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.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.
3.Efficacy and Safety of Fexuprazan in Patients with Acute or Chronic Gastritis
Gwang Ha KIM ; Myung-Gyu CHOI ; Jin Il KIM ; Soo Teik LEE ; Hoon Jai CHUN ; Kook Lae LEE ; Suk Chei CHOI ; Jae-Young JANG ; Yong Chan LEE ; Jae Gyu KIM ; Ki Bae KIM ; Ki-Nam SHIM ; Chong Il SOHN ; Sung Kook KIM ; Sang Gyun KIM ; Jin Seok JANG ; Nayoung KIM ; Hwoon-Yong JUNG ; Hyojin PARK ; Kyu Chan HUH ; Kwang Jae LEE ; Su Jin HONG ; Song BAEK ; Jin Joo HAN ; Oh Young LEE
Gut and Liver 2023;17(6):884-893
Background/Aims:
Fexuprazan is a novel potassium-competitive acid blocker that could be of benefit to patients with gastric mucosal injury. The aim of this study was to assess the 2-week efficacy and safety of fexuprazan in patients with acute or chronic gastritis.
Methods:
In this study, 327 patients with acute or chronic gastritis who had one or more gastric erosions on endoscopy and subjective symptoms were randomized into three groups receiving fexuprazan 20 mg once a day (q.d.), fexuprazan 10 mg twice a day (b.i.d.), or placebo for 2 weeks. The posttreatment assessments were the primary endpoint (erosion improvement rate), secondary endpoints (cure rates of erosion and edema and improvement rates of redness, hemorrhage, and subjective symptoms), and drug-related adverse events.
Results:
Among the patients, 57.8% (59/102), 65.7% (67/102), and 40.6% (39/96) showed erosion improvement 2 weeks after receiving fexuprazan 20 mg q.d., fexuprazan 10 mg b.i.d., and placebo, respectively. Both fexuprazan 20 mg q.d. and 10 mg b.i.d. showed superior efficacy to the placebo (p=0.017 and p<0.001, respectively). Likewise, both fexuprazan 20 mg q.d. and 10 mg b.i.d. also showed higher erosion healing rates than the placebo (p=0.033 and p=0.010, respectively). No difference was noted in the edema healing rate and the improvement rates for redness, hemorrhage, and subjective symptoms between the fexuprazan and placebo groups.No significant difference was noted in the incidence of adverse drug reactions.
Conclusions
Fexuprazan 20 mg q.d. and 10 mg b.i.d. for 2 weeks showed therapeutic efficacy superior to that of placebo in patients with acute or chronic gastritis (ClinicalTrials.gov identifier NCT04341454).
4.Trends and Meta-Analysis of Research on the Operation of Programs for Bereaved Families in South Korea
Myung-Nam LEE ; Jung Won SUK ; Hyunsook Zin LEE
Korean Journal of Hospice and Palliative Care 2023;26(3):126-139
Purpose:
This study aimed to analyze interventions for bereaved families and evaluate their effectiveness, with the ultimate goal of supporting evidence-based nursing for bereaved families.
Methods:
Research trends were identified based on a search of domestic databases from January 2000 to December 2022, and a meta-analysis was conducted on interventions for bereaved families. Forty-five papers were selected, and information was extracted on participants, research design, and interventions. A meta-analysis of seven papers was performed, and the effect size was calculated.
Results:
Fourteen papers dealt with interventions for middle-aged women who had lost their spouses, 20 used qualitative research methods, and 20 were on art therapy programs. Thirty studies had fewer than 10 participants, and most interventions had 60~120 minutes per session and 9~16 sessions in total.There were seven randomized controlled trials, and all studies included in the quality evaluation showed a low risk of bias. Four papers measured grief as an outcome, and the effect size was -1.9577 (95% CI: -2.9206 to -0.9947), indicating that the treatment significantlydecreased grief (P<0.001). Six papers measured depression as an outcome, and the effectsize was -1.6775 (95% CI: -2.1835 to -1.1716), showing that the treatment significantly decreased depression (P<0.001).
Conclusion
Intervention programs for bereaved families were shown to be effective in relieving grief and depression. However, programs should be developed that target middle-aged men who have lost their spouses and children who have lost their parents. Randomized controlled trials should also be conducted on interventions to reduce grief and depression.
5.Safety and efficacy of nilotinib in adult patients with chronic myeloid leukemia: a post-marketing surveillance study in Korea
Seo-Yeon AHN ; Sang Kyun SON ; Gyu Hyung LEE ; Inho KIM ; June-Won CHEONG ; Won Sik LEE ; Byung Soo KIM ; Deog-Yeon JO ; Chul Won JUNG ; Chu Myoung SEONG ; Jae Hoon LEE ; Young Jin YUH ; Min Kyoung KIM ; Hun-Mo RYOO ; Moo-Rim PARK ; Su-Hee CHO ; Hoon-Gu KIM ; Dae Young ZANG ; Jinny PARK ; Hawk KIM ; Seryeon LEE ; Sung-Hyun KIM ; Myung Hee CHANG ; Ho Sup LEE ; Chul Won CHOI ; Jihyun KWON ; Sung-Nam LIM ; Suk-Joong OH ; Inkyung JOO ; Dong-Wook KIM
Blood Research 2022;57(2):144-151
Background:
Nilotinib is a tyrosine kinase inhibitor approved by the Ministry of Food and Drug Safety for frontline and 2nd line treatment of Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML). This study aimed to confirm the safety and efficacy of nilotinib in routine clinical practice within South Korea.
