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.Colon cancer: the 2023 Korean clinical practice guidelines for diagnosis and treatment
Hyo Seon RYU ; Hyun Jung KIM ; Woong Bae JI ; Byung Chang KIM ; Ji Hun KIM ; Sung Kyung MOON ; Sung Il KANG ; Han Deok KWAK ; Eun Sun KIM ; Chang Hyun KIM ; Tae Hyung KIM ; Gyoung Tae NOH ; Byung-Soo PARK ; Hyeung-Min PARK ; Jeong Mo BAE ; Jung Hoon BAE ; Ni Eun SEO ; Chang Hoon SONG ; Mi Sun AHN ; Jae Seon EO ; Young Chul YOON ; Joon-Kee YOON ; Kyung Ha LEE ; Kyung Hee LEE ; Kil-Yong LEE ; Myung Su LEE ; Sung Hak LEE ; Jong Min LEE ; Ji Eun LEE ; Han Hee LEE ; Myong Hoon IHN ; Je-Ho JANG ; Sun Kyung JEON ; Kum Ju CHAE ; Jin-Ho CHOI ; Dae Hee PYO ; Gi Won HA ; Kyung Su HAN ; Young Ki HONG ; Chang Won HONG ; Jung-Myun KWAK ;
Annals of Coloproctology 2024;40(2):89-113
Colorectal cancer is the third most common cancer in Korea and the third leading cause of death from cancer. Treatment outcomes for colon cancer are steadily improving due to national health screening programs with advances in diagnostic methods, surgical techniques, and therapeutic agents.. The Korea Colon Cancer Multidisciplinary (KCCM) Committee intends to provide professionals who treat colon cancer with the most up-to-date, evidence-based practice guidelines to improve outcomes and help them make decisions that reflect their patients’ values and preferences. These guidelines have been established by consensus reached by the KCCM Guideline Committee based on a systematic literature review and evidence synthesis and by considering the national health insurance system in real clinical practice settings. Each recommendation is presented with a recommendation strength and level of evidence based on the consensus of the committee.
5.Protein Arginine Methyltransferases: Emerging Targets in Cardiovascular and Metabolic Disease
Yan ZHANG ; Shibo WEI ; Eun-Ju JIN ; Yunju JO ; Chang-Myung OH ; Gyu-Un BAE ; Jong-Sun KANG ; Dongryeol RYU
Diabetes & Metabolism Journal 2024;48(4):487-502
Cardiovascular diseases (CVDs) and metabolic disorders stand as formidable challenges that significantly impact the clinical outcomes and living quality for afflicted individuals. An intricate comprehension of the underlying mechanisms is paramount for the development of efficacious therapeutic strategies. Protein arginine methyltransferases (PRMTs), a class of enzymes responsible for the precise regulation of protein methylation, have ascended to pivotal roles and emerged as crucial regulators within the intrinsic pathophysiology of these diseases. Herein, we review recent advancements in research elucidating on the multifaceted involvements of PRMTs in cardiovascular system and metabolic diseases, contributing significantly to deepen our understanding of the pathogenesis and progression of these maladies. In addition, this review provides a comprehensive analysis to unveil the distinctive roles of PRMTs across diverse cell types implicated in cardiovascular and metabolic disorders, which holds great potential to reveal novel therapeutic interventions targeting PRMTs, thus presenting promising perspectives to effectively address the substantial global burden imposed by CVDs and metabolic disorders.
6.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.
7.Subtyping of Performance Trajectory During Medical School, Medical Internship, and the First Year of Residency in Training Physicians:A Longitudinal Cohort Study
Je-Yeon YUN ; Hyunjin RYU ; Ju Whi KIM ; Hyun Bae YOON ; Seung CHOI ; Wan Beom PARK ; Eun Jung BAE ; Jae-Joon YIM ; Sun Jung MYUNG
Journal of Korean Medical Science 2024;39(33):e239-
Background:
Developmental trajectories of clinical skills in training physicians vary among tasks and show interindividual differences. This study examined the predictors of medical internship performance and residency entrance and found subtypes of performance trajectory in training physicians.
