1.Comparative Efficacy of Rosuvastatin Monotherapy and Rosuvastatin/Ezetimibe Combination Therapy on Insulin Sensitivity and Vascular Inflammatory Response in Patients with Type 2 Diabetes Mellitus
Ji Hye HAN ; Kyong Hye JOUNG ; Jun Choul LEE ; Ok Soon KIM ; Sorim CHOUNG ; Ji Min KIM ; Yea Eun KANG ; Hyon-Seung YI ; Ju Hee LEE ; Bon Jeong KU ; Hyun Jin KIM
Diabetes & Metabolism Journal 2024;48(1):112-121
Background:
Type 2 diabetes mellitus (T2DM) induces endothelial dysfunction and inflammation, which are the main factors for atherosclerosis and cardiovascular disease. The present study aimed to compare the effects of rosuvastatin monotherapy and rosuvastatin/ezetimibe combination therapy on lipid profile, insulin sensitivity, and vascular inflammatory response in patients with T2DM.
Methods:
A total of 101 patients with T2DM and dyslipidemia were randomized to either rosuvastatin monotherapy (5 mg/day, n=47) or rosuvastatin/ezetimibe combination therapy (5 mg/10 mg/day, n=45) and treated for 12 weeks. Serum lipids, glucose, insulin, soluble intercellular adhesion molecule-1 (sICAM-1), and peroxiredoxin 4 (PRDX4) levels were determined before and after 12 weeks of treatment.
Results:
The reduction in low density lipoprotein cholesterol (LDL-C) by more than 50% from baseline after treatment was more in the combination therapy group. The serum sICAM-1 levels increased significantly in both groups, but there was no difference between the two groups. The significant changes in homeostasis model assessment of insulin resistance (HOMA-IR) and PRDX4 were confirmed only in the subgroup in which LDL-C was reduced by 50% or more in the combination therapy group. However, after adjusting for diabetes mellitus duration and hypertension, the changes in HOMA-IR and PRDX4 were not significant between the two groups.
Conclusion
Although rosuvastatin/ezetimibe combination therapy had a greater LDL-C reduction effect than rosuvastatin monotherapy, it had no additional effects on insulin sensitivity and vascular inflammatory response. Further studies are needed on the effect of long-term treatment with ezetimibe on insulin sensitivity and vascular inflammatory response.
2.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.
3.Endoclip-Assisted Cannulation for a Hidden Duodenal Papilla: Three Cases
Il Soon JUNG ; Ki Bae KIM ; Jun Su LEE ; Joung-Ho HAN ; Seon Mee PARK
Korean Journal of Pancreas and Biliary Tract 2024;29(4):167-171
Selective cannulation during endoscopic retrograde cholangiopancreatography can be particularly challenging when the papilla is invisible, either due to an intradiverticular papilla (IDP) or because it is covered by a mucosal fold. Endoclipassisted cannulation is an effective and safe technique for everting and fixing the papilla and it can be used alone or in combination with other devices. In this report, we achieved successful papillary cannulation in two cases of IDP and one case where the papilla was covered by a mucosal fold. In two cases, cannulation was accomplished by repositioning the invisible papilla using an endoclip alone, while in one case, we used an endoclip-assisted technique to push a redundant fold with a catheter. Endoclipassisted papillary cannulation can be applied in different situations, either alone or in combination with other devices.
4.Increased Pro-Inflammatory T Cells, Senescent T Cells, and Immune-Check Point Molecules in the Placentas of Patients With Gestational Diabetes Mellitus
Yea Eun KANG ; Hyon-Seung YI ; Min-Kyung YEO ; Jung Tae KIM ; Danbit PARK ; Yewon JUNG ; Ok Soon KIM ; Seong Eun LEE ; Ji Min KIM ; Kyong Hye JOUNG ; Ju Hee LEE ; Bon Jeong KU ; Mina LEE ; Hyun Jin KIM
Journal of Korean Medical Science 2022;37(48):e338-
Background:
Gestational diabetes mellitus (GDM) is the most common metabolic complication of pregnancy. To define the altered pathway in GDM placenta, we investigated the transcriptomic profiles from human placenta between GDM and controls.
Methods:
Clinical parameters and postpartum complications were reviewed in all participants.Differentially expressed canonical pathways were analyzed between the GDM and control groups based on transcriptomic analysis. CD4 + T, CD8 + T, and senescent T cell subsets were determined by flow cytometry based on staining for specific intracellular cytokines.
