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.Sodium/glucose Co-Transporter 2 Inhibitor, Empagliflozin, Alleviated Transient Expression of SGLT2 after Myocardial Infarction
Soo Yong LEE ; Tae Wook LEE ; Gyu Tae PARK ; Jae Ho KIM ; Hyun-Chae LEE ; Jung-Hwa HAN ; Aeseon YOON ; Dahye YOON ; Shukmann KIM ; Soon Myung JUNG ; Jin Hee CHOI ; Min Ku CHON ; Sang Hyun LEE ; Ki Won HWANG ; Jeongsu KIM ; Yong Hyun PARK ; June Hong KIM ; Kook Jin CHUN ; Jin HUR
Korean Circulation Journal 2021;51(3):251-262
Background and Objectives:
Large clinical studies of sodium/glucose cotransporter 2 (SGLT2) inhibitors have shown a significant beneficial effect on heart failure-associated hospitalization and cardiovascular events. As SGLT2 is known to be absent in heart cells, improved cardiovascular outcomes are thought to be accounted for by the indirect effects of the drug. We sought to confirm whether such benefits were mediated through SGLT2 expressed in the heart using myocardial infarction (MI) model.
Methods:
Mice pre-treated with empagliflozin (EMPA), an SGLT2 inhibitor, showed a significantly reduced infarct size compared with the vehicle group three days post-MI.Interestingly, we confirmed SGLT2 localized in the infarct zone. The sequential changes of SGLT2 expression after MI were also evaluated.
Results:
One day after MI, SGLT2 transiently appeared in the ischemic areas in the vehicle group and increased until 72 hours. The appearance of SGLT2 was delayed and less in amount compared with the vehicle group. Additionally, there was a significant difference in metabolites, including glucose and amino acids in the 1 H nuclear magnetic resonance analysis between groups.
Conclusions
Our work demonstrates that SGLT2 is transiently expressed in heart tissue early after MI and EMPA may directly operate on SGLT2 to facilitate metabolic substrates shifts.
3.Sodium/glucose Co-Transporter 2 Inhibitor, Empagliflozin, Alleviated Transient Expression of SGLT2 after Myocardial Infarction
Soo Yong LEE ; Tae Wook LEE ; Gyu Tae PARK ; Jae Ho KIM ; Hyun-Chae LEE ; Jung-Hwa HAN ; Aeseon YOON ; Dahye YOON ; Shukmann KIM ; Soon Myung JUNG ; Jin Hee CHOI ; Min Ku CHON ; Sang Hyun LEE ; Ki Won HWANG ; Jeongsu KIM ; Yong Hyun PARK ; June Hong KIM ; Kook Jin CHUN ; Jin HUR
Korean Circulation Journal 2021;51(3):251-262
Background and Objectives:
Large clinical studies of sodium/glucose cotransporter 2 (SGLT2) inhibitors have shown a significant beneficial effect on heart failure-associated hospitalization and cardiovascular events. As SGLT2 is known to be absent in heart cells, improved cardiovascular outcomes are thought to be accounted for by the indirect effects of the drug. We sought to confirm whether such benefits were mediated through SGLT2 expressed in the heart using myocardial infarction (MI) model.
Methods:
Mice pre-treated with empagliflozin (EMPA), an SGLT2 inhibitor, showed a significantly reduced infarct size compared with the vehicle group three days post-MI.Interestingly, we confirmed SGLT2 localized in the infarct zone. The sequential changes of SGLT2 expression after MI were also evaluated.
Results:
One day after MI, SGLT2 transiently appeared in the ischemic areas in the vehicle group and increased until 72 hours. The appearance of SGLT2 was delayed and less in amount compared with the vehicle group. Additionally, there was a significant difference in metabolites, including glucose and amino acids in the 1 H nuclear magnetic resonance analysis between groups.
Conclusions
Our work demonstrates that SGLT2 is transiently expressed in heart tissue early after MI and EMPA may directly operate on SGLT2 to facilitate metabolic substrates shifts.
