by body surface area (LV BSA), liver-to-spleen SI ratio (LSSR), MRI parameter-adjusted LSSR (aLSSR), LSSR x LV BSA, and aLSSR x LV BSA, and the indocyanine green retention rate at 15 minutes (ICG-R15), and determined the diagnostic performance of the DLA-based MRI indices to detect ICG-R15 ≥ 20%.
Results:
In the test dataset, the mean DSS was 0.977 for liver segmentation and 0.946 for spleen segmentation. The BlandAltman 95% LOAs were 0.08% ± 3.70% for the liver volume, 0.20% ± 7.89% for the spleen volume, -0.02% ± 1.28% for the liver SI, and -0.01% ± 1.70% for the spleen SI. Among DLA-based MRI indices, aLSSR x LV BSA showed the strongest correlation with ICG-R15 (r = -0.54, p < 0.001), with area under receiver operating characteristic curve of 0.932 (95% confidence interval, 0.895–0.959) to diagnose ICG-R15 ≥ 20%.
Conclusion
Our DLA can accurately measure the volume and SI of the liver and spleen and may be useful for assessing functional liver capacity using gadoxetic acid-enhanced HBP-MRI.
4.Lung ultrasound for early diagnosis and severity assessment of pneumonia in patients with coronavirus disease 2019
Young-Jae CHO ; Kyoung-Ho SONG ; Yunghee LEE ; Joo Heung YOON ; Ji Young PARK ; Jongtak JUNG ; Sung Yoon LIM ; Hyunju LEE ; Ho Il YOON ; Kyoung Un PARK ; Hong Bin KIM ; Eu Suk KIM
The Korean Journal of Internal Medicine 2022;37(3):699-
5.Liver-to-Spleen Volume Ratio Automatically Measured on CT Predicts Decompensation in Patients with B Viral Compensated Cirrhosis
Ji Hye KWON ; Seung Soo LEE ; Jee Seok YOON ; Heung-Il SUK ; Yu Sub SUNG ; Ho Sung KIM ; Chul-min LEE ; Kang Mo KIM ; So Jung LEE ; So Yeon KIM
Korean Journal of Radiology 2021;22(12):1985-1995
Objective:
Although the liver-to-spleen volume ratio (LSVR) based on CT reflects portal hypertension, its prognostic role in cirrhotic patients has not been proven. We evaluated the utility of LSVR, automatically measured from CT images using a deep learning algorithm, as a predictor of hepatic decompensation and transplantation-free survival in patients with hepatitis B viral (HBV)-compensated cirrhosis.
Materials and Methods:
A deep learning algorithm was used to measure the LSVR in a cohort of 1027 consecutive patients (mean age, 50.5 years; 675 male and 352 female) with HBV-compensated cirrhosis who underwent liver CT (2007–2010).Associations of LSVR with hepatic decompensation and transplantation-free survival were evaluated using multivariable Cox proportional hazards and competing risk analyses, accounting for either the Child-Pugh score (CPS) or Model for End Stage Liver Disease (MELD) score and other variables. The risk of the liver-related events was estimated using Kaplan-Meier analysis and the Aalen-Johansen estimator.
Results:
After adjustment for either CPS or MELD and other variables, LSVR was identified as a significant independent predictor of hepatic decompensation (hazard ratio for LSVR increase by 1, 0.71 and 0.68 for CPS and MELD models, respectively; p < 0.001) and transplantation-free survival (hazard ratio for LSVR increase by 1, 0.8 and 0.77, respectively; p < 0.001). Patients with an LSVR of < 2.9 (n = 381) had significantly higher 3-year risks of hepatic decompensation (16.7% vs. 2.5%, p < 0.001) and liver-related death or transplantation (10.0% vs. 1.1%, p < 0.001) than those with an LSVR ≥ 2.9 (n = 646). When patients were stratified according to CPS (Child-Pugh A vs. B–C) and MELD (< 10 vs. ≥ 10), an LSVR of < 2.9 was still associated with a higher risk of liver-related events than an LSVR of ≥ 2.9 for all Child-Pugh (p ≤ 0.045) and MELD (p ≤ 0.009) stratifications.
Conclusion
The LSVR measured on CT can predict hepatic decompensation and transplantation-free survival in patients with HBV-compensated cirrhosis.
6.Lung ultrasound for early diagnosis and severity assessment of pneumonia in patients with coronavirus disease 2019
Young-Jae CHO ; Kyoung-Ho SONG ; Yunghee LEE ; Joo Heung YOON ; Ji Young PARK ; Jongtak JUNG ; Sung Yoon LIM ; Hyunju LEE ; Ho Il YOON ; Kyoung Un PARK ; Hong Bin KIM ; Eu Suk KIM
The Korean Journal of Internal Medicine 2020;35(4):771-781
Background/Aims:
Current evidence supports lung ultrasound as a point-ofcare alternative diagnostic tool for various respiratory diseases. We sought to determine the utility of lung ultrasound for early detection of pneumonia and for assessment of respiratory failure among patients with coronavirus disease 2019 (COVID-19).