Results:
Gene ontology analysis revealed that the placenta of GDM revealed upregulation of diverse mitochondria or DNA replication related pathways and downregulation of T-cell immunity related pathways. The maternal placenta of the GDM group had a higher proportion of CD4 + T and CD8 + T cells than the control group. Interestingly, senescent CD4 + T cells tended to increase and CD8 + T cells were significantly increased in GDM compared to controls, along with increased programmed cell death-1 (CD274 + ) expression. Programmed death-ligand 1 expression in syncytotrophoblasts was also significantly increased in patients with GDM.
Conclusion
This study demonstrated increased proinflammatory T cells, senescent T cells and immune-check point molecules in GDM placentas, suggesting that changes in senescent T cells and immune-escape signaling might be related to the pathophysiology of GDM.
5.Ambient air pollution and endocrinologic disorders in childhood
Annals of Pediatric Endocrinology & Metabolism 2021;26(3):158-170
Ambient air pollution has been proposed as an important environmental risk factor that increases global mortality and morbidity. Over the past decade, several human and animal studies have reported an association between exposure to air pollution and altered metabolic and endocrine systems in children. However, the results for these studies were mixed and inconclusive and did not demonstrate causality because different outcomes were observed due to different study designs, exposure periods, and methodologies for exposure measurements. Current proposed mechanisms include altered immune response, oxidative stress, neuroinflammation, inadequate placental development, and epigenetic modulation. In this review, we summarized the results of previous pediatric studies that reported effects of prenatal and postnatal air pollution exposure on childhood type 1 diabetes mellitus, obesity, insulin resistance, thyroid dysfunction, and timing of pubertal onset, along with underlying related mechanisms.
6.The Nationwide Incidence of Retinal Vein Occlusion Following Dialysis due to End-stage Renal Disease in Korea, 2004 through 2013
Tae Hwan MOON ; Joung-Ho HAN ; Minseok KANG ; Ji Soo KIM ; Jin Young KIM ; Ju Byung CHAE ; Soon Kil KWON ; Gilwon KANG ; Dong Yoon KIM
Journal of Korean Medical Science 2021;36(30):e201-
Background:
We investigated the incidence and risk of retinal vein occlusion (RVO) in endstage renal disease (ESRD) patients on dialysis in Korea.
Methods:
In this nationwide cohort study, we used Korean National Health Insurance Service data between 2004 and 2013 for analysis. ESRD patients who started dialysis from 2004 to 2013 and an equal number of controls were selected through propensity score matching. RVO incidence in both cohorts were calculated for 2004–2013 using washout data from 2003. The multivariable Cox proportional hazards model was used to assess the risk of RVO in dialysis cohort. The Kaplan-Meier method was used to generate the cumulative RVO incidence curve.Whether the dialysis modality affects the development of RVO was also evaluated.
Results:
In this study, 74,551 ESRD patients on dialysis and the same number of controls were included. The incidence of RVO was significantly higher in the dialysis cohort than in the control cohort (dialysis = 7.3/1,000 person-years [PY]; control = 1.9/1,000 PY; P < 0.001). The cumulative-incidence of RVO was also significantly higher in the dialysis cohort than in the control cohort (P < 0.001; log-rank test). However, there was no significant difference in the incidence of RVO between the two dialysis methods (P = 0.550; log-rank test).
Conclusion
This study provided epidemiological evidence that receiving dialysis for ESRD could increase the risk of developing RVO. We also found a rapid increase in the incidence of RVO with a longer dialysis period. These results strengthen the relationship between retinal vascular disease and renal function.
7.Ambient air pollution and endocrinologic disorders in childhood
Annals of Pediatric Endocrinology & Metabolism 2021;26(3):158-170
Ambient air pollution has been proposed as an important environmental risk factor that increases global mortality and morbidity. Over the past decade, several human and animal studies have reported an association between exposure to air pollution and altered metabolic and endocrine systems in children. However, the results for these studies were mixed and inconclusive and did not demonstrate causality because different outcomes were observed due to different study designs, exposure periods, and methodologies for exposure measurements. Current proposed mechanisms include altered immune response, oxidative stress, neuroinflammation, inadequate placental development, and epigenetic modulation. In this review, we summarized the results of previous pediatric studies that reported effects of prenatal and postnatal air pollution exposure on childhood type 1 diabetes mellitus, obesity, insulin resistance, thyroid dysfunction, and timing of pubertal onset, along with underlying related mechanisms.
8.The Nationwide Incidence of Retinal Vein Occlusion Following Dialysis due to End-stage Renal Disease in Korea, 2004 through 2013
Tae Hwan MOON ; Joung-Ho HAN ; Minseok KANG ; Ji Soo KIM ; Jin Young KIM ; Ju Byung CHAE ; Soon Kil KWON ; Gilwon KANG ; Dong Yoon KIM
Journal of Korean Medical Science 2021;36(30):e201-
Background:
We investigated the incidence and risk of retinal vein occlusion (RVO) in endstage renal disease (ESRD) patients on dialysis in Korea.
