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.Assessment of acute inhalation toxicity of citric acid and sodium hypochlorite in rats
Jinhee KIM ; Chul-Min PARK ; Su Hyun CHOI ; Mi Jin YANG ; Ju-Yeon LEE ; Byung-Suk JEON ; Hyun-Ok KU ; Min-Seok KIM
Journal of Veterinary Science 2023;24(2):e22-
Background:
Citric acid (CA) and sodium hypochlorite (NaOCl) have been used to disinfect animals to protect them against avian influenza and foot-and-mouth disease.
Objectives:
We performed a good laboratory practice (GLP)-compliant animal toxicity study to assess the acute toxic effects of CA and NaOCl aerosol exposure in Sprague-Dawley rats.
Methods:
Groups of five rats per sex were exposed for 4 h to four concentrations of the two chemicals, i.e., 0.00, 0.22, 0.67, and 2.00 mg/L, using a nose-only exposure. After a single exposure to the chemicals, clinical signs, body weight, and mortality was observed during the observation period. On day 15, an autopsy, and then gross findings, and histopathological analysis were performed.
Results:
After exposure to CA and NaOCl, body weight loss was observed but recovered.Two males died in the CA 2.00 mg/L group and, two males and one female died in the 2.00 mg/L NaOCl group. In the gross findings and histopathological analysis, discoloration of the lungs was observed in the CA exposed group and inflammatory lesions with discoloration of the lungs were observed in the NaOCl exposed group. These results suggest that the lethal concentration 50 (LC50) of CA is 1.73390 mg/L for males and > 1.70 mg/L for females. For NaOCl, the LC50 was 2.22222 mg/L for males and 2.39456 mg/L for females.
Conclusions
The Globally Harmonized System is category 4 for both CA and NaOCl. In this study, the LC50 results were obtained through a GLP-based acute inhalation toxicity assessment. These results provide useful data to reset safety standards for CA and NaOCl use.
6.The Efficiency of Radiation Shielding Sheet to Reduce Radiation Exposure during C-arm Fluoroscopy
Hosang JEON ; Won Chul SHIN ; Hee Yun SEOL ; Yongkan KI ; Kyeong Baek KIM ; Ki Seok CHOO ; Sang Don LEE ; Suk-Woong KANG
Journal of the Korean Fracture Society 2023;36(4):111-117
Purpose:
This study evaluates the radiation shielding performance of a new lead-free tungsten-based sheet to reduce the radiation exposure of operators and patients under C-arm fluoroscopy.
Materials and Methods:
A non-lead radiation shielding sheet (ROO201128; Pentas, Korea) was fabri-cated using tungsten and bismuth. The dose measurements were conducted using a C-arm fluoroscopy machine at 64 kVp and 1.5 mA, assuming two possible scenarios according to the position of the sheet. In each scenario, measurements were conducted at three distances (30, 60, and 90 cm) away from the beam center and in three directions (cephal, caudal, and operator’s direction).
Results:
In the area within a radius of 60 cm from the beam center, the measured doses were reduced by 66.3% on mean, and the doses measured at distances more than 60 cm were less than 0.1 mSv/h in both scenarios. The most beneficial utilization of the lead-free shielding sheet was verified during C-arm fluoroscopy by placing the sheet on the X-ray tube. The operator’s radiation exposure was reduced by 56.6% when the sheet was placed under the phantom, and by 81.0% when the sheet was placed on the X-ray tube.
Conclusion
The use of lead-free radiation shielding sheets under C-arm fluoroscopy was effective in reducing radiation exposure, and the most beneficial scenario in which the sheet can be utilized was verified when the sheet was placed on the X-ray tube.
