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 between Atherosclerosis and High-Risk Colorectal Adenomas based on Cardio-Ankle Vascular Index and Ankle-Brachial Index
Jung Ho LEE ; Hyunseok CHO ; Sang Hoon LEE ; Sung Joon LEE ; Chang Don KANG ; Dae Hee CHOI ; Jin Myung PARK ; Seung-Joo NAM ; Tae Suk KIM ; Ji Hyun KIM ; Sung Chul PARK
The Korean Journal of Gastroenterology 2024;83(4):143-149
Background/Aims:
Colorectal adenomas are precancerous lesions that may lead to colorectal cancer. Recent studies have shown that colorectal adenomas are associated with atherosclerosis. The cardio-ankle vascular index (CAVI) and ankle-brachial index (ABI) are noninvasive methods for evaluating atherosclerosis. This study examined the association between atherosclerosis and high-risk colorectal adenomas based on the CAVI and ABI.
Methods:
The data of patients aged ≥50 years who had a colonoscopy and CAVI and ABI measurements from August 2015 to December 2021 at the Kangwon National University Hospital were analyzed retrospectively. After the colonoscopy, subjects were divided into no, overall, and high-risk (size ≥1 cm, high-grade dysplasia or villous adenoma, three or more adenomas) adenoma groups based on the pathology findings. The data were subjected to univariate and multivariate logistic regression analyses.
Results:
Among the 1,164 subjects, adenomas and high-risk adenomas were found in 613 (52.6%) and 118 (10.1%) patients, respectively. The rate of positive ABI (<0.9) and positive CAVI (≥9.0) were significantly higher in the high-risk adenoma group (22.0% and 55.9%) than in the no adenoma (12.3% and 39.6%) and the overall adenoma group (15.7% and 44.0%) (p=0.008 and p=0.006, respectively). Multivariate analysis revealed a positive CAVI and smoking status to be significantly associated with high-risk adenoma with an odds ratio of 1.595 (95% confidence interval 1.055–2.410, p=0.027) and 1.579 (1.072–2.324, p=0.021), respectively.
Conclusions
In this study, a significant correlation between positive CAVI and high-risk adenomas was observed. Therefore, CAVI may be a significant predictor for high-risk colorectal adenoma.
4.Predictive role of absolute lymphocyte count in daratumumab-treated patients with relapsed/ refractory multiple myeloma
Hee Jeong CHO ; Jae-Cheol JO ; Yoo Jin LEE ; Myung Won LEE ; Do Young KIM ; Ho Jin SHIN ; Sung Nam IM ; Ji Hyun LEE ; Sung Hwa BAE ; Young Rok DO ; Won Sik LEE ; Min Kyung KIM ; Jina JUNG ; Jung Min LEE ; Ju-Hyung KIM ; Dong Won BAEK ; Sang-Kyun SOHN ; Joon Ho MOON
The Korean Journal of Internal Medicine 2023;38(2):238-247
Background/Aims:
Daratumumab has shown an encouraging antitumor effect in patients with multiple myeloma (MM), and was known to alter the immune properties by off-targeting immunosuppressive cells. Here, we aimed to evaluate the change in absolute lymphocyte count (ALC) as a surrogate marker for predicting survival outcomes of patients treated with daratumumab.
Methods:
Between 2018 and 2021, the medical records of patients with relapsed/refractory MM (RRMM) treated with daratumumab monotherapy at 10 centers in South Korea were reviewed. We collected the ALC data at pre-infusion (D0), day 2 after the first infusion (D2), and prior to the third cycle of daratumumab therapy (D56).
