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.Evaluation of the Current Urgency-Based Lung Allocation System in Korea with Simulation of the Eurotransplant Lung Allocation Score
Woo Sik YU ; Sun Mi CHOI ; Hye Ju YEO ; Dong Kyu OH ; Sung Yoon LIM ; Young Tae KIM ; Kyeongman JEON ; Jin Gu LEE
Yonsei Medical Journal 2024;65(8):463-471
Purpose:
Due to the shortage of lung donors relative to the number of patients waiting for lung transplantation (LTx), more than one-third of patients on the waitlist have died without receiving LTx in Korea. Therefore, the importance of fair and effective allocation policies has been emphasized. This study investigated the characteristics of the current urgency-based allocation system in Korea by simulating the Eurotransplant lung allocation score (ET-LAS) using a nationwide multi-institutional registry for LTx in Korea.
Materials and Methods:
This study used data from the Korean Organ Transplantation Registry (KOTRY), along with additional retrospective data for ET-LAS calculation. A total of 194 patients were included in this study between January 2015 and December 2019. The Korean urgency definition classifies an LTx candidate as having statuses 0–3 according to urgency. The ET-LAS was analyzed according to the Korean urgency status.
Results:
In total, 92 patients received lung transplants at status 0, 85 at status 1, and 17 at status 2/3. The ET-LAS showed a bimodal distribution with distinct peaks corresponding to status 0 and non-status 0. There was no significant difference in the ET-LAS among non-status 0 patients. In logistic and decision tree analyses, oxygen supplementation methods, particularly oxygen masks and high-flow nasal cannulas, were significantly associated with a high ET-LAS (≥50) among non-status 0 patients.
Conclusion
Simulation of the ET-LAS with KOTRY data showed that the Korean urgency definition may not allocate lungs by urgency, especially for patients in non-status 0; therefore, it needs to be revised.
3.Real-World Study of Osimertinib in Korean Patients with Epidermal Growth Factor Receptor T790M Mutation–Positive Non–Small Cell Lung Cancer
Jang Ho LEE ; Eun Young KIM ; Cheol-Kyu PARK ; Shin Yup LEE ; Min ki LEE ; Seong-Hoon YOON ; Jeong Eun LEE ; Sang Hoon LEE ; Seung Joon KIM ; Sung Yong LEE ; Jun Hyeok LIM ; Tae-Won JANG ; Seung Hun JANG ; Kye Young LEE ; Seung Hyeun LEE ; Sei Hoon YANG ; Dong Won PARK ; Chan Kwon PARK ; Hye Seon KANG ; Chang Dong YEO ; Chang-Min CHOI ; Jae Cheol LEE
Cancer Research and Treatment 2023;55(1):112-122
Purpose:
Although osimertinib is the standard-of-care treatment of epidermal growth factor receptor (EGFR) T790M mutation–positive non–small cell lung cancer, real-world evidence on the efficacy of osimertinib is not enough to reflect the complexity of the entire course of treatment. Herein, we report on the use of osimertinib in patients with EGFR T790M mutation–positive non–small cell lung cancer who had previously received EGFR tyrosine kinase inhibitor (TKI) treatment in Korea.
Materials and Methods:
Patients with confirmed EGFR T790M after disease progression of prior EGFR-TKI were enrolled and administered osimertinib 80 mg daily. The primary effectiveness outcome was progression-free survival, with time-to-treatment discontinuation, treatment and adverse effects leading to treatment discontinuation, and overall survival being the secondary endpoints.
Results:
A total of 558 individuals were enrolled, and 55.2% had investigator-assessed responses. The median progression-free survival was 14.2 months (95% confidence interval [CI], 13.0 to 16.4), and the median time-to-treatment discontinuation was 15.0 months (95% CI, 14.1 to 15.9). The median overall survival was 36.7 months (95% CI, 30.9 to not reached). The benefit with osimertinib was consistent regardless of the age, sex, smoking history, and primary EGFR mutation subtype. However, hepatic metastases at the time of diagnosis, the presence of plasma EGFR T790M, and the shorter duration of prior EGFR-TKI treatment were poor predictors of osimertinib treatment. Ten patients (1.8%), including three with pneumonitis, had to discontinue osimertinib due to severe adverse effects.
