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.Early Prediction of Mortality for Septic Patients Visiting Emergency Room Based on Explainable Machine Learning: A Real-World Multicenter Study
Sang Won PARK ; Na Young YEO ; Seonguk KANG ; Taejun HA ; Tae-Hoon KIM ; DooHee LEE ; Dowon KIM ; Seheon CHOI ; Minkyu KIM ; DongHoon LEE ; DoHyeon KIM ; Woo Jin KIM ; Seung-Joon LEE ; Yeon-Jeong HEO ; Da Hye MOON ; Seon-Sook HAN ; Yoon KIM ; Hyun-Soo CHOI ; Dong Kyu OH ; Su Yeon LEE ; MiHyeon PARK ; Chae-Man LIM ; Jeongwon HEO ; On behalf of the Korean Sepsis Alliance (KSA) Investigators
Journal of Korean Medical Science 2024;39(5):e53-
Background:
Worldwide, sepsis is the leading cause of death in hospitals. If mortality rates in patients with sepsis can be predicted early, medical resources can be allocated efficiently. We constructed machine learning (ML) models to predict the mortality of patients with sepsis in a hospital emergency department.
Methods:
This study prospectively collected nationwide data from an ongoing multicenter cohort of patients with sepsis identified in the emergency department. Patients were enrolled from 19 hospitals between September 2019 and December 2020. For acquired data from 3,657 survivors and 1,455 deaths, six ML models (logistic regression, support vector machine, random forest, extreme gradient boosting [XGBoost], light gradient boosting machine, and categorical boosting [CatBoost]) were constructed using fivefold cross-validation to predict mortality. Through these models, 44 clinical variables measured on the day of admission were compared with six sequential organ failure assessment (SOFA) components (PaO 2 /FIO 2 [PF], platelets (PLT), bilirubin, cardiovascular, Glasgow Coma Scale score, and creatinine).The confidence interval (CI) was obtained by performing 10,000 repeated measurements via random sampling of the test dataset. All results were explained and interpreted using Shapley’s additive explanations (SHAP).
Results:
Of the 5,112 participants, CatBoost exhibited the highest area under the curve (AUC) of 0.800 (95% CI, 0.756–0.840) using clinical variables. Using the SOFA components for the same patient, XGBoost exhibited the highest AUC of 0.678 (95% CI, 0.626–0.730). As interpreted by SHAP, albumin, lactate, blood urea nitrogen, and international normalization ratio were determined to significantly affect the results. Additionally, PF and PLTs in the SOFA component significantly influenced the prediction results.
Conclusion
Newly established ML-based models achieved good prediction of mortality in patients with sepsis. Using several clinical variables acquired at the baseline can provide more accurate results for early predictions than using SOFA components. Additionally, the impact of each variable was identified.
3.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.
4.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.
5.Erratum: Correction of Affiliations inthe Article “Outcomes of Patients on the Lung Transplantation Waitlist in Korea: A Korean Network for Organ Sharing Data Analysis”
Hye Ju YEO ; Dong Kyu OH ; Woo Sik YU ; Sun Mi CHOI ; Kyeongman JEON ; Mihyang HA ; Jin Gu LEE ; Woo Hyun CHO ; Young Tae KIM
Journal of Korean Medical Science 2023;38(15):e150-
6.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.
7.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.
8.Outcomes of Patients on the Lung Transplantation Waitlist in Korea:A Korean Network for Organ Sharing Data Analysis
Hye Ju YEO ; Dong Kyu OH ; Woo Sik YU ; Sun Mi CHOI ; Kyeongman JEON ; Mihyang HA ; Jin Gu LEE ; Woo Hyun CHO ; Young Tae KIM
Journal of Korean Medical Science 2022;37(41):e294-
Background:
The demand for lung transplants continues to increase in Korea, and donor shortages and waitlist mortality are critical issues. This study aimed to evaluate the factors that affect waitlist outcomes from the time of registration for lung transplantation in Korea.
Methods:
Data were obtained from the Korean Network for Organ Sharing for lung-only registrations between September 7, 2009, and December 31, 2020. Post-registration outcomes were evaluated according to the lung disease category, blood group, and age.
