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.Impact of Positron Emission Tomography Viability Imaging:Guided Revascularizations on Clinical Outcomes in Patients With Myocardial Scar on Single-Photon Emission Computed Tomography Scans
Jong Sung PARK ; Jang Hoon LEE ; Chae Moon HONG ; Bo Eun PARK ; Yoon Jung PARK ; Hong Nyun KIM ; Namkyun KIM ; Se Yong JANG ; Myung Hwan BAE ; Dong Heon YANG ; Hun Sik PARK ; Yongkeun CHO
Journal of Korean Medical Science 2023;38(46):e399-
Background:
Positron emission tomography (PET) viability scan is used to determine whether patients with a myocardial scar on single-photon emission computed tomography (SPECT) may need revascularization. However, the clinical utility of revascularization decision-making guided by PET viability imaging has not been proven yet. The purpose of this study was to investigate the impact of PET to determine revascularization on clinical outcomes.
Methods:
Between September 2012 and May 2021, 53 patients (37 males; mean age = 64 ± 11 years) with a myocardial scar on MIBI SPECT who underwent PET viability test were analyzed in this study. The primary outcome was a temporal change in echocardiographic findings.The secondary outcome was all-cause mortality.
Results:
Viable myocardium was presented by PET imaging in 29 (54.7%) patients.Revascularization was performed in 26 (49.1%) patients, including 18 (34.0%) with percutaneous coronary intervention (PCI) and 8 (15.1%) with coronary artery bypass grafting.There were significant improvements in echocardiographic findings in the revascularization group and the viable myocardium group. All-cause mortality was significantly lower in the revascularization group than in the medical therapy-alone group (19.2% vs. 44.4%, log-rank P = 0.002) irrespective of viable (21.4% vs. 46.7%, log-rank P = 0.025) or non-viable myocardium (16.7% vs. 41.7%, log-rank P = 0.046). All-cause mortality was significantly lower in the PCI group than in the medical therapy-alone group (11.1% vs. 44.4%, log-rank P < 0.001).
Conclusion
Revascularization improved left ventricular systolic function and survival of patients with a myocardial scar on SPECT scans, irrespective of myocardial viability on PET scans.
3.Impact of the COVID-19 Pandemic on Patient Delay and Clinical Outcomes for Patients With Acute Myocardial Infarction
Hyohun CHOI ; Jang Hoon LEE ; Hyuk Kyoon PARK ; Eunkyu LEE ; Myeong Seop KIM ; Hyeon Jeong KIM ; Bo Eun PARK ; Hong Nyun KIM ; Namkyun KIM ; Se Yong JANG ; Myung Hwan BAE ; Dong Heon YANG ; Hun Sik PARK ; Yongkeun CHO
Journal of Korean Medical Science 2022;37(21):e167-
Background:
It has been known that the fear of contagion during the coronavirus disease 2019 (COVID-19) creates time delays with subsequent impact on mortality in patients with acute myocardial infarction (AMI). However, difference of time delay and clinical outcome in patients with ST-segment elevation myocardial infarction (STEMI) or non-STEMI between the COVID-19 pandemic and pre-pandemic era has not been fully investigated yet in Korea. The aim of this study was to investigate the impact of COVID-19 pandemic on time delays and clinical outcome in patients with STEMI or non-STEMI compared to the same period years prior.
Methods:
A total of 598 patients with STEMI (n = 195) or non-STEMI (n = 403) who underwent coronary angiography during the COVID-19 pandemic (February 1 to April 30, 2020) and prepandemic era (February 1 to April 30, 2017, 2018, and 2019) were analyzed in this study. Main outcomes were the incidence of time delay, cardiac arrest, and in-hospital death.
