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.COVID-19 Vaccination Alters NK CellDynamics and Transiently Reduces HBsAg Titers Among Patients With Chronic Hepatitis B
Hyunjae SHIN ; Ha Seok LEE ; Ji Yun NOH ; June-Young KOH ; So-Young KIM ; Jeayeon PARK ; Sung Won CHUNG ; Moon Haeng HUR ; Min Kyung PARK ; Yun Bin LEE ; Yoon Jun KIM ; Jung-Hwan YOON ; Jae-Hoon KO ; Kyong Ran PECK ; Joon Young SONG ; Eui-Cheol SHIN ; Jeong-Hoon LEE
Immune Network 2023;23(5):e39-
Coronavirus disease 2019 (COVID-19) vaccination may non-specifically alter the host immune system. This study aimed to evaluate the effect of COVID-19 vaccination on hepatitis B surface Ag (HBsAg) titer and host immunity in chronic hepatitis B (CHB) patients. Consecutive 2,797 CHB patients who had serial HBsAg measurements during antiviral treatment were included in this study. Changes in the HBsAg levels after COVID-19 vaccination were analyzed. The dynamics of NK cells following COVID-19 vaccination were also examined using serial blood samples collected prospectively from 25 healthy volunteers. Vaccinated CHB patients (n=2,329) had significantly lower HBsAg levels 1–30 days post-vaccination compared to baseline (median, −21.4 IU/ml from baseline), but the levels reverted to baseline by 91–180 days (median, −3.8 IU/ml). The velocity of the HBsAg decline was transiently accelerated within 30 days after vaccination (median velocity: −0.06, −0.39, and −0.04 log 10 IU/ml/year in pre-vaccination period, days 1–30, and days 31–90, respectively). In contrast, unvaccinated patients (n=468) had no change in HBsAg levels. Flow cytometric analysis showed that the frequency of NK cells expressing NKG2A, an NK inhibitory receptor, significantly decreased within 7 days after the first dose of COVID-19 vaccine (median, −13.1% from baseline; p<0.001). The decrease in the frequency of NKG2A + NK cells was observed in the CD56dimCD16+ NK cell population regardless of type of COVID-19 vaccine. COVID-19 vaccination leads to a rapid, transient decline in HBsAg titer and a decrease in the frequency of NKG2A + NK cells.
3.Validation of three-dimensional digital model superimpositions based on palatal structures in patients with maximum anterior tooth retraction following premolar extraction
Jing LIU ; Kyong-Min KOH ; Sung-Hwan CHOI ; Ji-Hoi KIM ; Jung-Yul CHA
The Korean Journal of Orthodontics 2022;52(4):258-267
Objective:
This study aimed to evaluate the superimposition accuracy of digital modes for measuring tooth movement in patients requiring anterior retraction after premolar extraction based on the proposed reference regions.
Methods:
Forty patients treated with bilateral maxillary first premolar extraction were divided into two groups: moderate retraction (< 7.0 mm) and maximum retraction (≥ 7.0 mm). Central incisor displacement was measured using cephalometric superimpositions and three-dimensional (3D) digital superimpositions with the 3rd or 4th ruga as the reference point. The Wilcoxon signed-rank test and linear regression analyses were performed to test the significance of the differences and relationships between the two measurement techniques.
Results:
In the moderate retraction group, the central incisor anteroposterior displacement values did not differ significantly between 3D digital and cephalometric superimpositions. However, in the maximum-retraction group, significant differences were observed between the anteroposterior displacement evaluated by the 3rd ruga superimposition and cephalometric methods (p < 0.05).
Conclusions
This study demonstrated that 3D digital superimpositions were clinically as reliable as cephalometric superimpositions in assessing tooth movements in patients requiring moderate retraction. However, the reference point should be carefully examined in patients who require maximum retraction.
4.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.
5.Consensus guidelines for the definition of the end stage of disease and last days of life and criteria for medical judgment
Sang Min LEE ; Su Jung KIM ; Youn Seon CHOI ; Dae Seog HEO ; Sujin BAIK ; Bo Moon CHOI ; Daekyun KIM ; Jae Young MOON ; So Young PARK ; Yoon Jung CHANG ; In Cheol HWANG ; Jung Hye KWON ; Sun Hyun KIM ; Yu Jung KIM ; Jeanno PARK ; Ho Jung AHN ; Hyun Woo LEE ; Ivo KWON ; Do Kyong KIM ; Ock Joo KIM ; Sang Ho YOO ; Yoo Seock CHEONG ; Younsuck KOH
Journal of the Korean Medical Association 2018;61(8):509-521
In Korea, the Hospice, Palliative Care, and Life-sustaining Treatment Decision-making Act was enacted in February 2016 in order to ensure that the patient's self-determination in end-of-life care processes is respected. To enhance physicians' understanding of this act and to provide proper criteria for medical judgment in variety of clinical settings, consensus guidelines were published in November 2016. In this article, the characteristics of these guidelines and related issues regarding the definitions of ‘the end stage of disease’ and ‘last days of life’ and the criteria for medical judgment are presented and summarized. According to the guidelines, the term ‘end stage of disease’ refers to a state in which there is no possibility of a fundamental recovery and the symptoms are expected to worsen within months. The terms ‘the last days of life’ and ‘the final days of life’ refer to a state in which, despite treatment, the patient's condition is worsening and death is impending, with no possibility of recovery. The attending physician and another relevant specialist should both judge a patient's medical condition as either ‘end stage of disease’ for hospice/palliative care or ‘the last days of life’ for dying patient care according to the law. Caregivers should provide appropriate medical information to eligible patients for palliative or ‘end stage of disease’ care through advance care planning. Therefore, it is critically necessary that caregivers understand the legitimate process of hospice/palliative and dying patient care based on the patient's wishes and best interests. Physicians should apply these consensus guidelines to eligible patients considering their clinical course and the patients' wishes.
