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.Insufficiency Fracture of Simultaneously Bilateral Femur Neck in Patient Treated with Long-Term Bisphosphonate Treatment - A Case Report -
Seong Kee SHIN ; Hyung Gon RYU ; Dae Won SHIN ; Beom Su HAN
Journal of the Korean Fracture Society 2022;35(3):109-113
Bisphosphonate is used widely for osteoporosis management. On the other hand, some studies have reported that prolonged use of bisphosphonate without a proper resting period can cause insufficiency fracture and, in rare cases, fractures on the femur neck. This paper reports a case of an elderly patient who suffered bilateral femur neck insufficiency fractures induced by non-stopped long-term bisphosphonate therapy. The patient complained of pain in her buttocks at the first visit. During the admission period, inguinal area pain newly developed. Both a femur neck insufficiency fracture was observed on the hip radiographic image. Hip pinning and postoperative parathyroid hormone treatment were performed. The patient was discharged without specific complications and reported improvement in symptoms on the last follow-up. Several authors have reported one-sided femoral neck insufficiency fractures due to bisphosphonate use, but the present case is uncommon in that it occurred simultaneously in both femur necks. In addition, in the case of bilateral femur fractures, the walking ability after surgery is lower than that of one-sided fracture cases, so active rehabilitation is necessary.
3.Summary of clinically diagnosed amniotic fluid embolism cases in Korea and disagreement with 4 criteria proposed for research purpose
Jin-ha KIM ; Hyun-Joo SEOL ; Won Joon SEONG ; Hyun-Mee RYU ; Jin-Gon BAE ; Joon Seok HONG ; Jeong In YANG ; Ji-Hee SUNG ; Suk-Joo CHOI ; Soo-young OH ; Cheong-Rae ROH
Obstetrics & Gynecology Science 2021;64(2):190-200
Objective:
This study aimed 1) to investigate the clinical characteristics of amniotic fluid embolism (AFE) cases clinically diagnosed by maternal fetal medicine (MFM) specialists in Korea, 2) to check the disagreement with 4 recently proposed criteria by the Society for Maternal-Fetal Medicine (SMFM) for research purpose, and 3) to compare maternal outcomes between cases satisfying all 4 criteria and cases with at least 1 missing criterion.
Methods:
This study included 12 patients clinically diagnosed with AFE from 7 referral hospitals in Korea. We collected information, including maternal age, symptoms of AFE, the amount of transfusion, and maternal mortality.
Results:
The median maternal age was 33 years (range, 28–40 years). Regarding symptoms, cardiovascular arrest, hypotension, respiratory compromise, clinical coagulopathy, and neurologic signs were observed in 41.7%, 83.3%, 83.3%, 100%, and 66.7% of the cases, respectively. Among the 12 cases, 5 women died and 2 suffered severe neurologic disability, showing an intact survival rate of 41.7%. Disagreement with all 4 criteria proposed by the SMFM was found in 66.7% of the cases, due to the lack of criteria for disseminated intravascular coagulation or strict onset time (<30 minutes after delivery). There was no difference in maternal mortality and the amount of transfusion between cases satisfying all 4 criteria and cases with at least 1 missing criterion.
Conclusion
Two-thirds of clinically confirmed AFE cases did not satisfy all 4 criteria proposed by the SMFM, despite similar rates of maternal mortality with cases satisfying all 4 criteria. Our study suggests that there may be some discrepancy between the clinical diagnosis of AFE and the recent diagnostic criteria proposed by the SMFM for research purpose.
