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.First-in-Human Evaluation of a Polymer-Free Everolimus-Eluting Stent Using a Titanium Dioxide Film
Doo Sun SIM ; Kyung Hoon CHO ; Dae Young HYUN ; Dae Sung PARK ; Jun-Kyu PARK ; Dae-Heung BYEON ; Won-Il JO ; Sang-Wook KIM ; Joon Ho AHN ; Seung Hun LEE ; Min Chul KIM ; Young Joon HONG ; Ju Han KIM ; Youngkeun AHN ; Myung Ho JEONG
Journal of Korean Medical Science 2024;39(33):e234-
Background:
In patients with coronary artery disease treated with permanent polymercoated drug-eluting stents (DES), the persistent presence of a less biocompatible polymer might delay arterial healing. Thin strut polymer-free DES have the potential to improve clinical outcomes and reduce the duration of dual antiplatelet therapy (DAPT). The purpose of this first-in-human study was to assess the safety and effectiveness of a novel polymer-free DES in patients with de novo coronary lesions. The TIGERevolutioN® stent (CG Bio Co., Ltd., Seoul, Korea) consists of a cobalt chromium platform with a strut thickness of 70 μm and a surface treated with titanium dioxide onto which everolimus-eluting stent (EES) is applied abluminally (6 µg/mm of stent length) without utilization of a polymer.
Methods:
A total of 20 patients were enrolled, with de novo coronary lesions (stable or unstable angina) and > 50% diameter stenosis in a vessel 2.25 to 4.00 mm in diameter and ≤ 40 mm in length for angiographic, optical coherence tomography (OCT), and clinical assessment at 8 months. All patients received DAPT after stent implantation. The primary endpoint was angiographic in-stent late lumen loss (LLL) at 8 months.
Results:
Twenty patients with 20 lesions were treated with TIGERevolutioN® . At 8 months, in-stent LLL was 0.7 ± 0.4 mm. On OCT, percent area stenosis was 29.2 ± 9.4% and stent strut coverage was complete in all lesions. No adverse cardiovascular event occurred at 8 months.
Conclusion
The new polymer-free EES was safe and effective with low LLL and excellent strut coverage at 8 months of follow-up.
3.Latarjet Procedure Screw Guide Designed with a 3.5 mm Locking Compression Plate Piece: Technical Note
Heung Sub SHIN ; Hyung Lae CHO ; Hong Ki JIN ; Won Kyu JANG
The Journal of the Korean Orthopaedic Association 2024;59(2):148-153
Traditional soft tissue Bankart repair has high failure rates in the setting of a critical glenoid bone defect in recurrent shoulder dislocation.Hence, coracoid transfer, particularly the Latarjet procedure, can be performed to reduce the recurrence. A commercialized guide can be used during the Latarjet procedure. On the other hand, it is difficult to handle the guide parallel to the glenoid articular surface because of the predetermined fixed direction of the guide, and the guide pin is so thin that it can be broken in the wrong direction of insertion. Screw holes can also be drilled using the free hand technique without a guide, but it is inaccurate in maintaining a parallel direction or constant spacing between the screw holes. This study devised an instrument by cutting a 3.5 mm locking compression plate used in fracture surgeries, and the Latarjet procedure was performed relatively easily.
4.Species identification and pyrethroid resistance genotyping of recently resurgent Cimex lectularius and Cimex hemipterus in Korea
Susie CHO ; Heung Chul KIM ; Hoonsik EOM ; Jae Rok LEE ; Chung Hyun KO ; E-hyun SHIN ; Won Kyu LEE ; Si Hyeock LEE ; Ju Hyeon KIM
Parasites, Hosts and Diseases 2024;62(2):251-256
The global resurgence of bed bug infestations, exacerbated by increasing international travel, trade, and insecticide resistance, has significantly impacted Korea. This study identified the bed bug species and performed pyrethroid resistance genotyping of recently resurgent bed bugs in Korea. Thirty-one regional bed bug samples were collected from 5 administrative regions: Gyeonggi-do (n=14), Seoul (n=13), Busan (n=2), Jeonllanam-do (n=1), and Chungcheongbuk-do (n=1). The samples underwent morphological and molecular identification. Twenty-four regional samples (77.4%) were identified as the tropical bed bug, Cimex hemipterus, and the remaining 7 regional samples (22.6%) were identified as the common bed bug, Cimex lectularius. The C. hemipterus regional samples carried at least three mutations associated with knockdown resistance (kdr), including 2 super-kdr mutations. The 7 C. lectularius regional samples possessed at least one of the 3 kdr-related mutations associated with pyrethroid resistance. This study confirms that the prevalent bed bug species recently in Korea is C. hemipterus, replacing the previously endemic C. lectularius. Additionally, the rise in bed bug populations with pyrethroid resistance underscores the necessity of introducing alternative insecticides.