Methods:
Six patients with confirmed COVID-19 by reverse transcription-polymerase chain reaction were enrolled. All had undergone chest X-ray and chest computed tomography (CT) on the day of admission and underwent multiple point-of-care lung ultrasound scans over the course of their hospitalization.
Results:
Lung ultrasound detected early abnormal findings of representative B-lines in a patient with a normal chest X-ray, corresponding to ground-glass opacities on the chest CT scan. The ultrasound findings improved as her clinical condition improved and her viral load decreased. In another minimally symptomatic patient without significant chest X-ray findings, the ultrasound showed B-lines, an early sign of pneumonia before abnormalities were detected on the chest CT scan. In two critically ill patients, ultrasound was performed to assess for evaluation of disease severity. In both patients, the clinicians conducted emergency rapid sequence intubation based on the ultrasound findings without awaiting the laboratory results and radiological reports. In two children, ultrasound was used to assess the improvement in their pneumonia, thus avoiding further imaging tests such as chest CT.
Conclusions
Lung ultrasound is feasible and useful as a rapid, sensitive, and affordable point-of-care screening tool to detect pneumonia and assess the severity of respiratory failure in patients hospitalized with COVID-19.
7.Deep Learning Algorithm for Automated Segmentationand Volume Measurement of the Liver and Spleen UsingPortal Venous Phase Computed Tomography Images
Yura AHN ; Jee Seok YOON ; Seung Soo LEE ; Heung-Il SUK ; Jung Hee SON ; Yu Sub SUNG ; Yedaun LEE ; Bo-Kyeong KANG ; Ho Sung KIM
Korean Journal of Radiology 2020;21(8):987-997
Objective:
Measurement of the liver and spleen volumes has clinical implications. Although computed tomography (CT)volumetry is considered to be the most reliable noninvasive method for liver and spleen volume measurement, it has limitedapplication in clinical practice due to its time-consuming segmentation process. We aimed to develop and validate a deeplearning algorithm (DLA) for fully automated liver and spleen segmentation using portal venous phase CT images in variousliver conditions.
Materials and Methods:
A DLA for liver and spleen segmentation was trained using a development dataset of portal venousCT images from 813 patients. Performance of the DLA was evaluated in two separate test datasets: dataset-1 which included150 CT examinations in patients with various liver conditions (i.e., healthy liver, fatty liver, chronic liver disease, cirrhosis,and post-hepatectomy) and dataset-2 which included 50 pairs of CT examinations performed at ours and other institutions.The performance of the DLA was evaluated using the dice similarity score (DSS) for segmentation and Bland-Altman 95%limits of agreement (LOA) for measurement of the volumetric indices, which was compared with that of ground truth manualsegmentation.
Results:
In test dataset-1, the DLA achieved a mean DSS of 0.973 and 0.974 for liver and spleen segmentation, respectively,with no significant difference in DSS across different liver conditions (p = 0.60 and 0.26 for the liver and spleen, respectively).For the measurement of volumetric indices, the Bland-Altman 95% LOA was -0.17 ± 3.07% for liver volume and -0.56 ± 3.78%for spleen volume. In test dataset-2, DLA performance using CT images obtained at outside institutions and our institutionwas comparable for liver (DSS, 0.982 vs. 0.983; p = 0.28) and spleen (DSS, 0.969 vs. 0.968; p = 0.41) segmentation.
Conclusion
The DLA enabled highly accurate segmentation and volume measurement of the liver and spleen using portalvenous phase CT images of patients with various liver conditions.
8.The Risk Factors Influencing between the Early and Late Recurrence in Systemic Recurrent Breast Cancer.
Won Jong SONG ; Kwan Il KIM ; Sang Hyun PARK ; Mi Seon KWON ; Tae Hoon LEE ; Heung Kyu PARK ; Jung Suk AN
Journal of Breast Cancer 2012;15(2):218-223
PURPOSE: Patients with recurrent breast cancer usually die of their disease, even after radical surgery and adjuvant therapies which could reduce the odds of dying. Many studies analyzed and compared patients who died of recurrent disease with those that died without recurrent disease. However, less attention has been paid to evaluating factors associated with the timing of recurrence. Thus, the objective of this study is to investigate the correlation between various factors and the timing of recurrence. METHODS: We retrospectively reviewed the data of 95 recurrent breast cancer patients who underwent curative surgery to determine the prognostic factors such as menopausal status, operation method, stage, nodal status, histologic grade, nuclear grade, extensive intraductal carcinoma component, hormone receptor, p53, c-erbB-2, Ki-67, and molecular subtype. We had attempted to compare the recurrent patients within 2 years after operation and adjuvant chemotherapies as the early recurrence with those over 2 years as the late recurrence. RESULTS: Histologic grade (p=0.005), nuclear grade (p<0.001), p53 (p=0.022), and Ki-67 (p<0.001) were significant different factors that influenced the systemic recurrence between early recurrence and late recurrence. In stage I/II, histologic grade (p=0.001), nuclear grade (p<0.001), and Ki-67 (p=0.005) were significant factors that influenced the systemic early recurrence. In stage III, nuclear grade (p=0.024), and Ki-67 (p=0.001) were significant factors that influenced the systemic early recurrence. But subtypes (p=0.189, p=0.132, p=0.593, p=0.083) are not associated with the timing of recur rence. CONCLUSION: In systemic recurrent breast cancer patients, the risk factors such as histologic grade, nuclear grade, p53 and Ki-67 are also associated with the timing of recurrence. We sug gest that these patients should be proper treated and be closely followed up.