4.Euryhelmis squamula (Digenea: Heterophyidae) Recovered from Korean Raccoon Dog, Nyctereutes procyonoides koreensis, in Korea
Hyeon Cheol KIM ; Eui Ju HONG ; Si Yun RYU ; Jinho PARK ; Jeong Gon CHO ; Do Hyeon YU ; Joon Seok CHAE ; Kyoung Seong CHOI ; Bae Keun PARK
The Korean Journal of Parasitology 2021;59(3):303-309
In this study, we intended to describe an unrecorded species of heterophyid trematode recovered from the small intestine of a Korean raccoon dog, Nyctereutes procyonoides koreensis, in Korea. A total of 13 small flukes were collected from a deceased Korean raccoon dog which was found in Chuncheon-si, Gangwon-do, Korea in May 2017. The trematode body were covered with many small spines, rectangular, broader than long, 807-1,103 µm long and 1,270-1,550 µm wide. Oral sucker in the anterior end slightly smaller than acetabulum. Pharynx muscular and well developed. Esophagus relatively long and sigmoid. Acetabulum small and located at median in anterior 2/5 portion. Ceca bifurcated at the anterior of genital pore and acetabulum and terminated at testis level. Testes larger, deeply lobed and located at the near of posterior end of body. Ovary small, triangular and located at the slight left of median and the anterior of left testis. Vitelline follicles dendritic and extend from the middle level of esophagus to the posterior portion of body. Eggs embryonated, operculated, small and 33-35×15-16 µm in size. Based on the morphological characteristics, the small heterophyid flukes recovered from the small intestines of Korean raccoon dog, N. procyonoides koreensis, were identified as Euryhelmis squamula (Digenea: Heterophyidae). Accordingly, this species of heterophyid flukes is to be a new trematode fauna in Korea by this study.
5.Summary of clinically diagnosed amniotic fluid embolism cases in Korea and disagreement with 4 criteria proposed for research purpose
Jin-ha KIM ; Hyun-Joo SEOL ; Won Joon SEONG ; Hyun-Mee RYU ; Jin-Gon BAE ; Joon Seok HONG ; Jeong In YANG ; Ji-Hee SUNG ; Suk-Joo CHOI ; Soo-young OH ; Cheong-Rae ROH
Obstetrics & Gynecology Science 2021;64(2):190-200
Objective:
This study aimed 1) to investigate the clinical characteristics of amniotic fluid embolism (AFE) cases clinically diagnosed by maternal fetal medicine (MFM) specialists in Korea, 2) to check the disagreement with 4 recently proposed criteria by the Society for Maternal-Fetal Medicine (SMFM) for research purpose, and 3) to compare maternal outcomes between cases satisfying all 4 criteria and cases with at least 1 missing criterion.
Methods:
This study included 12 patients clinically diagnosed with AFE from 7 referral hospitals in Korea. We collected information, including maternal age, symptoms of AFE, the amount of transfusion, and maternal mortality.
Results:
The median maternal age was 33 years (range, 28–40 years). Regarding symptoms, cardiovascular arrest, hypotension, respiratory compromise, clinical coagulopathy, and neurologic signs were observed in 41.7%, 83.3%, 83.3%, 100%, and 66.7% of the cases, respectively. Among the 12 cases, 5 women died and 2 suffered severe neurologic disability, showing an intact survival rate of 41.7%. Disagreement with all 4 criteria proposed by the SMFM was found in 66.7% of the cases, due to the lack of criteria for disseminated intravascular coagulation or strict onset time (<30 minutes after delivery). There was no difference in maternal mortality and the amount of transfusion between cases satisfying all 4 criteria and cases with at least 1 missing criterion.
Conclusion
Two-thirds of clinically confirmed AFE cases did not satisfy all 4 criteria proposed by the SMFM, despite similar rates of maternal mortality with cases satisfying all 4 criteria. Our study suggests that there may be some discrepancy between the clinical diagnosis of AFE and the recent diagnostic criteria proposed by the SMFM for research purpose.
6.Euryhelmis squamula (Digenea: Heterophyidae) Recovered from Korean Raccoon Dog, Nyctereutes procyonoides koreensis, in Korea
Hyeon Cheol KIM ; Eui Ju HONG ; Si Yun RYU ; Jinho PARK ; Jeong Gon CHO ; Do Hyeon YU ; Joon Seok CHAE ; Kyoung Seong CHOI ; Bae Keun PARK
The Korean Journal of Parasitology 2021;59(3):303-309
In this study, we intended to describe an unrecorded species of heterophyid trematode recovered from the small intestine of a Korean raccoon dog, Nyctereutes procyonoides koreensis, in Korea. A total of 13 small flukes were collected from a deceased Korean raccoon dog which was found in Chuncheon-si, Gangwon-do, Korea in May 2017. The trematode body were covered with many small spines, rectangular, broader than long, 807-1,103 µm long and 1,270-1,550 µm wide. Oral sucker in the anterior end slightly smaller than acetabulum. Pharynx muscular and well developed. Esophagus relatively long and sigmoid. Acetabulum small and located at median in anterior 2/5 portion. Ceca bifurcated at the anterior of genital pore and acetabulum and terminated at testis level. Testes larger, deeply lobed and located at the near of posterior end of body. Ovary small, triangular and located at the slight left of median and the anterior of left testis. Vitelline follicles dendritic and extend from the middle level of esophagus to the posterior portion of body. Eggs embryonated, operculated, small and 33-35×15-16 µm in size. Based on the morphological characteristics, the small heterophyid flukes recovered from the small intestines of Korean raccoon dog, N. procyonoides koreensis, were identified as Euryhelmis squamula (Digenea: Heterophyidae). Accordingly, this species of heterophyid flukes is to be a new trematode fauna in Korea by this study.