Conclusion
Osimertinib demonstrated its clinical effectiveness and survival benefit for EGFR T790M mutation–positive in Korean patients with no new safety signals.
4.Prediction of Postoperative Lung Function in Lung Cancer Patients Using Machine Learning Models
Oh Beom KWON ; Solji HAN ; Hwa Young LEE ; Hye Seon KANG ; Sung Kyoung KIM ; Ju Sang KIM ; Chan Kwon PARK ; Sang Haak LEE ; Seung Joon KIM ; Jin Woo KIM ; Chang Dong YEO
Tuberculosis and Respiratory Diseases 2023;86(3):203-215
Background:
Surgical resection is the standard treatment for early-stage lung cancer. Since postoperative lung function is related to mortality, predicted postoperative lung function is used to determine the treatment modality. The aim of this study was to evaluate the predictive performance of linear regression and machine learning models.
Methods:
We extracted data from the Clinical Data Warehouse and developed three sets: set I, the linear regression model; set II, machine learning models omitting the missing data: and set III, machine learning models imputing the missing data. Six machine learning models, the least absolute shrinkage and selection operator (LASSO), Ridge regression, ElasticNet, Random Forest, eXtreme gradient boosting (XGBoost), and the light gradient boosting machine (LightGBM) were implemented. The forced expiratory volume in 1 second measured 6 months after surgery was defined as the outcome. Five-fold cross-validation was performed for hyperparameter tuning of the machine learning models. The dataset was split into training and test datasets at a 70:30 ratio. Implementation was done after dataset splitting in set III. Predictive performance was evaluated by R2 and mean squared error (MSE) in the three sets.
Results:
A total of 1,487 patients were included in sets I and III and 896 patients were included in set II. In set I, the R2 value was 0.27 and in set II, LightGBM was the best model with the highest R2 value of 0.5 and the lowest MSE of 154.95. In set III, LightGBM was the best model with the highest R2 value of 0.56 and the lowest MSE of 174.07.
Conclusion
The LightGBM model showed the best performance in predicting postoperative lung function.
5.Nationwide Trends in the Prevalence of Cigarette and E-cigarette Smoking among Korean Adults between 2014-2021: A Representative Serial Study of 1.2 Million Individuals.
Minji KIM ; Wonyoung CHO ; Jinseok LEE ; Yong Sung CHOI ; Seung Geun YEO ; Young Joo LEE ; Sang Youl RHEE ; Chanyang MIN ; Dong Keon YON
Biomedical and Environmental Sciences 2023;36(10):996-998
6.Analysis of clinical risk factors of failed electrical cardioversion in patients with persistent atrial fibrillation or atrial flutter
Ki‑Hun KIM ; Ha‑Young CHOI ; Jino PARK ; Yeo‑Jeong SONG ; Seunghwan KIM ; Dong‑Kie KIM ; Sang‑Hoon SEOL ; Doo‑Il KIM ; Pil‑Sung YANG ; Hong Euy LIM ; Junbeum PARK ; Jae‑Min SHIM ; Jinhee AHN ; Sung Ho LEE ; Sung Il IM ; Ju Youn KIM
International Journal of Arrhythmia 2023;24(3):17-
Background:
Although rhythm control could be the best for symptomatic atrial fibrillation (AF), some patients fail to achieve sinus rhythm (SR). This study aimed to identify clinical risk factors of failed electrical cardioversion (ECV).
Methods:
A total of 248 patients who received ECV for persistent AF or atrial flutter (AFL) were retrospectivelyreviewed. Patients were divided into three groups: Group 1 maintained SR for > 1 year, group 2 maintained SR ≤ 1 yearafter ECV, and group 3 failed ECV. SR maintenance was assessed using regular electrocardiography or Holter monitoring.