Results:
Fifty patients who were administered at least two cycles of daratumumab were included. Overall response rate was 54.0% after two cycles of daratumumab treatment. On D2, almost all patients experienced a marked reduction in ALC. However, an increase in ALC on D56 (ALCD56) was observed in patients with non-progressive disease, whereas failure of ALC recovery was noted in those with progressive disease. Patients with ALCD56 > 700/μL (n = 39, 78.0%) had prolonged progression- free survival (PFS) and overall survival (OS) than those with ALCD56 ≤ 700/μL (median PFS: 5.8 months vs. 2.6 months, p = 0.025; median OS: 24.1 months vs. 6.1 months, p = 0.004). In addition, ALCD56 >700/μL was a significant favorable prognostic factor for PFS (hazard ratio [HR], 0.22; p = 0.003) and OS (HR, 0.23; p = 0.012).
Conclusions
Increase in ALC during daratumumab treatment was significantly associated with prolonged survival outcomes in patients with RRMM. The ALC value can predict clinical outcomes in patients treated with daratumumab.
5.Guideline for the Surgical Management of Locally Invasive Differentiated Thyroid Cancer From the Korean Society of Head and Neck Surgery
Jun-Ook PARK ; Joo Hyun KIM ; Young Hoon JOO ; Sang-Yeon KIM ; Geun-Jeon KIM ; Hyun Bum KIM ; Dong-Hyun LEE ; Hyun Jun HONG ; Young Min PARK ; Eun-Jae CHUNG ; Yong Bae JI ; Kyoung Ho OH ; Hyoung Shin LEE ; Dong Kun LEE ; Ki Nam PARK ; Myung Jin BAN ; Bo Hae KIM ; Do Hun KIM ; Jae-Keun CHO ; Dong Bin AHN ; Min-Su KIM ; Jun Girl SEOK ; Jeon Yeob JANG ; Hyo Geun CHOI ; Hee Jin KIM ; Sung Joon PARK ; Eun Kyung JUNG ; Yeon Soo KIM ; Yong Tae HONG ; Young Chan LEE ; Ho-Ryun WON ; Sung-Chan SHIN ; Seung-Kuk BAEK ; Soon Young KWON
Clinical and Experimental Otorhinolaryngology 2023;16(1):1-19
The aim of this study was to develop evidence-based recommendations for determining the surgical extent in patients with locally invasive differentiated thyroid cancer (DTC). Locally invasive DTC with gross extrathyroidal extension invading surrounding anatomical structures may lead to several functional deficits and poor oncological outcomes. At present, the optimal extent of surgery in locally invasive DTC remains a matter of debate, and there are no adequate guidelines. On October 8, 2021, four experts searched the PubMed, Embase, and Cochrane Library databases; the identified papers were reviewed by 39 experts in thyroid and head and neck surgery. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to assess the quality of evidence, and to develop and report recommendations. The strength of a recommendation reflects the confidence of a guideline panel that the desirable effects of an intervention outweigh any undesirable effects, across all patients for whom the recommendation is applicable. After completing the draft guidelines, Delphi questionnaires were completed by members of the Korean Society of Head and Neck Surgery. Twenty-seven evidence-based recommendations were made for several factors, including the preoperative workup; surgical extent of thyroidectomy; surgery for cancer invading the strap muscles, recurrent laryngeal nerve, laryngeal framework, trachea, or esophagus; and surgery for patients with central and lateral cervical lymph node involvement. Evidence-based guidelines were devised to help clinicians make safer and more efficient clinical decisions for the optimal surgical treatment of patients with locally invasive DTC.
6.Assessing the Fear Factor of Coronavirus Disease 2019 (COVID-19) in Korea Using the COVID-19 Phobia Scale: A Cross-Sectional Study
Hocheol LEE ; Hye Ji KIM ; Dan Hee KWON ; Myung Bae PARK ; Sang Mi KIM ; Kyeong Na KIM ; Eun Woo NAM
Journal of Korean Medical Science 2023;38(7):e52-
Background:
A study on coronavirus disease 2019 (COVID-19) phobia among students revealed that fear of contracting COVID-19 was associated with commuting to school and spending time with others at school. Therefore, it is the need-of-the-hour for the Korean government to identify factors affecting COVID-19 phobia among university students and to consider these factors while framing the policy direction for the process of returning to normalcy in university education. Consequently, we aimed to identify the current state of COVID-19 phobia among Korean undergraduate and graduate students and the factors affecting COVID-19 phobia.
