Alzheimer’s disease (AD) is characterized by progressive cognitive deterioration and significant depression. However, the mechanisms linking depression to AD pathology remain unclear. Here, we investigated whether Notch2 signaling mediates depressionlike behaviors in presenilin-2 (PS2) N141I mutant mice, an early-onset AD model. PS2 wild-type (WT) and mutant (MT) mice aged 12-15 months were subjected to unpredictable chronic mild stress (UCMS) for 4 weeks, followed by sucrose preference, tail-hanging, and forced swimming tests. Behavioral assessments showed that UCMS exacerbated anhedonia and immobility only in PS2 MT mice. Molecular analysis revealed concomitant increases in plasma corticosterone, hippocampal γ-secretase activity, and Notch2 expression, and elevated total and phosphorylated glucocorticoid receptor levels in PS2 MT-UCMS mice. Gene expression profiling of human hippocampal datasets confirmed upregulation of NOTCH2 in Alzheimer’s disease and depression.Pharmacological inhibition of γ-secretase and Notch signaling with DAPT normalizes depressive behavior, reduces corticosterone release, attenuates GR phosphorylation, and inhibits Notch2 signaling in PS2 MT mice. These findings identify Notch2 as a pivotal mediator linking chronic stress to molecular changes associated with depression and AD, and suggest that targeting Notch2 signaling may provide therapeutic benefits for comorbid mood and neurodegenerative disorders.

Background/Aims: Hepatocellular carcinoma (HCC) exhibits significant sex disparities in incidence, yet its molecular mechanisms remain unclear. We explored the role of telomerase reverse transcriptase (TERT) genetic alterations and hepatitis B virus (HBV) integration, both known major contributors to HCC, in sex-specific risk for HBV-related HCC. Methods: We examined 310 HBV-related HCC tissues to investigate sex-specific TERT promoter (TERT-pro) mutations and HBV integration profiles, stratified by sex and age, and validated with single-cell RNA sequencing (scRNA-seq) data. Results: Tumors predominantly exhibited TERT-pro mutations (26.0% vs. 0%) and HBV-TERT integration (37.0% vs. 3.0%) compared to non-tumorous tissues. While TERT-pro mutations increased with age in both sexes, younger males (≤60 years) showed marked predominance compared to younger females. Males had significantly more HBV integrations at younger ages, while females initially had fewer integrations that gradually increased with age. Younger males' integrations showed significantly greater enrichment in the TERT locus compared to younger females, alongside a preference for promoters, PreS/S regions, and CpG islands. Overall, TERT genetic alterations were significantly sex-differential in younger individuals (75.3% in males vs. 23.1% in females) but not in older individuals (76.9% vs. 83.3%, respectively). These alterations were associated with increased TERT expression. The skewed TERT abnormalities in younger males were further corroborated by independent scRNA-seq data. Conclusions Our findings highlight the critical role of TERT alterations and HBV integration patterns in the male predominance of HCC incidence among younger HBV carriers, offering insights for future exploration to optimize sex-specific patient care and HCC surveillance strategies.

Background/Aims: Hepatocellular carcinoma (HCC) exhibits significant sex disparities in incidence, yet its molecular mechanisms remain unclear. We explored the role of telomerase reverse transcriptase (TERT) genetic alterations and hepatitis B virus (HBV) integration, both known major contributors to HCC, in sex-specific risk for HBV-related HCC. Methods: We examined 310 HBV-related HCC tissues to investigate sex-specific TERT promoter (TERT-pro) mutations and HBV integration profiles, stratified by sex and age, and validated with single-cell RNA sequencing (scRNA-seq) data. Results: Tumors predominantly exhibited TERT-pro mutations (26.0% vs. 0%) and HBV-TERT integration (37.0% vs. 3.0%) compared to non-tumorous tissues. While TERT-pro mutations increased with age in both sexes, younger males (≤60 years) showed marked predominance compared to younger females. Males had significantly more HBV integrations at younger ages, while females initially had fewer integrations that gradually increased with age. Younger males' integrations showed significantly greater enrichment in the TERT locus compared to younger females, alongside a preference for promoters, PreS/S regions, and CpG islands. Overall, TERT genetic alterations were significantly sex-differential in younger individuals (75.3% in males vs. 23.1% in females) but not in older individuals (76.9% vs. 83.3%, respectively). These alterations were associated with increased TERT expression. The skewed TERT abnormalities in younger males were further corroborated by independent scRNA-seq data. Conclusions Our findings highlight the critical role of TERT alterations and HBV integration patterns in the male predominance of HCC incidence among younger HBV carriers, offering insights for future exploration to optimize sex-specific patient care and HCC surveillance strategies.

