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.Effects of Omicron Infection and Changes in Serum Antibody Response to Wild-Type, Delta, and Omicron After a Booster Dose With BNT163b2 Vaccine in Korean Healthcare Workers
Sung Hee LIM ; Han Jo KIM ; Se Hyung KIM ; Seong Hyeok CHOI ; Bora KIM ; Ji Youn KIM ; Young Sok JI ; Tark KIM ; Eun Ju CHOO ; Jung Chan JUNG ; Ji Eun MOON ; Chan Kyu KIM ; Seong Kyu PARK ; Jina YUN
Journal of Korean Medical Science 2023;38(13):e103-
Background:
Although the primary vaccine coverage rate for coronavirus disease 2019 (COVID-19) in South Korea has exceeded 80%, the coronavirus continues to spread, with reports of a rapid decline in vaccine effectiveness. South Korea is administering booster shots despite concerns about the effectiveness of the existing vaccine.
Methods:
Neutralizing antibody inhibition scores were evaluated in two cohorts after the booster dose. For the first cohort, neutralizing activity against the wild-type, delta, and omicron variants after the booster dose was evaluated. For the second cohort, we assessed the difference in neutralizing activity between the omicron infected and uninfected groups after booster vaccination. We also compared the effectiveness and adverse events (AEs) between homologous and heterologous booster doses for BNT162b2 or ChAdOx1 vaccines.
Results:
A total of 105 healthcare workers (HCWs) that were additionally vaccinated with BNT162b2 at Soonchunhyang University Bucheon Hospital were enrolled in this study.Significantly higher surrogate virus neutralization test (sVNT) inhibition (%) was observed for the wild-type and delta variants compared to sVNT (%) for the omicron after the booster dose (97%, 98% vs. 75%; P < 0.001). No significant difference in the neutralizing antibody inhibition score was found between variants in the BNT/BNT/BNT group (n = 48) and the ChA/ChA/BNT group (n = 57). Total AEs were not significantly different between the ChA/ ChA/BNT group (85.96%) and the BNT/BNT group (95.83%; P = 0.11). In the second cohort with 58 HCWs, markedly higher sVNT inhibition to omicron was observed in the omicroninfected group (95.13%) compared to the uninfected group (mean of 48.44%; P < 0.001) after four months of the booster dose. In 41 HCWs (39.0%) infected with the omicron variant, no difference in immunogenicity, AEs, or effectiveness between homogeneous and heterogeneous boosters was observed.
Conclusion
Booster vaccination with BNT162b2 was significantly less effective for the neutralizing antibody responses to omicron variant compared to the wild-type or delta variant in healthy population. Humoral immunogenicity was sustained significantly high after 4 months of booster vaccine in the infected population after booster vaccination.Further studies are needed to understand the characteristics of immunogenicity in these populations.
3.Improvement of IgA Nephropathy and Kidney Regeneration by Functionalized Hyaluronic Acid and Gelatin Hydrogel
Sureerat KHUNMANEE ; Sureerat KHUNMANEE ; So Young CHUN ; Yun-Sok HA ; Jun Nyung LEE ; Bum Soo KIM ; Wei-Wei GAO ; In Yong KIM ; Dong Keun HAN ; Seungkwon YOU ; Tae Gyun KWON ; Hansoo PARK
Tissue Engineering and Regenerative Medicine 2022;19(3):643-658
BACKGROUND:
Immunoglobulin A (IgA) nephropathy (IgAN) is one of an important cause of progressive kidney disease and occurs when IgA settles in the kidney resulted in disrupts kidney’s ability to filter waste and excess water.Hydrogels are promising material for medical applications owing to their excellent adaptability and filling ability. Herein, we proposed a hyaluronic acid/gelatin (CHO-HA/Gel-NH2 ) bioactive hydrogel as a cell carrier for therapeutic kidney regeneration in IgAN.
METHODS:
CHO-HA/Gel-NH2 hydrogel was fabricated by Schiff-base reaction without any additional crosslinking agents. The hydrogel concentrations and ratios were evaluated to enhance adequate mechanical properties and biocompatibility for further in vivo study. High serum IgA ddY mice kidneys were treated with human urine-derived renal progenitor cells encapsulated in the hydrogel to investigate the improvement of IgA nephropathy and kidney regeneration.
RESULTS:
The stiffness of the hydrogel was significantly enhanced and could be modulated by altering the concentrations and ratios of hydrogel. CHO-HA/Gel-NH2 at a ratio of 3/7 provided a promising milieu for cells viability and cells proliferation. From week four onwards, there was a significant reduction in blood urea nitrogen and serum creatinine level in Cell/Gel group, as well as well-organized glomeruli and tubules. Moreover, the expression of pro-inflammatory and profibrotic molecules significantly decreased in the Gel/Cell group, whereas anti-inflammatory gene expression was elevated compared to the Cell group.
