Background/Aims: Combination immunotherapy, exemplified by atezolizumab plus bevacizumab, has become the standard of care for inoperable hepatocellular carcinoma (HCC). However, the lack of predictive biomarkers and limited understanding of response mechanisms remain a challenge. Methods: Using data from the IMbrave150plus cohort, we applied an immune signature score (ISS) predictor to stratify HCC patients treated with atezolizumab plus bevacizumab or with sorafenib alone into potential high and low response groups. By applying multiple statistical approaches including a Bayesian covariate prediction algorithm, we refined the signature to 10 key genes (ISS10) for clinical use while maintaining similar predictive power to the full model. We further validated ISS10 in an independent HCC cohort treated with nivolumab plus ipilimumab. Results: The study identified a significant association between the ISS and treatment response. Among patients classified as high responders, those treated with the atezolizumab plus bevacizumab combination exhibited improved overall and progression-free survival as well as better objective response rate compared to those treated with sorafenib. We also observed a significant correlation between ISS10 and response to nivolumab plus ipilimumab treatment. Analysis of immune cell subpopulations revealed distinct characteristics associated with ISS subtypes. In particular, the ISS10 high subtype displayed a more favorable immune environment with higher proportions of antitumor macrophages and activated T-cells, potentially explaining its better response. Conclusions Our study suggests that ISS and ISS10 are promising predictive biomarkers for enhanced therapeutic outcomes in HCC patients undergoing combination immunotherapy. These markers are crucial for refining patient stratification and personalized treatment approaches to advance the effectiveness of standard-of-care regimens.

Objectives: Bisphenol A (BPA) is used in the electrical, mechanical, medical, and food industries. Previous studies have suggested that BPA is an endocrine disruptor. Regulation of BPA has led to increased use of bisphenol F (BPF) and bisphenol S (BPS). However, few studies have investigated the associations of BPF and BPS with thyroid dysfunction in children. Our study investigated the associations of prenatal BPA and early childhood BPA, BPF, and BPS exposure with thyroid function in 6-year-old children. Methods: Prenatal BPA concentrations were measured during the second trimester of pregnancy in an established prospective birth cohort. We measured urinary BPA, BPF, and BPS concentrations and thyroid hormone levels (thyroid-stimulating hormone, total T3, and free T4) in 6-year-old children (n=574). We examined the associations between urinary bisphenol concentrations and percentage change of thyroid hormone concentrations using multivariate linear regression. We also compared thyroid hormone levels by dividing the cohort according to BPA, BPF, and BPS concentrations. Results: The associations between prenatal BPA and total T3 levels were statistically significant in all models, except for girls when using a crude model. The associations between urinary BPA and BPS concentrations and levels of all thyroid hormones were not statistically significant. However, we observed that lower free T4 levels (-1.94%; 95% confidence interval, -3.82 to -0.03) were associated with higher urinary BPF concentrations in girls only. Conclusions Our findings identified significant associations between prenatal BPA exposure and total T3 levels in all children and between BPF exposure and free T4 levels in girls only.

Background: School-aged children born very preterm have been suggested to have worse cognitive and behavioral outcomes than children born full-term. Executive function (EF) is a higher level of cognitive function related to academic achievement. The present study aimed to evaluate the cognitive (including EF) and behavioral outcomes of Korean children born extremely preterm (EP) and to analyze any biological or socioeconomic risk factors for poor cognitive outcomes in this population. Methods: A total of 71 infants weighing < 1,000 g at birth or born before 30 weeks of gestation (EP group) who were admitted to the neonatal intensive care unit from 2008 to 2009 were included in this study and compared with 40 term-birth controls. The Korean Wechsler Intelligence Scale for Children-Fourth Edition, Advanced Test of Attention (ATA), Stroop test, Children's Color Trails Test (CCTT), and Wisconsin Card Sorting Test (WCST) were used.Additionally, the Korean Child Behavior Checklist (K-CBCL) and Korean ADHD Rating Scale (K-ARS) were completed. Perinatal and demographic data were collected and analyzed. Results: The mean full-scale intelligence quotient (FSIQ) score in the EP group was significantly lower than that of the term control group (89.1 ± 18.3 vs. 107.1 ± 12.7; P < 0.001).In the EP group, 26 (37%) children had an FSIQ score below 85, compared to only one child (3%) in the control group. Furthermore, the EP group showed significantly worse EF test results (ATA, Stroop test, CCTT, WCST). Except for the higher social immaturity subscore in the EP group, the K-CBCL and K-ARS scores were not different between the two groups. EP children who received laser treatment for retinopathy of prematurity (ROP) had an 8.8-fold increased risk of a low FSIQ score, and a 1-point increase in the discharge weight Z-score decreased the risk of a low FSIQ score by approximately half in this EP cohort. Conclusion This is the first Korean study to investigate the cognitive and behavioral outcomes of school-aged children born EP. In the study cohort, EP children exhibited significantly lower FSIQ scores and EF than their full-term peers, and 37% of them had cognitive problems. Nonetheless, except for social immaturity, the behavioral problems werenot different in EP children. Severe ROP and low discharge weight Z-score were identified as independent risk factors for low FSIQ score after adjusting for birth weight.