Background/Aims: Hepatocellular carcinoma (HCC) exhibits significant sex disparities in incidence, yet its molecular mechanisms remain unclear. We explored the role of telomerase reverse transcriptase (TERT) genetic alterations and hepatitis B virus (HBV) integration, both known major contributors to HCC, in sex-specific risk for HBV-related HCC. Methods: We examined 310 HBV-related HCC tissues to investigate sex-specific TERT promoter (TERT-pro) mutations and HBV integration profiles, stratified by sex and age, and validated with single-cell RNA sequencing (scRNA-seq) data. Results: Tumors predominantly exhibited TERT-pro mutations (26.0% vs. 0%) and HBV-TERT integration (37.0% vs. 3.0%) compared to non-tumorous tissues. While TERT-pro mutations increased with age in both sexes, younger males (≤60 years) showed marked predominance compared to younger females. Males had significantly more HBV integrations at younger ages, while females initially had fewer integrations that gradually increased with age. Younger males' integrations showed significantly greater enrichment in the TERT locus compared to younger females, alongside a preference for promoters, PreS/S regions, and CpG islands. Overall, TERT genetic alterations were significantly sex-differential in younger individuals (75.3% in males vs. 23.1% in females) but not in older individuals (76.9% vs. 83.3%, respectively). These alterations were associated with increased TERT expression. The skewed TERT abnormalities in younger males were further corroborated by independent scRNA-seq data. Conclusions Our findings highlight the critical role of TERT alterations and HBV integration patterns in the male predominance of HCC incidence among younger HBV carriers, offering insights for future exploration to optimize sex-specific patient care and HCC surveillance strategies.

Purpose: To report a nationwide survey on neuroblastoma conducted by the Korean Association of Pediatric Surgeons (KAPS) in 2020. Methods: The clinical data of pediatric patients diagnosed with and treated for neuroblastoma from 2005 to 2019 in 19 hospitals of KAPS members were collected. Survival and prognostic factor analyses were performed using the log rank test and Cox proportional hazard analysis. A p-value <0.05 was considered significant. Results: A total of 669 patients with neuroblastoma were registered for the study. The results were presented and discussed at the 36th annual meeting of the KAPS, which was held in Seoul on August 21, 2020. Conclusion This study provides information on patient demographics, prognostic outcomes, and comprehensive treatment outcomes for neuroblastoma. The study is expected to be an important reference for improving pediatric surgeons’ understanding and treatment of neuroblastoma.

Proliferative myositis (PM) is a rare benign soft tissue neoplasm with a distinctive pseudosarcomatous proliferative reaction of muscles in tumors. Its rapid growth and bizarre microscopic appearance often require a differential diagnosis from a sarcomatous lesion. It has been reported occasionally, mostly as case reports in adult patients. Herein, we present a neonatal case of PM. To the best of our knowledge, this is the first report in the neonatal period.

Purpose: This study provides insights into the prevalence at birth, clinical characteristics, and outcomes of gastroschisis and omphalocele in Korea over the past decade, addressing the lack of localized data despite advanced healthcare capabilities. Methods: The study retrospectively analyzed data from 20 pediatric surgical centers in Korea from January 2012 to December 2021, including 269 patients diagnosed with gastroschisis or omphalocele. Data variables included gender, gestational age, birth weight, associated anomalies, type of defect, surgical interventions, and outcomes. Results: The study covered 269 patients, with 80 gastroschisis and 189 omphalocele cases. Gastroschisis prevalence at birth remained stable at 2.15 per 100,000 live births, while omphalocele increased to 5.08 per 100,000. Both conditions had similar gender ratios (0.95). Gastroschisis patients had lower birth weights (2,463.90±505.50 g) and smaller head circumferences (31.97±1.86 cm) compared to omphalocele patients (2,757.65±761.24 g, 32.78±2.64 cm). Omphalocele cases had more associated anomalies, especially cardiovascular issues. Prenatal diagnosis rates were high: 93.7% for gastroschisis and 86.4% for omphalocele. About 96.3% of gastroschisis and 84.1% of omphalocele patients were born in their treatment hospitals. Gastroschisis patients underwent surgery sooner (average 3.5 days) and started feeding later (16.5 days) than omphalocele patients (average 56.5 days to surgery, 6.6 days to start feeding). Hospital stays and follow-up durations were similar, averaging around 782.6 days for gastroschisis and 800.3 days for omphalocele patients. Survival rates were 89.7% for gastroschisis and 87.1% for omphalocele. Conclusion The study highlights the need for early diagnosis, centralized care, and specialized surgical approaches to optimize outcomes for gastroschisis and omphalocele patients in Korea. Enhanced prenatal screening and surgical protocols are recommended to improve these patients' prognosis.

