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.Contemporary Statistics of Acute Ischemic Stroke and Transient Ischemic Attack in 2021: Insights From the CRCS-K-NIH Registry
Do Yeon KIM ; Tai Hwan PARK ; Yong-Jin CHO ; Jong-Moo PARK ; Kyungbok LEE ; Minwoo LEE ; Juneyoung LEE ; Sang Yoon BAE ; Da Young HONG ; Hannah JUNG ; Eunvin KO ; Hyung Seok GUK ; Beom Joon KIM ; Jun Yup KIM ; Jihoon KANG ; Moon-Ku HAN ; Sang-Soon PARK ; Keun-Sik HONG ; Hong-Kyun PARK ; Jeong-Yoon LEE ; Byung-Chul LEE ; Kyung-Ho YU ; Mi Sun OH ; Dong-Eog KIM ; Dong-Seok GWAK ; Soo Joo LEE ; Jae Guk KIM ; Jun LEE ; Doo Hyuk KWON ; Jae-Kwan CHA ; Dae-Hyun KIM ; Joon-Tae KIM ; Kang-Ho CHOI ; Hyunsoo KIM ; Jay Chol CHOI ; Joong-Goo KIM ; Chul-Hoo KANG ; Sung-il SOHN ; Jeong-Ho HONG ; Hyungjong PARK ; Sang-Hwa LEE ; Chulho KIM ; Dong-Ick SHIN ; Kyu Sun YUM ; Kyusik KANG ; Kwang-Yeol PARK ; Hae-Bong JEONG ; Chan-Young PARK ; Keon-Joo LEE ; Jee Hyun KWON ; Wook-Joo KIM ; Ji Sung LEE ; Hee-Joon BAE ;
Journal of Korean Medical Science 2024;39(34):e278-
This report presents the latest statistics on the stroke population in South Korea, sourced from the Clinical Research Collaborations for Stroke in Korea-National Institute for Health (CRCS-K-NIH), a comprehensive, nationwide, multicenter stroke registry. The Korean cohort, unlike western populations, shows a male-to-female ratio of 1.5, attributed to lower risk factors in Korean women. The average ages for men and women are 67 and 73 years, respectively.Hypertension is the most common risk factor (67%), consistent with global trends, but there is a higher prevalence of diabetes (35%) and smoking (21%). The prevalence of atrial fibrillation (19%) is lower than in western populations, suggesting effective prevention strategies in the general population. A high incidence of large artery atherosclerosis (38%) is observed, likely due to prevalent intracranial arterial disease in East Asians and advanced imaging techniques.There has been a decrease in intravenous thrombolysis rates, from 12% in 2017–2019 to 10% in 2021, with no improvements in door-to-needle and door-to-puncture times, worsened by the coronavirus disease 2019 pandemic. While the use of aspirin plus clopidogrel for noncardioembolic stroke and direct oral anticoagulants for atrial fibrillation is well-established, the application of direct oral anticoagulants for non-atrial fibrillation cardioembolic strokes in the acute phase requires further research. The incidence of early neurological deterioration (13%) and the cumulative incidence of recurrent stroke at 3 months (3%) align with global figures. Favorable outcomes at 3 months (63%) are comparable internationally, yet the lack of improvement in dependency at 3 months highlights the need for advancements in acute stroke care.
3.Beneficial Effects of a Curcumin Derivative and Transforming Growth Factor-β Receptor I Inhibitor Combination on Nonalcoholic Steatohepatitis
Kyung Bong HA ; Eun Soo LEE ; Na Won PARK ; Su Ho JO ; Soyeon SHIM ; Dae-Kee KIM ; Chan Mug AHN ; Choon Hee CHUNG
Diabetes & Metabolism Journal 2023;47(4):500-513
Background:
Curcumin 2005-8 (Cur5-8), a derivative of curcumin, improves fatty liver disease via AMP-activated protein kinase activation and autophagy regulation. EW-7197 (vactosertib) is a small molecule inhibitor of transforming growth factor β (TGF-β) receptor I and may scavenge reactive oxygen species and ameliorate fibrosis through the SMAD2/3 canonical pathway. This study aimed to determine whether co-administering these two drugs having different mechanisms is beneficial.
