1.Efficacy and Safety of Metformin and Atorvastatin Combination Therapy vs. Monotherapy with Either Drug in Type 2 Diabetes Mellitus and Dyslipidemia Patients (ATOMIC): Double-Blinded Randomized Controlled Trial
Jie-Eun LEE ; Seung Hee YU ; Sung Rae KIM ; Kyu Jeung AHN ; Kee-Ho SONG ; In-Kyu LEE ; Ho-Sang SHON ; In Joo KIM ; Soo LIM ; Doo-Man KIM ; Choon Hee CHUNG ; Won-Young LEE ; Soon Hee LEE ; Dong Joon KIM ; Sung-Rae CHO ; Chang Hee JUNG ; Hyun Jeong JEON ; Seung-Hwan LEE ; Keun-Young PARK ; Sang Youl RHEE ; Sin Gon KIM ; Seok O PARK ; Dae Jung KIM ; Byung Joon KIM ; Sang Ah LEE ; Yong-Hyun KIM ; Kyung-Soo KIM ; Ji A SEO ; Il Seong NAM-GOONG ; Chang Won LEE ; Duk Kyu KIM ; Sang Wook KIM ; Chung Gu CHO ; Jung Han KIM ; Yeo-Joo KIM ; Jae-Myung YOO ; Kyung Wan MIN ; Moon-Kyu LEE
Diabetes & Metabolism Journal 2024;48(4):730-739
Background:
It is well known that a large number of patients with diabetes also have dyslipidemia, which significantly increases the risk of cardiovascular disease (CVD). This study aimed to evaluate the efficacy and safety of combination drugs consisting of metformin and atorvastatin, widely used as therapeutic agents for diabetes and dyslipidemia.
Methods:
This randomized, double-blind, placebo-controlled, parallel-group and phase III multicenter study included adults with glycosylated hemoglobin (HbA1c) levels >7.0% and <10.0%, low-density lipoprotein cholesterol (LDL-C) >100 and <250 mg/dL. One hundred eighty-five eligible subjects were randomized to the combination group (metformin+atorvastatin), metformin group (metformin+atorvastatin placebo), and atorvastatin group (atorvastatin+metformin placebo). The primary efficacy endpoints were the percent changes in HbA1c and LDL-C levels from baseline at the end of the treatment.
Results:
After 16 weeks of treatment compared to baseline, HbA1c showed a significant difference of 0.94% compared to the atorvastatin group in the combination group (0.35% vs. −0.58%, respectively; P<0.0001), whereas the proportion of patients with increased HbA1c was also 62% and 15%, respectively, showing a significant difference (P<0.001). The combination group also showed a significant decrease in LDL-C levels compared to the metformin group (−55.20% vs. −7.69%, P<0.001) without previously unknown adverse drug events.
Conclusion
The addition of atorvastatin to metformin improved HbA1c and LDL-C levels to a significant extent compared to metformin or atorvastatin alone in diabetes and dyslipidemia patients. This study also suggested metformin’s preventive effect on the glucose-elevating potential of atorvastatin in patients with type 2 diabetes mellitus and dyslipidemia, insufficiently controlled with exercise and diet. Metformin and atorvastatin combination might be an effective treatment in reducing the CVD risk in patients with both diabetes and dyslipidemia because of its lowering effect on LDL-C and glucose.
2.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.
3.Association of decreased estimated glomerular filtration rate with lung cancer risk in the Korean population
Soonsu SHIN ; Min-Ho KIM ; Chang-Mo OH ; Hyejin CHUN ; Eunhee HA ; Hyo Choon LEE ; Seong Ho MOON ; Dong-Young LEE ; Dosang CHO ; Sangho LEE ; Min Hyung JUNG ; Jae-Hong RYOO
Epidemiology and Health 2024;46(1):e2024041-
OBJECTIVES:
Inconsistent results are available regarding the association between low estimated glomerular filtration rate (eGFR) and lung cancer risk. We aimed to explore the risk of lung cancer according to eGFR category in the Korean population.
METHODS:
We included 358,293 adults who underwent health checkups between 2009 and 2010, utilizing data from the National Health Insurance Service-National Sample Cohort. Participants were categorized into 3 groups based on their baseline eGFR, as determined using the Chronic Kidney Disease Epidemiology Collaboration equation: group 1 (eGFR ≥90 mL/min/1.73 m2), group 2 (eGFR ≥60 to <90 mL/min/1.73 m2), and group 3 (eGFR <60 mL/min/1.73 m2). Incidences of lung cancer were identified using the corresponding codes from the International Classification of Diseases, 10th revision. Multivariate Cox proportional hazard models were employed to calculate the adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for lung cancer incidence up to 2019.
