1.Exploring methylation signatures for high de novo recurrence risk in hepatocellular carcinoma
Da-Won KIM ; Jin Hyun PARK ; Suk Kyun HONG ; Min-Hyeok JUNG ; Ji-One PYEON ; Jin-Young LEE ; Kyung-Suk SUH ; Nam-Joon YI ; YoungRok CHOI ; Kwang-Woong LEE ; Young-Joon KIM
Clinical and Molecular Hepatology 2025;31(2):563-576
Background/Aims:
Hepatocellular carcinoma (HCC) exhibits high de novo recurrence rates post-resection. Current post-surgery recurrence prediction methods are limited, emphasizing the need for reliable biomarkers to assess recurrence risk. We aimed to develop methylation-based markers for classifying HCC patients and predicting their risk of de novo recurrence post-surgery.
Methods:
In this retrospective cohort study, we analyzed data from HCC patients who underwent surgical resection in Korea, excluding those with recurrence within one year post-surgery. Using the Infinium Methylation EPIC array on 140 samples in the discovery cohort, we classified patients into low- and high-risk groups based on methylation profiles. Distinctive markers were identified through random forest analysis. These markers were validated in the cancer genome atlas (n=217), Validation cohort 1 (n=63) and experimental Validation using a methylation-sensitive high-resolution melting (MS-HRM) assay in Validation cohort 1 and Validation cohort 2 (n=63).
Results:
The low-risk recurrence group (methylation group 1; MG1) showed a methylation average of 0.73 (95% confidence interval [CI] 0.69–0.77) with a 23.5% recurrence rate, while the high-risk group (MG2) had an average of 0.17 (95% CI 0.14–0.20) with a 44.1% recurrence rate (P<0.03). Validation confirmed the applicability of methylation markers across diverse populations, showing high accuracy in predicting the probability of HCC recurrence risk (area under the curve 96.8%). The MS-HRM assay confirmed its effectiveness in predicting de novo recurrence with 95.5% sensitivity, 89.7% specificity, and 92.2% accuracy.
Conclusions
Methylation markers effectively classified HCC patients by de novo recurrence risk, enhancing prediction accuracy and potentially offering personalized management strategies.
2.Exploring methylation signatures for high de novo recurrence risk in hepatocellular carcinoma
Da-Won KIM ; Jin Hyun PARK ; Suk Kyun HONG ; Min-Hyeok JUNG ; Ji-One PYEON ; Jin-Young LEE ; Kyung-Suk SUH ; Nam-Joon YI ; YoungRok CHOI ; Kwang-Woong LEE ; Young-Joon KIM
Clinical and Molecular Hepatology 2025;31(2):563-576
Background/Aims:
Hepatocellular carcinoma (HCC) exhibits high de novo recurrence rates post-resection. Current post-surgery recurrence prediction methods are limited, emphasizing the need for reliable biomarkers to assess recurrence risk. We aimed to develop methylation-based markers for classifying HCC patients and predicting their risk of de novo recurrence post-surgery.
Methods:
In this retrospective cohort study, we analyzed data from HCC patients who underwent surgical resection in Korea, excluding those with recurrence within one year post-surgery. Using the Infinium Methylation EPIC array on 140 samples in the discovery cohort, we classified patients into low- and high-risk groups based on methylation profiles. Distinctive markers were identified through random forest analysis. These markers were validated in the cancer genome atlas (n=217), Validation cohort 1 (n=63) and experimental Validation using a methylation-sensitive high-resolution melting (MS-HRM) assay in Validation cohort 1 and Validation cohort 2 (n=63).
Results:
The low-risk recurrence group (methylation group 1; MG1) showed a methylation average of 0.73 (95% confidence interval [CI] 0.69–0.77) with a 23.5% recurrence rate, while the high-risk group (MG2) had an average of 0.17 (95% CI 0.14–0.20) with a 44.1% recurrence rate (P<0.03). Validation confirmed the applicability of methylation markers across diverse populations, showing high accuracy in predicting the probability of HCC recurrence risk (area under the curve 96.8%). The MS-HRM assay confirmed its effectiveness in predicting de novo recurrence with 95.5% sensitivity, 89.7% specificity, and 92.2% accuracy.