Methods:
Hepatocellular fibrosis was induced in mouse hepatocytes (alpha mouse liver 12 [AML12]) and human hepatic stellate cells (LX-2) using TGF-β (2 ng/mL). The cells were then treated with Cur5-8 (1 μM), EW-7197 (0.5 μM), or both. In animal experiments were also conducted during which, methionine-choline deficient diet, Cur5-8 (100 mg/kg), and EW-7197 (20 mg/kg) were administered orally to 8-week-old C57BL/6J mice for 6 weeks.
Results:
TGF-β-induced cell morphological changes were improved by EW-7197, and lipid accumulation was restored on the administration of EW-7197 in combination with Cur5-8. In a nonalcoholic steatohepatitis (NASH)-induced mouse model, 6 weeks of EW-7197 and Cur5-8 co-administration alleviated liver fibrosis and improved the nonalcoholic fatty liver disease (NAFLD) activity score.
Conclusion
Co-administering Cur5-8 and EW-7197 to NASH-induced mice and fibrotic hepatocytes reduced liver fibrosis and steatohepatitis while maintaining the advantages of both drugs. This is the first study to show the effect of the drug combination against NASH and NAFLD. Similar effects in other animal models will confirm its potential as a new therapeutic agent.
4.Corrigendum to "Assessment of the Suitability of Trauma Triage According to Physiological Criteria in Korea" J Acute Care Surg 2022;12(3):120-124
Gil Hwan KIM ; Jae Hun KIM ; Hohyun KIM ; Seon Hee KIM ; Sung Jin PARK ; Sang Bong LEE ; Chan Ik PARK ; Dong Yeon RYU ; Kang Ho LEE ; Sun Hyun KIM ; Na Hyeon LEE ; Il Jae WANG
Journal of Acute Care Surgery 2023;13(2):82-82
5.Corrigendum to "Emergency Department Laparotomy Can Be a Resuscitative Option for Patient with Cardiac Arrest and Impending Arrest due to Intra-Abdominal Hemorrhage" J Acute Care Surg 2020;10(3):112-117
Chan Ik PARK ; Jae Hun KIM ; Kang Ho LEE ; Dong Yeon RYU ; Hyun-Woo SUN ; Gil Hwan KIM ; Sang Bong LEE ; Sung Jin PARK ; Hohyun KIM ; Seok Ran YEOM
Journal of Acute Care Surgery 2023;13(2):81-81
6.Validation of the Patient Health Questionnaire–9 and Patient Health Questionnaire–2 in the General Korean Population
Minah KIM ; Sanghyup JUNG ; Jee Eun PARK ; Jee Hoon SOHN ; Su Jeong SEONG ; Byung-Soo KIM ; Sung Man CHANG ; Jin Pyo HONG ; Bong-Jin HAHM ; Chan-Woo YEOM
Psychiatry Investigation 2023;20(9):853-860
Objective:
The Patient Health Questionnaire–9 (PHQ-9) and PHQ-2 have not been validated in the general Korean population. This study aimed to validate and identify the optimal cutoff scores of the PHQ-9 and PHQ-2 in screening for major depression in the general Korean population.
Methods:
We used data from 6,022 participants of the Korean Epidemiological Catchment Area Study for Psychiatric Disorders in 2011. Major depression was diagnosed according to the Korean Composite International Diagnostic Interview. Validity, reliability, and receiver operating characteristic curve analyses were performed using the results of the PHQ-9 and Euro Quality of life-5 dimension (EQ-5d).
Results:
Of the 6,022 participants, 150 were diagnosed with major depression (2.5%). Both PHQ-9 and PHQ-2 demonstrated relatively high reliability and their scores were highly correlated with the “anxiety/depression” score of the EQ-5d. The optimal cutoff score of the PHQ-9 was 5, with a sensitivity of 89.9%, specificity of 84.1%, positive predictive value (PPV) of 12.6%, negative predictive value (NPV) of 99.7%, positive likelihood ratio (LR+) of 5.6, and negative likelihood ratio (LR-) of 0.12. The optimal cutoff score of the PHQ-2 was 2, with a sensitivity of 85.3%, specificity of 83.2%, PPV of 11.6%, NPV of 99.5%, LR+ of 5.1, and LR- of 0.18.