RESULTS:
In multivariate analysis, group 2 exhibited a 26% higher risk of developing lung cancer than group 1 (HR, 1.26; 95% CI, 1.19 to 1.35). Furthermore, group 3 demonstrated a 72% elevated risk of lung cancer relative to group 1 (HR, 1.72; 95% CI, 1.58 to 1.89). Among participants with dipstick proteinuria of 2+ or greater, group 3 faced a significantly higher risk of lung cancer than group 1 (HR, 2.93; 95% CI, 1.37 to 6.24).
CONCLUSIONS
Low eGFR was significantly associated with increased lung cancer risk within the Korean population. A particularly robust association was observed in individuals with severe proteinuria, emphasizing the need for further investigation.
4.The prevalence of advanced liver fibrosis among patients with type 2 diabetes mellitus: A single-centre experience in Penang, Malaysia
Xe Hui Lee ; Lisa Mohamed Nor ; Choon Seong Ang ; Toh Peng Yeow ; Shueh Lin Lim
Journal of the ASEAN Federation of Endocrine Societies 2023;38(1):52-61
Objectives:
This study aimed to compare the severity of COVID-19, inflammatory parameters and clinical outcomes
among patients with normal and subnormal levels of Vitamin D.
Methodology:
This is a retrospective cohort study of 135 patients admitted in a tertiary hospital for COVID-19. Patients
were grouped according to their Vitamin D level. Primary outcome measure was the composite of all-cause mortality and
morbidity. Other outcome measures determined were the comparison among the groups on the severity of COVID-19
infection, changes in inflammatory parameters, length of hospital stay and duration of respiratory support.
Results:
There was a significant trend of higher ICU admission, mortality (p-value= 0.006) and poor clinical outcome
(p-value=0.009) among the Vitamin D deficient group. No significant difference was found for most of the inflammatory
parameters, duration of hospital stay and respiratory support. Overall, patients with deficient, but not insufficient Vitamin
D level had 6 times higher odds of composite poor outcome than those with normal Vitamin D (crude OR=5.18, p-value=
0.003; adjusted OR =6.3, p-value=0.043).
Conclusion
The inverse relationship between Vitamin D level and poor composite outcome observed in our study
suggests that low Vitamin D may be a risk factor for poor prognosis among patients admitted for COVID-19.
type 2 diabetes mellitus
;
Non-alcoholic Fatty Liver disease
5.Role of Post-Treatment 18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography in Patients Receiving Definitive Chemoradiation for Locally Advanced Head and Neck Squamous Cell Carcinomas
Jae-Joon KIM ; Sang-Bo OH ; Ki Sun JUNG ; Kwonoh PARK ; Seong-Jang KIM ; Yongkan KI ; Jin-Choon LEE ; So Yeon OH
Korean Journal of Otolaryngology - Head and Neck Surgery 2022;65(11):697-704
Background and Objectives:
18F-fluorodeoxyglucose PET/CT scans can be a useful method to detect recurrence. However, its role in locally advanced head and neck squamous cell carcinomas (HNSCCs) patients after definitive chemoradiotherapy (CRT) has not yet been determined. The current study was performed to identify the role of therapeutic response evaluation using PET/CT after definitive CRT.Subjects and Method We conducted a retrospective review of patients with locally advanced HNSCCs, and who have undergone definitive CRT from 2009 to 2017 at a single institution. The patients were divided into two groups according to their responses to the treatment (metabolic complete remission [mCR] group or non-mCR group), assessed by PET/CT scans after definitive CRT.
Results:
Twenty-eight patients were consecutively enrolled. The most common primary site of cancer was the oropharynx, followed by the oral cavity, hypopharynx, and nasal cavity. The therapeutic response assessed by PET/CT scans was mCR in 14 patients. The median progression- free survival (PFS) was not reached in the mCR group but was 13.3 months for the non-mCR group (p=0.001). The median overall survival was significantly longer for the mCR group (52.5 months) than for the non-mCR group (15.2 months, p=0.002). A multivariate analysis showed PET/CT response and high-sensitivity C-reactive protein (hsCRP) as independent prognostic factors for PFS (mCR: p=0.027; hsCRP: p=0.042) and for the overall survival (mCR: p=0.006; hsCRP: p=0.020).