Conclusions
Methylation markers effectively classified HCC patients by de novo recurrence risk, enhancing prediction accuracy and potentially offering personalized management strategies.
3.Exploring methylation signatures for high de novo recurrence risk in hepatocellular carcinoma
Da-Won KIM ; Jin Hyun PARK ; Suk Kyun HONG ; Min-Hyeok JUNG ; Ji-One PYEON ; Jin-Young LEE ; Kyung-Suk SUH ; Nam-Joon YI ; YoungRok CHOI ; Kwang-Woong LEE ; Young-Joon KIM
Clinical and Molecular Hepatology 2025;31(2):563-576
Background/Aims:
Hepatocellular carcinoma (HCC) exhibits high de novo recurrence rates post-resection. Current post-surgery recurrence prediction methods are limited, emphasizing the need for reliable biomarkers to assess recurrence risk. We aimed to develop methylation-based markers for classifying HCC patients and predicting their risk of de novo recurrence post-surgery.
Methods:
In this retrospective cohort study, we analyzed data from HCC patients who underwent surgical resection in Korea, excluding those with recurrence within one year post-surgery. Using the Infinium Methylation EPIC array on 140 samples in the discovery cohort, we classified patients into low- and high-risk groups based on methylation profiles. Distinctive markers were identified through random forest analysis. These markers were validated in the cancer genome atlas (n=217), Validation cohort 1 (n=63) and experimental Validation using a methylation-sensitive high-resolution melting (MS-HRM) assay in Validation cohort 1 and Validation cohort 2 (n=63).
Results:
The low-risk recurrence group (methylation group 1; MG1) showed a methylation average of 0.73 (95% confidence interval [CI] 0.69–0.77) with a 23.5% recurrence rate, while the high-risk group (MG2) had an average of 0.17 (95% CI 0.14–0.20) with a 44.1% recurrence rate (P<0.03). Validation confirmed the applicability of methylation markers across diverse populations, showing high accuracy in predicting the probability of HCC recurrence risk (area under the curve 96.8%). The MS-HRM assay confirmed its effectiveness in predicting de novo recurrence with 95.5% sensitivity, 89.7% specificity, and 92.2% accuracy.
Conclusions
Methylation markers effectively classified HCC patients by de novo recurrence risk, enhancing prediction accuracy and potentially offering personalized management strategies.
4.Clinical Patterns and Risk Factors of Occupational Contact Dermatitis in Hairdressers: A Questionnaire-based Cross-sectional Study
Jin Ju LEE ; Da Yeon KIM ; Heera LEE ; Ji Yeon BYUN ; You Won CHOI ; Joo Young ROH ; Hae Young CHOI
Annals of Dermatology 2025;37(3):162-168
Background:
Occupational contact dermatitis (OCD) is prevalent among hairdressers due to frequent exposure to chemicals like hair dyes and bleaching agents. Despite the risks, awareness among hairdressers remains low, leading to underreporting and inadequate preventive measures.
Objective:
This study evaluated hairdressers’ awareness of harmful hair dye ingredients, their experiences with OCD, and the association with product usage patterns.
Methods:
A cross-sectional study involving 100 hairdressers in Korea examined the relationship between work experience, product usage, and OCD. Chi-square tests and multivariate regression identified significant correlations.
Results:
Among the participants, 51% reported experiencing adverse skin reactions, with the hands being the most commonly affected area. Longer work experience as a hairdresser was significantly associated with the occurrence of adverse effects ( p=0.046). Notably, shampoo was identified as a suspected causative material significantly more often by the severe group compared to the non-severe group (28.0% vs. 3.8%, p=0.04).
Conclusion
Chemical exposure and frequent wet work contribute to high rates of OCD among hairdressers. Poor glove usage, especially during shampooing due to inconvenience, is a major risk factor. Raising awareness, promoting proper glove use, and improving workplace safety training are essential for reducing these skin conditions.