Methods:
This cross-sectional survey was conducted to identify the factors affecting COVID-19 phobia among Korean undergraduate and graduate students. The survey collected 460 responses from April 5 to April 16, 2022. The questionnaire was developed based on the COVID-19 Phobia Scale (C19P-S). Multiple linear regression was performed on the C19P-S scores using five models with the following dependent variables: Model 1, total C19P-S score; Model 2, psychological subscale score; Model 3, psychosomatic subscale score; Model 4, social subscale score; and Model 5, economic subscale score. The fit of these five models was established, and a P-value of less than 0.05 (F test) was considered statistically significant.
Results:
An analysis of the factors affecting the total C19P-S score led to the following findings: women significantly outscored men (difference: 4.826 points, P = 0.003); the group that favored the government’s COVID-19 mitigation policy scored significantly lower than those who did not favor it (difference: 3.161 points, P = 0.037); the group that avoided crowded places scored significantly higher than the group that did not avoid crowded places (difference: 7.200 points, P < 0.001); and those living with family/friends scored significantly higher than those in other living situations (difference: 4.606 points, P = 0.021). Those in favor of the COVID-19 mitigation policy had significantly lower psychological fear than those who were against it (difference: -1.686 points, P = 0.004). Psychological fear was also significantly higher for those who avoided crowded places compared to those who did not difference: 2.641 points, P < 0.001). Fear was significantly higher in people cohabitating than those living alone (difference: 1.543 points, P= 0.043).
Conclusion
The Korean government, in their pursuit of a policy that eases COVID-19-related restrictions, will also have to spare no efforts in providing correct information to prevent the escalation of COVID-19 phobia among people with a high fear of contracting the disease. This should be done through trustworthy information sources, such as the media, public agencies, and COVID-19 professionals.
7.Predictive role of absolute lymphocyte count in daratumumab-treated patients with relapsed/ refractory multiple myeloma
Hee Jeong CHO ; Jae-Cheol JO ; Yoo Jin LEE ; Myung Won LEE ; Do Young KIM ; Ho Jin SHIN ; Sung Nam IM ; Ji Hyun LEE ; Sung Hwa BAE ; Young Rok DO ; Won Sik LEE ; Min Kyung KIM ; Jina JUNG ; Jung Min LEE ; Ju-Hyung KIM ; Dong Won BAEK ; Sang-Kyun SOHN ; Joon Ho MOON
The Korean Journal of Internal Medicine 2023;38(4):578-578
8.Erratum: Correction of Affiliations in the Article “Establishment of a Nationwide Korean Imaging Cohort of Coronavirus Disease 2019”
Soon Ho YOON ; Soo-Youn HAM ; Bo Da NAM ; Kum Ju CHAE ; Dabee LEE ; Jin Young YOO ; So Hyeon BAK ; Jin Young KIM ; Jin Hwan KIM ; Ki Beom KIM ; Jung Im JUNG ; Jae-Kwang LIM ; Jong Eun LEE ; Myung Jin CHUNG ; Young Kyung LEE ; Young Seon KIM ; Ji Eun JO ; Sang Min LEE ; Woocheol KWON ; Chang Min PARK ; Yun-Hyeon KIM ; Yeon Joo JEONG
Journal of Korean Medical Science 2023;38(34):e298-
9.Osteoporosis Is Associated with an Increased Risk of Colorectal Adenoma and High-Risk Adenoma: A Retrospective, Multicenter, Cross-Sectional, Case-Control Study
Ji Hyung NAM ; Myung KOH ; Hyoun Woo KANG ; Kum Hei RYU ; Dong Seok LEE ; Su Hwan KIM ; Dong Kee JANG ; Ji Bong JEONG ; Ji Won KIM ; Kook Lae LEE ; Dong Jun OH ; Yun Jeong LIM ; Seong-Joon KOH ; Jong Pil IM ; Joo Sung KIM
Gut and Liver 2022;16(2):269-276
Background/Aims:
The protective effects of vitamin D and calcium on colorectal neoplasms are known. Bone mineral density (BMD) may be a reliable biomarker that reflects the long-term anticancer effect of vitamin D and calcium. This study aimed to evaluate the association between BMD and colorectal adenomas including high-risk adenoma.
