Purpose: To assess long-term outcomes of vesicostomy on bladder capacity (BC) and voiding function in non-neurogenic bladder, and explore the association between kidney ultrasonographic findings and renal function. Materials and Methods: Thirty-four patients under 2 years at the time of vesicostomy formation (2005–2020) with ≥3 years of follow-up were reviewed. Patients were further stratified based on neurogenic bladder status. Twenty-one patients were nonneurogenic. A subgroup analysis of 7 patients under 3 months with primary vesicoureteral reflux (VUR) and compromised renal function was conducted. Results: The median age at vesicostomy formation was 1.0 months (interquartile range [IQR] 0.0–3.5); the median duration of vesicostomy was 16.0 months (IQR 8.0–21.0). At a median age of 93.0 months (IQR 59.5–117.5), all patients achieved spontaneous micturition and continence. Eleven patients (52.4%) showed bell-shaped voiding patterns. Five patients showed interrupted (n=2) or plateau (n=3) patterns. With the exemption one patient, all patients with primary VUR showed bell-shaped curves. None initiated clean intermittent catheterization during follow-up. The median BC-to-estimated BC in patients with non-neurogenic bladder and primary VUR was 0.9 (IQR 0.7–1.1) and 0.9 (IQR 0.8–1.1), respectively. Three patients underwent revision due to prolapse. The glomerular filtration rate (GFR) was improved by 68.9% compared to the baseline (p=0.045). Parenchymal abnormalities on kidney ultrasonography were associated with decrease in GFR. Conclusions Vesicostomy in non-neurogenic bladder patients was associated with recovery of BC, preservation of continence, and improved renal function. Parenchymal abnormalities on ultrasonography predicted lower GFR.

Phytochemical investigation of the water extract and alkaloid fraction of Areca catechu L. led to theisolation of one new methoxyflavonoid rutinoside (1), together with eleven known compounds (2−12), five of which (8−12) belong to the pyridine alkaloid class. The structure of the new compound was elucidated through extensive spectroscopic analyses, including 1D and 2D NMR experiments and high-resolution mass spectrometry.Notably, rhamnazin-3-O-rutinoside (2) is reported here for the first time from this species. The isolated compounds were evaluated for their inhibitory activity against protein tyrosine phosphatase 1B (PTP1B) using a p-nitrophenyl phosphate assay. Flavonoids (3 and 4) and stilbene (5) exhibited notable inhibitory activity, with IC50 values of 13.30 ± 0.71, 13.44 ± 0.84, and 8.68 ± 0.12 μM, respectively. In contrast, methoxyflavonoid rutinosides (1 and 2) and pyridine alkaloids (8−12) did not show significant inhibitory activity against PTP1B.These findings provide additional chemical insights into A. catechu and its constituents in relation to PTP1B inhibition.

Purpose: Neoadjuvant treatment (NAT) is now the standard for borderline resectable pancreatic cancer (RPC) and is being considered for RPC. Early recurrence after curative surgery in RPC is often seen as a treatment failure, prompting considerations for NAT. Our goal was to develop an artificial intelligence (AI)-based predictive model utilizing preoperatively available factors to forecast early recurrences of resected RPC. Methods: This study included 469 patients who underwent surgery for RPC between 2011 and 2019. Clinicopathologic and oncologic data were retrospectively reviewed. Preoperative variables, including laboratory data and imaging findings, were collected. Early recurrence was defined as recurrence occurring within a year after surgery. Deep neural networks were then used to select variables by assessing their importance. A new model predicting early recurrence of RPC was subsequently developed. Results: Of the patients evaluated, 199 (42.4%) experienced early recurrence. The predictive model included 14 preoperative variables: CA 19-9, preoperative pancreatitis, serum albumin, platelet count, lymphocyte count, the American Society of Anesthesiologists physical status classification, tumor size, monocyte count, age, body mass index, CRP, hemoglobin, WBC count, and CEA. The area under the curve for the model was 0.786 in the training set and 0.734 in the test set. Conclusion We developed an AI-based model to predict the early recurrence of RPC using preoperative parameters. By identifying patients at risk of early recurrence, optimal individualized treatments such as NAT can be considered. Future prospective studies are crucial to establish clear indications for NAT in RPC.

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.