5.Early Prediction of Mortality for Septic Patients Visiting Emergency Room Based on Explainable Machine Learning: A Real-World Multicenter Study
Sang Won PARK ; Na Young YEO ; Seonguk KANG ; Taejun HA ; Tae-Hoon KIM ; DooHee LEE ; Dowon KIM ; Seheon CHOI ; Minkyu KIM ; DongHoon LEE ; DoHyeon KIM ; Woo Jin KIM ; Seung-Joon LEE ; Yeon-Jeong HEO ; Da Hye MOON ; Seon-Sook HAN ; Yoon KIM ; Hyun-Soo CHOI ; Dong Kyu OH ; Su Yeon LEE ; MiHyeon PARK ; Chae-Man LIM ; Jeongwon HEO ; On behalf of the Korean Sepsis Alliance (KSA) Investigators
Journal of Korean Medical Science 2024;39(5):e53-
Background:
Worldwide, sepsis is the leading cause of death in hospitals. If mortality rates in patients with sepsis can be predicted early, medical resources can be allocated efficiently. We constructed machine learning (ML) models to predict the mortality of patients with sepsis in a hospital emergency department.
Methods:
This study prospectively collected nationwide data from an ongoing multicenter cohort of patients with sepsis identified in the emergency department. Patients were enrolled from 19 hospitals between September 2019 and December 2020. For acquired data from 3,657 survivors and 1,455 deaths, six ML models (logistic regression, support vector machine, random forest, extreme gradient boosting [XGBoost], light gradient boosting machine, and categorical boosting [CatBoost]) were constructed using fivefold cross-validation to predict mortality. Through these models, 44 clinical variables measured on the day of admission were compared with six sequential organ failure assessment (SOFA) components (PaO 2 /FIO 2 [PF], platelets (PLT), bilirubin, cardiovascular, Glasgow Coma Scale score, and creatinine).The confidence interval (CI) was obtained by performing 10,000 repeated measurements via random sampling of the test dataset. All results were explained and interpreted using Shapley’s additive explanations (SHAP).
Results:
Of the 5,112 participants, CatBoost exhibited the highest area under the curve (AUC) of 0.800 (95% CI, 0.756–0.840) using clinical variables. Using the SOFA components for the same patient, XGBoost exhibited the highest AUC of 0.678 (95% CI, 0.626–0.730). As interpreted by SHAP, albumin, lactate, blood urea nitrogen, and international normalization ratio were determined to significantly affect the results. Additionally, PF and PLTs in the SOFA component significantly influenced the prediction results.
Conclusion
Newly established ML-based models achieved good prediction of mortality in patients with sepsis. Using several clinical variables acquired at the baseline can provide more accurate results for early predictions than using SOFA components. Additionally, the impact of each variable was identified.
6.Five-Year Overall Survival and Prognostic Factors in Patients with Lung Cancer: Results from the Korean Association of Lung Cancer Registry (KALC-R) 2015
Da Som JEON ; Ho Cheol KIM ; Se Hee KIM ; Tae-Jung KIM ; Hong Kwan KIM ; Mi Hyung MOON ; Kyongmin Sarah BECK ; Yang-Gun SUH ; Changhoon SONG ; Jin Seok AHN ; Jeong Eun LEE ; Jeong Uk LIM ; Jae Hyun JEON ; Kyu-Won JUNG ; Chi Young JUNG ; Jeong Su CHO ; Yoo-Duk CHOI ; Seung-Sik HWANG ; Chang-Min CHOI ; ;
Cancer Research and Treatment 2023;55(1):103-111
Purpose:
This study aimed to provide the clinical characteristics, prognostic factors, and 5-year relative survival rates of lung cancer diagnosed in 2015.