Methods:
An open-label, multicenter, single-arm, 12-week observational post-marketing surveillance (PMS) study was conducted on 669 Korean adult patients with Ph + CML from December 24, 2010, to December 23, 2016. The patients received nilotinib treatment in routine clinical practice settings. Safety was evaluated by all types of adverse events (AEs) during the study period, and efficacy was evaluated by the complete hematological response (CHR) and cytogenetic response.
Results:
During the study period, AEs occurred in 61.3% (410 patients, 973 events), adverse drug reactions (ADRs) in 40.5% (271/669 patients, 559 events), serious AEs in 4.5% (30 patients, 37 events), and serious ADRs in 0.7% (5 patients, 8 events). Furthermore, unexpected AEs occurred at a rate of 6.9% (46 patients, 55 events) and unexpected ADRs at 1.2% (8 patients, 8 events). As for the efficacy results, CHR was achieved in 89.5% (442/494 patients), and minor cytogenetic response or major cytogenetic response was achieved in 85.8% (139/162 patients).
Conclusion
This PMS study shows consistent results in terms of safety and efficacy compared with previous studies. Nilotinib was well tolerated and efficacious in adult Korean patients with Ph + CML in routine clinical practice settings.
6.Factors Associated with Clinical Outcomes of Palliative Stenting for Malignant Colonic Obstruction
Sang-Jae KWON ; Jiyoung YOON ; Eun Hye OH ; Jeongseok KIM ; Nam Seok HAM ; Sung Wook HWANG ; Sang Hyoung PARK ; Byong Duk YE ; Jeong-Sik BYEON ; Seung-Jae MYUNG ; Suk-Kyun YANG ; Dong-Hoon YANG
Gut and Liver 2021;15(4):579-587
Background/Aims:
Self-expandable metal stents (SEMSs) can be applied to relieve colorectal obstruction secondary to incurable primary colorectal cancer or extracolonic malignancy. We aimed to identify factors associated with clinical success and the reintervention-free survival (RFS) after palliative stenting.
Methods:
Cases of palliative SEMS placement between 2005 and 2019 were retrieved from the institutional database and reviewed retrospectively. Logistic regression and log-rank testing followed by Cox proportional hazard analyses were performed to investigate the predictors of the clinical success of palliative stenting and factors associated with RFS, respectively.
Results:
A total of 593 patients underwent palliative stenting for malignant colonic obstruction (MCO). The technical and clinical success rates were 92.9% and 83.5%, respectively. Peritoneal carcinomatosis was a predictor of clinical failure (odds ratio, 0.33; 95% confidence interval [CI], 0.17 to 0.65) in the multivariate analysis. Peritoneal carcinomatosis (hazard ratio [HR], 2.48; 95% CI, 1.69 to 3.64) and stent expansion >90% on day 1 (HR, 1.62; 95% CI, 1.05 to 2.50) were associated with a shorter RFS. Neither clinical success nor RFS was associated with extracolonic malignancy. Re-obstruction, stent migration, and perforation were responsible for most reinterventions after clinically successful palliative stenting.
Conclusions
In patients requiring palliative stenting for MCO, peritoneal carcinomatosis was associated with both clinical failure and short RFS. Stent expansion >90% on postprocedural day 1 was another predictor of a short RFS after clinically successful stenting. A large prospective study is warranted to establish factors associated with RFS after successful palliative stenting for MCO.
7.Factors Associated with Clinical Outcomes of Palliative Stenting for Malignant Colonic Obstruction
Sang-Jae KWON ; Jiyoung YOON ; Eun Hye OH ; Jeongseok KIM ; Nam Seok HAM ; Sung Wook HWANG ; Sang Hyoung PARK ; Byong Duk YE ; Jeong-Sik BYEON ; Seung-Jae MYUNG ; Suk-Kyun YANG ; Dong-Hoon YANG
Gut and Liver 2021;15(4):579-587
Background/Aims:
Self-expandable metal stents (SEMSs) can be applied to relieve colorectal obstruction secondary to incurable primary colorectal cancer or extracolonic malignancy. We aimed to identify factors associated with clinical success and the reintervention-free survival (RFS) after palliative stenting.
Methods:
Cases of palliative SEMS placement between 2005 and 2019 were retrieved from the institutional database and reviewed retrospectively. Logistic regression and log-rank testing followed by Cox proportional hazard analyses were performed to investigate the predictors of the clinical success of palliative stenting and factors associated with RFS, respectively.