Conclusion
PET/CT scans after definitive CRT predicted the prognosis in patients with locally advanced HNSCCs. CRP was a prognostic factor affecting the outcomes of treatments.
6.A Case of African Tick-Bite Fever in a Returning Traveler from Southern Africa
Woonji LEE ; Hye SEONG ; Jung Ho KIM ; Heun CHOI ; Jun Hyoung KIM ; Jin Young AHN ; Su Jin JEONG ; Nam Su KU ; Jun Yong CHOI ; Choon-Mee KIM ; Dong-Min KIM ; Joon-sup YEOM
Infection and Chemotherapy 2022;54(1):202-207
African tick-bite fever (ATBF), caused by Rickettsia africae, is the second most frequent cause of fever after malaria in travelers returning from Southern Africa. As the Korean outbound travelers are increasing every year, tick-borne rickettsial diseases as a cause of febrile illness are likely to increase. We describe a febrile Korean returning traveler who showed two eschars after visiting the rural field in Manzini, Swaziland. We performed nested polymerase chain reaction using the eschar and diagnosed the patient with ATBF. He was treated with oral doxycycline for 7 days, and recovered without any complications. We believe that the present case is the first ATBF case diagnosed in a Korean traveler.
7.A Case of Migrated Esophageal Foreign Body Removal Through Cervical Approach Under C-Arm Fluoroscopic Guidance
Seong-Wook CHOI ; Minhyung LEE ; Jin-Choon LEE ; Eui-Suk SUNG
Korean Journal of Otolaryngology - Head and Neck Surgery 2022;65(5):288-292
Foreign bodies in the upper airway and the esophagus are common and often removed in the outpatient setting using the rigid or flexible laryngoscope. Although most esophageal foreign bodies are removed from the digestive tract, in some cases, surgical intervention is required due to its difficult location. Esophageal foreign bodies often removed by esophagogastroduodenoscopy, but when they penetrate the esophagus and move to deep neck spaces, other approaches should be taken into consideration. We report a rare case of a 13-year-old patient whose esophageal foreign body moved to a deep neck compartment, which was embedded in the anterior vertebral muscle. We decided to perform neck exploration under C-arm guidance, successfully targeted and removed the foreign body.
8.Application of an Intraoperative Neuromonitoring System Using a Surface Pressure Sensor in Parotid Surgery: A Rabbit Model Study
Eui-Suk SUNG ; Hyun-Keun KWON ; Sung-Chan SHIN ; Young-Il CHEON ; Jung-Woo LEE ; Da-Hee PARK ; Seong-Wook CHOI ; Hwa-Bin KIM ; Hye-Jin PARK ; Jin-Choon LEE ; Jung-Hoon RO ; Byung-Joo LEE
Clinical and Experimental Otorhinolaryngology 2021;14(1):131-136
Objectives:
. Facial nerve monitoring (FNM) can be used to identify the facial nerve, to obtain information regarding its course, and to evaluate its status during parotidectomy. However, there has been disagreement regarding the efficacy of FNM in reducing the incidence of facial nerve palsy during parotid surgery. Therefore, instead of using electromyography (EMG) to identify the location and state of the facial nerve, we applied an intraoperative neuromonitoring (IONM) system using a surface pressure sensor to detect facial muscle twitching. The objective of this study was to investigate the feasibility of using the IONM system with a surface pressure sensor to detect facial muscle twitching during parotidectomy.
Methods:
. We evaluated the stimulus thresholds for the detection of muscle twitching in the orbicularis oris and orbicularis oculi, as well as the amplitude and latency of EMG and the surface pressure sensor in 13 facial nerves of seven rabbits, using the same stimulus intensity.
Results:
. The surface pressure sensor detected muscle twitching in the orbicularis oris and orbicularis oculi in response to a stimulation of 0.1 mA in all 13 facial nerves. The stimulus threshold did not differ between the surface pressure sensor and EMG.
Conclusion
. The application of IONM using a surface pressure sensor during parotidectomy is noninvasive, reliable, and feasible. Therefore, the IONM system with a surface pressure sensor to measure facial muscle twitching may be an alternative to EMG for verifying the status of the facial nerve.