4.Prognostic Value of Alpha-Fetoprotein in Patients Who Achieve a Complete Response to Transarterial Chemoembolization for Hepatocellular Carcinoma
Jae Seung LEE ; Young Eun CHON ; Beom Kyung KIM ; Jun Yong PARK ; Do Young KIM ; Sang Hoon AHN ; Kwang-Hyub HAN ; Wonseok KANG ; Moon Seok CHOI ; Geum-Youn GWAK ; Yong-Han PAIK ; Joon Hyeok LEE ; Kwang Cheol KOH ; Seung Woon PAIK ; Hwi Young KIM ; Tae Hun KIM ; Kwon YOO ; Yeonjung HA ; Mi Na KIM ; Joo Ho LEE ; Seong Gyu HWANG ; Soon Sun KIM ; Hyo Jung CHO ; Jae Youn CHEONG ; Sung Won CHO ; Seung Ha PARK ; Nae-Yun HEO ; Young Mi HONG ; Ki Tae YOON ; Mong CHO ; Jung Gil PARK ; Min Kyu KANG ; Soo Young PARK ; Young Oh KWEON ; Won Young TAK ; Se Young JANG ; Dong Hyun SINN ; Seung Up KIM ;
Yonsei Medical Journal 2021;62(1):12-20
Purpose:
Alpha-fetoprotein (AFP) is a prognostic marker for hepatocellular carcinoma (HCC). We investigated the prognostic value of AFP levels in patients who achieved complete response (CR) to transarterial chemoembolization (TACE) for HCC.
Materials and Methods:
Between 2005 and 2018, 890 patients with HCC who achieved a CR to TACE were recruited. An AFP responder was defined as a patient who showed elevated levels of AFP (>10 ng/mL) during TACE, but showed normalization or a >50% reduction in AFP levels after achieving a CR.
Results:
Among the recruited patients, 569 (63.9%) with naïve HCC and 321 (36.1%) with recurrent HCC after complete resection were treated. Before TACE, 305 (34.3%) patients had multiple tumors, 219 (24.6%) had a maximal tumor size >3 cm, and 22 (2.5%) had portal vein tumor thrombosis. The median AFP level after achieving a CR was 6.36 ng/mL. After a CR, 473 (53.1%) patients experienced recurrence, and 417 (46.9%) died [median progression-free survival (PFS) and overall survival (OS) of 16.3 and 62.8 months, respectively]. High AFP levels at CR (>20 ng/mL) were independently associated with a shorter PFS [hazard ratio (HR)=1.403] and OS (HR=1.284), together with tumor multiplicity at TACE (HR=1.518 and 1.666, respectively). AFP non-responders at CR (76.2%, n=359 of 471) showed a shorter PFS (median 10.5 months vs. 15.5 months, HR=1.375) and OS (median 41.4 months vs. 61.8 months, HR=1.424) than AFP responders (all p=0.001).
Conclusion
High AFP levels and AFP non-responders were independently associated with poor outcomes after TACE. AFP holds clinical implications for detailed risk stratification upon achieving a CR after TACE.
5.Large Focal Extrapleural Hematoma of Chest Wall: A Case Report
Hohyoung LEE ; Sung Ho HAN ; Min Koo LEE ; Oh Sang KWON ; Kyoung Hwan KIM ; Jung Suk KIM ; Soon Ho CHON ; Sung Ho SHINN
Journal of the Korean Society of Traumatology 2019;32(2):115-117
Although hemothorax and pneumothorax are common complications seen in rib fractures, focal extrapleural hematoma is quite rare. We report a 63-year-old female patient that developed large focal extrapleural hematoma after falling off a second floor veranda. The patient had sustained 3, 4, 5th costal cartilage rib fractures and a sternum fracture. She had developed suspected empyema with loculations with small amount of hemothorax. She underwent a planned early decortication/adhesiolysis by video assisted thoracoscopic surgery at the 12th post-trauma day due to failed drainage. Unexpectedly, she had no adhesions or any significant retained hematoma mimicking a mass, but was found with the focal extrapleural chest wall hematoma. She was discharged on postoperative 46th day for other reasons and is doing fine today.
