1.Post‑transplant cyclophosphamide plus anti‑thymocyte globulin decreased serum IL‑6 levels when compared with post‑transplant cyclophosphamide alone after haploidentical hematopoietic stem cell transplantation
Jeong Suk KOH ; Myung‑Won LEE ; Thi Thuy Duong PHAM ; Bu Yeon HEO ; Suyoung CHOI ; Sang‑Woo LEE ; Wonhyoung SEO ; Sora KANG ; Seul Bi LEE ; Chul Hee KIM ; Hyewon RYU ; Hyuk Soo EUN ; Hyo‑Jin LEE ; Hwan‑Jung YUN ; Deog‑Yeon JO ; Ik‑Chan SONG
Blood Research 2025;60():5-
Background:
Post-transplantation cyclophosphamide (PTCy) and anti-thymocyte globulin (ATG) are common pro‑ phylactic strategies for graft-versus-host disease (GVHD) after haploidentical hematopoietic stem cell transplantation (haplo-HSCT). Interleukin (IL)-6 is a surrogate marker for cytokine release syndrome (CRS) and acute GVHD.Method The clinical outcomes and complications of haplo-HSCT with PTCy plus ATG versus PTCy monotherapy were compared according to serum IL-6 levels at Chungnam National University Hospital (Daejeon, South Korea) from Jan‑ uary 2019 to February 2023.
Results:
Forty patients who underwent haplo-HSCT were analyzed. A significant difference in IL-6 levels was observed between the PTCy plus ATG and PTCy alone groups (7.47 ± 10.55 vs. 117.65 ± 127.67; p = 0.003). More patients in the PTCy plus ATG group had a CRS grade of 0 than in the PTCy alone group (p < 0.001). Serum IL-6 levels were associated with grades II–IV acute GVHD (r = 0.547, p < 0.001). The cumulative incidence (CI) of grades II–IV acute GVHD was significantly higher in the PTCy alone group (67.9% vs. 4.8%; p < 0.001). No significant difference in the CI for chronic GVHD was detected between the PTCy plus ATG and PTCy alone groups (72.1% vs. 82.0%; p = 0.730). The CI of 1-year non-relapse mortality was significantly higher in the PTCy alone group than in the PTCy plus ATG group (42.2% vs. 15.9%; p = 0.022). The 1-year overall survival (OS) was significantly better in the PTCy plus ATG group (75.9% vs. 35.3%; p = 0.011). The 1-year GVHD-free, relapse-free survival rate was 29.4% in the PTCy alone group and 54.0% in the PTCy plus ATG group (p = 0.038).
Conclusion
Serum IL-6 levels were higher in the PTCy alone group than in the PTCy plus ATG group. The addition of ATG before stem cell infusion affected IL-6 levels and reduced the incidences of CRS and grade II–IV acute GVHD in haplo-HSCT patients. This study suggests that PTCy plus ATG as GVHD prophylaxis in haplo-HSCT is beneficial in terms of clinical outcomes and complications of HSCT.
2.Post‑transplant cyclophosphamide plus anti‑thymocyte globulin decreased serum IL‑6 levels when compared with post‑transplant cyclophosphamide alone after haploidentical hematopoietic stem cell transplantation
Jeong Suk KOH ; Myung‑Won LEE ; Thi Thuy Duong PHAM ; Bu Yeon HEO ; Suyoung CHOI ; Sang‑Woo LEE ; Wonhyoung SEO ; Sora KANG ; Seul Bi LEE ; Chul Hee KIM ; Hyewon RYU ; Hyuk Soo EUN ; Hyo‑Jin LEE ; Hwan‑Jung YUN ; Deog‑Yeon JO ; Ik‑Chan SONG
Blood Research 2025;60():5-
Background:
Post-transplantation cyclophosphamide (PTCy) and anti-thymocyte globulin (ATG) are common pro‑ phylactic strategies for graft-versus-host disease (GVHD) after haploidentical hematopoietic stem cell transplantation (haplo-HSCT). Interleukin (IL)-6 is a surrogate marker for cytokine release syndrome (CRS) and acute GVHD.Method The clinical outcomes and complications of haplo-HSCT with PTCy plus ATG versus PTCy monotherapy were compared according to serum IL-6 levels at Chungnam National University Hospital (Daejeon, South Korea) from Jan‑ uary 2019 to February 2023.
