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.

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.

Purpose: Developmentally regulated GTP-binding protein 2 (DRG2) regulates microtubule dynamics and G2/M arrest during docetaxel treatment. Poly ADP-ribose polymerase (PARP) acts as an important repair system for DNA damage caused by docetaxel treatment. This study investigated whether DRG2 expression affects response to PARP inhibitors (olaparib) using prostate cancer cell lines PC3, DU145, LNCaP-FGC, and LNCaP-LN3. Materials and Methods: The cell viability and DRG2 expression levels were assessed using colorimetric-based cell viability assay and western blot. Cells were transfected with DRG2 siRNA, and pcDNA6/V5-DRG2 was used to overexpress DRG2. Flow cytometry was applied for cell cycle assay and apoptosis analysis using the Annexing V cell death assay. Results: The expression of DRG2 was highest in LNCaP-LN3 and lowest in DU145 cells. Expressions of p53 in PC3, DU145, and the two LNCaP cell lines were null-type, high-expression, and medium-expression, respectively. In PC3 (DRG2 high, p53 null) cells, docetaxel increased G2/M arrest without apoptosis; however, subsequent treatment with olaparib promoted apoptosis. In DU145 and LNCaP-FGC (DRG2 low), docetaxel increased sub-G1 but not G2/M arrest and induced apoptosis, whereas olaparib had no additional effect. In LNCaP-LN3 (DRG2 high, p53 wild-type), docetaxel increased sub-G1 and G2/M arrest, furthermore olaparib enhanced cell death. Docetaxel and olaparib combination treatment had a slight effect on DRG2 knockdown PC3, but increased apoptosis in DRG2-overexpressed DU145 cells. Conclusions DRG2 and p53 expressions play an important role in prostate cancer cell lines treated with docetaxel, and DRG2 levels can predict the response to PARP inhibitors.

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.

Purpose: This phase II, open-label, multicenter study aimed to investigate the efficacy and safety of a rituximab intensification for the 1st cycle with every 21-day of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP-21) among patients with previously untreated advanced-stage or bulky diffuse large B-cell lymphoma (DLBCL). Materials and Methods: Ninety-two patients with stage III/IV or bulky DLBCL from 21 institutions were administered 8 cycles of R-CHOP-21 with an additional one dose of rituximab intensification on day 0 of the 1st cycle (RR-CHOP). The primary endpoint was a complete response (CR) rate after 3 cycles of chemotherapy. Results: Among the 92 DLBCL patients assessed herein, the response rate after 3 cycles of chemotherapy was 88.0% (38.0% CR+50.0% partial response [PR]). After the completion of 8 cycles of chemotherapy, the overall response rate was observed for 68.4% (58.7% CR+9.8% PR). The 3-year progression-free survival rate was 64.0%, and the 3-year overall survival rate was 70.4%. Febrile neutropenia was one of the most frequent grade 3 adverse events (40.0%) and 5 treatment-related deaths occurred. Compared with the clinical outcomes of patients who received R-CHOP chemotherapy as a historical control, the interim CR rate was higher in male patients with RR-CHOP (20.5% vs. 48.8%, p=0.016). Conclusion Rituximab intensification on days 0 to the 1st cycle of the standard 8 cycles R-CHOP-21 for advanced DLBCL yielded favorable response rates after the 3 cycles of chemotherapy and acceptable toxicities, especially for male patients. ClinicalTrials.gov ID: NCT01054781.

Background: There is growing evidence that abnormal liver function tests (LFTs) are common in patients with coronavirus disease 2019 (COVID-19). However, it is not known whether viral involvement in the liver differs according to the strain. We investigated the impact on liver injury in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Delta (B.1.617.2) variants. Materials and Methods: We conducted a single-center, retrospective cohort study, including 372 patients admitted during the pre-Delta period (PDP: between February 1 and November 30, 2020) and 137 patients admitted during the Delta period (DP: between August 1 and August 31, 2021). Initial liver injury was defined as alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels ≥3 × the upper limit of normal (ULN) or alkaline phosphatase (ALP) or total bilirubin ≥2 × the ULN within 3 days from admission. Results: Of 509 patients with COVID-19 included in our study, 38 (7.5%) patients had initial liver injury. The DP group had a significantly higher rate of initial liver injury than the PDP group (PDP: 5.9% vs. DP: 11.7%, P = 0.028). The DP group (adjusted odds ratio [aOR]: 2.737, 95% confidence interval [CI]: 1.322 – 5.666) was independently associated with initial liver injury. During hospitalization, 160 (31.4%) patients had severe COVID-19. The DP group and initial liver injury had higher odds of progressing to severe COVID-19 (aOR: 2.664, 95% CI: 1.526 - 4.648, and aOR: 4.409, 95% CI: 1.816 - 10.707, respectively). The mediation analysis suggested that initial liver injury mediates the relationship between SARS-CoV-2 Delta variant infection and severe COVID-19 (unstandardized beta coefficient = 0.980, Standard error = 0.284, P = 0.001). Conclusion Initial liver injury is more common in COVID-19 patients with Delta variants. Also, Delta variants and initial liver injury are associated with poor clinical outcomes.