Results:
There was 13.5% reduction in the number of patients hospitalized with AMI during the pandemic compared to pre-pandemic era. In patients with STEMI, door to balloon time tended to be longer during the pandemic compared to pre-pandemic era (55.7 ± 12.6 minutes vs. 60.8 ± 13.0 minutes, P = 0.08). There were no significant differences in cardiac arrest (15.6% vs. 10.4%, P = 0.397) and in-hospital mortality (15.6% vs. 10.4%, P = 0.397) between pre-pandemic and the pandemic era. In patients with non-STEMI, symptom to door time was significantly longer (310.0 ± 346.2 minutes vs. 511.5 ± 635.7 minutes, P = 0.038) and the incidence of cardiac arrest (0.9% vs. 3.5%, P = 0.017) and in-hospital mortality (0.3% vs.2.3%, P = 0.045) was significantly greater during the pandemic compared to pre-pandemic era. Among medications, angiotensin converting enzyme inhibitors/angiotensin type 2 receptor blockers (ACE-I/ARBs) were underused in STEMI (64.6% vs. 45.8%, P = 0.021) and non-STEMI (67.8% vs. 57.0%, P = 0.061) during the pandemic.
Conclusion
During the COVID-19 pandemic, there has been a considerable reduction in hospital admissions for AMI, time delay, and underuse of ACE-I/ARBs for the management of AMI, and this might be closely associated with the excess death in Korea.
4.Impact of Cardiovascular Risk Factors and Cardiovascular Diseases on Outcomes in Patients Hospitalized with COVID-19 in Daegu Metropolitan City
Bo Eun PARK ; Jang Hoon LEE ; Hyuk Kyoon PARK ; Hong Nyun KIM ; Se Yong JANG ; Myung Hwan BAE ; Dong Heon YANG ; Hun Sik PARK ; Yongkeun CHO ; Bong Yul LEE ; Chang Wook NAM ; Jin Bae LEE ; Ung KIM ; Shung Chull CHAE ;
Journal of Korean Medical Science 2021;36(2):e15-
Background:
Data regarding the association between preexisting cardiovascular risk factors (CVRFs) and cardiovascular diseases (CVDs) and the outcomes of patients requiring hospitalization for coronavirus disease 2019 (COVID-19) are limited. Therefore, the aim of this study was to investigate the impact of preexisting CVRFs or CVDs on the outcomes of patients with COVID-19 hospitalized in a Korean healthcare system.
Methods:
Patients with COVID-19 admitted to 10 hospitals in Daegu Metropolitan City, Korea, were examined. All sequentially hospitalized patients between February 15, 2020, and April 24, 2020, were enrolled in this study. All patients were confirmed to have COVID-19 based on the positive results on the polymerase chain reaction testing of nasopharyngeal samples. Clinical outcomes during hospitalization, such as requiring intensive care and invasive mechanical ventilation (MV) and death, were evaluated. Moreover, data on baseline comorbidities such as a history of diabetes, hypertension, dyslipidemia, current smoking, heart failure, coronary artery disease, cerebrovascular accidents, and other chronic cardiac diseases were obtained.
Results:
Of all the patients enrolled, 954 (42.0%) had preexisting CVRFs or CVDs. Among the CVRFs, the most common were hypertension (28.8%) and diabetes mellitus (17.0%). The prevalence rates of preexisting CVRFs or CVDs increased with age (P < 0.001). The number of patients requiring intensive care (P < 0.001) and invasive MV (P < 0.001) increased with age.The in-hospital death rate increased with age (P < 0.001). Patients requiring intensive care (5.3% vs. 1.6%; P < 0.001) and invasive MV (4.3% vs. 1.7%; P < 0.001) were significantly greater in patients with preexisting CVRFs or CVDs. In-hospital mortality (12.9% vs. 3.1%; P < 0.001) was significantly higher in patients with preexisting CVRFs or CVDs. Among the CVRFs, diabetes mellitus and hypertension were associated with increased requirement of intensive care and invasive MV and in-hospital death. Among the known CVDs, coronary artery disease and congestive heart failure were associated with invasive MV and in-hospital death. In multivariate analysis, preexisting CVRFs or CVDs (odds ratio [OR], 1.79; 95% confidence interval [CI], 1.07–3.01; P = 0.027) were independent predictors of in-hospital death adjusting for confounding variables. Among individual preexisting CVRF or CVD components, diabetes mellitus (OR, 2.43; 95% CI, 1.51–3.90; P < 0.001) and congestive heart failure (OR, 2.43; 95% CI, 1.06–5.87; P = 0.049) were independent predictors of in-hospital death.
