Background/Aims: Spinal cord injury (SCI) frequently impairs defecation, severely affecting the quality of life. This study examines compensatory neural remodeling after SCI, focusing on basal colonic contractility, neural responses to electrical field stimulation, and alterations in excitatory cholinergic and inhibitory nitrergic pathways. Methods: Female Sprague–Dawley rats underwent either sham surgery or T10 spinal cord transection and were categorized into 3 groups: sham, 1-week post-SCI (acute), and 4-week post-SCI (chronic). Colonic contractility was assessed in an organ bath using electrical field stimulation in the presence of a nitric oxide synthase inhibitor. Neural protein expression was analyzed by immunofluorescence and Western blotting. Results: SCI produced region- and time-dependent impairments in colonic contractility, with distinct alterations in the proximal circular and longitudinal muscles across acute and chronic phases. Neural excitability shifted dynamically, showing enhanced excitatory activity in the proximal longitudinal muscle at 1-week and the distal circular muscle at 4-week post-SCI. Protein analysis revealed increased neuronal nitric oxide synthase in the proximal colon, decreasedsoluble guanylyl cyclase in the distal colon, upregulated muscarinic M3 receptor in the proximal colon, and reduced vaso-active intestinal peptide receptor 1 in both proximal and distal regions. Conclusion SCI induces spatiotemporal remodeling of excitatory and inhibitory neural pathways, contributing to colonic dysmotility and revealing potential targets for therapeutic intervention.

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 and Objectives: Primary prevention (PP) implantable cardioverter-defibrillator (ICD) therapy for ischemic cardiomyopathy (ICM) is underused in Asian countries, including South Korea. Both clinical and hospital factors may influence appropriate ICD use. We evaluated whether determinants of PP ICD implantation differ by hospital implantation volume. Methods: In this prospective, multicenter observational registry (blinded for review), patients eligible for PP ICD were enrolled. Factors associated with ICD implantation—clinical characteristics and hospital-level systems—were examined across 4 large-volume hospitals (≥ 15 implants during the study) and 12 small-volume hospitals (< 15). Multivariable logistic regression identified independent predictors. Results: Among 3,083 ICM patients (2,403 men; median age 70 years), PP ICD implantation rates were 10.8% in large-volume and 5.7% in small-volume hospitals. Across groups, male sex and chronic kidney disease independently predicted ICD implantation. Regarding hospital factors, non-monetary incentives for referral were the sole independent predictor in large-volume centers (odds ratio [OR], 3.55; 95% confidence interval [CI], 2.07–6.10;P < 0.001). In small-volume centers, heart failure conferences (OR, 12.73; 95% CI, 1.72–94.37;P = 0.013), structured education systems (OR, 11.72; 95% CI, 2.45–56.12; P = 0.02), and pacemaker clinics (OR, 11.4; 95% CI, 2.24–58.39; P = 0.003) were independently associated with implantation. Conclusions Clinical predictors of PP ICD use were consistent across hospital volumes, but hospital-level determinants differed. Referral incentives characterized large-volume centers, whereas conferences, education systems, and pacemaker clinics were key in smallvolume centers. Tailored institutional strategies by hospital volume may help close the PP ICD underuse gap and improve evidence-based implementation.

Purpose: This study evaluated the clinical outcomes and prognostic factors in patients with borderline resectable pancreatic cancer (BRPC) and locally advanced pancreatic cancer (LAPC) treated with upfront FOLFIRINOX followed by local-regional therapy (LRT), surgical resection (SR), and radiotherapy (RT). We aimed to identify specific patient subgroups for which RT may serve as a reasonable alternative to SR for local tumor control. Methods: We retrospectively analyzed 116 patients (SR group, n= 70; RT group, n= 46) at a single center between 2015 and 2020. Survival outcomes were compared based on LRT modalities, focusing on identifying subgroups in which RT provided an efficacy comparable to that of SR. Results: Among 116 patients, the SR group achieved a significantly higher 5-year overall survival (OS) than the RT group (27.1% vs. 8.7%, P< 0.0001), despite similar progression-free survival (P= 0.23). Significant prognostic factors for OS included carbohydrate antigen 19-9 (CA19-9) response in BRPC (P= 0.02) and radiologic partial response in LAPC (P= 0.05). Subgroup analysis revealed that, while SR provided a survival advantage in CA19-9 responders, no significant difference in OS was observed between SR and RT in CA19-9 non-responders (P= 0.37). Conclusion Although surgery remains the gold standard, RT may be considered a justifiable local alternative for CA19-9 non-responders and surgically ineligible patients with LAPC, yielding comparable outcomes in these specific, biologically unfavorable subgroups.