Background: School-aged children born very preterm have been suggested to have worse cognitive and behavioral outcomes than children born full-term. Executive function (EF) is a higher level of cognitive function related to academic achievement. The present study aimed to evaluate the cognitive (including EF) and behavioral outcomes of Korean children born extremely preterm (EP) and to analyze any biological or socioeconomic risk factors for poor cognitive outcomes in this population. Methods: A total of 71 infants weighing < 1,000 g at birth or born before 30 weeks of gestation (EP group) who were admitted to the neonatal intensive care unit from 2008 to 2009 were included in this study and compared with 40 term-birth controls. The Korean Wechsler Intelligence Scale for Children-Fourth Edition, Advanced Test of Attention (ATA), Stroop test, Children's Color Trails Test (CCTT), and Wisconsin Card Sorting Test (WCST) were used.Additionally, the Korean Child Behavior Checklist (K-CBCL) and Korean ADHD Rating Scale (K-ARS) were completed. Perinatal and demographic data were collected and analyzed. Results: The mean full-scale intelligence quotient (FSIQ) score in the EP group was significantly lower than that of the term control group (89.1 ± 18.3 vs. 107.1 ± 12.7; P < 0.001).In the EP group, 26 (37%) children had an FSIQ score below 85, compared to only one child (3%) in the control group. Furthermore, the EP group showed significantly worse EF test results (ATA, Stroop test, CCTT, WCST). Except for the higher social immaturity subscore in the EP group, the K-CBCL and K-ARS scores were not different between the two groups. EP children who received laser treatment for retinopathy of prematurity (ROP) had an 8.8-fold increased risk of a low FSIQ score, and a 1-point increase in the discharge weight Z-score decreased the risk of a low FSIQ score by approximately half in this EP cohort. Conclusion This is the first Korean study to investigate the cognitive and behavioral outcomes of school-aged children born EP. In the study cohort, EP children exhibited significantly lower FSIQ scores and EF than their full-term peers, and 37% of them had cognitive problems. Nonetheless, except for social immaturity, the behavioral problems werenot different in EP children. Severe ROP and low discharge weight Z-score were identified as independent risk factors for low FSIQ score after adjusting for birth weight.

Background/Aims: To date, prospective data are limited on efficacy and safety profiles of statin therapy in Korean hypercholesterolemic patients. Hence, the aim of this study was to evaluate the practice patterns of statin therapy and its efficacy and safety through the prospective Daegu and Gyeongbuk statin registry. Methods: Statin naïve patients who were prescribed statins according to the criteria of Korean Guidelines for Management of Dyslipidemia were enrolled. Clinical and laboratory evaluations were performed at baseline and at week 8, where the efficacy was assessed with the same guidelines. Results: Of 908 patients, atorvastatin and rosuvastatin were most frequently prescribed statins (63.1% and 29.3%, respectively). High intensity statins (atorvastatin 40 mg or rosuvastatin 20 mg) were prescribed in 24.7% of all patients and in 79.5% of high and very high risk groups. The total and low density lipoprotein (LDL) cholesterol levels decreased from 203.7 ± 43.0 to 140.6 ± 28.6 mg/dL and 134.4 ± 35.7 to 79.5 ± 21.3 mg/dL, respectively. The achievement rate of the LDL target goal was 98.6% in low risk, 95.0% in moderate risk, 88.1% in high risk, and 42.1% in very high risk patients (59.7% in overall). There was no significant difference in the efficacy between atorvastatin and rosuvastatin. Adverse events were observed in 12.0% of patients and led to 1.4% of treatment cessation. Conclusions The efficacy of the usual starting dose of statins in daily practice was relatively insufficient for Korean hypercholesterolemic patients with high or very high risks. Short-term adverse events of statin therapy were not common in Korean patients with a low discontinuation rate.

Background: Implantable loop recorders (ILRs) can provide an enhanced possibility to detect atrial fibrillation (AF), but the accuracy, especially the positive predictive value (PPV), is controversial. This study aimed to evaluate the accuracy of ILRs for detecting AF through a comparison with Holter. Method and results: Thirteen patients who underwent AF ablation were enrolled. ILRs were implanted in all patients, who were scheduled to have Holter monitorings after the procedure. The incidence of AF was compared between the two modalities and analyzed for any correlations. A total of 51 Holters (67,985.5 min) and concomitant ILRs were available for the comparison. The judgment of the presence of AF did not perfectly correlate between the ILR and Holter (Kappa = 0.866, P < 0.001). In the ILR data, the sensitivity of detecting AF on the Holter was 81.6% (95% confidence interval [CI] 0.812–0.820; P < 0.001). The specificity was 99.9% (95% CI 0.998–0.999; P < 0.001). When the ILR detected AF, the PPV was 99.5% (95% CI 0.994–0.995), but the ILR did not detect AF, and the negative predictive value was 94.2% (95% CI 0.941–0.944). A separate analysis of AF/atrial tachycardia (AT) showed that the AT detection rate of the ILR was 2.3%. Conclusion The ILR had a low false positive value and high PPV for AF events. However, it was limited in identifying AT.

Objectives: Prenatal cadmium (Cd) exposure may be associated with attention-deficit/hyperactivity disorder (ADHD) in children. Therefore, the objective of this study was to examine the relationship between Cd exposure during gestation and ADHD at 6 years of age. Methods: As part of an ongoing cohort study (the Environment and Development of Children study), 479 mother-child pairs from Seoul, Korea were included for analysis between 2008 and 2011. The whole blood concentration of Cd was analyzed using atomic absorption spectrophotometry. The parents were surveyed about ADHD behaviors in their children at age 6. Multivariable linear regression models were used to investigate the relationship between prenatal exposure to Cd and ADHD at 6 years of age. Results: Increased prenatal Cd concentrations were associated with increased scores for ADHD for girls, but not for boys, at age 6. A 2-fold increase in the prenatal Cd level was significantly associated with a 22.3% (95% confidence interval, 11.6 to 34.1) increase in ADHD in girls at 6 years of age, as indicated by the linear regression model. Conclusions Our results identified significant associations between prenatal Cd exposure and ADHD scores in 6-year-old girls.