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.Korean Thyroid Association Guidelines on the Management of Differentiated Thyroid Cancers; Part I. Initial Management of Differentiated Thyroid Cancers - Chapter 5. Evaluation of Recurrence Risk Postoperatively and Initial Risk Stratification in Differentiated Thyroid Cancer 2024
Eun Kyung LEE ; Young Shin SONG ; Ho-Cheol KANG ; Sun Wook KIM ; Dong Gyu NA ; Shin Je MOON ; Dong-Jun LIM ; Kyong Yeun JUNG ; Yun Jae CHUNG ; Chan Kwon JUNG ; Young Joo PARK ;
International Journal of Thyroidology 2024;17(1):68-96
The American Joint Committee on Cancer/Union for International Cancer Control (AJCC/UICC) staging classification of thyroid cancer can predict death but cannot determine the type and frequency of follow-up testing. Risk stratification is a concept proposed by the American Thyroid Association that uses additional prognostic factors that are not included in the AJCC/UICC classification, such as number or size of metastatic lymph nodes, genetic mutations, and vascular invasion in follicular cancer, to further refine the prognosis of thyroid cancer. The risk of recurrence was categorized as low, intermediate, and high risk, and the need for total thyroidectomy, radioiodine therapy, or thyroid-stimulating hormone suppression was determined depending on each risk level. This approach has been accepted worldwide, and the previous recommendations of the Korean Thyroid Association followed a similar line of thinking but these have been modified in the revised 2024 guidelines.For the revised initial risk stratification, after careful review of the results of the recent meta-analyses and large observational studies and after a multidisciplinary meeting, four major changes were made: 1) thyroid cancer was reclassified according to the World Health Organization (WHO) 2022 tumor classification system; 2) recurrence risk was stratified by combining encapsulated follicular variant papillary thyroid cancer, follicular thyroid cancer, and oncocytic thyroid cancer, which have similar recurrence risk and associated factors, into follicular-patterned tumor; 3) low-risk groups were defined as those with a known recurrence rate of ≤5%, high-risk groups were upgraded to those with a known recurrence rate of ≥30%, and intermediate-risk groups were those with a recurrence risk of 5–30%; and 4) the intermediate risk group had the recurrence rate presented according to various clinicopathological factors, mainly based on reports from Korea. Thus, it is recommended to evaluate the initial risk group by predicting the recurrence rate by combining each clinical factor in individual patients, rather than applying the recurrence rate caused by single risk factor.
3.Korean Thyroid Association Guidelines on the Management of Differentiated Thyroid Cancers; Overview and Summary 2024
Young Joo PARK ; Eun Kyung LEE ; Young Shin SONG ; Bon Seok KOO ; Hyungju KWON ; Keunyoung KIM ; Mijin KIM ; Bo Hyun KIM ; Won Gu KIM ; Won Bae KIM ; Won Woong KIM ; Jung-Han KIM ; Hee Kyung KIM ; Hee Young NA ; Shin Je MOON ; Jung-Eun MOON ; Sohyun PARK ; Jun-Ook PARK ; Ji-In BANG ; Kyorim BACK ; Youngduk SEO ; Dong Yeob SHIN ; Su-Jin SHIN ; Hwa Young AHN ; So Won OH ; Seung Hoon WOO ; Ho-Ryun WON ; Chang Hwan RYU ; Jee Hee YOON ; Ka Hee YI ; Min Kyoung LEE ; Sang-Woo LEE ; Seung Eun LEE ; Sihoon LEE ; Young Ah LEE ; Joon-Hyop LEE ; Ji Ye LEE ; Jieun LEE ; Cho Rok LEE ; Dong-Jun LIM ; Jae-Yol LIM ; Yun Kyung JEON ; Kyong Yeun JUNG ; Ari CHONG ; Yun Jae CHUNG ; Chan Kwon JUNG ; Kwanhoon JO ; Yoon Young CHO ; A Ram HONG ; Chae Moon HONG ; Ho-Cheol KANG ; Sun Wook KIM ; Woong Youn CHUNG ; Do Joon PARK ; Dong Gyu NA ;
International Journal of Thyroidology 2024;17(1):1-20
Differentiated thyroid cancer demonstrates a wide range of clinical presentations, from very indolent cases to those with an aggressive prognosis. Therefore, diagnosing and treating each cancer appropriately based on its risk status is important. The Korean Thyroid Association (KTA) has provided and amended the clinical guidelines for thyroid cancer management since 2007. The main changes in this revised 2024 guideline include 1) individualization of surgical extent according to pathological tests and clinical findings, 2) application of active surveillance in low-risk papillary thyroid microcarcinoma, 3) indications for minimally invasive surgery, 4) adoption of World Health Organization pathological diagnostic criteria and definition of terminology in Korean, 5) update on literature evidence of recurrence risk for initial risk stratification, 6) addition of the role of molecular testing, 7) addition of definition of initial risk stratification and targeting thyroid stimulating hormone (TSH) concentrations according to ongoing risk stratification (ORS), 8) addition of treatment of perioperative hypoparathyroidism, 9) update on systemic chemotherapy, and 10) addition of treatment for pediatric patients with thyroid cancer.