Results:
Forty patients who underwent haplo-HSCT were analyzed. A significant difference in IL-6 levels was observed between the PTCy plus ATG and PTCy alone groups (7.47 ± 10.55 vs. 117.65 ± 127.67; p = 0.003). More patients in the PTCy plus ATG group had a CRS grade of 0 than in the PTCy alone group (p < 0.001). Serum IL-6 levels were associated with grades II–IV acute GVHD (r = 0.547, p < 0.001). The cumulative incidence (CI) of grades II–IV acute GVHD was significantly higher in the PTCy alone group (67.9% vs. 4.8%; p < 0.001). No significant difference in the CI for chronic GVHD was detected between the PTCy plus ATG and PTCy alone groups (72.1% vs. 82.0%; p = 0.730). The CI of 1-year non-relapse mortality was significantly higher in the PTCy alone group than in the PTCy plus ATG group (42.2% vs. 15.9%; p = 0.022). The 1-year overall survival (OS) was significantly better in the PTCy plus ATG group (75.9% vs. 35.3%; p = 0.011). The 1-year GVHD-free, relapse-free survival rate was 29.4% in the PTCy alone group and 54.0% in the PTCy plus ATG group (p = 0.038).
Conclusion
Serum IL-6 levels were higher in the PTCy alone group than in the PTCy plus ATG group. The addition of ATG before stem cell infusion affected IL-6 levels and reduced the incidences of CRS and grade II–IV acute GVHD in haplo-HSCT patients. This study suggests that PTCy plus ATG as GVHD prophylaxis in haplo-HSCT is beneficial in terms of clinical outcomes and complications of HSCT.
3.Post‑transplant cyclophosphamide plus anti‑thymocyte globulin decreased serum IL‑6 levels when compared with post‑transplant cyclophosphamide alone after haploidentical hematopoietic stem cell transplantation
Jeong Suk KOH ; Myung‑Won LEE ; Thi Thuy Duong PHAM ; Bu Yeon HEO ; Suyoung CHOI ; Sang‑Woo LEE ; Wonhyoung SEO ; Sora KANG ; Seul Bi LEE ; Chul Hee KIM ; Hyewon RYU ; Hyuk Soo EUN ; Hyo‑Jin LEE ; Hwan‑Jung YUN ; Deog‑Yeon JO ; Ik‑Chan SONG
Blood Research 2025;60():5-
Background:
Post-transplantation cyclophosphamide (PTCy) and anti-thymocyte globulin (ATG) are common pro‑ phylactic strategies for graft-versus-host disease (GVHD) after haploidentical hematopoietic stem cell transplantation (haplo-HSCT). Interleukin (IL)-6 is a surrogate marker for cytokine release syndrome (CRS) and acute GVHD.Method The clinical outcomes and complications of haplo-HSCT with PTCy plus ATG versus PTCy monotherapy were compared according to serum IL-6 levels at Chungnam National University Hospital (Daejeon, South Korea) from Jan‑ uary 2019 to February 2023.
Results:
Forty patients who underwent haplo-HSCT were analyzed. A significant difference in IL-6 levels was observed between the PTCy plus ATG and PTCy alone groups (7.47 ± 10.55 vs. 117.65 ± 127.67; p = 0.003). More patients in the PTCy plus ATG group had a CRS grade of 0 than in the PTCy alone group (p < 0.001). Serum IL-6 levels were associated with grades II–IV acute GVHD (r = 0.547, p < 0.001). The cumulative incidence (CI) of grades II–IV acute GVHD was significantly higher in the PTCy alone group (67.9% vs. 4.8%; p < 0.001). No significant difference in the CI for chronic GVHD was detected between the PTCy plus ATG and PTCy alone groups (72.1% vs. 82.0%; p = 0.730). The CI of 1-year non-relapse mortality was significantly higher in the PTCy alone group than in the PTCy plus ATG group (42.2% vs. 15.9%; p = 0.022). The 1-year overall survival (OS) was significantly better in the PTCy plus ATG group (75.9% vs. 35.3%; p = 0.011). The 1-year GVHD-free, relapse-free survival rate was 29.4% in the PTCy alone group and 54.0% in the PTCy plus ATG group (p = 0.038).