9.Serial Observations of Muscle and Fat Mass as Prognostic Factors for Deceased Donor Liver Transplantation
Jisun LEE ; Woo Kyoung JEONG ; Jae-Hun KIM ; Jong Man KIM ; Tae Yeob KIM ; Gyu Seong CHOI ; Choon Hyuck DAVID KWON ; Jae-Won JOH ; Sang-Yong EOM
Korean Journal of Radiology 2021;22(2):189-197
Objective:
Muscle depletion in patients undergoing liver transplantation affects the recipients’ prognosis and therefore cannot be overlooked. We aimed to evaluate whether changes in muscle and fat mass during the preoperative period are associated with prognosis after deceased donor liver transplantation (DDLT).
Materials and Methods:
This study included 72 patients who underwent DDLT and serial computed tomography (CT) scans.Skeletal muscle index (SMI) and fat mass index (FMI) were calculated using the muscle and fat area in CT performed 1 year prior to surgery (1 yr Pre-LT), just before surgery (Pre-LT), and after transplantation (Post-LT). Simple aspects of serial changes in muscle and fat mass were analyzed during three measurement time points. The rate of preoperative changes in body composition parameters were calculated (preoperative ΔSMI [%] = [SMI at Pre-LT - SMI at 1 yr Pre-LT] / SMI at Pre-LT x 100;preoperative ΔFMI [%] = [FMI at Pre-LT - FMI at 1 yr Pre-LT] / FMI at Pre-LT x 100) and assessed for correlation with patient survival.
Results:
SMI significantly decreased during the preoperative period (mean preoperative ΔSMI, -13.04%, p < 0.001). In the multivariable analysis, preoperative ΔSMI (p = 0.016) and model for end-stage liver disease score (p = 0.011) were independent prognostic factors for overall survival. The mean survival time for patients with a threshold decrease in the preoperative ΔSMI (≤ -30%) was significantly shorter than for other patients (p = 0.007). Preoperative ΔFMI was not a prognostic factor but FMI increased during the postoperative period (p = 0.009) in all patients.
Conclusion
A large reduction in preoperative SMI was significantly associated with reduced survival after DDLT. Therefore, changes in muscle mass during the preoperative period can be considered as a prognostic factor for survival after DDLT.
10.Upregulation of receptor tyrosine kinase-like orphan receptor 2 in idiopathic pulmonary fibrosis
Ji-Hye SON ; Jong-Uk LEE ; Susie CHIN ; Eun-Suk GO ; Jai-Seong PARK ; Hwa-Kyun SHIN ; Hun Soo CHANG ; Jong-Sook PARK ; Choon-Sik PARK
The Korean Journal of Internal Medicine 2021;36(4):914-923
Background/Aims:
Receptor tyrosine kinase-like orphan receptor 2 (ROR2) is a major regulator of Wnt signaling, which is involved in fibroblast dysfunction. Because its role has not been evaluated in idiopathic pulmonary fibrosis (IPF), we examined the clinical implications of ROR2 expression.
Methods:
ROR2 mRNA expression was measured using reverse transcription polymerase chain reaction in lung tissue-derived fibroblasts from IPF patients (n = 14) and from controls (n = 10). ROR2 protein was measured using enzyme-linked immunosorbent assay in primary fibroblasts from IPF patients (n = 14) and controls (n = 10), and in bronchoalveolar lavage (BAL) fluids obtained from normal controls (NC; n = 30). IPF patients (n = 84), and other patients with interstitial lung diseases, including nonspecific interstitial pneumonia (NSIP; n = 10), hypersensitivity pneumonitis (HP; n = 10), and sarcoidosis (n = 10).
Results:
ROR2 mRNA and protein levels were significantly higher in IPF fibroblasts than in controls (p = 0.003, p = 0.0017, respectively). ROR2 protein levels in BAL fluids from patients with IPF were significantly higher than in those from NC (p < 0.001), and from patients with NSIP (p = 0.006), HP (p = 0.004), or sarcoidosis (p = 0.004). Receiver operating characteristic curves showed a clear difference between IPF and NC in ROR2 protein level (area under the curve, 0.890; confidence interval, 0.829 to 0.950; p < 0.001). ROR2 protein levels were significantly higher in GAP stage III than in GAP stages I and II (p = 0.016).
Conclusions
ROR2 may be related to the development of IPF, and its protein level may be a useful and severity-dependent candidate marker for IPF.


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