4.Vaccine Effect on Household Transmission of Omicron and Delta SARS-CoV-2 Variants
Yong Chan KIM ; Bongyoung KIM ; Nak-Hoon SON ; Namwoo HEO ; Yooju NAM ; Areum SHIN ; Andrew Jihoon YANG ; Min Hyung KIM ; Taeyoung KYONG ; Eawha KANG ; Yoon Soo PARK ; Heejung KIM
Journal of Korean Medical Science 2023;38(1):e9-
Background:
We evaluated the household secondary attack rate (SAR) of the omicron and delta severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants, according to the vaccination status of the index case and household contacts; further, in vaccinated index cases, we evaluated the effect of the antibody levels on household transmission.
Methods:
A prospective cross-sectional study of 92 index cases and 197 quarantined household contacts was performed. Tests for SARS-CoV-2 variant type and antibody level were conducted in index cases, and results of polymerase chain reaction tests (during the quarantine period) were collected from contacts. Association of antibody levels in vaccinated index cases and SAR was evaluated by multivariate regression analysis.
Results:
The SAR was higher in households exposed to omicron variant (42%) than in those exposed to delta variant (27%) (P = 0.040). SAR was 35% and 23% for unvaccinated and vaccinated delta variant exposed contacts, respectively. SAR was 44% and 41% for unvaccinated and vaccinated omicron exposed contacts, respectively. Booster dose immunisation of contacts or vaccination of index cases reduced SAR of vaccinated omicron variant exposed contacts. In a model with adjustment, anti-receptor-binding domain antibody levels in vaccinated index cases were inversely correlated with household transmission of both delta and omicron variants.Neutralising antibody levels had a similar relationship.
Conclusion
Immunisation of household members may help to mitigate the current pandemic.
5.A Novel Therapeutic Effect of a New Variant of CTLA4-Ig with Four Antennas That Are Terminally Capped with Sialic Acid in the CTLA4 Region
Yongwei PIAO ; So Yoon YUN ; Hee Soo KIM ; Bo Kyung PARK ; Hae Chan HA ; Zhicheng FU ; Ji Min JANG ; Moon Jung BACK ; In Chul SHIN ; Jong Hoon WON ; Dae Kyong KIM
Biomolecules & Therapeutics 2022;30(6):529-539
Rheumatoid arthritis (RA) is a multifactorial immune-mediated disease, the pathogenesis of which involves different cell types. T-cell activation plays an important role in RA. Therefore, inhibiting T-cell activation is one of the current therapeutic strategies.Cytotoxic T-lymphocyte antigen 4-immunoglobulin (CTLA4-Ig), also known as abatacept, reduces cytokine secretion by inhibiting T-cell activation. To achieve a homeostatic therapeutic effect, CTLA4-Ig has to be administered repeatedly over several weeks, which limits its applicability in RA treatment. To overcome this limitation, we increased the number of sialic acid-capped antennas by genetically engineering the CTLA4 region to increase the therapeutic effect of CTLA4-Ig. N-acetylglucosaminyltransferase (GnT) and α2,6-sialyltransferase (α2,6-ST) were co-overexpressed in Chinese hamster ovary (CHO) cells to generate a highly sialylated CTLA4-Ig fusion protein, named ST6. The therapeutic and immunogenic effects of ST6 and CTLA4-Ig were compared. ST6 dose-dependently decreased paw edema in a mouse model of collagen-induced arthritis and reduced cytokine levels in a co-culture cell assay in a similar manner to CTLA4-Ig. ST6- and CTLA4-Ig-induced T cell-derived cytokines were examined in CD4 T cells isolated from peripheral blood mononuclear cells after cell killing through irradiation followed by flow- and magnetic-beadassisted separation. Interestingly, compared to CTLA4-Ig, ST6 was substantially less immunogenic and more stable and durable. Our data suggest that ST6 can serve as a novel, less immunogenic therapeutic strategy for patients with RA.