Conclusion
Serum IL-6 levels were higher in the PTCy alone group than in the PTCy plus ATG group. The addition of ATG before stem cell infusion affected IL-6 levels and reduced the incidences of CRS and grade II–IV acute GVHD in haplo-HSCT patients. This study suggests that PTCy plus ATG as GVHD prophylaxis in haplo-HSCT is beneficial in terms of clinical outcomes and complications of HSCT.
4.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.
5.Characteristics of Hyaluronic Acid and Its Use in Ocular Surface Diseases Including Dry Eye
Jinu KIM ; Jae Woong KOH ; Hyuk Jin CHOI ; Yong-Soo BYUN ; Ji Won JUNG ; Sang-Mok LEE
Journal of the Korean Ophthalmological Society 2023;64(2):170-183
Hyaluronic acid (HA) is a polysaccharide found in the extracellular matrix of the epithelial, nervous, and connective tissues of vertebrates. It is widely used in the treatment of ocular surface diseases (OSDs), including dry eye, due to its high water-retaining capacity, viscoelasticity, and role as a signaling molecule in inflammation and wound healing. This paper reviews the physicochemical and biological properties of HA related to the treatment of OSDs and the results of published preclinical studies, clinical trials, and meta-analyses on the effects of HA eye drops on the tear film, the mechanism of action of HA eye drops, and its clinical effects and adverse events in OSDs, such as corneal/conjunctival epithelial defects, dry eye, and postoperative dry eye. This review should help inform clinical judgments by providing clinical evidence and precautions on the use of HA eye drops in OSDs, including dry eye.
6.Current Status of Low-Density Lipoprotein Cholesterol Target Achievement in Patients with Type 2 Diabetes Mellitus in Korea Compared with Recent Guidelines
Soo Jin YUN ; In-Kyung JEONG ; Jin-Hye CHA ; Juneyoung LEE ; Ho Chan CHO ; Sung Hee CHOI ; SungWan CHUN ; Hyun Jeong JEON ; Ho-Cheol KANG ; Sang Soo KIM ; Seung-Hyun KO ; Gwanpyo KOH ; Su Kyoung KWON ; Jae Hyuk LEE ; Min Kyong MOON ; Junghyun NOH ; Cheol-Young PARK ; Sungrae KIM
Diabetes & Metabolism Journal 2022;46(3):464-475
Background:
We evaluated the achievement of low-density lipoprotein cholesterol (LDL-C) targets in patients with type 2 diabetes mellitus (T2DM) according to up-to-date Korean Diabetes Association (KDA), European Society of Cardiology (ESC)/European Atherosclerosis Society (EAS), and American Diabetes Association (ADA) guidelines.
Methods:
This retrospective cohort study collected electronic medical record data from patients with T2DM (≥20 years) managed by endocrinologists from 15 hospitals in Korea (January to December 2019). Patients were categorized according to guidelines to assess LDL-C target achievement. KDA (2019): Very High-I (atherosclerotic cardiovascular disease [ASCVD]) <70 mg/dL; Very High-II (target organ damage [TOD], or cardiovascular risk factors [CVRFs]) <70 mg/dL; high (others) <100 mg/dL. ESC/EAS (2019): Very High-I (ASCVD): <55 mg/dL; Very High-II (TOD or ≥3-CVRF) <55 mg/dL; high (diabetes ≥10 years without TOD plus any CVRF) <70 mg/dL; moderate (diabetes <10 years without CVRF) <100 mg/dL. ADA (2019): Very High-I (ASCVD); Very High-II (age ≥40+ TOD, or any CVRF), for high intensity statin or statin combined with ezetimibe.
Results:
Among 2,000 T2DM patients (mean age 62.6 years; male 55.9%; mean glycosylated hemoglobin 7.2%) ASCVD prevalence was 24.7%. Of 1,455 (72.8%) patients treated with statins, 73.9% received monotherapy. According to KDA guidelines, LDL-C target achievement rates were 55.2% in Very High-I and 34.9% in Very High-II patients. With ESC/EAS guidelines, target attainment rates were 26.6% in Very High-I, 15.7% in Very High-II, and 25.9% in high risk patients. Based on ADA guidelines, most patients (78.9%) were very-high risk; however, only 15.5% received high-intensity statin or combination therapy.