Purpose: To report five cases of macular hole (MH) coexisting with uveal melanoma (UM) and review the literature. Methods: Seventeen patients (5 new and 12 from previous reports) with coexisting MH and UM were reviewed. The patients were divided into two groups based on whether the MH was diagnosed before or after tumor treatment. The clinical features, pathogenesis, management options, and clinical outcomes were reviewed. Results: Of 505 patients with UM in our institution, 5 (1.0%) had a concurrent MH in the ipsilateral eye. The 17 patients reviewed had a mean age of 63.9 years at the time of MH diagnosis. Of 16 patients with available data on sex, 11 (64.7%) were female. There were no major differences in the demographic or clinical data of the groups. Of the 15 known tumor locations, 6 (35.3%) were juxtapapillary or macular. In patients who developed MH after UM treatment, the durations from tumor treatment (radiotherapy or transpupillary thermotherapy) to MH diagnosis were 3 to 56 months (median, 8.5 months). MH surgery was performed in nine eyes, and hole closure was achieved in seven eyes with postoperative data. The mean visual acuity showed a tendency of improvement after surgery. No intraocular or extraocular tumor dissemination associated with surgery was observed. Conclusions MH is observed in approximately 1% of patients with UM, either before or after tumor treatment. Of patients with coexisting MH and UM, MH surgery appears to be safe and effective in those with stable tumors and visual potential.

Background: This study analyzed the epidemiology and treatment outcomes of germ cell tumorpatients at a single institution. Methods: A retrospective analysis was conducted on intracranial germ cell tumor (iGCT) pa-tients treated at a single tertiary hospital from 2004 to 2019. Patients were categorized based on treatment modality: Korean Society for Pediatric Neuro-Oncology (KSPNO) protocol or bleomycin, etoposide, and cisplatin with radiation therapy. Results: Forty-nine iGCT patients treated with combined chemotherapy and radiotherapywere analyzed. The median age was 19 years (range: 6–40), with a median follow-up duration of 148.0 months (range: 10.5–265.5). Tumors were most common in the pineal gland (51.0%). Although no significant differences in outcomes were observed between treatment modalities, outcomes varied significantly by pathological type. The 10-year progression-free survival rates for germinoma and non-germinomatous germ cell tumors (NGGCTs) were 88.1% and 32.7%, respectively (p=0.003), while the 10-year overall survival rates were 92.9% and 67.5%, respectively (p<0.001). Fourteen patients experienced CTCAE (Common Terminology Criteria for Adverse Events) grade ≥3 adverse events, with one eventrelated death. Conclusion Pure germinoma demonstrated higher survival and lower recurrence rates comparedto NGGCT. The KSPNO protocol appears to be an acceptable and safe treatment option for iGCT patients. Further multi-institutional studies with larger cohorts are warranted.

Background: Active surveillance (AS) has emerged as a viable management strategy for low-risk papillary thyroid microcarcinoma (PTMC), following pioneering trials at Kuma Hospital and the Cancer Institute Hospital in Japan. Numerous prospective cohort studies have since validated AS as a management option for low-risk PTMC, leading to its inclusion in thyroid cancer guidelines across various countries. From 2016 to 2020, the Multicenter Prospective Cohort Study of Active Surveillance on Papillary Thyroid Microcarcinoma (MAeSTro) enrolled 1,177 patients, providing comprehensive data on PTMC progression, sonographic predictors of progression, quality of life, surgical outcomes, and cost-effectiveness when comparing AS to immediate surgery. The second phase of MAeSTro (MAeSTro-EXP) expands AS to low-risk papillary thyroid carcinoma (PTC) tumors larger than 1 cm, driven by the hypothesis that overall risk assessment outweighs absolute tumor size in surgical decision-making. Methods: This protocol aims to address whether limiting AS to tumors smaller than 1 cm may result in unnecessary surgeries for low-risk PTCs detected during their rapid initial growth phase. By expanding the AS criteria to include tumors up to 1.5 cm, while simultaneously refining and standardizing the criteria for risk assessment and disease progression, we aim to minimize overtreatment and maintain rigorous monitoring to improve patient outcomes. Conclusion This study will contribute to optimizing AS guidelines and enhance our understanding of the natural course and appropriate management of low-risk PTCs. Additionally, MAeSTro-EXP involves a multinational collaboration between South Korea and Australia. This cross-country study aims to identify cultural and racial differences in the management of low-risk PTC, thereby enriching the global understanding of AS practices and their applicability across diverse populations.