Methods:
In this nationwide cohort study, we used Korean National Health Insurance Service data between 2004 and 2013 for analysis. ESRD patients who started dialysis from 2004 to 2013 and an equal number of controls were selected through propensity score matching. RVO incidence in both cohorts were calculated for 2004–2013 using washout data from 2003. The multivariable Cox proportional hazards model was used to assess the risk of RVO in dialysis cohort. The Kaplan-Meier method was used to generate the cumulative RVO incidence curve.Whether the dialysis modality affects the development of RVO was also evaluated.
Results:
In this study, 74,551 ESRD patients on dialysis and the same number of controls were included. The incidence of RVO was significantly higher in the dialysis cohort than in the control cohort (dialysis = 7.3/1,000 person-years [PY]; control = 1.9/1,000 PY; P < 0.001). The cumulative-incidence of RVO was also significantly higher in the dialysis cohort than in the control cohort (P < 0.001; log-rank test). However, there was no significant difference in the incidence of RVO between the two dialysis methods (P = 0.550; log-rank test).
Conclusion
This study provided epidemiological evidence that receiving dialysis for ESRD could increase the risk of developing RVO. We also found a rapid increase in the incidence of RVO with a longer dialysis period. These results strengthen the relationship between retinal vascular disease and renal function.
9.New strategy to prevent implant displacement in transaxillary endoscopic augmentation mammaplasty
Sang-Gue KANG ; Joung-Ki KIM ; Soon Chan UM
Archives of Aesthetic Plastic Surgery 2020;26(1):41-45
Breast augmentation is one of the most popular cosmetic procedures in Korea and worldwide. In breast augmentation, it is crucial to place the implant in the proper position by creating an adequate pocket considering the size of the implant. This prevents subsequent displacement of the implant. When using an endoscope, the operation is performed without direct vision and in a narrow surgical space, leading to limitations in practice. Inexperienced physicians face a steep learning curve in their efforts to overcome this difficulty. In this study, we attempted to overcome this challenge by specifying the medial and lateral dissection ranges. The extent of the dissection is determined based on the pinnate of the pectoralis major muscle when dissecting medially and the fascia of the pectoralis major, the pectoralis minor, and the serratus anterior muscles when dissecting laterally. In addition, the structure made from the medial and lateral sides can support the implant like a funnel and can prevent further downward, inward, and outward displacement.
10.Clinical Targeted Next-Generation sequencing Panels for Detection of Somatic Variants in Gliomas
Hyemi SHIN ; Jason K. SA ; Joon Seol BAE ; Harim KOO ; Seonwhee JIN ; Hee Jin CHO ; Seung Won CHOI ; Jong Min KYOUNG ; Ja Yeon KIM ; Yun Jee SEO ; Je-Gun JOUNG ; Nayoung K. D. KIM ; Dae-Soon SON ; Jongsuk CHUNG ; Taeseob LEE ; Doo-Sik KONG ; Jung Won CHOI ; Ho Jun SEOL ; Jung-Il LEE ; Yeon-Lim SUH ; Woong-Yang PARK ; Do-Hyun NAM
Cancer Research and Treatment 2020;52(1):41-50
Purpose:
Targeted next-generation sequencing (NGS) panels for solid tumors have been useful in clinical framework for accurate tumor diagnosis and identifying essential molecular aberrations. However, most cancer panels have been designed to address a wide spectrum of pan-cancer models, lacking integral prognostic markers that are highly specific to gliomas.
Materials and Methods:
To address such challenges, we have developed a glioma-specific NGS panel, termed “GliomaSCAN,” that is capable of capturing single nucleotide variations and insertion/deletion, copy number variation, and selected promoter mutations and structural variations that cover a subset of intron regions in 232 essential glioma-associated genes. We confirmed clinical concordance rate using pairwise comparison of the identified variants from whole exome sequencing (WES), immunohistochemical analysis, and fluorescence in situ hybridization.
Results:
Our panel demonstrated high sensitivity in detecting potential genomic variants that were present in the standard materials. To ensure the accuracy of our targeted sequencing panel, we compared our targeted panel to WES. The comparison results demonstrated a high correlation. Furthermore, we evaluated clinical utility of our panel in 46 glioma patients to assess the detection capacity of potential actionable mutations. Thirty-two patients harbored at least one recurrent somatic mutation in clinically actionable gene.
Conclusion
We have established a glioma-specific cancer panel. GliomaSCAN highly excelled in capturing somatic variations in terms of both sensitivity and specificity and provided potential clinical implication in facilitating genome-based clinical trials. Our results could provide conceptual advance towards improving the response of genomically guided molecularly targeted therapy in glioma patients.

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