7.Semiautomated Algorithm for the Diagnosis of Multiple System Atrophy With Predominant Parkinsonism
Woong-Woo LEE ; Han-Joon KIM ; Hong Ji LEE ; Han Byul KIM ; Kwang Suk PARK ; Chul-Ho SOHN ; Beomseok JEON
Journal of Movement Disorders 2022;15(3):232-240
Objective:
Putaminal iron deposition is an important feature that helps differentiate multiple system atrophy with predominant parkinsonism (MSA-p) from Parkinson’s disease (PD). Most previous studies used visual inspection or quantitative methods with manual manipulation to perform this differentiation. We investigated the value of a new semiautomated diagnostic algorithm using 3T-MR susceptibility-weighted imaging for MSA-p.
Methods:
This study included 26 MSA-p, 68 PD, and 41 normal control (NC) subjects. The algorithm was developed in 2 steps: 1) determine the image containing the remarkable putaminal margin and 2) calculate the phase-shift values, which reflect the iron concentration. The next step was to identify the best differentiating conditions among several combinations. The highest phaseshift value of each subject was used to assess the most effective diagnostic set.
Results:
The raw phase-shift values were present along the lateral margin of the putamen in each group. It demonstrates an anterior- to-posterior gradient that was identified most frequently in MSA-p. The average of anterior 5 phase shift values were used for normalization. The highest area under the receiver operating characteristic curve (0.874, 80.8% sensitivity, and 86.7% specificity) of MSA-p versus PD was obtained under the combination of 3 or 4 vertical pixels and one dominant side when the normalization methods were applied. In the subanalysis for the MSA-p patients with a longer disease duration, the performance of the algorithm improved.
Conclusion
This algorithm detected the putaminal lateral margin well, provided insight into the iron distribution of the putaminal rim of MSA-p, and demonstrated good performance in differentiating MSA-p from PD.
8.Machine-Learning-Based Approach to Differential Diagnosis in Tuberculous and Viral Meningitis
Young-Seob JEONG ; Minjun JEON ; Joung Ha PARK ; Min-Chul KIM ; Eunyoung LEE ; Se Yoon PARK ; Yu-Mi LEE ; Sungim CHOI ; Seong Yeon PARK ; Ki-Ho PARK ; Sung-Han KIM ; Min Huok JEON ; Eun Ju CHOO ; Tae Hyong KIM ; Mi Suk LEE ; Tark KIM
Infection and Chemotherapy 2021;53(1):53-62
Background:
Tuberculous meningitis (TBM) is the most severe form of tuberculosis, but differentiating between the diagnosis of TBM and viral meningitis (VM) is difficult. Thus, we have developed machine-learning modules for differentiating TBM from VM.Material and Methods: For the training data, confirmed or probable TBM and confirmed VM cases were retrospectively collected from five teaching hospitals in Korea between January 2000 - July 2018. Various machine-learning algorithms were used for training. The machinelearning algorithms were tested by the leave-one-out cross-validation. Four residents and two infectious disease specialists were tested using the summarized medical information.
Results:
The training study comprised data from 60 patients with confirmed or probable TBM and 143 patients with confirmed VM. Older age, longer symptom duration before the visit, lower serum sodium, lower cerebrospinal fluid (CSF) glucose, higher CSF protein, and CSF adenosine deaminase were found in the TBM patients. Among the various machinelearning algorithms, the area under the curve (AUC) of the receiver operating characteristics of artificial neural network (ANN) with ImperativeImputer for matrix completion (0.85; 95% confidence interval 0.79 - 0.89) was found to be the highest. The AUC of the ANN model was statistically higher than those of all the residents (range 0.67 - 0.72, P <0.001) and an infectious disease specialist (AUC 0.76; P = 0.03).
Conclusion
The machine-learning techniques may play a role in differentiating between TBM and VM. Specifically, the ANN model seems to have better diagnostic performance than the non-expert clinician.