Results:
Patients were divided into group 1 (73, 29%), group 2 (146, 59%), and group 3 (29, 12%). The mean ageof patients was 60 ± 10 years, and 197 (79%) were male. Age, sex, and baseline characteristics were similar amonggroups. However, increased cardiac size, digoxin use, heart failure (HF), and decreased left ventricular ejection frac‑ tion (LVEF) were more common in group 3. Univariate analysis of clinical risk factors for failed ECV was increasedcardiac size [hazard ratio (HR) 2.14 (95% confidence interval [CI], 1.06–4.34, p = 0.030)], digoxin use [HR 2.66 (95% CI, 1.15–6.14), p = 0.027], HF [HR 2.60 (95% CI, 1.32–5.09), p = 0.005], LVEF < 40% [HR 3.45 (95% CI, 1.00–11.85), p = 0.038], and decreased LVEF [HR 2.49 (95% CI, 1.18–5.25), p = 0.012]. Among them, HF showed clinical significance only by multivariate analysis [HR 3.01 (95% CI, 1.13–7.99), p = 0.027].
Conclusions
Increased cardiac size, digoxin use, HF, LVEF < 40%, and decreased LVEF were related to failed ECV for persistent AF or AFL. Among these, HF was the most important risk factor. Further multi-center studies including greater number of participants are planned.
7.Current Status and Physicians’ Perspectives of Childhood Cancer Survivorship in Korea: A Nationwide Survey of Pediatric Hematologists/ Oncologists
Ji Won LEE ; Yohwan YEO ; Hee Young JU ; Hee Won CHO ; Keon Hee YOO ; Ki Woong SUNG ; Hong Hoe KOO ; Su-Min JEONG ; Dong Wook SHIN ; Hee Jo BAEK ; Hoon KOOK ; Nack-Gyun CHUNG ; Bin CHO ; Young Ae KIM ; Hyeon Jin PARK ; Yun-Mi SONG
Journal of Korean Medical Science 2023;38(29):e230-
Background:
Data on the status of long-term follow-up (LTFU) care for childhood cancer survivors (CCSs) in Korea is lacking. This study was conducted to evaluate the current status of LTFU care for CCSs and relevant physicians’ perspectives.
Methods:
A nationwide online survey of pediatric hematologists/oncologists in the Republic of Korea was undertaken.
Results:
Overall, 47 of the 74 board-certified Korean pediatric hematologists/oncologists currently providing pediatric hematology/oncology care participated in the survey (response rate = 63.5%). Forty-five of the 47 respondents provided LTFU care for CCSs five years after the completion of primary cancer treatment. However, some of the 45 respondents provided LTFU care only for CCS with late complications or CCSs who requested LTFU care. Twenty of the 45 respondents oversaw LTFU care for adult CCSs, although pediatric hematologists/ oncologists experienced more difficulties managing adult CCSs. Many pediatric hematologists/oncologists did not perform the necessary screening test, although CCSs had risk factors for late complications, mostly because of insurance coverage issues and the lack of Korean LTFU guidelines. Regarding a desirable LTFU care system for CCSs in Korea, 27 of the 46 respondents (58.7%) answered that it is desirable to establish a multidisciplinary CCSs care system in which pediatric hematologists/oncologists and adult physicians cooperate.
Conclusion
The LTFU care system for CCS is underdeveloped in the Republic of Korea. It is urgent to establish an LTFU care system to meet the growing needs of Korean CCSs, which should include Korean CCSs care guidelines, provider education plans, the establishment of multidisciplinary care systems, and a supportive national healthcare policy.
8.Botulinum Toxin A Ameliorates Neuroinflammation in the MPTP and 6-OHDA-Induced Parkinson’s Disease Models
Hyeon Joo HAM ; In Jun YEO ; Seong Hee JEON ; Jun Hyung LIM ; Sung Sik YOO ; Dong Ju SON ; Sung-Su JANG ; Haksup LEE ; Seung-Jin SHIN ; Sang Bae HAN ; Jae Suk YUN ; Jin Tae HONG
Biomolecules & Therapeutics 2022;30(1):90-97
Recently, increasing evidence suggests that neuroinflammation may be a critical factor in the development of Parkinson’s disease (PD) in addition to the ratio of acetylcholine/dopamine because dopaminergic neurons are particularly vulnerable to inflammatory attack. In this study, we investigated whether botulinum neurotoxin A (BoNT-A) was effective for the treatment of PD through its anti-neuroinflammatory effects and the modulation of acetylcholine and dopamine release. We found that BoNT-A ameliorated MPTP and 6-OHDA-induced PD progression, reduced acetylcholine release, levels of IL-1β, IL-6 and TNF-α as well as GFAP expression, but enhanced dopamine release and tyrosine hydroxylase expression. These results indicated that BoNT-A had beneficial effects on MPTP or 6-OHDA-induced PD-like behavior impairments via its anti-neuroinflammation properties, recovering dopamine, and reducing acetylcholine release.