Results:
Among the 1,671 registered patients, 49.1% had idiopathic pulmonary fibrosis (group C), 37.0% had acute respiratory distress syndrome and other interstitial lung diseases (group D), 7.2% had chronic obstructive pulmonary disease (group A), and 6.6% had primary pulmonary hypertension (group B). Approximately half of the patients (46.1%) were transplanted within 1 year of registration, while 31.8% died without receiving a lung transplant within 1 year of registration. Data from 1,611 patients were used to analyze 1-year postregistration outcomes, which were classified as transplanted (46.1%, n = 743), still awaiting (21.1%, n = 340), removed (0.9%, n = 15), and death on waitlist (31.8%, n = 513). No significant difference was found in the transplantation rate according to the year of registration. However, significant differences occurred between the waitlist mortality rates (P = 0.008) and the still awaiting rates (P = 0.009). The chance of transplantation after listing varies depending on the disease category, blood type, age, and urgency status. Waitlist mortality within 1 year was significantly associated with non-group A disease (hazard ratio [HR], 2.76, P < 0.001), age ≥ 65 years (HR, 1.48, P < 0.001), and status 0 at registration (HR, 2.10, P < 0.001).
Conclusion
Waitlist mortality is still higher in Korea than in other countries. Future revisions to the lung allocation system should take into consideration the high waitlist mortality and donor shortages.
9.Strategy for salvaging infected breast implants: lessons from the recovery of seven consecutive patients
Hyeonjung YEO ; Dongkyu LEE ; Jin Soo KIM ; Pil Seon EO ; Dong Kyu KIM ; Joon Seok LEE ; Ki Tae KWON ; Jeeyeon LEE ; Ho Yong PARK ; Jung Dug YANG
Archives of Plastic Surgery 2021;48(2):165-174
Background:
In recent years, implant-based breast reconstruction has been performed because of its simplicity, short operation time, and rapid recovery of patients. Several studies have reported treatment methods for implant surgery-related infection, which is a serious complication. The aim of this study was to introduce our strategy for salvaging infected implants and to evaluate its effectiveness.
Methods:
The authors performed a retrospective study of 145 cases from 132 patients who underwent implant-based breast reconstruction from January 2012 to December 2018. Empirical antibiotics were immediately administered to patients with suspected infections. The patients then underwent salvage treatment including appropriate antibiotics, ultrasonography-guided aspiration, debridement, antibiotic lavage, and implant exchange through a multidisciplinary approach. Patient demographics, operative data, duration until drain removal, adjuvant treatment, and complications were analyzed.
Results:
The total infection rate was 5.5% (8/145). A longer indwelling catheter period and adjuvant treatment were significantly associated with infection. The salvage treatment showed a success rate of 87.5% (7/8). Seven patients who received early aggressive salvage treatment recovered from infection. One patient with methicillin-resistant Staphylococcus aureus, who received salvage treatment 11 days after symptom onset, did not respond to drainage and antibiotic treatment. That patient subsequently underwent explantation.
Conclusions
In implant-based breast reconstruction, prevention of infection is of the utmost importance. However, if an infection is suspected, proactive empirical antibiotic therapy and collaboration with the necessary departments are required. Through a multidisciplinary approach and proactive early management, swift and appropriate salvage should be performed.
10.Awareness and Use of Complementary and Alternative Medicine in Korean Lung Cancer Patients
Joon Young CHOI ; Wonjun JI ; Chang-Min CHOI ; Chaeuk CHUNG ; Jae Myoung NOH ; Cheol-Kyu PARK ; In-Jae OH ; Hong In YOON ; Hyeong Ryul KIM ; Ho Young KIM ; Chang Dong YEO ; Seung Hun JANG ;
Tuberculosis and Respiratory Diseases 2021;84(2):105-114
Background:
Complementary and alternative medicine (CAM) has been used frequently, and its use continues to increase in lung cancer patients, despite insufficient scientific of its efficacy. To investigate this situation, we analyzed the current awareness and use of CAM in Korean lung-cancer patients. Methods: This prospective survey–based study was performed at seven medical centers in South Korea between August and October 2019. The survey assessed general patient characteristics and the awareness and use of CAM. We analyzed differences in the clinical parameters of patients aware and not aware of CAM and of CAM non-users and users.
Results:
Of the 434 patients included in this study, 68.8% responded that they were aware of CAM and 30.9% said they had experienced it. In univariate analysis, the patients aware of CAM were younger with poor performance status, had advanced-stage lung cancer, received more systemic therapy, and received concurrent chemoradiation therapy (CCRT). By multiple logistic regression, younger age, poor performance status, advanced stage, and prior CCRT were identified as independent risk factors for CAM awareness. There were no significant differences in the general characteristics and cancer-associated clinical parameters of CAM non-users and users.
Conclusion
Specific clinical parameters were associated with patients’ awareness of CAM, although there were no significantly different characteristics between CAM users and non-users.

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