Conclusion
The PHQ-9 and PHQ-2 are valid tools for screening major depression in the general Korean population, with suggested cutoff values of 5 and 2 points, respectively.
7.Avoiding unnecessary intraoperative sentinel lymph node frozen section biopsy of patients with early breast cancer
Jongwon KANG ; Tae-Kyung YOO ; Ahwon LEE ; Jun KANG ; Chang Ik YOON ; Bong Joo KANG ; Sung Hun KIM ; Woo Chan PARK
Annals of Surgical Treatment and Research 2022;102(5):241-247
Purpose:
After the publication of the ACOSOG (American College of Surgeons Oncology Group) Z0011 trial, the rate of axillary lymph node dissection has reduced. Thus, the need for intraoperative frozen section biopsy of sentinel lymph nodes (SLNs) has become controversial. We identified patients for whom intraoperative SLN frozen section biopsy could be omitted and found that frozen section biopsy rate can be reduced.
Methods:
We reviewed the records of patients with tumors ≤5 cm in diameter who underwent breast-conserving surgery between January 2013 and December 2019 at Seoul St. Mary’s Hospital. Clinicopathological and imaging characteristics were compared according to number of positive SLNs (0–2 SLNs positive vs. ≥3 SLNs positive).
Results:
A total of 1,983 patients were included in this study. Thirty-two patients (1.6%) had at least 3 positive SLNs. Patients with ≥3 positive SLNs had significantly larger tumors and were more frequently high-grade tumors (P < 0.001 and P = 0.002, respectively). Identification of suspicious lymph nodes on imaging studies was also associated with the presence of ≥3 positive SLNs (hazard ratio, 11.54; 95% confidence interval, 4.42–30.10). All patients with none or only 1 suspicious lymph node on any imaging modality (n = 647, 32.6%) had 0–2 positive SLNs. Also, among patients with clinical T1-stage tumors and at least 2 suspicious lymph nodes on only 1 imaging modality (n = 514, 25.9%), only 2 cases had ≥3 positive SLNs.
Conclusion
We found that intraoperative SLN frozen biopsy could be omitted in patients using tumor size and axillary lymph node status on imaging modality.
8.Clinical efficacy of adjuvant chemotherapy in stage IB (< 4 cm) non-small cell lung cancer patients with high-risk factors
Juwhan CHOI ; Jee Youn OH ; Young Seok LEE ; Kyung Hoon MIN ; Jae Jeong SHIM ; Sue In CHOI ; Dong Won PARK ; Chan Kwon PARK ; Eun Joo KANG ; Hwan Seok YONG ; Bong Kyung SHIN ; Hyun Koo KIM ; Sung Yong LEE
The Korean Journal of Internal Medicine 2022;37(1):127-136
Background/Aims:
Adjuvant chemotherapy is the standard of care for resected stage II-IIIA non-small cell lung cancer (NCSLC). The efficacy of adjuvant chemotherapy in stage IB (< 4 cm) NSCLC with high-risk factors is controversial.
Methods:
This retrospective multicenter study included 285 stage IB NSCLC patients with high-risk factors according to the 8th edition tumor, node, metastasis (TNM) classification from four academic hospitals. High-risk factors included visceral pleural invasion, vascular invasion, lymphatic invasion, lung neuroendocrine tumors, and micropapillary histology patterns.
Results:
Of the 285 patients, 127 (44.6%) were included in the adjuvant chemotherapy group and 158 (55.4%) were included in the non-adjuvant chemotherapy group. The median follow-up was 41.5 months. Patients in the adjuvant chemotherapy group had a significantly reduced recurrence rate and risk of mortality than those in the non-adjuvant chemotherapy group (hazards ratio, 0.408; 95% confidence interval, 0.221 to 0.754; p = 0.004 and hazards ratio, 0.176; 95% confidence interval, 0.057 to 0.546; p = 0.003, respectively). Adjuvant chemotherapy should be particularly considered for the high-risk factors such as visceral pleural involvement or vascular invasion. Based on the subgroup analysis, adjuvant chemotherapy should be considered when visceral pleural involvement is present, even if the tumor size is < 3 cm.