Conclusion
Based on the findings of this study, the patients with confirmed COVID-19 with preexisting CVRFs or CVDs had worse clinical outcomes. Caution is required in dealing with these patients at triage.after
5.Efficacy and Safety of Treatment with Quadruple Oral Hypoglycemic Agents in Uncontrolled Type 2 Diabetes Mellitus: A Multi-Center, Retrospective, Observational Study
Jun Sung MOON ; Sunghwan SUH ; Sang Soo KIM ; Heung Yong JIN ; Jeong Mi KIM ; Min Hee JANG ; Kyung Ae LEE ; Ju Hyung LEE ; Seung Min CHUNG ; Young Sang LYU ; Jin Hwa KIM ; Sang Yong KIM ; Jung Eun JANG ; Tae Nyun KIM ; Sung Woo KIM ; Eonju JEON ; Nan Hee CHO ; Mi-Kyung KIM ; Hye Soon KIM ; Il Seong NAM-GOONG ; Eun Sook KIM ; Jin Ook CHUNG ; Dong-Hyeok CHO ; Chang Won LEE ; Young Il KIM ; Dong Jin CHUNG ; Kyu Chang WON ; In Joo KIM ; Tae Sun PARK ; Duk Kyu KIM ; Hosang SHON
Diabetes & Metabolism Journal 2021;45(5):675-683
Only few studies have shown the efficacy and safety of glucose-control strategies using the quadruple drug combination. Therefore, the aim of the present study was to investigate the usefulness of the quadruple combination therapy with oral hypoglycemic agents (OHAs) in patients with uncontrolled type 2 diabetes mellitus (T2DM). From March 2014 to December 2018, data of patients with T2DM, who were treated with quadruple hypoglycemic medications for over 12 months in 11 hospitals in South Korea, were reviewed retrospectively. We compared glycosylated hemoglobin (HbA1c) levels before and 12 months after quadruple treatment with OHAs. The safety, maintenance rate, and therapeutic patterns after failure of the quadruple therapy were also evaluated. In total, 357 patients were enrolled for quadruple OHA therapy, and the baseline HbA1c level was 9.0%±1.3% (74.9±14.1 mmol/mol). After 12 months, 270 patients (75.6%) adhered to the quadruple therapy and HbA1c was significantly reduced from 8.9%±1.2% to 7.8%±1.3% (mean change, −1.1%±1.2%; This study shows the therapeutic efficacy of the quadruple OHA regimen T2DM and demonstrates that it can be an option for the management of T2DM patients who cannot use insulin or reject injectable therapy.
6.A Case of Lymphocyte-Rich Hepatocellular Carcinoma in a Patient Who Was Treated for Colon Cancer
Jae Won SONG ; Ho Soo CHUN ; Jae Seung LEE ; Hye Won LEE ; Beom Kyung KIM ; Seung Up KIM ; Jun Yong PARK ; Sang Hoon AHN ; Young Nyun PARK ; Dai Hoon HAN ; Do Young KIM
Journal of Liver Cancer 2021;21(1):69-75
Hepatocellular carcinoma (HCC) primarily originates in the liver with hepatic differentiation. However, HCCs are not homogenous, and approximately 35% of HCC cases are classified as histopathological variants that present distinct pathologic characteristics. In particular, the lymphocyte-rich variant is the rarest subtype accounting for less than 1% of HCCs, which is not well known to date about molecular features and pathophysiology. Herein, we present a case of a patient who was suspected of metastatic liver cancer and confirmed as lymphocyte-rich HCC pathologically. A 78-year-old woman who underwent a right hemicolectomy for colon cancer was referred to our hospital for a newly detected liver mass. We could not make a decision because of insufficient evidence for diagnosis from imaging studies. After resection, we found that it was a lymphocyte-rich HCC. The pathologic features and prognostic trends of this subtype are also discussed.