CONCLUSION
Based on in vivo studies, the renal regenerative ability of the progenitor cells could be further increased by this hydrogel system.
4.Improvement of IgA Nephropathy and Kidney Regeneration by Functionalized Hyaluronic Acid and Gelatin Hydrogel
Sureerat KHUNMANEE ; So Young CHUN ; Yun-Sok HA ; Jun Nyung LEE ; Bum Soo KIM ; Wei-Wei GAO ; In Yong KIM ; Dong Keun HAN ; Seungkwon YOU ; Tae Gyun KWON ; Hansoo PARK
Tissue Engineering and Regenerative Medicine 2022;19(3):643-658
BACKGROUND:
Immunoglobulin A (IgA) nephropathy (IgAN) is one of an important cause of progressive kidney disease and occurs when IgA settles in the kidney resulted in disrupts kidney’s ability to filter waste and excess water.Hydrogels are promising material for medical applications owing to their excellent adaptability and filling ability. Herein, we proposed a hyaluronic acid/gelatin (CHO-HA/Gel-NH2 ) bioactive hydrogel as a cell carrier for therapeutic kidney regeneration in IgAN.
METHODS:
CHO-HA/Gel-NH2 hydrogel was fabricated by Schiff-base reaction without any additional crosslinking agents. The hydrogel concentrations and ratios were evaluated to enhance adequate mechanical properties and biocompatibility for further in vivo study. High serum IgA ddY mice kidneys were treated with human urine-derived renal progenitor cells encapsulated in the hydrogel to investigate the improvement of IgA nephropathy and kidney regeneration.
RESULTS:
The stiffness of the hydrogel was significantly enhanced and could be modulated by altering the concentrations and ratios of hydrogel. CHO-HA/Gel-NH2 at a ratio of 3/7 provided a promising milieu for cells viability and cells proliferation. From week four onwards, there was a significant reduction in blood urea nitrogen and serum creatinine level in Cell/Gel group, as well as well-organized glomeruli and tubules. Moreover, the expression of pro-inflammatory and profibrotic molecules significantly decreased in the Gel/Cell group, whereas anti-inflammatory gene expression was elevated compared to the Cell group.
CONCLUSION
Based on in vivo studies, the renal regenerative ability of the progenitor cells could be further increased by this hydrogel system.
5.Exploring sex differences in Korean emergency physicians using nationwide survey
Kyung Su BAE ; Kyung Hye PARK ; Ji Hun KANG ; Donghune KEY ; In Byung KIM ; Hong-jae KIM ; Song Yi PARK ; Beom Sok SEO ; In Hwan YEO ; Yoo Sang YOON ; Mi Jin LEE ; Eu Sun LEE ; Hyung Min LEE ; Daesung LIM ; Woo Jin JUNG ; Kwang Hyun CHO ; Youngmin JOO ; Chang Gun JEE ; Suk Jae CHOI ; JaeHun HAN
Journal of the Korean Society of Emergency Medicine 2022;33(4):11-19
Objective:
In this study, we compared differences based on the gender of Korean emergency physicians to provide basic data for future emergency medicine development plans.
Methods:
We used data from the emergency physician survey (2020) conducted by the Korean Society of Emergency Medicine. A total of 1,303 emergency physicians responded to the survey. We adjusted demographic data relating to age, position, and work duration as an emergency physician, which could affect the differences based on gender. After propensity score matching, we compared working hours, work burden, income, motives for applying for emergency medicine, and future plans of the emergency physicians by sex.
Results:
The total working hours per month and night shifts per month were higher in men compared to the women. The women felt more pressure in the following areas: number of emergency patients, relationships with administrative agencies, insufficient emergency medical technician manpower, patients’ compliance, and relationships with other emergency physicians. Monthly income was higher in men. Women placed a higher value on ‘Acquiring a range of knowledge’ and ‘Degree of interest in working in the emergency room’ than men as motivation for applying for positions in emergency medicine. Regarding future plans, women placed less value on income and more on having enough free time and avoiding burnout. The retirement age was about 3 years lower for women than for men.
Conclusion
This study revealed gender differences in working hours, income, motivation for applying for emergency medicine, work burden, and future plans. It is expected that these differences are caused by physical limitations and socio-cultural backgrounds. It is recommended that more detailed investigations be carried out through qualitative research. These results could help in gender considerations while hiring emergency physicians.
6.IL-10 Deficiency Aggravates Renal Inflammation, Fibrosis and Functional Failure in High-Fat Dieted Obese Mice
Dae Hwan KIM ; So Young CHUN ; EunHye LEE ; Bomi KIM ; BoHyun YOON ; Haejung GIL ; Man-Hoon HAN ; Yun-Sok HA ; Jun Nyung LEE ; Tae Gyun KWON ; Bum Soo KIM ; Byung Ik JANG
Tissue Engineering and Regenerative Medicine 2021;18(3):399-410
BACKGROUND:
High-fat diet-induced obesity is one of the major cause of chronic renal failure. This obesity-related renal failure is mainly caused by inflammatory processes. However, the role of the major anti-inflammatory cytokine interleukin (IL)-10 has not been researched intensively.