Purpose: The Korean Association of Pediatric Surgeons (KAPS) conducts annual nationwide surveys on various aspects of pediatric surgical diseases, with the results being discussed during KAPS’s annual spring meetings. Methods: KAPS conducted two national surveys, in 1995 and 2016, to investigate esophageal atresia (EA) with or without tracheoesophageal fistula (TEF). The authors analyzed data from these surveys to identify differences or changes in the annual occurrence, demographic characteristics, clinical presentation, preoperative diagnostic methods, anatomical type, associated anomalies, surgical treatment, and postoperative outcomes among patients with EA/TEF treated by KAPS members. Results: The first and second national surveys included 148 and 211 patients with EA/TEF, respectively. Excessive salivation was the most prevalent clinical symptom in both surveys. Type C was the most common form of EA/TEF in both surveys. The first survey included 126 patients, all of whom underwent open surgery. In the second survey, 152 (78.4%) of 194 patients underwent open surgery, while 34 (17.5%) underwent thoracoscopic surgery. Primary esophageal repair was performed on 96 (76.2%) of 126 patients in the first survey and on 160 (82.5%) of 194 patients in the second survey. Anastomotic strictures developed in 21.4% and 32.5% of patients, anastomotic leakage in 22.2% and 10.3%, recurrent fistula in 2.4% and 4.2% during the first and second surveys, respectively. The respective survival rates for group A were 90.2% and 98.3% in the first and second surveys. For group B, the rates were 73.9% and 98.1%, and for group C, they were 34.5% and 68.1%, respectively, according to the Waterston classifications. Conclusion These nationwide surveys provide comprehensive information on the status, detailed treatment, and outcomes for Korean pediatric patients with EA/TEF. They are anticipated to be an invaluable resource and guide for pediatric surgeons seeking to expand their knowledge on EA/TEF and its treatment options.

Purpose: Surgical management of obstructive left colon cancer (OLCC) is still a matter of debate. The classic Hartmann procedure (HP) has a disadvantage that requires a second major operation. Subtotal colectomy/total abdominal colectomy (STC/TC) with ileosigmoid or ileorectal anastomosis is proposed as an alternative procedure to avoid stoma and anastomotic leakage. However, doubts about morbidity and functional outcome and lack of long-term outcomes have made surgeons hesitate to perform this procedure. Therefore, this trial was designed to provide data for morbidity, functional outcomes, and long-term outcomes of STC/TC. Methods: This study retrospectively analyzed consecutive cases of OLCC that were treated by STC/TC between January 2000 and November 2020 at a single tertiary referral center. Perioperative outcomes and long-term outcomes of STC/TC were analyzed. Results: Twenty-five descending colon cancer (45.5%) and 30 sigmoid colon cancer cases (54.5%) were enrolled in this study. Postoperative complications occurred in 12 patients. The majority complication was postoperative ileus (10 of 12). Anastomotic leakage and perioperative mortality were not observed. At 6 to 12 weeks after the surgery, the median frequency of defecation was twice per day (interquartile range, 1–3 times per day). Eight patients (14.5%) required medication during this period, but only 3 of 8 patients required medication after 1 year. The 3-year disease-free survival was 72.7% and 3-year overall survival was 86.7%. Conclusion The risk of anastomotic leakage is low after STC/TC. Functional and long-term outcomes are also acceptable. Therefore, STC/TC for OLCC is a safe, 1-stage procedure that does not require diverting stoma.

The new Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations without a race coefficient have gained recognition across the United States. We aimed to test whether these new equations performed well in Korean patients with chronic kidney disease (CKD). Methods: This study included 2,149 patients with CKD G1–G5 without kidney replacement therapy from the Korean Cohort Study for Outcome in Patients with CKD (KNOW-CKD). The estimated glomerular filtration rate (eGFR) was calculated using the new CKD-EPI equations with serum creatinine and cystatin C. The primary outcome was 5-year risk of kidney failure with replacement therapy (KFRT). Results: When we adopted the new creatinine equation [eGFRcr (NEW)], 81 patients (23.1%) with CKD G3a based on the current creatinine equation (eGFRcr) were reclassified as CKD G2. Accordingly, the number of patients with eGFR of <60 mL/min/1.73 m2 decreased from 1,393 (64.8%) to 1,312 (61.1%). The time-dependent area under the receiver operating characteristic curve for 5-year KFRT risk was comparable between the eGFRcr (NEW) (0.941; 95% confidence interval [CI], 0.922–0.960) and eGFRcr (0.941; 95% CI, 0.922–0.961). The eGFRcr (NEW) showed slightly better discrimination and reclassification than the eGFRcr. However, the new creatinine and cystatin C equation [eGFRcr-cys (NEW)] performed similarly to the current creatinine and cystatin C equation. Furthermore, eGFRcr-cys (NEW) did not show better performance for KFRT risk than eGFRcr (NEW). Conclusion: Both the current and the new CKD-EPI equations showed excellent predictive performance for 5-year KFRT risk in Korean patients with CKD. These new equations need to be further tested for other clinical outcomes in Koreans.