6.Current Status of Low-Density Lipoprotein Cholesterol Target Achievement in Patients with Type 2 Diabetes Mellitus in Korea Compared with Recent Guidelines
Soo Jin YUN ; In-Kyung JEONG ; Jin-Hye CHA ; Juneyoung LEE ; Ho Chan CHO ; Sung Hee CHOI ; SungWan CHUN ; Hyun Jeong JEON ; Ho-Cheol KANG ; Sang Soo KIM ; Seung-Hyun KO ; Gwanpyo KOH ; Su Kyoung KWON ; Jae Hyuk LEE ; Min Kyong MOON ; Junghyun NOH ; Cheol-Young PARK ; Sungrae KIM
Diabetes & Metabolism Journal 2022;46(3):464-475
Background:
We evaluated the achievement of low-density lipoprotein cholesterol (LDL-C) targets in patients with type 2 diabetes mellitus (T2DM) according to up-to-date Korean Diabetes Association (KDA), European Society of Cardiology (ESC)/European Atherosclerosis Society (EAS), and American Diabetes Association (ADA) guidelines.
Methods:
This retrospective cohort study collected electronic medical record data from patients with T2DM (≥20 years) managed by endocrinologists from 15 hospitals in Korea (January to December 2019). Patients were categorized according to guidelines to assess LDL-C target achievement. KDA (2019): Very High-I (atherosclerotic cardiovascular disease [ASCVD]) <70 mg/dL; Very High-II (target organ damage [TOD], or cardiovascular risk factors [CVRFs]) <70 mg/dL; high (others) <100 mg/dL. ESC/EAS (2019): Very High-I (ASCVD): <55 mg/dL; Very High-II (TOD or ≥3-CVRF) <55 mg/dL; high (diabetes ≥10 years without TOD plus any CVRF) <70 mg/dL; moderate (diabetes <10 years without CVRF) <100 mg/dL. ADA (2019): Very High-I (ASCVD); Very High-II (age ≥40+ TOD, or any CVRF), for high intensity statin or statin combined with ezetimibe.
Results:
Among 2,000 T2DM patients (mean age 62.6 years; male 55.9%; mean glycosylated hemoglobin 7.2%) ASCVD prevalence was 24.7%. Of 1,455 (72.8%) patients treated with statins, 73.9% received monotherapy. According to KDA guidelines, LDL-C target achievement rates were 55.2% in Very High-I and 34.9% in Very High-II patients. With ESC/EAS guidelines, target attainment rates were 26.6% in Very High-I, 15.7% in Very High-II, and 25.9% in high risk patients. Based on ADA guidelines, most patients (78.9%) were very-high risk; however, only 15.5% received high-intensity statin or combination therapy.
Conclusion
According to current dyslipidemia management guidelines, LDL-C goal achievement remains suboptimal in Korean patients with T2DM.
7.Comparison of patient-reported quality of life and functional outcomes following laparoscopic and transanal total mesorectal excision of rectal cancer
Ryun Kyong HA ; Sung Chan PARK ; Boram PARK ; Sung Sil PARK ; Dae Kyung SOHN ; Hee Jin CHANG ; Jae Hwan OH
Annals of Surgical Treatment and Research 2021;101(1):1-12
Purpose:
The effect of transanal total mesorectal excision (TaTME) on patients’ quality of life and functional outcomes is not fully understood. This study aimed to compare the quality of life and bowel, anorectal, and urogenital functions after laparoscopic and TaTME.
Methods:
Laparoscopic or TaTME was performed for 202 propensity score-matched patient pairs with rectal cancer between January 2014 and December 2017 at the National Cancer Center, Korea. The outcomes for all patients were assessed using anorectal manometry, the European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life Questionnaire (QLQ-C30) and Colorectal Cancer-Specific Quality of Life Questionnaire (QLQ-CR38), low anterior resection syndrome (LARS) score, Fecal Incontinence Severity Index, and International Prostate Symptom Score (IPSS). This retrospective comparative study included patients who completed anorectal manometry and the questionnaires before treatment and at 1 year after surgery.
Results:
The EORTC QLQ-C30 and QLQ-CR38 showed comparable outcomes regarding the quality of life in both groups. More patients experienced major LARS in the transanal group at 1 year postoperatively (31.0% vs. 6.8% in the laparoscopic group, P = 0.004). Multivariable analysis revealed no significant difference in the LARS score between the groups at 1 year postoperatively (odds ratio, 2.30; 95% confidence interval, 0.79–6.72; P = 0.127). Significant differences in the IPSS were not noted between the groups.