Breast
;
Breast Neoplasms
;
Carcinoma, Intraductal, Noninfiltrating
;
Humans
;
Recurrence
;
Retrospective Studies
;
Risk Factors
9.The Financial Burden of Asthma: A Nationwide Comprehensive Survey Conducted in the Republic of Korea.
Chang yup KIM ; Heung Woo PARK ; Su Kyoung KO ; Suk Il CHANG ; Hee Bom MOON ; You Young KIM ; Sang Heon CHO
Allergy, Asthma & Immunology Research 2011;3(1):34-38
PURPOSE: Asthma-related morbidity and mortality are increasing, and the financial burden imposed by this condition will substantially increase. Nevertheless, little information is available regarding the nature and magnitude of the burden due to asthma at the national level. This study was conducted to characterize the financial burden imposed by asthma in the Republic of Korea at the national level. METHODS: The overall prevalence of asthma and the costs of related medical services were determined using data from the National Health Insurance Corporation, which is responsible for the National Health Insurance scheme. Indirect costs, including expenditures on complementary and alternative medicines, and the economic impact of an impaired quality of life (intangible costs) were estimated by surveying 660 asthmatics, and these estimates were transformed to the national level using the prevalence of asthma. RESULTS: The prevalence of asthma and total costs related to the disease in 2004 were 4.19% and $2.04 billion, respectively. Direct costs and indirect costs contributed equally to total costs (46.9% and 53.1%, respectively). However, when intangible costs were included, total costs rose to $4.11 billion, which was equivalent to 0.44% of the national gross domestic product in 2004. CONCLUSIONS: The results provide evidence that asthma is a major health cost factor in the Republic of Korea and that intangible costs associated with asthma are significant cost drivers.
Asthma
;
Gross Domestic Product
;
Health Care Costs
;
Health Expenditures
;
National Health Programs
;
Prevalence
;
Quality of Life
;
Republic of Korea
10.Photodynamic Therapy for Choroidal Neovascularization Secondary to Age-Related Macular Degeneration.
Hyeong Gon YU ; Se Woong KANG ; Woo Ho NAM ; Hyoung Jun KOH ; Hyung Woo KWAK ; Oh Woong KWON ; Si Yeol KIM ; In Taek KIM ; Ha Kyoung KIM ; Hyun Woong KIM ; Young Jung ROH ; Jun Woong MOON ; Kyu Hyung PARK ; Suk Ho BYEON ; Su Jeong SONG ; Jae Kyoun AHN ; Boo Sup OUM ; Jae Ryung OH ; Seung Young YU ; Ill Han YOON ; Sung Chul LEE ; Won Ki LEE ; Jae Heung LEE ; Jeong Hee LEE ; Ji Eun LEE ; Tae Gon LEE ; Gwang Ju CHOI ; Don Il HAM ; Kuhl HUH ; Hum CHUNG
Journal of the Korean Ophthalmological Society 2007;48(6):789-798
PURPOSE: To investigate the effects of repeated photodynamic therapy (PDT) for subfoveal choroidal neovascularization secondary to age-related macular degeneration (AMD) in Korean patients. METHODS: Clinical data of patients who were treated with repeated (3 times or more) PDT for subfoveal choroidal neovascularization secondary to AMD and followed up for more than 6 months were collected from 17 hospitals around the country. Visual outcomes at 12 and 24 months, follow-up were compared between subtypes of choroidal neovascularization. The factors related to final visual prognosis and PDT-related adverse effects were evaluated. RESULTS: 244 patients (244 eyes) were recruited (male: 60%, age: 67.7+/-9.1 years). The portion of patients with predominantly classic, minimally classic, and occult without classic choroidal neovascularization was 57%, 13%, and 24%, respectively and that of patients with visual improvements or less than moderate visual loss at 24 months follow-up were 28%, 38%, 30% and 47%, 56%, and 65%, respectively. Baseline visual acuity and age were significantly related to the final visual prognosis (p<0.05). PDT-related adverse events developed in 15 (6.1%) patients, but most were mild and transient. CONCLUSIONS: Repeated PDT for subfoveal choroidal neovascularization secondary to AMD has effects comparable to those of previous prospective, controlled trials without any significant safety concerns in Korea.
Choroid*
;
Choroidal Neovascularization*
;
Follow-Up Studies
;
Humans
;
Korea
;
Macular Degeneration*
;
Photochemotherapy*
;
Prognosis
;
Visual Acuity

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