9.Usefulness of Prostate-Specific Antigen Density as an Indicator for Recommending Prebiopsy Magnetic Resonance Imaging to Prevent Missed Prostate Cancer Diagnoses
Jin Hyung JEON ; Kyo Chul KOO ; Byung Ha CHUNG ; Kwang Suk LEE
Korean Journal of Urological Oncology 2021;19(3):155-163
Purpose:
To identify the indication for recommending prebiopsy magnetic resonance imaging (MRI) to prevent prostate cancer missed diagnoses in cases without prebiopsy MRI.
Materials and Methods:
Between January 2017 and September 2020, 585 patients suspected with prostate cancer underwent prostate biopsy after MRI. For patients with visible lesions, MRI-targeted biopsy using an image-based fusion program was performed in addition to the 12- core systematic biopsy. Patients for whom MRI was performed in other institutions (n=4) and patients who underwent target biopsy alone (n=7) were excluded.
Results:
Of 574 patients (median prostate-specific antigen [PSA] level, 6.88 ng/mL; mean age, 68.2 years), 342 (59.6%) were diagnosed with prostate cancer (visible lesions=312/449 [69.5%]; nonvisible lesions=30/123 [24.0%]). The detection rates of visible lesions stratified using the Prostate Imaging Reporting and Data System score (3 vs. 4 vs. 5) were 30.9% (54 of 175), 61.2% (150 of 245), and 90.1% (127 of 141), respectively. Multivariate analysis showed that PSA density was a significant factor for presence of visible lesions, prostate cancer, and significant prostate cancer diagnosis. Among patients with positive lesions, 27 (8.2%) were diagnosed with prostate cancer concomitant with negative systematic biopsy results. A PSA density of 0.15 ng/mL/cm3 was identified as the significant cutoff value for predicting positive target biopsy in groups with negative systematic biopsy. Sixty of the negative target lesions (26.1%) were diagnosed using systematic biopsy.
Conclusions
To maximize cancer detection rates, both targeted and systematic biopsies should be implemented. PSA density was identified as a useful factor for recommending prebiopsy MRI to patients suspected with prostate cancer.
10.Machine-Learning-Based Approach to Differential Diagnosis in Tuberculous and Viral Meningitis
Young-Seob JEONG ; Minjun JEON ; Joung Ha PARK ; Min-Chul KIM ; Eunyoung LEE ; Se Yoon PARK ; Yu-Mi LEE ; Sungim CHOI ; Seong Yeon PARK ; Ki-Ho PARK ; Sung-Han KIM ; Min Huok JEON ; Eun Ju CHOO ; Tae Hyong KIM ; Mi Suk LEE ; Tark KIM
Infection and Chemotherapy 2021;53(1):53-62
Background:
Tuberculous meningitis (TBM) is the most severe form of tuberculosis, but differentiating between the diagnosis of TBM and viral meningitis (VM) is difficult. Thus, we have developed machine-learning modules for differentiating TBM from VM.Material and Methods: For the training data, confirmed or probable TBM and confirmed VM cases were retrospectively collected from five teaching hospitals in Korea between January 2000 - July 2018. Various machine-learning algorithms were used for training. The machinelearning algorithms were tested by the leave-one-out cross-validation. Four residents and two infectious disease specialists were tested using the summarized medical information.
Results:
The training study comprised data from 60 patients with confirmed or probable TBM and 143 patients with confirmed VM. Older age, longer symptom duration before the visit, lower serum sodium, lower cerebrospinal fluid (CSF) glucose, higher CSF protein, and CSF adenosine deaminase were found in the TBM patients. Among the various machinelearning algorithms, the area under the curve (AUC) of the receiver operating characteristics of artificial neural network (ANN) with ImperativeImputer for matrix completion (0.85; 95% confidence interval 0.79 - 0.89) was found to be the highest. The AUC of the ANN model was statistically higher than those of all the residents (range 0.67 - 0.72, P <0.001) and an infectious disease specialist (AUC 0.76; P = 0.03).
Conclusion
The machine-learning techniques may play a role in differentiating between TBM and VM. Specifically, the ANN model seems to have better diagnostic performance than the non-expert clinician.

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