METHODS:
To evaluate the effect of IL-10 deficiency on obesity-related renal failure, the in vivo study was carried with four animal groups; (1) Low-fat dieted C57BL/6 mice, (2) Low-fat dieted IL-10 knockout (KO) mice, (3) High-fat dieted C57BL/6 mice and (4) High-fat dieted IL-10 KO mice group. The analysis was carried with blood/urine chemistry, H&E, Oil-Red-O, periodic acid-Schiff and Masson’s trichrome staining immunohistochemistry and real-time PCR methods.
RESULTS:
At week 12, high-fat dieted IL-10 KO mice showed 1) severe lipid accumulation in kidneys, cholesterol elevation (in total, serum kidney) and low-density lipoprotein increasion through the SCAP-SREBP2-LDLr pathway; (2) serious histopathologic alterations showing glomerulosclerosis, tubulointerstitial fibrosis and immune cell infiltration; (3) increased pro-inflammatory cytokines and chemokines expression; (4) enhanced renal fibrosis; and (5) serious functional failure with high serum creatinine and BUN and proteinuria excretion compared to other groups.
CONCLUSION
IL-10 deficiency aggravates renal inflammation, fibrosis and functional failure in high-fat dieted obese mice, thus IL-10 therapy could be applied to obesity-related chronic renal failure.
7.Analysis on the ratio of emergency department visits by elderly and non-elderly patients based on disease and particulate matter concentration in South Korea: a multicenter cross-sectional observational study
Geon Hee HAN ; Suyeon PARK ; Youngjoo LEE ; Hye Young JANG ; Young Shin CHO ; Heajin CHUNG ; Sang-Il KIM ; Beom Sok SEO ; Young Wha SOHN ; Joonbum PARK
Journal of the Korean Society of Emergency Medicine 2021;32(6):698-711
Objective:
Many previous studies have reported relationships between particulate matter < 10 μm (PM10) and asthma in emergency department (ED) settings, but few have examined its effect on cerebrovascular diseases. We evaluate the “Lag effect” between PM10 and asthma, chronic obstructive pulmonary disease (COPD), myocardial infarction (MI), and ischemic and hemorrhagic stroke among patients that visited an ED.
Methods:
This study was retrospectively conducted on 96,077 patients that visited one of the 137 EDs in Seoul, Incheon, and Gyeonggi Province in South Korea in 2017. Medical information and 10th revision International Classification of Disease codes were obtained from the National Emergency Department Information System and PM10 levels from AirKorea. We used Poisson regression analysis to evaluate the lag effects of PM10 on diseases of interest. “Lag day 0” was defined as the day when PM10 > 80 μg/m3, and the PM10 values on the 5 following days were recorded. To assess the cumulative effects of PM10, we calculated relative risk (RR) by analyzing the cumulative effects over 6 days (lag days 0 to 5).
Results:
Asthma, COPD, and ischemic stroke patients (< 65 years old) showed a positive correlation between PM10 (asthma on lag day 5: RR, 2.587; 95% confidence interval [CI], 2.001-3.344; COPD on lag day 4: RR, 3.727; 95% CI, 2.988-4.650; and ischemic stroke on lag day 4: RR, 1.573; 95% CI, 1.168-2.118). MI in those≥65 showed the highest RR on lag day 1 (RR, 1.471; 95% CI, 1.042-2.077). Hemorrhagic stroke was not found to be significantly correlated with PM10 in either age group.
Conclusion
An increase in PM10 is associated with ED visits by patients<65 years old with asthma, COPD, or ischemic stroke, and with MI for those≥65 years.
8.Colon Polyp Detection in Primary Health Care Institutions of Korea: Detection Rate and Issues with Following the Guidelines
Sang Hyun PARK ; Kwang Il HONG ; Hyun Chul PARK ; Young Sun KIM ; Gene Hyun BOK ; Kyung Ho KIM ; Dong Suk SHIN ; Jae Yong HAN ; Young Kwan KIM ; Yeun Jong CHOI ; Soo Hoon EUN ; Byung Hoon LIM ; Kyeong Kun KWACK ; The Korean Society of Digestive Endoscopy (KSDE) Polyp Study Workgroup
The Korean Journal of Gastroenterology 2021;78(6):328-336
Background/Aims:
There have been few multicenter studies on colonic polyps conducted by primary medical institutions. This study examined the detection rate of colonic polyps in primary health care institutions and the related factors while following the guidelines.