7.Efficacy and Safety of Treatment with Quadruple Oral Hypoglycemic Agents in Uncontrolled Type 2 Diabetes Mellitus: A Multi-Center, Retrospective, Observational Study
Jun Sung MOON ; Sunghwan SUH ; Sang Soo KIM ; Heung Yong JIN ; Jeong Mi KIM ; Min Hee JANG ; Kyung Ae LEE ; Ju Hyung LEE ; Seung Min CHUNG ; Young Sang LYU ; Jin Hwa KIM ; Sang Yong KIM ; Jung Eun JANG ; Tae Nyun KIM ; Sung Woo KIM ; Eonju JEON ; Nan Hee CHO ; Mi-Kyung KIM ; Hye Soon KIM ; Il Seong NAM-GOONG ; Eun Sook KIM ; Jin Ook CHUNG ; Dong-Hyeok CHO ; Chang Won LEE ; Young Il KIM ; Dong Jin CHUNG ; Kyu Chang WON ; In Joo KIM ; Tae Sun PARK ; Duk Kyu KIM ; Hosang SHON
Diabetes & Metabolism Journal 2021;45(5):675-683
Only few studies have shown the efficacy and safety of glucose-control strategies using the quadruple drug combination. Therefore, the aim of the present study was to investigate the usefulness of the quadruple combination therapy with oral hypoglycemic agents (OHAs) in patients with uncontrolled type 2 diabetes mellitus (T2DM). From March 2014 to December 2018, data of patients with T2DM, who were treated with quadruple hypoglycemic medications for over 12 months in 11 hospitals in South Korea, were reviewed retrospectively. We compared glycosylated hemoglobin (HbA1c) levels before and 12 months after quadruple treatment with OHAs. The safety, maintenance rate, and therapeutic patterns after failure of the quadruple therapy were also evaluated. In total, 357 patients were enrolled for quadruple OHA therapy, and the baseline HbA1c level was 9.0%±1.3% (74.9±14.1 mmol/mol). After 12 months, 270 patients (75.6%) adhered to the quadruple therapy and HbA1c was significantly reduced from 8.9%±1.2% to 7.8%±1.3% (mean change, −1.1%±1.2%; This study shows the therapeutic efficacy of the quadruple OHA regimen T2DM and demonstrates that it can be an option for the management of T2DM patients who cannot use insulin or reject injectable therapy.
8.A Case of Lymphocyte-Rich Hepatocellular Carcinoma in a Patient Who Was Treated for Colon Cancer
Jae Won SONG ; Ho Soo CHUN ; Jae Seung LEE ; Hye Won LEE ; Beom Kyung KIM ; Seung Up KIM ; Jun Yong PARK ; Sang Hoon AHN ; Young Nyun PARK ; Dai Hoon HAN ; Do Young KIM
Journal of Liver Cancer 2021;21(1):69-75
Hepatocellular carcinoma (HCC) primarily originates in the liver with hepatic differentiation. However, HCCs are not homogenous, and approximately 35% of HCC cases are classified as histopathological variants that present distinct pathologic characteristics. In particular, the lymphocyte-rich variant is the rarest subtype accounting for less than 1% of HCCs, which is not well known to date about molecular features and pathophysiology. Herein, we present a case of a patient who was suspected of metastatic liver cancer and confirmed as lymphocyte-rich HCC pathologically. A 78-year-old woman who underwent a right hemicolectomy for colon cancer was referred to our hospital for a newly detected liver mass. We could not make a decision because of insufficient evidence for diagnosis from imaging studies. After resection, we found that it was a lymphocyte-rich HCC. The pathologic features and prognostic trends of this subtype are also discussed.