Conclusion
According to current dyslipidemia management guidelines, LDL-C goal achievement remains suboptimal in Korean patients with T2DM.
7.Long-term Clinical Outcomes and Prognostic Factors After Endovascular Treatment in Patients With Chronic Limb Threatening Ischemia
Jung-Joon CHA ; Jong-Youn KIM ; Hyoeun KIM ; Young-Guk KO ; Donghoon CHOI ; Jae-Hwan LEE ; Chang-Hwan YOON ; In-Ho CHAE ; Cheol Woong YU ; Seung Whan LEE ; Sang-Rok LEE ; Seung Hyuk CHOI ; Yoon Seok KOH ; Pil-Ki MIN ;
Korean Circulation Journal 2022;52(6):429-440
Background and Objectives:
Endovascular therapy (EVT) first strategy has been widely adopted for the treatment of chronic limb threatening ischemia (CLTI) patients in realworld practice. This study aimed to investigate long-term outcomes of CLTI patients who underwent EVT and identify prognostic factors.
Methods:
From the retrospective cohorts of a Korean multicenter endovascular therapy registry, 1,036 patients with CLTI (792 men, 68.8 ± 9.5 years) were included. The primary endpoint was amputation-free survival (AFS) defined as the absence of major amputation or death. Secondary endpoints were major adverse limb events (MALE; a composite of major amputation, minor amputation, and reintervention).
Results:
Five-year AFS and freedom from MALE were 69.8% and 61%, respectively. After multivariate analysis, age (hazard ratio [HR], 1.476; p<0.001), end-stage renal disease (ESRD; HR, 2.340; p<0.001), Rutherford category (RC) 6 (HR, 1.456; p=0.036), and suboptimal EVT (HR, 1.798; p=0.005) were identified as predictors of major amputation or death, whereas smoking (HR, 0.594; p=0.007) was protective. Low body mass index (HR, 1.505; p=0.046), ESRD (HR, 1.648; p=0.001), femoropopliteal lesion (HR, 1.877; p=0.004), RC-6 (HR, 1.471;p=0.008), and suboptimal EVT (HR, 1.847; p=0.001) were predictors of MALE. The highest hazard rates were observed during the first 6 months for both major amputation or death and MALE. After that, the hazard rate decreased and rose again after 3–4 years.
Conclusions
In CLTI patients, long-term outcomes of EVT were acceptable. ESRD, RC-6, and suboptimal EVT were common predictors for poor clinical outcomes.
8.Weight change and microvascular outcomes in patients with new-onset diabetes: a nationwide cohort study
Eun Sil KOH ; Kyung Do HAN ; Mee Kyoung KIM ; Eun Sook KIM ; Min-Kyung LEE ; Ga Eun NAM ; Hyuk-Sang KWON
The Korean Journal of Internal Medicine 2021;36(4):932-941
Background/Aims:
Because weight control is important in treatment of type 2 diabetes, it is essential to understand the associations between weight change and the risk of microvascular complications among patients with type 2 diabetes. We examined whether weight changes early after new-onset diabetes have an impact on the clinical outcomes of diabetic nephropathy and retinopathy.
Methods:
Using the Korean National Health Insurance Service-National Health Screening Cohort database, 181,872 patients newly diagnosed with type 2 diabetes who were free of end-stage renal disease (ESRD) and proliferative diabetic retinopathy (PDR) during 2007 to 2012 were followed to the end of 2016. Weight change was defined as the difference in body weight from the time of diabetes diagnosis to 2 years later.
Results:
We identified 180 cases of ESRD and 780 cases of PDR followed up for a median of 5.5 years from the index year at 2 years after diagnosis. Those with 5% to 10% weight gain showed a significantly higher hazard ratio (HR) for ESRD, compared with those with ≤ 5% weight change after adjusting for several confounding factors, including the baseline estimated glomerular filtration rate (HR, 1.75; 95% confidence interval [CI], 1.14 to 2.70). Those with ≥ 10% weight loss showed the lowest HR for PDR (HR, 0.52; 95% CI, 0.33 to 0.83), whereas those with ≥ 10% weight gain showed the highest HR for PDR (HR, 3.20; 95% CI, 2.51 to 4.08).