6.Consensus guidelines for the definition of the end stage of disease and last days of life and criteria for medical judgment
Sang Min LEE ; Su Jung KIM ; Youn Seon CHOI ; Dae Seog HEO ; Sujin BAIK ; Bo Moon CHOI ; Daekyun KIM ; Jae Young MOON ; So Young PARK ; Yoon Jung CHANG ; In Cheol HWANG ; Jung Hye KWON ; Sun Hyun KIM ; Yu Jung KIM ; Jeanno PARK ; Ho Jung AHN ; Hyun Woo LEE ; Ivo KWON ; Do Kyong KIM ; Ock Joo KIM ; Sang Ho YOO ; Yoo Seock CHEONG ; Younsuck KOH
Journal of the Korean Medical Association 2018;61(8):509-521
In Korea, the Hospice, Palliative Care, and Life-sustaining Treatment Decision-making Act was enacted in February 2016 in order to ensure that the patient's self-determination in end-of-life care processes is respected. To enhance physicians' understanding of this act and to provide proper criteria for medical judgment in variety of clinical settings, consensus guidelines were published in November 2016. In this article, the characteristics of these guidelines and related issues regarding the definitions of ‘the end stage of disease’ and ‘last days of life’ and the criteria for medical judgment are presented and summarized. According to the guidelines, the term ‘end stage of disease’ refers to a state in which there is no possibility of a fundamental recovery and the symptoms are expected to worsen within months. The terms ‘the last days of life’ and ‘the final days of life’ refer to a state in which, despite treatment, the patient's condition is worsening and death is impending, with no possibility of recovery. The attending physician and another relevant specialist should both judge a patient's medical condition as either ‘end stage of disease’ for hospice/palliative care or ‘the last days of life’ for dying patient care according to the law. Caregivers should provide appropriate medical information to eligible patients for palliative or ‘end stage of disease’ care through advance care planning. Therefore, it is critically necessary that caregivers understand the legitimate process of hospice/palliative and dying patient care based on the patient's wishes and best interests. Physicians should apply these consensus guidelines to eligible patients considering their clinical course and the patients' wishes.
Advance Care Planning
;
Caregivers
;
Consensus
;
Hospices
;
Humans
;
Judgment
;
Jurisprudence
;
Korea
;
Palliative Care
;
Patient Care
;
Specialization
7.Sleepiness and Depression in Parkinson's Disease Patients Treated with Ropinirole and Levodopa.
Suk Yun KANG ; Ho Sung RYU ; Mun Kyung SUNWOO ; Sang Jin KIM ; Jong Sam BAIK ; Mee Young PARK ; Hyung Eun PARK ; Joong Seok KIM ; Kyum Yil KWON ; Seong Beom KOH ; Young Eun KIM ; Mi Kyong LEE ; Jong Min KIM ; Sun Ju CHUNG ; Young Ho SOHN
Journal of Movement Disorders 2017;10(3):123-129
OBJECTIVE: We aimed to investigate the effect of ropinirole on excessive daytime sleepiness (EDS) and depression in Parkinson’s disease (PD) with a large population. METHODS: We conducted a cross-sectional observational study at nine hospitals in Korea between April 24, 2013, and April 22, 2015. We analyzed the demographic and clinical features, other medical history, history of antiparkinsonian medication within 6 months, Hoehn and Yahr stage (HY stage), Unified Parkinson’s Disease Rating Scale (UPDRS) part II and III, Epworth Sleepiness Scale (ESS), and 30-item Geriatric Depression Scale (GDS-30). RESULTS: Four-hundred-thirteen patients with PD (mean age: 65.2 ± 9.0 years; men: 227 patients) were analyzed. Multivariate logistic regression analysis showed that age at examination, UPDRS II, and GDS-30 were independent risk factors for EDS and that sex, UPDRS II, and ESS were independent risk factors for depression. CONCLUSION: Our large group study did not find any significant associations of ropinirole with EDS and depression in Korean PD patients.