Conclusions
Adjuvant chemotherapy may be useful for patients with stage IB NSCLC with high-risk factors and is more relevant for patients with visceral pleural involvement or vascular invasion.
9.Assessment of the Suitability of Trauma Triage According to Physiological Criteria in Korea
Gil Hwan KIM ; Jae Hun KIM ; Hohyun KIM ; Seon Hee KIM ; Sung Jin PARK ; Sang Bong LEE ; Chan Ik PARK ; Dong Yeon RYU ; Kang Ho LEE ; Sun Hyun KIM ; Na Hyeon LEE ; Il Jae WANG
Journal of Acute Care Surgery 2022;12(3):120-124
Purpose:
A trauma center project for treating patients with trauma has been established in Korea. A trauma team is activated based on the Centers for Disease Control and Prevention (CDC) field triage Step 1 for patient triage. Here, we determined if the currently applied criteria were appropriate for the triage of patients with trauma in Korea.
Methods:
This retrospective study included patients who were taken to the regional trauma center from January 1, 2016 to December 31, 2019, and were registered in the Korean Trauma database. The rates for undertriage and overtriage were calculated from the in-field and in-hospital triage according to the CDC guidelines Step 1.
Results:
Among the 9,383 patients transferred to the trauma center, 3,423 were directly transferred from the site and were investigated. The overall rates for undertriage and overtriage of these patients were 28.13% and 30.35%, respectively. For the patients who received in-field triage and were directly transferred to the trauma center, the rates for undertriage and overtriage were 27.92% and 32.39%, and 25.92% and 29.11% for in-hospital triage, respectively. The concordance rate of triage was 87.09%.
Conclusion
The current use of in-hospital triage physiological criteria as set out in the CDC guidelines Step 1, indicated an undertriage rate which was high and an overtriage rate within the acceptable range. Further studies on triaging patients with trauma are warranted. Improvements in the guidelines of the trauma center project are necessary and this needs to be supported by resources and training for field personnel.
10.Relevant Clinical Findings of Patients with Extraperitoneal Bladder Injury Associated with Pelvic Fracture Who Underwent Operative Management: A 6-Year Retrospective Study
Sung Jin PARK ; Hohyun KIM ; Chang Ho JEON ; Jae Hoon JANG ; Jae Hun KIM ; Sun Hyun KIM ; Chan Ik PARK ; Sang Bong LEE ; Seon Hee KIM ; Chan Yong PARK ; Seok Ran YEOM
Journal of Acute Care Surgery 2021;11(1):14-21
Purpose:
Management options for extraperitoneal bladder injury (EBI) associated with pelvic fracture are variable. Predictive factors of operative management (OM) in patients with EBI associated pelvic fracture have not been previously addressed. This study assessed the current epidemiology of blunt traumatic urinary bladder injury and evaluated relevant clinical findings of patients with EBI associated with pelvic fracture who received OM.
Methods:
Patients with urinary bladder injury with or without pelvic fracture from blunt trauma from January 1, 2014 to December 31, 2019 were identified from the institute trauma registry (n = 12,891). Demographics, mechanism of injury, type of urinary bladder injury, pelvic fracture configuration, and management options were analysed in the study population (n = 9,894).
Results:
Of the 1,400 patients who had pelvic and/or acetabular fracture, 32 (2.3%) had urinary bladder injury. Of the 8,494 patients without pelvic and/or acetabular fracture, 12 (0.1%) had nonpelvic fracture urinary bladder injury. The total incidence of urinary bladder injuries in the study population was 0.4% (44/9,894). Patients with EBI associated with pelvic fracture who underwent OM, had a higher frequency of high-grade pelvic injury (100% vs 0%, p = 0.015), concomitant pelvic surgery (75.0% vs 0%, p = 0.001), and non-lateral compression type pelvic fracture (62.5% vs 10.0%, p = 0.043) compared with patients who underwent non-operative management of EBI.
Conclusions
These data suggest that OM may be considered especially in patients with EBI associated with pelvic fracture with high grade pelvic injury, concomitant pelvic surgery, and nonlateral compression type pelvic fracture.

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