Methods:
This retrospective cohort study involved 888 training physicians who completed a medical internship between 2015 and 2019. After the internship, 627 physicians applied for residency training between 2016 and 2020. Finally, 160 of them completed their first-year residency in internal medicine, surgery, pediatrics, and psychiatry departments between 2016 and 2020. Pearson’s correlation coefficients of internship performance and first year-residency performance (n = 160) were calculated. Latent profile analysis identified performance trajectory subtypes according to medical school grade point average (GPA), internship performance, English proficiency, and residency selection procedures. Multivariate logistic regression models of residency acceptance (n = 627) and performance in the top 30%/lower 10% in the first year of residency were also constructed.
Results:
Medical internship performance showed a significant positive correlation with the medical school GPA (r = 0.194) and the written score for the medical licensing examination (r = 0.125). Higher scores in the interview (adjusted odds ratio [aOR], 2.57) and written examination (aOR, 1.45) of residency selection procedures and higher medical internship performance (aOR, 1.19) were associated with a higher chance of residency acceptance. The latent profile analyses identified three training physician subgroups: average performance, consistently high performance (top 30%), and adaptation to changes (lowest 10%). Higher scores in the interview for residency selection (aOR, 1.35) and lower scores for medical internship performance (aOR, 0.79) were associated with a higher chance of performing in the top 30% or lowest 10% in the first year of residency, respectively.
Conclusion
Performance in the interview and medical internship predicted being among the top 30% and lowest 10% of performers in the first year of residency training, respectively.Individualized educational programs to enhance the prospect of trainees becoming highfunctioning physicians are needed.
8.Prevalence and Risk Factors of Germline Pathogenic Variants in Pancreatic Ductal Adenocarcinoma
Kum Hei RYU ; Sunhwa PARK ; Jung Won CHUN ; Eunhae CHO ; Jongmun CHOI ; Dong-Eun LEE ; Hyoeun SHIM ; Yun-Hee KIM ; Sung-Sik HAN ; Sang-Jae PARK ; Sang Myung WOO ; Sun-Young KONG
Cancer Research and Treatment 2023;55(4):1303-1312
Purpose:
The genetic attribution for pancreatic ductal adenocarcinoma (PDAC) has been reported as 5%-10%. However, the incidence of germline pathogenic variants (PVs) in Korean PDAC patients has not been thoroughly investigated. Therefore, we studied to identify the risk factors and prevalence of PV for future treatment strategies in PDAC.
Materials and Methods:
Total of 300 (155 male) patients with a median age of 65 years (range, 33 to 90 years) were enrolled in National Cancer Center in Korea. Cancer predisposition genes, clinicopathologic characteristics, and family history of cancer were analyzed.
Results:
PVs were detected in 20 patients (6.7%, median age 65) in ATM (n=7, 31.8%), BRCA1 (n=3, 13.6%), BRCA2 (n=3), and RAD51D (n=3). Each one patient showed TP53, PALB2, PMS2, RAD50, MSH3, and SPINK1 PV. Among them, two likely PVs were in ATM and RAD51D, respectively. Family history of various types of cancer including pancreatic cancer (n=4) were found in 12 patients. Three patients with ATM PVs and a patient with three germline PVs (BRCA2, MSH3, and RAD51D) had first-degree relatives with pancreatic cancer. Familial pancreatic cancer history and PVs detection had a significant association (4/20, 20% vs. 16/264, 5.7%; p=0.035).
Conclusion
Our study demonstrated that germline PVs in ATM, BRCA1, BRCA2, and RAD51D are most frequent in Korean PDAC patients and it is comparable to those of different ethnic groups. Although this study did not show guidelines for germline predisposition gene testing in patients with PDAC in Korea, it would be emphasized the need for germline testing for all PDAC patients.