Methods:
A multicenter, cross-sectional, case-control study was conducted among participants with average risk of colorectal cancer who underwent BMD and screening colonoscopy between 2015 and 2019. The main outcome was the detection of colorectal neoplasms. The variable under consideration was low BMD (osteopenia/osteoporosis). The logistic regression model included baseline demographics, components of metabolic syndrome, fatty liver disease status, and aspirin and multivitamin use.
Results:
A total of 2,109 subjects were enrolled. The mean age was 52.1±10.8 years and 42.6% were male. The adenoma detection rate was 43%. Colorectal adenoma and high-risk adenoma were both more prevalent in subjects with low BMD than those with normal BMD (48.2% vs 38.8% and 12.1% vs 9.1%). In the univariate analysis, old age, male sex, smoking, metabolic components, fatty liver, and osteoporosis were significantly associated with the risk of adenoma and high-risk adenoma. In the multivariate analysis, osteoporosis was independently associated with risk of colorectal adenoma (odds ratio [OR], 1.65; 95% confidence interval [CI], 1.11 to 2.46; p=0.014) and high-risk adenoma (OR, 1.94; 95% CI, 1.14 to 3.29; p=0.014).
Conclusions
Osteoporosis is an independent risk factor of colorectal adenoma and high-risk adenoma
10.Long-term Outcomes of Undifferentiated-Type Early Gastric Cancer with Positive Horizontal Margins after Endoscopic Resection
Hyo-Joon YANG ; Wan-Sik LEE ; Bong Eun LEE ; Ji Yong AHN ; Jae-Young JANG ; Joo Hyun LIM ; Su Youn NAM ; Jie-Hyun KIM ; Byung-Hoon MIN ; Moon Kyung JOO ; Jae Myung PARK ; Woon Geon SHIN ; Hang Lak LEE ; Tae-Geun GWEON ; Moo In PARK ; Jeongmin CHOI ; Chung Hyun TAE ; Young-Il KIM ; Il Ju CHOI
Gut and Liver 2021;15(5):723-731
Background/Aims:
This study examined the long-term outcomes of undifferentiated-type early gastric cancer (UD EGC) with positive horizontal margins (HMs) after endoscopic resection (ER) and compared them between additional surgery and nonsurgical management.
Methods:
From 2005 to 2015, a total of 1,124 patients with UD EGC underwent ER at 18 tertiary hospitals in Korea. Of them, 92 patients with positive HMs as the only noncurative factor (n=25) or with both positive HMs and tumor size >2 cm (n=67) were included. These patients underwent additional surgery (n=40), underwent additional endoscopic treatment (n=6), or were followed up without further treatment (n=46).
Results:
No lymph node (LN) metastasis was found in patients who underwent additional surgery. During a median follow-up of 57.7 months (interquartile range, 27.6 to 68.8 months), no LN or distant metastases or gastric cancer-related deaths occurred in the overall cohort. At baseline, the residual cancer rate was 57.8% (26/45) after additional surgery or ER. The 5-year local recurrence rate was 33.6% among patients who were followed up without additional treatment. The 5-year overall survival rates were 95.0% and 87.8% after additional surgery and nonsurgical management (endoscopic treatment or close follow-up), respectively (log-rank p=0.224). In the multivariate Cox regression analysis, nonsurgical management was not associated with an increased risk of mortality.
Conclusions
UD EGC with positive HMs after ER may have favorable long-term outcomes and a very low risk of LN metastasis. Nonsurgical management may be suggested as an alternative, particularly for patients with old age or chronic illness.

Result Analysis
Print
Save
E-mail