6.Bilateral Chylothorax Due to Blunt Spine Hyperextension Injury: A Case Report
Hohyoung LEE ; Sung Ho HAN ; Min Koo LEE ; Oh Sang KWON ; Kyoung Hwan KIM ; Jung Suk KIM ; Soon Ho CHON ; Sung Ho SHINN
Journal of the Korean Society of Traumatology 2019;32(2):107-110
Bilateral chylothorax due to blunt trauma is extremely rare. We report a 74-year-old patient that developed delayed bilateral chylothorax after falling off a ladder. The patient had a simple 12th rib fracture and T12 lamina fracture. All other findings seemed normal. He was sent home and on the 5th day visited our emergency center at Halla Hospital with symptoms of dyspnea and lower back pain. Computer tomography of his chest presented massive fluid collection in his right pleural cavity and moderate amounts in his left pleural cavity with 12th rib fracture and T11-12 intervertebral space widening with bilateral facet fractures. Chest tubes were placed bilaterally and chylothorax through both chest tubes was discovered. Conservative treatment for 2 weeks failed, and thus, thoracic duct ligation was done by video assisted thoracoscopic surgery. Thoracic duct embolization was not an option. Postoperatively, the patient is now doing well and happy with the results. Early surgical treatment must be considered in the old patient, whom large amounts of chylothorax are present.
7.Effectiveness after Designation of a Trauma Center: Experience with Operating a Trauma Team at a Private Hospital
Kyoung Hwan KIM ; Sung Ho HAN ; Soon Ho CHON ; Joongsuck KIM ; Oh Sang KWON ; Min Koo LEE ; Hohyoung LEE
Journal of the Korean Society of Traumatology 2019;32(1):1-7
PURPOSE:
The present study aimed to evaluate the influence of how the trauma care system applied on the management of trauma patient within the region.
METHODS:
We divided the patients in a pre-trauma system group and a post-trauma system group according to the time when we began to apply the trauma care system in the Halla Hospital after designation of a trauma center. We compared annual general characteristics, injury severity score, the average numbers of the major trauma patients, clinical outcomes of the emergency department, and mortality rates between the two groups.
RESULTS:
No significant differences were found in the annual patients' average age (54.1±20.0 vs. 52.8±18.2, p=0.201), transportation pathways (p=0.462), injury mechanism (p=0.486), injury severity score (22.93 vs. 23.96, p=0.877), emergency room (ER) stay in minutes (199.17 vs. 194.29, p=0.935), time to operation or procedure in minutes (154.07 vs. 142.1, p=0.767), time interval to intensive care unit (ICU) in minutes (219.54 vs. 237.13, p=0.662). The W score and Z score indicated better outcomes in post-trauma system group than in pre-trauma system group (W scores, 2.186 vs. 2.027; Z scores, 2.189 vs. 1.928). However, when analyzing survival rates for each department, in the neurosurgery department, in comparison with W score and Z score, both W score were positive and Z core was higher than +1.96. (pre-trauma group: 3.426, 2.335 vs. post-trauma group: 4.17, 1.967). In other than the neurosurgery department, W score was positive after selection, but Z score was less than +1.96, which is not a meaningful outcome of treatment (pre-trauma group: −0.358, −0.271 vs. post-trauma group: 1.071, 0.958).
CONCLUSIONS
There were significant increases in patient numbers and improvement in survival rate after the introduction of the trauma system. However, there were no remarkable change in ER stay, time to ICU admission, time interval to emergent procedure or operation, and survival rates except neurosurgery. To achieve meaningful survival rates and the result of the rise of the trauma index, we will need to secure sufficient manpower, including specialists in various surgical area as well as rapid establishment of the trauma center.