5.Preliminary Investigation on Efficacy and Safety of Substance P-Coated Stent for Promoting Re-Endothelialization: A Porcine Coronary Artery Restenosis Model
Dae Sung PARK ; Seok OH ; Yu Jeong JIN ; Mi Hyang NA ; Munki KIM ; Jeong Ha KIM ; Dae Young HYUN ; Kyung Hoon CHO ; Young Joon HONG ; Ju Han KIM ; Youngkeun AHN ; Manuel HERMIDA-PRIETO ; José Manuel VÁZQUEZ-RODRIGUEZ ; Juan Luis GUTIÉRREZ- CHICO ; Luis MARINÃS-PARDO ; Kyung Seob LIM ; Jun-Kyu PARK ; Dae-Heung BYEON ; Young-Nan CHO ; Seung-Jung KEE ; Doo Sun SIM ; Myung Ho JEONG
Tissue Engineering and Regenerative Medicine 2024;21(1):53-64
BACKGROUND:
Current polymer-based drug-eluting stents (DESs) have fundamental issues about inflammation and delayed re-endothelializaton of the vessel wall. Substance-P (SP), which plays an important role in inflammation and endothelial cells, has not yet been applied to coronary stents. Therefore, this study compares poly lactic-co-glycolic acid (PLGA)-based everolimus-eluting stents (PLGA-EESs) versus 2-methacryloyloxyethyl phosphorylcholine (MPC)-based SP-eluting stents (MPC-SPs) in in-vitro and in-vivo models.
METHODS:
The morphology of the stent surface and peptide/drug release kinetics from stents were evaluated. The invitro proliferative effect of SP released from MPC-SP is evaluated using human umbilical vein endothelial cell. Finally, the safety and efficacy of the stent are evaluated after inserting it into a pig’s coronary artery.
RESULTS:
Similar to PLGA-EES, MPC-SP had a uniform surface morphology with very thin coating layer thickness (2.074 lm). MPC-SP showed sustained drug release of SP for over 2 weeks. Endothelial cell proliferation was significantly increased in groups treated with SP (n = 3) compared with the control (n = 3) and those with everolimus (n = 3) (SP:118.9 ± 7.61% vs. everolimus: 64.3 ± 12.37% vs. the control: 100 ± 6.64%, p < 0.05). In the animal study, the percent stenosis was higher in MPC-SP group (n = 7) compared to PLGA-EES group (n = 7) (MPC-SP: 28.6 ± 10.7% vs. PLGAEES: 16.7 ± 6.3%, p < 0.05). MPC-SP group showed, however, lower inflammation (MPC-SP: 0.3 ± 0.26 vs. PLGAEES: 1.2 ± 0.48, p < 0.05) and fibrin deposition (MPC-SP: 1.0 ± 0.73 vs. PLGA-EES: 1.5 ± 0.59, p < 0.05) around the stent strut. MPC-SP showed more increased expression of cluster of differentiation 31, suggesting enhanced reendothelialization.
CONCLUSION
Compared to PLGA-EES, MPC-SP demonstrated more decreased inflammation of the vascular wall and enhanced re-endothelialization and stent coverage. Hence, MPC-SP has the potential therapeutic benefits for the treatment of coronary artery disease by solving limitations of currently available DESs.
6.Nonsimultaneous Bilateral Internal Oblique Muscle Rupture in a Professional Baseball Batter: A Case Report
Heung Sub SHIN ; Hyung Lae CHO ; Hong Ki JIN ; Won Kyu JANG
The Korean Journal of Sports Medicine 2023;41(4):246-249
Abdominal oblique muscle injuries are relatively common in professional baseball players and can result in substantial loss of playing time. It is usually caused by a sudden movement of the torso in sports involving repetitive activity requiring trunk rotation and it tend to occur on the contralateral side of the dominant arm. We report a unique case of sequentially occurred bilateral abdominal internal oblique muscle rupture in a right-handed professional baseball batter over two seasons. Each internal oblique rupture had a different mechanism of the injury, the non-dominant side occurred during bat swing and the dominant side during bent leg sliding. After rest and rehabilitation, each injury was recovered to play in about 1 month.
7.Subsequent pregnancy and long-term safety after breast cancer: a retrospective analysis of Korean health insurance data
Minsun KANG ; Yong Soon CHUN ; Heung Kyu PARK ; Eun Kyung CHO ; Jaehun JUNG ; Yunyeong KIM
Annals of Surgical Treatment and Research 2022;102(2):73-82
Purpose:
Long-term safety of pregnancy after breast cancer (BC) remains controversial, especially with respect to BC biological subtypes.