9.Hemiballism, a rare complication of coil embilization
Sung Ho KIM ; Dong Kyu YEO ; Gwang Soo LEE
Journal of Cerebrovascular and Endovascular Neurosurgery 2022;24(4):366-371
Thromboembolism is one of the major complications during coil embolization of an aneurysm, which usually causes familiar neurological deficits, such as, weakness, aphasia, etc. We report a rare complication by thromboembolism after coil embolization causing hemiballism. A 69-year-old female presented with unruptured posterior communicating artery aneurysm and was treated by coil embolization. After the procedure, the patient showed global aphasia and right hemiparesis, and there were small multiple, scattered infarctions on the left middle cerebral artery territory. The neurologic deficit subsided after five days, but hemballism occurred thereafter. There was no other medical history to explain the hemiballism. The patient was treated with clonazepam and antiepileptics and the hemiballism subsided at postoperative day 20. We report a case of rare complication, hemiballism, during coil embolization.
10.Factors Affecting the Extrusion Rate and Complications After Ventilation Tube Insertion: A Multicenter Registry Study on the Effectiveness of Ventilation Tube Insertion in Pediatric Patients With Chronic Otitis Media With Effusion—Part II
Myung Hoon YOO ; Yang-Sun CHO ; June CHOI ; Yun Hoon CHOUNG ; Jae-Ho CHUNG ; Jong Woo CHUNG ; Gyu Cheol HAN ; Beom Cho JUN ; Dong-Kee KIM ; Kyu Sung KIM ; Jun Ho LEE ; Kyu-Yup LEE ; Seung Hwan LEE ; In Seok MOON ; Hong Ju PARK ; Shi Nae PARK ; Jihye RHEE ; Jae Hyun SEO ; Seung Geun YEO
Clinical and Experimental Otorhinolaryngology 2022;15(4):326-334
Objectives:
. The impacts of ventilation tube (VT) type and effusion composition on the VT extrusion rate and complications in children with otitis media remain unclear. This part II study evaluated the factors affecting the extrusion rate, recurrence rate, and complications of VT insertion.
Methods:
. A prospective study was conducted between June 2014 and December 2016 (the EVENT study [analysis of the effectiveness of ventilation tube insertion in pediatric patients with chronic otitis media]), with follow-up data collected until the end of 2017. Patients aged <15 years diagnosed with otitis media with effusion who received VT insertion were recruited at 15 tertiary hospitals. The primary outcomes were time to extrusion of VT, time to effusion recurrence, and complications.
Results:
. Data from 401 patients were analyzed. After excluding the results of long-lasting tubes (Paparella type II and T-tubes), silicone tubes (Paparella type I) exhibited a significantly longer extended time to extrusion (mean, 400 days) than titanium tubes (collar-button-type 1.0 mm: mean, 312 days; P<0.001). VT material (hazard ratio [HR], 2.117, 95% confidence interval [CI], 1.254–3.572; P=0.005), age (HR, 3.949; 95% CI, 1.239–12.590; P=0.02), and effusion composition (P=0.005) were significantly associated with the time to recurrence of middle ear effusion. Ears with purulent (mean, 567 days) and glue-like (mean, 588 days) effusions exhibited a shorter time to recurrence than ears with serous (mean, 846 days) or mucoid (mean, 925 days) effusions. The revision VT rates during follow-up were 3.5%, 15.5%, 10.4%, and 38.9% in ears with serous, mucoid, glue-like, and purulent effusions, respectively (P<0.001). The revision surgery rates were higher among patients aged <7 years than among those aged ≥7 years.
Conclusion
. Silicone tubes (Paparella type I) were less prone to early extrusion than titanium 1.0 mm tubes. VT type, patient age, and effusion composition affected the time to recurrence of effusion.

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