Conclusions
Weight gain after new-onset diabetes was associated with increased risk of ESRD and PDR whereas weight loss with decreased risk of PDR, but not ESRD.
9.Weight change and microvascular outcomes in patients with new-onset diabetes: a nationwide cohort study
Eun Sil KOH ; Kyung Do HAN ; Mee Kyoung KIM ; Eun Sook KIM ; Min-Kyung LEE ; Ga Eun NAM ; Hyuk-Sang KWON
The Korean Journal of Internal Medicine 2021;36(4):932-941
Background/Aims:
Because weight control is important in treatment of type 2 diabetes, it is essential to understand the associations between weight change and the risk of microvascular complications among patients with type 2 diabetes. We examined whether weight changes early after new-onset diabetes have an impact on the clinical outcomes of diabetic nephropathy and retinopathy.
Methods:
Using the Korean National Health Insurance Service-National Health Screening Cohort database, 181,872 patients newly diagnosed with type 2 diabetes who were free of end-stage renal disease (ESRD) and proliferative diabetic retinopathy (PDR) during 2007 to 2012 were followed to the end of 2016. Weight change was defined as the difference in body weight from the time of diabetes diagnosis to 2 years later.
Results:
We identified 180 cases of ESRD and 780 cases of PDR followed up for a median of 5.5 years from the index year at 2 years after diagnosis. Those with 5% to 10% weight gain showed a significantly higher hazard ratio (HR) for ESRD, compared with those with ≤ 5% weight change after adjusting for several confounding factors, including the baseline estimated glomerular filtration rate (HR, 1.75; 95% confidence interval [CI], 1.14 to 2.70). Those with ≥ 10% weight loss showed the lowest HR for PDR (HR, 0.52; 95% CI, 0.33 to 0.83), whereas those with ≥ 10% weight gain showed the highest HR for PDR (HR, 3.20; 95% CI, 2.51 to 4.08).
Conclusions
Weight gain after new-onset diabetes was associated with increased risk of ESRD and PDR whereas weight loss with decreased risk of PDR, but not ESRD.
10.Differential efficacy between stenting and plain balloon angioplasty for femoropopliteal disease with or without total occlusion
In-Ho CHAE ; Chang-Hwan YOON ; Young-Guk KO ; Pil-Ki MIN ; Jae-Hwan LEE ; Cheol Woong YU ; Seung Whan LEE ; Sang-Rok LEE ; Seung Hyuk CHOI ; Yoon Seok KOH ; Donghoon CHOI
The Korean Journal of Internal Medicine 2020;35(5):1114-1124
Background/Aims:
Whether the presence of chronic total occlusion (CTO) affects patency after stenting in femoropopliteal lesions is unknown. We determined the effects of plain balloon angioplasty (POBA) in comparison with those of stenting on patency for femoropopliteal CTO and stenosis (non-CTO).
Methods:
We analyzed data from the Korean Vascular Intervention Society Endovascular Therapy in Lower-Limb Artery Diseases Registry, a multicenter cohort of patients with lower extremity peripheral arterial disease. Data from 1,329 patients and 1558 limbs treated with endovascular intervention for at least one femoropopliteal lesion were evaluated.
Results:
Among the 1,558 limbs, 345, 432, 275, and 506 were in the non-CTO-POBA,non-CTO-stent, CTO-POBA, and CTO-stent groups, respectively. During follow-up, loss of clinical primary patency, a composite of freedom from restenosis or clinically driven target lesion revascularization, occurred in 65 (18.8%), 68 (15.7%), 62 (22.5%), and 113 limbs (22.3%) in the non-CTO-POBA, non-CTO-stent, CTO-POBA, and CTO-stent groups, respectively. The patients in the non-CTOstent group showed a significantly better clinical primary patency than those in the no-CTO-POBA group, whereas those in the CTO-stent and CTO-POBAgroups showed no significant differences. After inverse probability of treatment weighting to balance the differences among covariates between the non-CTOstent and non-CTO-POBA groups, the non-CTO-stent group still showed superior clinical primary patency as compared with the non-CTO-POBA group.
Conclusions
In the patients with femoropopliteal stenosis without CTO, stenting resulted in better clinical outcomes than balloon angioplasty. The presence of CTO in the femoropopliteal lesion should be considered when selecting a suitable device for performing endovascular procedures.

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