Materials and Methods:
The demographic risk factors of lung cancer were calculated using the KALC-R (Korean Association of Lung Cancer Registry) cohort in 2015, with survival follow-up until December 31, 2020. The 5-year relative survival rates were estimated using Ederer II methods, and the general population data used the death rate adjusted for sex and age published by the Korea Statistical Information Service from 2015 to 2020.
Results:
We enrolled 2,657 patients with lung cancer who were diagnosed in South Korea in 2015. Of all patients, 2,098 (79.0%) were diagnosed with non–small cell lung cancer (NSCLC) and 345 (13.0%) were diagnosed with small cell lung cancer (SCLC), respectively. Old age, poor performance status, and advanced clinical stage were independent risk factors for both NSCLC and SCLC. In addition, the 5-year relative survival rate declined with advanced stage in both NSCLC (82%, 59%, 16%, 10% as the stage progressed) and SCLC (16%, 4% as the stage progressed). In patients with stage IV adenocarcinoma, the 5-year relative survival rate was higher in the presence of epidermal growth factor receptor (EGFR) mutation (19% vs. 11%) or anaplastic lymphoma kinase (ALK) translocation (38% vs. 11%).
Conclusion
In this Korean nationwide survey, the 5-year relative survival rates of NSCLC were 82% at stage I, 59% at stage II, 16% at stage III, and 10% at stage IV, and the 5-year relative survival rates of SCLC were 16% in cases with limited disease, and 4% in cases with extensive disease.
7.Apalutamide for metastatic castration-sensitive prostate cancer: final analysis of the Asian subpopulation in the TITAN trial.
Byung Ha CHUNG ; Jian HUANG ; Hiroji UEMURA ; Young Deuk CHOI ; Zhang-Qun YE ; Hiroyoshi SUZUKI ; Taek Won KANG ; Da-Lin HE ; Jae Young JOUNG ; Sabine D BROOKMAN-MAY ; Sharon MCCARTHY ; Amitabha BHAUMIK ; Anildeep SINGH ; Suneel MUNDLE ; Simon CHOWDHURY ; Neeraj AGARWAL ; Ding-Wei YE ; Kim N CHI ; Hirotsugu UEMURA
Asian Journal of Andrology 2023;25(6):653-661
The final analysis of the phase 3 Targeted Investigational Treatment Analysis of Novel Anti-androgen (TITAN) trial showed improvement in overall survival (OS) and other efficacy endpoints with apalutamide plus androgen deprivation therapy (ADT) versus ADT alone in patients with metastatic castration-sensitive prostate cancer (mCSPC). As ethnicity and regional differences may affect treatment outcomes in advanced prostate cancer, a post hoc final analysis was conducted to assess the efficacy and safety of apalutamide in the Asian subpopulation. Event-driven endpoints were OS, and time from randomization to initiation of castration resistance, prostate-specific antigen (PSA) progression, and second progression-free survival (PFS2) on first subsequent therapy or death. Efficacy endpoints were assessed using the Kaplan-Meier method and Cox proportional-hazards models without formal statistical testing and adjustment for multiplicity. Participating Asian patients received once-daily apalutamide 240 mg ( n = 111) or placebo ( n = 110) plus ADT. After a median follow-up of 42.5 months and despite crossover of 47 placebo recipients to open-label apalutamide, apalutamide reduced the risk of death by 32% (hazard ratio [HR]: 0.68; 95% confidence interval [CI]: 0.42-1.13), risk of castration resistance by 69% (HR: 0.31; 95% CI: 0.21-0.46), PSA progression by 79% (HR: 0.21; 95% CI: 0.13-0.35) and PFS2 by 24% (HR: 0.76; 95% CI: 0.44-1.29) relative to placebo. The outcomes were comparable between subgroups with low- and high-volume disease at baseline. No new safety issues were identified. Apalutamide provides valuable clinical benefits to Asian patients with mCSPC, with an efficacy and safety profile consistent with that in the overall patient population.