Depression*
;
Humans
;
Korea
;
Levodopa*
;
Logistic Models
;
Male
;
Observational Study
;
Parkinson Disease*
;
Risk Factors
8.Two Cases of Refractory Adult-Onset Still's Disease Responding to Anakinra.
Ji Min OH ; Hyungjin KIM ; Jaejoon LEE ; Joong Kyong AHN ; You Sun LEE ; Eun Mi KOH ; Hoon Suk CHA
Korean Journal of Medicine 2012;82(4):520-524
Adult-onset Still's disease (AOSD) is a systemic inflammatory disorder with variable clinical features. The interleukin (IL)-1 receptor antagonist anakinra has been proposed as an alternative effective treatment in refractory AOSD. We report, for the first time in Korea, two cases of refractory AOSD in which anakinra treatment produced a clinical response. The first patient had frequent clinical flare-ups with fever, sore throat, myalgia, and pleuritic chest pain despite treatment with methotrexate and etanercept. In the second patient, treatments with various immunosuppressive agents failed to control the disease activity. Treatment with anakinra 100 mg/day was initiated in both cases. A complete clinical remission and improvement in the laboratory parameters were observed. The steroid dose was tapered without further clinical flare-ups. Anakinra appears to be an effective alternative treatment modality in patients with AOSD refractory to conventional disease-modifying anti-rheumatic drugs and corticosteroid therapy.
Antirheumatic Agents
;
Chest Pain
;
Fever
;
Humans
;
Immunoglobulin G
;
Immunosuppressive Agents
;
Interleukin 1 Receptor Antagonist Protein
;
Interleukins
;
Korea
;
Methotrexate
;
Pharyngitis
;
Receptors, Tumor Necrosis Factor
;
Still's Disease, Adult-Onset
;
Etanercept
9.Two Cases of Refractory Adult-Onset Still's Disease Responding to Anakinra
Ji Min OH ; Hyungjin KIM ; Jaejoon LEE ; Joong Kyong AHN ; You Sun LEE ; Eun Mi KOH ; Hoon Suk CHA
Korean Journal of Medicine 2012;82(4):520-524
Adult-onset Still's disease (AOSD) is a systemic inflammatory disorder with variable clinical features. The interleukin (IL)-1 receptor antagonist anakinra has been proposed as an alternative effective treatment in refractory AOSD. We report, for the first time in Korea, two cases of refractory AOSD in which anakinra treatment produced a clinical response. The first patient had frequent clinical flare-ups with fever, sore throat, myalgia, and pleuritic chest pain despite treatment with methotrexate and etanercept. In the second patient, treatments with various immunosuppressive agents failed to control the disease activity. Treatment with anakinra 100 mg/day was initiated in both cases. A complete clinical remission and improvement in the laboratory parameters were observed. The steroid dose was tapered without further clinical flare-ups. Anakinra appears to be an effective alternative treatment modality in patients with AOSD refractory to conventional disease-modifying anti-rheumatic drugs and corticosteroid therapy.
Antirheumatic Agents
;
Chest Pain
;
Fever
;
Humans
;
Immunoglobulin G
;
Immunosuppressive Agents
;
Interleukin 1 Receptor Antagonist Protein
;
Interleukins
;
Korea
;
Methotrexate
;
Pharyngitis
;
Receptors, Tumor Necrosis Factor
;
Still's Disease, Adult-Onset
;
Etanercept
10.Exacerbation of Psoriatic Skin Lesion followed by TNF-alpha Antagonist Treatment.
Ji Min OH ; Eun Mi KOH ; Hyungjin KIM ; Jaejoon LEE ; Joong Kyong AHN ; Hoon Suk CHA ; Joo Heung LEE ; Kee Taek JANG
The Journal of the Korean Rheumatism Association 2010;17(2):200-204
TNF-alpha antagonists have been successfully utilized in the treatment of autoimmune diseases, including psoriasis and psoriatic arthritis. Paradoxically, new onset or exacerbation of psoriatic lesions during treatment with TNF-alpha antagonists have been reported. It has been postulated that TNF-alpha blockade may cause disruption in the balance between TNF-alpha and type 1 interferon (IFN)-alpha, which are the key players in the pathogenesis of psoriasis. We report a case of psoriasis exacerbation during TNF-alpha antagonist therapy in a 53-years-old man with ankylosing spondylitis. The patient has been treated with etanercept for 3 years and 7 months when he developed accelerated deterioration of psoriasis. His condition was previously under control solely by local treatment. Physical examination revealed vigorous desquamative lesions with silvery scale in both lower legs. Deterioration of psoriasis was attributed to etanercept therapy and was subsequently discontinued. Clinical improvement of psoriasis has been observed 2 months following cessation of etanercept.
Arthritis, Psoriatic
;
Autoimmune Diseases
;
Humans
;
Etanercept
;
Immunoglobulin G
;
Interferons
;
Leg
;
Physical Examination
;
Psoriasis
;
Receptors, Tumor Necrosis Factor
;
Skin
;
Spondylitis, Ankylosing
;
Tumor Necrosis Factor-alpha

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