Conclusion
The quality of life and functional outcomes were comparable between the laparoscopic and transanal approaches; however, our findings suggest a higher rate of LARS after TaTME.
8.A split-face study of moisturizer containing Centella asiatica extract after ablative fractional carbon dioxide laser resurfacing
Moon Seok KANG ; Kyong Chan PARK ; Seung Min NAM
Archives of Aesthetic Plastic Surgery 2021;27(2):56-60
Background:
Ablative fractional CO2 laser treatment is popular for improving atrophic acne scars; however, complications after laser treatment are unavoidable. The purpose of this study was to investigate the efficacy and safety of a moisturizer containing Centella asiatica extract when applied after ablative fractional CO2 laser resurfacing.
Methods:
A split-face study was conducted between September 2020 and December 2020 on 34 patients (16 females and 18 males) who were treated with ablative fractional CO2 laser resurfacing. After laser treatment, C. asiatica extract was applied to the right side of the face and purified water was applied to the left side. We compared the right and left sides of the face at various time points after laser treatment using an automatic skin analysis device to investigate the degree of moisture and post-inflammatory hyperpigmentation.
Results:
No significant difference in the degree of moisture was found between the two sides of the face immediately after laser treatment (P=0.059), but there was a significant difference at 1 and 4 hours after post-laser treatment care (P<0.001). Regarding post-inflammatory hyperpigmentation, there was no significant difference between the two sides of the face before laser treatment (P=0.184), but a significant difference was found at 6 weeks after laser treatment (P<0.001).
Conclusions
Our results show that applying C. asiatica extract is a novel post-laser treatment modality that can provide satisfactory results without complications after ablative fractional CO2 laser resurfacing.
9.Impaction of a continuous glucose monitoring sensor
Kyong Chan PARK ; Hwan Jun CHOI
Archives of Plastic Surgery 2021;48(4):392-394
A 33-year-old man presented to the plastic surgery department for foreign body removal 1 month after the insertion of a continuous glucose monitoring (CGM) sensor (Dexcom G5) in the left upper arm. The patient had used the CGM system for 5 years, and the insertion was done in the usual manner. The entire sensor wire was visible on simple radiography and ultrasonography. In the operating room, and the sensor wire was identified in the intermuscular septum and removed. No foreign body reaction or inflammatory signs were found around the CGM, and the extracted wire measured 2.5 cm. Thus, it was assumed that the whole sensor wire was detached from the transmitter, not fractured. No remnant foreign body was observed on follow-up simple radiography.
10.Comparison of patient-reported quality of life and functional outcomes following laparoscopic and transanal total mesorectal excision of rectal cancer
Ryun Kyong HA ; Sung Chan PARK ; Boram PARK ; Sung Sil PARK ; Dae Kyung SOHN ; Hee Jin CHANG ; Jae Hwan OH
Annals of Surgical Treatment and Research 2021;101(1):1-12
Purpose:
The effect of transanal total mesorectal excision (TaTME) on patients’ quality of life and functional outcomes is not fully understood. This study aimed to compare the quality of life and bowel, anorectal, and urogenital functions after laparoscopic and TaTME.
Methods:
Laparoscopic or TaTME was performed for 202 propensity score-matched patient pairs with rectal cancer between January 2014 and December 2017 at the National Cancer Center, Korea. The outcomes for all patients were assessed using anorectal manometry, the European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life Questionnaire (QLQ-C30) and Colorectal Cancer-Specific Quality of Life Questionnaire (QLQ-CR38), low anterior resection syndrome (LARS) score, Fecal Incontinence Severity Index, and International Prostate Symptom Score (IPSS). This retrospective comparative study included patients who completed anorectal manometry and the questionnaires before treatment and at 1 year after surgery.
Results:
The EORTC QLQ-C30 and QLQ-CR38 showed comparable outcomes regarding the quality of life in both groups. More patients experienced major LARS in the transanal group at 1 year postoperatively (31.0% vs. 6.8% in the laparoscopic group, P = 0.004). Multivariable analysis revealed no significant difference in the LARS score between the groups at 1 year postoperatively (odds ratio, 2.30; 95% confidence interval, 0.79–6.72; P = 0.127). Significant differences in the IPSS were not noted between the groups.
Conclusion
The quality of life and functional outcomes were comparable between the laparoscopic and transanal approaches; however, our findings suggest a higher rate of LARS after TaTME.

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