7.Morphological and Molecular Characterization of Toxocara apodemi (Nematoda: Ascarididae) from Striped Field Mice, Apodemus agrarius, in Korea
Hyeon Cheol KIM ; Eui Ju HONG ; Si Yun RYU ; Jinho PARK ; Jeong Gon CHO ; Do Hyeon YU ; Joon Seok CHAE ; Kyoung Seong CHOI ; Bae Keun PARK
The Korean Journal of Parasitology 2020;58(4):403-411
Adult ascarid worms from the field mice, Apodemus agrarius, were observed with a light and scanning electron microscope, and molecularly analized with 18S rRNA gene. In the scanning electron microscope, 3 prominent labia were present in the anterior end of male and female worms, but the interlabia and gubernaculum were absent. Scanning electron micrographs showed cervical alae as vestigial organs that looked like a slightly uplifted superficial sewing stitch. Total 6 pairs of post-cloacal papillae were observed on the tail of the male worms. The tail of female worms was blunt and conical shape with a spine-like structure, mucron. The eggs were sub-globular, coated with the albuminous layer and 73 by 82 μm in average size. The superficial pits of T. apodemi egg (mean 8.6×6.7 μm) are obviously bigger than those of Toxocara spp. The partial sequence of 18S rRNA showed the sequence homology of Toxocara canis (99.6%), Toxocara cati (99.4%), Toxascaris leonina (99.4%), and Toxocara vitulorum (99.2%). Conclusively, it was confirmed that ascarid nematodes, Toxocara apodemi, recovered from striped field mice in Korea are taxonomically conspecific relationship with genus Toxocara and genetic divergence from other Toxocara species.
8.Effects of Banxia Xiexin Decoction () on Cisplatin-Induced Apoptosis of Human A549 Lung Cancer Cells.
Ha-Rim KIM ; Guem-San LEE ; Mi-Seong KIM ; Do-Gon RYU ; Hong-Seob SO ; Hyoung-Chul MOON ; Young-Rae LEE ; Sei-Hoon YANG ; Kang-Beom KWON
Chinese journal of integrative medicine 2018;24(6):436-441
OBJECTIVETo examinie the synergistic effects of Banxia Xiexin Decoction (, Known as Banhasasim-tang in Korean) extract (BXDE) on cisplatin-induced cytotoxicity in the A549 human lung cancer cell lines.
METHODSA549 cells were treated with varying concentrations (50-200 μg/mL) of cisplatin and BXDE alone or in combination for 96 h. We used 1-(4,5-dimethylthiazol-2-yl)-3,5-diphenylformazan assay and flow cytometry to analyze cell viability and apoptosis, respectively.
RESULTSThe exposure of cells to cisplatin and BXDE alone or in combination decreased cell viability dose- and time-dependently (P<0.05), which was found to be mediated by the apoptotic pathway as confirmed by the increase in the annexin V/propidium iodide- stained cell population and a ladder pattern of discontinuous DNA fragments. Furthermore, the apoptosis was inhibited by the pan-caspase inhibitor, benzyloxycarbonyl-Val-Ala-Asp (OMe) fluoromethylketone (z-VAD-FMK).
CONCLUSIONSBXDE significantly potentiated apoptotic effects of cisplatin in A549 cells. Moreover, apoptosis induced by BXDE might be the pivotal mechanism mediating its chemopreventative action against cancer.