Male
;
Humans
;
Prostatic Neoplasms/pathology*
;
Androgen Antagonists/therapeutic use*
;
Prostate-Specific Antigen
;
Castration
;
Prostatic Neoplasms, Castration-Resistant/drug therapy*
8.Short-Term Effectiveness of Oral Nirmatrelvir/Ritonavir Against the SARS-CoV-2 Omicron Variant and Culture-Positive Viral Shedding
Eunyoung LEE ; Sehee PARK ; Jae-Phil CHOI ; Min-Kyung KIM ; Eunmi YANG ; Sin Young HAM ; Seungjae LEE ; Bora LEE ; Jeong-Sun YANG ; Byoung Kwon PARK ; Da Sol KIM ; So-Young LEE ; Joo-Yeon LEE ; Hee-Chang JANG ; Jaehyun JEON ; Sang-Won PARK
Journal of Korean Medical Science 2023;38(8):e59-
Background:
Information on the effectiveness of nirmatrelvir/ritonavir against the omicron is limited. The clinical response and viral kinetics to therapy in the real world need to be evaluated.
Methods:
Mild to moderate coronavirus disease 2019 (COVID-19) patients with risk factors for severe illness were prospectively enrolled as a treatment group with nirmatrelvir/ritonavir therapy versus a control group with supportive care. Serial viral load and culture from the upper respiratory tract were evaluated for seven days, and clinical responses and adverse reactions were evaluated for 28 days.
Results:
A total of 51 patients were analyzed including 40 in the treatment group and 11 in the control group. Faster symptom resolution during hospitalization (P= 0.048) was observed in the treatment group. Only minor adverse reactions were reported in 27.5% of patients. The viral load on Day 7 was lower in the treatment group (P = 0.002). The viral culture showed a positivity of 67.6% (25/37) vs. 100% (6/6) on Day 1, 0% (0/37) vs. 16.7 (1/6) on Day 5, and 0% (0/16) vs. 50.0% (2/4) on Day 7 in the treatment and control groups, respectively.
Conclusions
Nirmatrelvir/ritonavir against the omicron was safe and resulted in negative viral culture conversion after Day 5 of treatment with better symptomatic resolution.
9.Experimental infection of a porcine kidney cell line with hepatitis A virus
Dong-Hwi KIM ; Da-Yoon KIM ; Jae-Hyeong KIM ; Kyu-Beom LIM ; Joong-Bok LEE ; Seung-Yong PARK ; Chang-Seon SONG ; Sang-Won LEE ; In-Soo CHOI
Korean Journal of Veterinary Research 2023;63(2):e15-
The hepatitis A virus (HAV) induces severe acute liver injury and is adapted to human and monkey cell lines but not other cells. In this study, the HAV was inoculated into porcine kidney (PK-15) cells to determine its infectivity in porcine cells. The growth pattern of the HAV in PK-15 cells was compared with its growth pattern in fetal rhesus kidney (FRhK-4) cells. The growth of HAV was less efficient in PK-15 cells. In conclusion, HAV replication was verified in PK-15 cells for the first time. Further investigations will be needed to identify the HAV-restrictive mechanisms in PK-15 cells.
10.Acute respiratory distress after metofluthrin insecticide ingestion in a 19-month-old girl
Da Yeon CHOI ; Kyung Won KIM ; Seo Hee YOON
Pediatric Emergency Medicine Journal 2023;10(3):99-103
Metofluthrin is a volatile pyrethroid insecticide. Despite being widely used as a safe household insecticide, it could cause severe systemic symptoms. A 19-month-old girl was taken to the emergency department after ingesting 1 mL of a mosquito repellent containing metofluthrin. After the arrival, the girl developed respiratory distress, which worsened progressively despite the administration of oxygen with nebulized salbutamol and budesonide. Additionally, she underwent application of high-flow nasal cannula, and administration of activated charcoal and systemic steroids. Her dyspnea gradually improved, and she was thus discharged on day 4 with oral prednisolone. All medications were discontinued 10 days after the discharge without any complication. Respiratory distress can develop after the ingestion of even a small amount of metofluthrin. Symptomatic and adjunctive steroid therapies can be effective therapeutic options.

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