Purpose: To investigate the diagnostic criteria of T1-weighted imaging (T1W) and time-of-flight (TOF) imaging for detecting intraplaque hemorrhage (IPH) of a vertebrobasilar artery (VBA) compared with simultaneous non-contrast angiography and intraplaque hemorrhage (SNAP) imaging. Materials and Methods: Eighty-seven patients with VBA atherosclerosis who underwent high resolution MR imaging for evaluation of VBA plaque were reviewed. The presence and location of VBA plaque and IPH on SNAP were determined. The signal intensity (SI) of the VBA plaque on T1W and TOF imaging was manually measured and the SI ratio against adjacent muscles was calculated. The receiveroperating characteristic (ROC) curve was used to compare the diagnostic accuracy for detecting VBA IPH. Results: Of 87 patients, 67 had IPH and 20 had no IPH on SNAP. The SI ratio between VBA IPH and temporalis muscle on T1W was significantly higher than that in the noIPH group (235.9 ± 16.8 vs. 120.0 ± 5.1, P < 0.001). The SI ratio between IPH and temporalis muscle on TOF was also significantly higher than that in the no-IPH group (236.8 ± 13.3 vs. 112.8 ± 7.4, P < 0.001). Diagnostic efficacies of SI ratios on TOF and TIW were excellent (AUC: 0.976 on TOF and 0.964 on T1W; cutoff value: 136.7% for TOF imaging and 135.1% for T1W imaging). Conclusion Compared with SNAP, cutoff levels of the SI ratio between VBA plaque and temporalis muscle on T1W and TOF imaging for detecting IPH were approximately 1.35 times.

Background: Because of the very low incidence of human immunodeficiency virus (HIV) coinfection in Korea, data on hepatitis C virus (HCV)/HIV coinfection are limited. This study aimed to investigate the clinical characteristics and treatment outcomes of patients with HCV/HIV coinfection in Korea. Methods: We performed a retrospective cohort study of all HCV-monoinfected and HCV/ HIV-coinfected patients treated with antivirals at National Medical Center in Seoul, Korea, between January 2009 and March 2020. Results: We enrolled 220 HCV-monoinfected and 23 HCV/HIV-coinfected patients treated with antivirals. The HCV/HIV-coinfected patients were younger (HCV vs. HCV/HIV: 57.3 ± 11.3 vs. 40.7 ± 10.1 years, P < 0.001) and had a higher proportion of men (HCV vs. HCV/ HIV: 54.5% [n = 120] vs. 91.3% [n = 21], P < 0.001) than the HCV-monoinfected patients.Genotype 1b and 2 were most common in both HCV monoinfection and HCV/HIV coinfection groups. HCV-monoinfected patients had a higher incidence of genotype 1b and 2 than HCV/HIV-coinfected patients (HCV vs. HCV/HIV: 95.4% [n = 210] vs. 73.9% [n = 17], P < 0.001), while the HCV/HIV-coinfected patients had genotype 1a (HCV vs. HCV/HIV: 1.8% [n = 4] vs. 21.7% [n = 5], P < 0.001). The fibrosis-4 index was significantly lower in the HCV/ HIV-coinfected patients than in the HCV-monoinfected patients (HCV vs. HCV/HIV: 3.81 ± 3.38 vs. 1.66 ± 1.10, P < 0.001). Among the direct-acting antivirals (DAA)-treated patients, the sustained viral response (SVR) rate did not differ significantly between both groups (HCV vs.HCV/HIV: 94.9% [93/99] vs. 90.9% [10/11], P = 0.480). Conclusion In Korea, the HCV/HIV-coinfected patients who received antiviral treatment were younger, had higher proportion of men and incidence of genotype 1a, and had less advanced fibrosis than the HCV-monoinfected patients. In actual clinical settings, HCV/HIV-coinfected patients show excellent SVR to DAA treatment, similar to HCVmonoinfected patients.

Background: Recently, a metabolic syndrome severity score (MS score) using a dataset of the Korea National Health and Nutrition Examination Surveys has been developed. We aimed to determine whether the newly developed score is a significant predictor of cardiovascular (CV) events among the Korean population. Methods: From the Korean National Health Insurance System, 2,541,364 (aged 40 to 59 years) subjects with no history of CV events (ischemic stroke or myocardial infarction [MI]), who underwent health examinations from 2009 to 2011 and were followed up until 2014 to 2017, were identified. Cox proportional hazard model was employed to investigate the association between MS score and CV events. Model performance of MS score for predicting CV events was compared to that of conventional metabolic syndrome diagnostic criteria (Adult Treatment Program III [ATP-III]) using the Akaike information criterion and the area under the receiver operating characteristic curve. Results: Over a median follow-up of 6 years, 15,762 cases of CV events were reported. MS score at baseline showed a linear association with incident CV events. In the multivariable-adjusted model, the hazard ratios (95% confidence intervals) comparing the highest versus lowest quartiles of MS score were 1.48 (1.36 to 1.60) for MI and 1.89 (1.74 to 2.05) for stroke. Model fitness and performance of the MS score in predicting CV events were superior to those of ATP-III. Conclusion The newly developed age- and sex-specific continuous MS score for the Korean population is an independent predictor of ischemic stroke and MI in Korean middle-aged adults even after adjusting for confounding factors.