A549 Cells ; Apoptosis ; drug effects ; Apoptosis Regulatory Proteins ; metabolism ; Caspase Inhibitors ; pharmacology ; Cisplatin ; pharmacology ; DNA Fragmentation ; drug effects ; Humans ; Plant Extracts ; pharmacology
9.Atypical Tuberculous Spondylitis: A Report of Two Cases.
Hak Jin MIN ; Hyung Gon RYU ; Seong Kee SHIN
Journal of Korean Society of Spine Surgery 2015;22(3):127-132
STUDY DESIGN: Case study of two cases. OBJECTIVES: The aim of our study is to describe atypical patterns of tuberculous spondylitis. SUMMARY OF LITERATURE REVIEW: Few reports of tuberculous spondylitis have discussed atypical cases, which resulted in a poor prognosis due to the delay in early diagnosis and proper treatment. MATERIALS AND METHODS: A 74-year-old female underwent an incision and drainage, and posterior decompression and fusion (PDF) due to tuberculous epidural abscess after vertebroplasty of a compression fracture at T12. A 52-year-old female underwent interbody fusion and posterior lateral fusion (PLF) because of aggravation of an abscess and neurologic symptoms following non-invasive intervention to treat atypical tuberculous spondylitis. RESULTS: Clinical symptoms and serological tests of the patients were improved at postoperative 6 months. CONCLUSIONS: When a patient presents with focal bony or soft tissue abnormality on an image study, the possibility of non-typical tuberculous spondylitis has to be considered when infective spondylitis or a tumor is detected. Moreover, an invasive diagnosis tool such as biopsy will be needed for proper management.
Abscess
;
Aged
;
Biopsy
;
Decompression
;
Diagnosis
;
Drainage
;
Early Diagnosis
;
Epidural Abscess
;
Female
;
Fractures, Compression
;
Humans
;
Middle Aged
;
Neurologic Manifestations
;
Prognosis
;
Serologic Tests
;
Spondylitis*
;
Vertebroplasty
10.Anthocyanins From the Fruit of Vitis coignetiae Pulliat Potentiate the Cisplatin Activity by Inhibiting PI3K/Akt Signaling Pathways in Human Gastric Cancer Cells.
Jing Nan LU ; Won Sup LEE ; Arulkumar NAGAPPAN ; Seong Hwan CHANG ; Yung Hyun CHOI ; Hye Jung KIM ; Gon Sup KIM ; Chung Ho RYU ; Sung Chul SHIN ; Jin Myung JUNG ; Soon Chan HONG
Journal of Cancer Prevention 2015;20(1):50-56
BACKGROUND: Cisplatin (cis-diaminedichloroplatinum, CDDP) is a widely used chemotherapeutic agent for the treatment of many cancers. However, initial resistance to CDDP is a serious problem in treating these cancers. Vitis coignetiae Pulliat (Meoru in Korea) have shown anti-nuclear factor kappa B and anti-epidermal growth factor receptor activities in cancer cells. METHODS: In this study, in order to seeking an approach to increase the anti-cancer effects of CDDP with natural products. Here, we investigated anthocyanins isolated from Vitis coignetiae Pulliat (anthocyanidins isolated from meoru, AIMs) can enhance anti-cancer effects of cisplatin (CDDP) in stomach cancer cells. The cell viability of SNU-1 and SNU-16 cells after treated with AIMs and CDDP were analyzed by MTT assay. The expressions of Akt and X-linked inhibitor of apoptosis protein (XIAP) proteins were examined by western blot in AIMs- and CDDP-treated cells. RESULTS: We found that AIMs enhanced anticancer effects of CDDP, which activity was additive but not synergistic. AIMs suppressed Akt activity of the cancer cells activated by CDDP. AIMs also suppressed in XIAP an anti-apoptotic protein. CONCLUSIONS: This study suggests that the anthocyanins isolated from fruits of Vitis coignetiae Pulliat enhanced anti-cancer effects of CDDP by inhibiting Akt activity activated by CDDP.
Anthocyanins*
;
Biological Products
;
Blotting, Western
;
Cell Survival
;
Cisplatin*
;
Fruit*
;
Humans*
;
Stomach Neoplasms*
;
Vitis*
;
X-Linked Inhibitor of Apoptosis Protein

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