9.Association between Decreased Estimated Glomerular Filtration Rates and Long-term Mortality in Korean Patients with Acute Myocardial Infarction
Mi Sook OH ; Seong Woo CHOI ; Myung Ho JEONG ; Eun Hui BAE ; Jong PARK ; So Yeon RYU ; Mi Ah HAN ; Min Ho SHIN
Chonnam Medical Journal 2023;59(1):87-97
A reduced estimated glomerular filtration rate (eGFR) is a predictor for mortality in patients with acute myocardial infarction (AMI). This study aimed to compare mortality according to the GFR and eGFR calculation methods during long-term clinical follow-ups. Using the Korean Acute Myocardial Infarction Registry-National Institutes of Health Data, 13,021 patients with AMI were included in this study. Patients were divided into the surviving (n=11,503, 88.3%) and deceased (n=1,518, 11.7%) groups.Clinical characteristics, cardiovascular risk factors, and 3-year mortality-related factors were analyzed. eGFR was calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and Modification of Diet in Renal Disease (MDRD) equations. The surviving group was younger than the deceased group (62.6±12.4 vs. 73.6±10.5 years, p<0.001), whereas the deceased group had higher hypertension and diabetes prevalences than the surviving group. A high Killip class was more frequently observed in the deceased group. eGFR was significantly lower in the deceased group (82.2±24.1 vs. 55.2±28.6 ml/min/1.73 m 2 , p<0.001). Multivariate analysis revealed that low eGFR was an independent risk factor for mortality during the 3-year follow-up. The CKD-EPI equation was more useful for predicting mortality than the MDRD equation (0.766; 95% confidence interval [CI], 0.753-0.779 vs. 0.738; 95% CI, 0.724-0.753; p=0.001). Decreased renal function was a significant predictor of mortality after 3 years in patients with AMI. The CKD-EPI equation was more useful for predicting mortality than the MDRD equation.
10.Volumetric Splenomegaly in Patients With Polycythemia Vera
Myung-Won LEE ; Sang-Hoon YEON ; Hyewon RYU ; Ik-Chan SONG ; Hyo-Jin LEE ; Hwan-Jung YUN ; Seon Young KIM ; Jeong Eun LEE ; Kyung Sook SHIN ; Deog-Yeon JO
Journal of Korean Medical Science 2022;37(11):e87-
Background:
Non-palpable splenomegaly in patients with polycythemia vera (PV) has seldom been addressed. In this retrospective study, we evaluated non-palpable, volumetric splenomegaly defined based on age- and body surface area (BSA)–matched criteria in patients with PV diagnosed according to the 2016 World Health Organization diagnostic criteria.
Methods:
Patients with PV who underwent abdominal computed tomography (CT) and who had palpable splenomegaly at diagnosis from January 1991 to December 2020 at Chungnam National University Hospital were enrolled. The spleen volume of each patient was determined by volumetric analysis of abdominal CT and adjusted for the patient’s age and BSA. Then the degree of splenomegaly was classified as no splenomegaly, borderline volumetric splenomegaly, overt volumetric splenomegaly, or palpable splenomegaly.
Results:
Of the 87 PV patients enrolled, 15 (17.2%) had no splenomegaly, whereas 17 (19.5%), 45 (51.7%), and 10 (11.5%) had borderline volumetric, overt volumetric, and palpable splenomegaly, respectively. The degree of splenomegaly did not affect the cumulative incidence of thrombotic vascular events (10-year incidence: 7.7%, 0%, 22.3%, and 50.7%, respectively, P = 0.414). By contrast, splenomegaly tended to adversely affect myelofibrotic transformation (10-year cumulative incidence: 0%, 0%, 7.1%, and 30.3%, respectively, P = 0.062). Moreover, the cumulative incidence of myelofibrotic transformation was significantly higher in patients with overt volumetric or palpable splenomegaly than those with no or borderline volumetric splenomegaly (10-year incidence: 0% vs. 10.3%, respectively; 15-year incidence: 0% vs. 26.3%, respectively, P = 0.020). Overall survival (OS) differed among patients with different degrees of splenomegaly (15-year OS: 100%, 78.6%, 71.7%, and 51.9%, respectively, P = 0.021).
Conclusion
The degree of splenomegaly, including volumetric splenomegaly, based on ageand BSA-matched reference spleen volumes at diagnosis reflects disease progression in PV patients. Therefore, volumetric splenomegaly should be evaluated at the time of diagnosis and taken into consideration when predicting the prognosis of patients with PV.

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