9.Surgical Strategy for Sacral Tumor Resection
Kwang-Ryeol KIM ; Kyung-Hyun KIM ; Jeong-Yoon PARK ; Dong-Ah SHIN ; Yoon HA ; Keung-Nyun KIM ; Dong-Kyu CHIN ; Keun-Su KIM ; Yong-Eun CHO ; Sung-Uk KUH
Yonsei Medical Journal 2021;62(1):59-67
Purpose:
This study aimed to present our experiences with a precise surgical strategy for sacrectomy.
Materials and Methods:
This study comprised a retrospective review of 16 patients (6 males and 10 females) who underwent sacrectomy from 2011 to 2019. The average age was 42.4 years old, and the mean follow-up period was 40.8 months. Clinical data, including age, sex, history, pathology, radiographs, surgical approaches, onset of recurrence, and prognosis, were analyzed.
Results:
The main preoperative symptom was non-specific local pain. Nine patients (56%) complained of bladder and bowel symptoms. All patients required spinopelvic reconstruction after sacrectomy. Three patients, one high, one middle, and one hemisacrectomy, underwent spinopelvic reconstruction. The pathology findings of tumors varied (chordoma, n=7; nerve sheath tumor, n=4; giant cell tumor, n=3, etc.). Adjuvant radiotherapy was performed for 5 patients, chemotherapy for three, and combined chemoradiotherapy for another three. Six patients (38%) reported postoperative motor weakness, and newly postoperative bladder and bowel symptoms occurred in 5 patients. Three patients (12%) experienced recurrence and expired.
Conclusion
In surgical resection of sacral tumors, the surgical approach depends on the size, location, extension, and pathology of the tumors. The recommended treatment option for sacral tumors is to remove as much of the tumor as possible. The level of root sacrifice is a predicting factor for postoperative neurologic functional impairment and the potential for morbidity. Pre-operative angiography and embolization are recommended to prevent excessive bleeding during surgery. Spinopelvic reconstruction must be considered following a total or high sacrectomy or sacroiliac joint removal.
10.Revision Surgery for a Failed Artificial Disc
Kwang-Ryeol KIM ; Dong-Kyu CHIN ; Keun-Su KIM ; Yong-Eun CHO ; Dong-Ah SHIN ; Keung-Nyun KIM ; Sung-Uk KUH
Yonsei Medical Journal 2021;62(3):240-248
Purpose:
This study aimed to present our experience with failures in C-TDR and revision surgery outcomes.
Materials and Methods:
We retrospectively examined patients who underwent revision surgery due to the failure of C-TDR between May 2005 to March 2019. Thirteen patients (8 males and 5 females) were included in this study. The mean age was 46.1 years (range: 22–61 years), and the average follow-up period was 19.5 months (range: 12–64 months). The outcome measures of pre- and post-operative neck and arm pain using a visual analogue scale (VAS) and functional impairment were assessed using a modified Japanese Orthopedic Association (JOA) scale and the Neck Disability Index (NDI).
Results:
The main complaints of patients were posterior neck pain (77%), radiculopathy (62%), and/or myelopathy (62%). The causes of failure of C-TDR were improper indications for the procedure, osteolysis and mobile implant use, inappropriate techniques, and postoperative infection. The most common surgical level was C5–6, followed by C4–5. After revision surgery, the neck and arm pain VAS (preoperative vs. postoperative: 5.46 vs. 1.31; 4.86 vs. 1.08), a modified JOA scale (14.46 vs. 16.69), and the NDI (29.77 vs. 9.31) scores were much improved.
Conclusion
C-TDR is good surgical option. However, it is very important to adhere to strict surgical indications and contraindications to avoid failure of C-TDR. The results of reoperations were good regardless of the approach. Therefore, various reoperation options could be considered in patients with failed C-TDR.

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