Methods:
The medical records of 14,029 patients who underwent colonoscopy between January-June 2020 at 40 primary medical institutions in Korea were analyzed. High-risk adenoma was defined as advanced adenoma, carcinoma, or ≥3 adenomas.
Results:
Most patients (71.2%) aged ≥50 years underwent re-colonoscopy within 5 years (51.3%) for diagnostic purposes (61.3%) in Korean primary medical institutions. The detection rates of colon polyps, adenoma, advanced adenoma, high-risk adenoma, and carcinoma was 59.9%, 38.9%, 5.9%, 11.4%, and 0.3% in all subjects and 59.8%, 37.5%, 8.5%, 12.9%, and 0.3% in average-risk patients, respectively. The incidences of adenoma in average-risk patients increased significantly with age (30s/40s/50s: 20.1%/29.4%/43% for adenoma, 4.4%/6.7%/10.3% for advanced adenoma, and 5.6%/9.5%/14.6% for high-risk adenoma; p<0.05). Before 50 years of age, high-risk adenoma was detected in 9.1% of patients in the first-time screening group, and the significant risk factors were being male and ≥40 years of age. The detection rate of high-risk adenoma in the normal index colonoscopy group within 5 years was 9.0%. The significant risk factors included older age, male sex, positive fecal occult blood test, stool form changes, and nonspecific symptoms (gas and indigestion).
Conclusions
More colonic adenoma studies targeting real-world clinical practice will be needed to revise the Korean guidelines for colorectal cancer screening and surveillance.
9.IL-10 Deficiency Aggravates Renal Inflammation, Fibrosis and Functional Failure in High-Fat Dieted Obese Mice
Dae Hwan KIM ; So Young CHUN ; EunHye LEE ; Bomi KIM ; BoHyun YOON ; Haejung GIL ; Man-Hoon HAN ; Yun-Sok HA ; Jun Nyung LEE ; Tae Gyun KWON ; Bum Soo KIM ; Byung Ik JANG
Tissue Engineering and Regenerative Medicine 2021;18(3):399-410
BACKGROUND:
High-fat diet-induced obesity is one of the major cause of chronic renal failure. This obesity-related renal failure is mainly caused by inflammatory processes. However, the role of the major anti-inflammatory cytokine interleukin (IL)-10 has not been researched intensively.
METHODS:
To evaluate the effect of IL-10 deficiency on obesity-related renal failure, the in vivo study was carried with four animal groups; (1) Low-fat dieted C57BL/6 mice, (2) Low-fat dieted IL-10 knockout (KO) mice, (3) High-fat dieted C57BL/6 mice and (4) High-fat dieted IL-10 KO mice group. The analysis was carried with blood/urine chemistry, H&E, Oil-Red-O, periodic acid-Schiff and Masson’s trichrome staining immunohistochemistry and real-time PCR methods.
RESULTS:
At week 12, high-fat dieted IL-10 KO mice showed 1) severe lipid accumulation in kidneys, cholesterol elevation (in total, serum kidney) and low-density lipoprotein increasion through the SCAP-SREBP2-LDLr pathway; (2) serious histopathologic alterations showing glomerulosclerosis, tubulointerstitial fibrosis and immune cell infiltration; (3) increased pro-inflammatory cytokines and chemokines expression; (4) enhanced renal fibrosis; and (5) serious functional failure with high serum creatinine and BUN and proteinuria excretion compared to other groups.
CONCLUSION
IL-10 deficiency aggravates renal inflammation, fibrosis and functional failure in high-fat dieted obese mice, thus IL-10 therapy could be applied to obesity-related chronic renal failure.
10.Metachronous Development of Peritoneal Carcinomatosis in a Patient with Autoimmune Pancreatitis
Kyu Won LEE ; Jae Hyuck CHANG ; Jeana KIM ; Tae Ho KIM ; Chang Whan KIM ; Jae Kwang KIM ; Sok Won HAN
The Korean Journal of Gastroenterology 2020;75(6):356-361
Autoimmune pancreatitis (AIP) is a rare and unique type of chronic pancreatitis. The prognosis of AIP, particularly when associated with pancreatic cancer or a related malignancy, is not known. Only a few cases, where metachronous pancreas-related cancer developed during follow-up, have been reported. Most of these patients either underwent surgery or steroid therapy. This paper reports a case of a 66-year-old woman with untreated type I AIP who developed peritoneal carcinomatosis more than 2 years later. Initially, the patient had a markedly elevated serum IgG4 level and a diffuse, infiltrative mass-like lesion in the pancreatic head, in which the biopsy results were consistent with type I AIP. The patient was not treated with steroids because of a cerebellar infarction. Twenty-eight months after the diagnosis of AIP, peritoneal carcinomatosis developed without noticeable changes in the pancreas from the initial findings.

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