Background: and Purpose Previous research on patients with acute ischemic stroke (AIS) has shown a 0.5% incidence of major gastrointestinal bleeding (GIB) requiring blood transfusion during hospitalization. The existing literature has insufficiently explored the long-term incidence in this population despite the decremental impact of GIB on stroke outcomes. Methods: We analyzed the data from a cohort of patients with AIS admitted to 14 hospitals as part of a nationwide multicenter prospective stroke registry between 2011 and 2013. These patients were followed up for up to 6 years. The occurrence of major GIB events, defined as GIB necessitating at least two units of blood transfusion, was tracked using the National Health Insurance Service claims data. Results: Among 10,818 patients with AIS (male, 59%; mean age, 68±13 years), 947 (8.8%) experienced 1,224 episodes of major GIB over a median follow-up duration of 3.1 years. Remarkably, 20% of 947 patients experienced multiple episodes of major GIB. The incidence peaked in the first month after AIS, reaching 19.2 per 100 person-years, and gradually decreased to approximately one-sixth of this rate by the 2nd year with subsequent stabilization. Multivariable analysis identified the following predictors of major GIB: anemia, estimated glomerular filtration rate <60 mL/min/1.73 m2 , and a 3-month modified Rankin Scale score of ≥4. Conclusion Patients with AIS are susceptible to major GIB, particularly in the first month after the onset of AIS, with the risk decreasing thereafter. Implementing preventive strategies may be important, especially for patients with anemia and impaired renal function at stroke onset and those with a disabling stroke.

Background and Objectives: Outcomes of deferring percutaneous coronary intervention (PCI) without invasive physiologic assessment for intermediate coronary lesions is uncertain.We sought to compare long-term outcomes between medical treatment and PCI of intermediate lesions without invasive physiologic assessment. Methods: A total of 899 patients with intermediate coronary lesions between 50% and 70% diameter-stenosis were randomized to the conservative group (n=449) or the aggressive group (n=450). For intermediate lesions, PCI was performed in the aggressive group, but was deferred in the conservative group. The primary endpoint was major adverse cardiac events (MACE, a composite of all-cause death, myocardial infarction [MI], or ischemia-driven any revascularization) at 3 years. Results: The number of treated lesions per patient was 0.8±0.9 in the conservative group and 1.7±0.9 in the aggressive group (p=0.001). At 3 years, the conservative group had a significantly higher incidence of MACE than the aggressive group (13.8% vs. 9.3%; hazard ratio [HR], 1.49; 95% confidence interval [CI], 1.00–2.21; p=0.049), mainly driven by revascularization of target intermediate lesion (6.5% vs. 1.1%; HR, 5.69; 95% CI, 2.20–14.73;p<0.001). Between 1 and 3 years after the index procedure, compared to the aggressive group, the conservative group had significantly higher incidence of cardiac death or MI (3.2% vs.0.7%; HR, 4.34; 95% CI, 1.24–15.22; p=0.022) and ischemia-driven any revascularization. Conclusions For intermediate lesions, medical therapy alone, guided only by angiography, was associated with a higher risk of MACE at 3 years compared with performing PCI, mainly due to increased revascularization.

Purpose: To report five cases of macular hole (MH) coexisting with uveal melanoma (UM) and review the literature. Methods: Seventeen patients (5 new and 12 from previous reports) with coexisting MH and UM were reviewed. The patients were divided into two groups based on whether the MH was diagnosed before or after tumor treatment. The clinical features, pathogenesis, management options, and clinical outcomes were reviewed. Results: Of 505 patients with UM in our institution, 5 (1.0%) had a concurrent MH in the ipsilateral eye. The 17 patients reviewed had a mean age of 63.9 years at the time of MH diagnosis. Of 16 patients with available data on sex, 11 (64.7%) were female. There were no major differences in the demographic or clinical data of the groups. Of the 15 known tumor locations, 6 (35.3%) were juxtapapillary or macular. In patients who developed MH after UM treatment, the durations from tumor treatment (radiotherapy or transpupillary thermotherapy) to MH diagnosis were 3 to 56 months (median, 8.5 months). MH surgery was performed in nine eyes, and hole closure was achieved in seven eyes with postoperative data. The mean visual acuity showed a tendency of improvement after surgery. No intraocular or extraocular tumor dissemination associated with surgery was observed. Conclusions MH is observed in approximately 1% of patients with UM, either before or after tumor treatment. Of patients with coexisting MH and UM, MH surgery appears to be safe and effective in those with stable tumors and visual potential.