Results:
A total of 593 patients underwent palliative stenting for malignant colonic obstruction (MCO). The technical and clinical success rates were 92.9% and 83.5%, respectively. Peritoneal carcinomatosis was a predictor of clinical failure (odds ratio, 0.33; 95% confidence interval [CI], 0.17 to 0.65) in the multivariate analysis. Peritoneal carcinomatosis (hazard ratio [HR], 2.48; 95% CI, 1.69 to 3.64) and stent expansion >90% on day 1 (HR, 1.62; 95% CI, 1.05 to 2.50) were associated with a shorter RFS. Neither clinical success nor RFS was associated with extracolonic malignancy. Re-obstruction, stent migration, and perforation were responsible for most reinterventions after clinically successful palliative stenting.
Conclusions
In patients requiring palliative stenting for MCO, peritoneal carcinomatosis was associated with both clinical failure and short RFS. Stent expansion >90% on postprocedural day 1 was another predictor of a short RFS after clinically successful stenting. A large prospective study is warranted to establish factors associated with RFS after successful palliative stenting for MCO.
8.C-reactive protein course after classical complication free total knee arthroplasty using navigation
Jun Ho NAM ; Myung Rae CHO ; Seo Ho LEE ; Suk-Kyoon SONG ; Won-Kee CHOI
The Journal of Korean Knee Society 2020;32(4):e56-
Purpose:
The purpose is to estimate the degree of normalization of C-reactive protein (CRP) at 2 weeks and 4 weeks after uncomplicated total knee arthroplasty (TKA) using computer navigation. We also wish to determine whether the degree of normalization of CRP at 2 and 4 weeks differs after TKA performed in one knee and after TKA performed sequentially in both knees. We also want to analyze the patient factors that may influence the normalization of CRP.
Methods:
We studied 400 knees who underwent primary computer-navigated TKA for treatment of advanced osteoarthritis: the TKAs were all performed by the same surgeon. We retrospectively analyzed CRP levels during the preoperative period, the early postoperative period (5–7 days), the 2-week postoperative period (12–14 days), and the 4-week postoperative period (25–30 days). We have assumed gender, age, body mass index (BMI), staged bilateral TKA, and preoperative CRP as the potential patient factors associated with CRP normalization.
Results:
In unilateral TKA, CRP was normalized in 94 cases (34.3%) and in 219 cases (81.4%) within 2 weeks and 4 weeks after surgery, respectively. In second-knee, staged bilateral TKA, CRP was normalized in 46 cases (35.1%) and in 104 cases (79.4%) within 2 weeks and 4 weeks after surgery, respectively. There were no statistical differences between unilateral TKA and second-knee, staged bilateral TKA during the 2-week postoperative and the 4-week postoperative period. Compared to women, men were 1.99 times less likely to have normalized CRP at 2 weeks after surgery (P = 0.02).
Conclusion
CRP was less likely to normalize during the 2-week postoperative period in men than it is in women, while there was no difference between men and women in the normalization of CRP during the 4-week postoperative period. There were no statistical differences in the course of CRP levels after unilateral TKA and staged bilateral TKA during the 2-week postoperative and the 4-week postoperative period.
9.Association between interstitial cells of Cajal and anti-vinculin antibody in human stomach
Ji Hyun KIM ; Seung Joo NAM ; Sung Chul PARK ; Sang Hoon LEE ; Tae Suk KIM ; Minjong LEE ; Jin Myung PARK ; Dae Hee CHOI ; Chang Don KANG ; Sung Joon LEE ; Young Joon RYU ; Kyungyul LEE ; So Young PARK
The Korean Journal of Physiology and Pharmacology 2020;24(2):185-191
Interstitial cells of Cajal (ICC) are known as the pacemaker cells of gastrointestinal tract, and it has been reported that acute gastroenteritis induces intestinal dysmotility through antibody to vinculin, a cytoskeletal protein in gut, resulting in small intestinal bacterial overgrowth, so that anti-vinculin antibody can be used as a biomarker for irritable bowel syndrome. This study aimed to determine correlation between serum anti-vinculin antibody and ICC density in human stomach. Gastric specimens from 45 patients with gastric cancer who received gastric surgery at Kangwon National University Hospital from 2013 to 2017 were used. ICC in inner circular muscle, and myenteric plexus were counted. Corresponding patient's blood samples were used to determine the amount of anti-vinculin antibody by enzyme-linked immunosorbent assay. Analysis was done to determine correlation between anti-vinculin antibody and ICC numbers. Patients with elevated anti-vinculin antibody titer (above median value) had significantly lower number of ICC in inner circular muscle (71.0 vs. 240.5, p = 0.047), and myenteric plexus (12.0 vs. 68.5, p < 0.01) compared to patients with lower anti-vinculin antibody titer. Level of serum anti-vinculin antibody correlated significantly with density of ICC in myenteric plexus (r = −0.379, p = 0.01; Spearman correlation). Increased level of circulating anti-vinculin antibody was significantly correlated with decreased density of ICC in myenteric plexus of human stomach.

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