Methods:
We analyzed a population-based retrospective cohort with BC from 2002 to 2017. Patient-level 1:1 matching was performed between pregnant and nonpregnant women. The study population was categorized into 6 biological subtypes based on the combination of prescribed therapies. Subanalyses were performed considering the time to pregnancy after BC diagnosis, systemic therapy, and pregnancy outcomes.
Results:
We identified 544 matched women with BC, who were assigned to the pregnant (cases, n = 272) or nonpregnant group (controls, n = 272) of similar characteristics, adjusted for guaranteed bias. These patients were followed up for 10 years, or disease and mortality occurrence after the diagnosis of BC. Survival estimates were calculated. The actuarial 10-year overall survival (OS) rates were 97.4% and 91.9% for pregnant and nonpregnant patients, respectively. The pregnant group showed significantly better OS (adjusted hazard ratio [aHR], 0.29; 95% confidence interval [CI], 0.12–0.68; P = 0.005) and did not have a significantly inferior disease-free survival (aHR, 1.10; 95% CI, 0.61–1.99; P = 0.760).
Conclusion
Consistent outcomes were observed in every subgroup analysis. Our observational data provides reassuring evidence on the long-term safety of pregnancy in young patients with BC regardless of the BC biological subtype.
8.Efficacy of hyaluronic acid film on perianal wound healing in a rat model
Jung Rae CHO ; Myoung-Han LEE ; Heung-Kwon OH ; Hyojin KIM ; Dong-Keon KWEON ; So Min KANG ; Baek Kyu KIM ; Chan Yeong HEO ; Duck-Woo KIM ; Sung-Bum KANG
Annals of Surgical Treatment and Research 2021;101(4):206-213
Purpose:
Postoperative pain and delayed wound healing are the main complications following anal surgery associated with poor quality of life. Hyaluronic acid (HA) supports tissue regeneration and rapid wound healing by promoting cell proliferation and migration. We investigated the effects of HA on perianal wound healing in a rat model.
Methods:
Forty-eight 8-week-old Sprague-Dawley rats with perianal wounds created by biopsy punch were divided into 3 groups: simple dressing with gauze (control), dressing with topical HA film, and dressing with topical HA gel. HA agents were not reapplied postoperatively. Wound healing was evaluated by measuring the healed area, and histological analyses were randomly performed using hematoxylin and eosin and Masson trichrome staining.
Results:
Fewer mean days were required for complete wound healing in the HA film and HA gel groups than in the control group (11.6 vs. 11.9 vs. 13.8 days, respectively; P = 0.010). The healed area in the HA film group on day 11 was larger than that in the HA gel and control groups (80.2% vs. 61.9% vs. 53.2%, respectively; P < 0.001). Histologically, the HA film group showed accelerated reepithelialization, a rapid transition to lymphocyte-predominant inflammation, and increased fibroblastic proliferation and collagen deposition compared to the other groups. There was no treatment-related toxicity in the HA application groups.
Conclusion
Topical application of HA film to perianal wounds improves the wound healing rate in a rat model. This finding suggests a potential benefit of HA film application in promoting wound healing after anal surgery in humans.
9.Erratum: Correction of Affiliations in the Article “Clinical Characteristics and Treatment Outcomes in Children, Adolescents, and Young-adults with Hodgkin's Lymphoma: a KPHOG Lymphoma Working-party, Multicenter, Retrospective Study”
Jae Min LEE ; Jung Yoon CHOI ; Kyung Taek HONG ; Hyoung Jin KANG ; Hee Young SHIN ; Hee Jo BAEK ; Hoon KOOK ; Seongkoo KIM ; Jae Wook LEE ; Nack-Gyun CHUNG ; Bin CHO ; Seok-Goo CHO ; Kyung Mi PARK ; Eu Jeen YANG ; Young Tak LIM ; Jin Kyung SUH ; Sung Han KANG ; Hyery KIM ; Kyung-Nam KOH ; Ho Joon IM ; Jong Jin SEO ; Hee Won CHO ; Hee Young JU ; Ji Won LEE ; Keon Hee YOO ; Ki Woong SUNG ; Hong Hoe KOO ; Kyung Duk PARK ; Jeong Ok HAH ; Min Kyoung KIM ; Jung Woo HAN ; Seung Min HAHN ; Chuhl Joo LYU ; Ye Jee SHIM ; Heung Sik KIM ; Young Rok DO ; Jae Won YOO ; Yeon Jung LIM ; In-Sang JEON ; Hee won CHUEH ; Sung Yong OH ; Hyoung Soo CHOI ; Jun Eun PARK ; Jun Ah LEE ; Hyeon Jin PARK ; Byung-Kiu PARK ; Soon Ki KIM ; Jae Young LIM ; Eun Sil PARK ; Sang Kyu PARK ; Eun Jin CHOI ; Young Bae CHOI ; Jong Hyung YOON ;
Journal of Korean Medical Science 2021;36(4):e37-
10.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.

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