8.Esophageal Rupture Due to Diving in Shallow Waters
Sung Ho HAN ; Soon Ho CHON ; Jong Hyun LEE ; Min Koo LEE ; Oh Sang KWON ; Kyoung Hwan KIM ; Jung Suk KIM ; Ho hyoung LEE ; June Raphael CHON
Journal of the Korean Society of Traumatology 2018;31(1):16-18
Delayed esophageal rupture due to blunt injury is not new. However, rupture due to suspected barotrauma is very rare. We describe a case of esophageal rupture in a male 24-year-old patient after diving in shallow waters. The patient was quadriplegic and could not experience the typical chest pain related to rupture and resulting mediastinitis. The rupture was discovered 4 days after emergency decompressive laminectomy and fusion for his cervical spine. The rupture was evidently caused by barotrauma and was discovered four days after admission. He underwent primary closure and pericardial flap as a life-saving procedure.
9.Rib Fixation for a Patient with Severely Displaced and Overlapped Costal Cartilage Fractures
Sung Ho HAN ; Soon Ho CHON ; Jong Hyun LEE ; Min Koo LEE ; Oh Sang KWON ; Kyoung Hwan KIM ; Jung Suk KIM ; Ho hyoung LEE
Journal of the Korean Society of Traumatology 2018;31(1):12-15
Rib fixations for flail chest or displaced rib fractures are not a new technique. However, reports on rib fixations involving costal cartilage fractures are very few and surprisingly there are no reports of internal fixations involving only the costal cartilage in the English literature. The diagnosis is difficult and the necessity of the procedure may be quite controversial. Placing plates in screws into the costal cartilage alone may seem unstable and easily dislodged or stripped through the cartilage. We report a 31-year-old male scuba diver instructor who underwent rib fixations over his 7th and 8th costal cartilage ribs for severe pain. The procedure was done with conventional plates and screws. He had the plates and screws removed 2 months later due to lingering pain, but with them removed he is now quite happy with the results without pain. The procedure for fixation of painful overlapped costal cartilage is quite simple and can be done with the usual conventional methods, fixating plate and screws directly over the cartilage alone without fixation over the bony rib.
10.Prognostic Factors and Scoring Model for Survival in Metastatic Biliary Tract Cancer.
Hyung Soon PARK ; Ji Soo PARK ; You Jin CHUN ; Yun Ho ROH ; Jieun MOON ; Hong Jae CHON ; Hye Jin CHOI ; Joon Seong PARK ; Dong Ki LEE ; Se Joon LEE ; Dong Sup YOON ; Hei Cheul JEUNG
Cancer Research and Treatment 2017;49(4):1127-1139
PURPOSE: Metastatic biliary tract cancer (mBTC) has a dismal prognosis. In this study, an independent dataset of patients with mBTC was used to implement and validate a routine clinico-laboratory parameter-based scoring model for risk group identification. MATERIALS AND METHODS: From September 2006 to February 2015, 482 patients with mBTC were assigned randomly (ratio, 7:3) into investigational (n=340) and validation datasets (n=142). The continuous variables were dichotomized using a normal range or the best cutoff values determined using the Contal and O'Quigley statistical methods. Following a Cox’s proportional hazard model, the scoring model was derived by summing the rounded chi-square scores for the factors identified by multivariate analysis. RESULTS: The performance status (Eastern Cooperative Oncology Group 3-4), hypoalbuminemia (< 3.4 mg/dL), carcinoembryonic antigen (≥ 9 ng/mL), neutrophil-to-lymphocyte ratio (≥ 3.0), and carbohydrate antigen 19-9 (≥ 120 U/mL) were identified as independent prognosticators (Harrell’s C index, 0.682; integrated area under the curve, 0.653). Survival was clearly correlated with the risk groups (low, intermediate, and high, 14.0, 7.3, and 2.3 months, respectively; p < 0.001). The prognosis was also discriminative in the validation data set (median survival, 16.7, 7.5, and 1.9 months, respectively; p < 0.001). Chemotherapy did not offer any survival benefits for high-risk patients. CONCLUSION: These proposed prognostic criteria for mBTC can facilitate accurate patient risk stratification and treatment-related decision-making.
Biliary Tract Neoplasms*
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Biliary Tract*
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Carcinoembryonic Antigen
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Dataset
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Drug Therapy
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Humans
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Hypoalbuminemia
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Multivariate Analysis
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Prognosis
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Proportional Hazards Models
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Reference Values
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Social Identification

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