Purpose: Limited treatment options exist for patients with metastatic castration-resistant prostate cancer (mCRPC) after the failure of taxane-based chemotherapy and novel hormonal therapy. Here, we report the safety and efficacy of ifosfamide and mesna in patients with mCRPC after the failure of taxane-based chemotherapy and novel hormonal therapy (NCT06236789). Materials and Methods: Patients with histologically confirmed prostate cancer who had failed taxane-based chemotherapy and novel hormonal therapy received ifosfamide 2,500 mg/m2 and mesna 1,500 mg/m2 on days 1–3, repeated every 21 days. Safety, objective response rate, disease control rate, reduction in serum prostate-specific antigen (PSA) concentration by >50% (PSA50) or >90% (PSA90), radiographic progression-free survival (rPFS), and overall survival (OS) were analyzed. Results: A total of 47 patients with mCRPC were included in the study. The median number of lines of treatment was 5 (range, 3 to 7). All patients were previously administered docetaxel and novel hormonal therapies including abiraterone (51.1%) and/or enzalutamide (61.7%). Thirty-eight patients (80.9%) were administered cabazitaxel. The objective response and disease control rates were 21.3% and 80.9%, respectively. PSA50 and PSA90 were achieved in 31.9% and 10.6%, respectively. During a median follow-up duration of 54.3 months, rPFS and OS were 5.0 and 9.0 months, respectively. All the patients experienced treatment-related adverse events of any grades; however, no new safety signs were detected. Genomic biomarker analysis revealed that alterations in the TP53 pathway were associated with inferior rPFS and OS. Conclusion Ifosfamide and mesna showed appreciable efficacy and manageable safety profiles in heavily treated patients with mCRPC.

Background: Adequate tissue oxygenation is a key determinant of diabetic foot ulcer (DFU) outcomes. Though transcutaneous oxygen pressure (TcPO2) is the gold standard for evaluating tissue oxygenation, its limited availability restricts routine clinical use. Consequently, toe pressure is frequently utilized as a practical surrogate; however, the direct correlation between these two modalities has yet to be rigorously investigated. This study aimed to assess the correlation and agreement between TcPO2 and toe pressure in patients with DFUs. Methods: A retrospective review was conducted on 837 DFU patients who received simultaneous TcPO2 and toe pressure assessments. The correlation between the two tests was analyzed using the Pearson correlation coefficient, and agreement was evaluated using Bland–Altman analysis. To aid interpretation, a scatterplot and Bland–Altman plot were generated. Results: TcPO2 and toe pressure demonstrated a strong correlation (R=0.66; 95% confidence interval, 0.62 to 0.70; P<0.001). Bland–Altman analysis showed a mean bias of 26.9 mmHg (standard deviation of differences, 28.8 mmHg; 95% limits of agreement, −28.9 to 82.6 mmHg) between toe pressure and TcPO2, reflecting limited agreement and increased variability at higher perfusion levels. Conclusion TcPO2 and toe pressure are strongly correlated. However, they are not interchangeable, particularly in DFU patients with high tissue perfusion.

Background: Intradialytic hypotension (IDH) is a critical complication related to worse outcomes in patients undergoing maintenance hemodialysis. Herein, we addressed the impact of IDH on mortality and other outcomes in patients with severe acute kidney injury (AKI) requiring intermittent hemodialysis. Methods: We retrospectively reviewed 1,009 patients who underwent intermittent hemodialysis due to severe AKI. IDH was defined as either dialysis discontinuation due to hemodynamic instability or a decrease in systolic blood pressure (BP) of ≥30 mmHg, with or without a nadir systolic BP of <90 mmHg during the first session. The primary outcome was all-cause mortality, and transfer to the intensive care unit (ICU) due to unstable status was additionally analyzed. Hazard ratios (HRs) of outcomes were calculated using a Cox regression model after adjusting for multiple variables. Risk factors for IDH were evaluated using a logistic regression model. Results: IDH occurred in 449 patients (44.5%) during the first hemodialysis session. Patients with IDH had a higher mortality rate than those without IDH (40% vs. 23%; HR, 1.30; 95% confidence interval [CI], 1.02–1.65). The rate of ICU transfer was higher in patients experiencing IDH than in those without IDH (17% vs. 11%; HR, 1.43; 95% CI, 1.02–2.02). Factors such as old age, high BP and pulse rate, active malignancy, cirrhosis, and hypoalbuminemia were associated with an increased risk of IDH episodes. Conclusion The occurrence of IDH is associated with worse outcomes in patients with AKI requiring intermittent hemodialysis. Therefore, careful monitoring and early intervention of IDH may be necessary in this patient subset.

Background: This study evaluated adherence to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) and Korean guidelines in the prescription patterns of respiratory specialists for stable chronic obstructive pulmonary disease (COPD) management. Methods: Data were collected on medications from 2011 to 2022 using the Korea COPD Subtype Study (KOCOSS) cohort. Patients were divided into two groups: those registered before and after 2019, and we analyzed the percentage of patients meeting the recommended treatment criteria established by each guideline. Results: Among 3,477 patients, 85.6% received pharmacological therapy, and 81.6% utilized inhaled medications. Compared to patients enrolled before 2019, there was an increase in inhaler prescriptions among those registered after 2019 (79.7% vs. 86.7%), with dual bronchodilators being the predominant therapy prescribed. Of the patients receiving treatment, 56.9% adhered to the Korean 2018 guideline. Compliance with the GOLD 2019 and GOLD 2023 guidelines was observed in 31.3% and 28.0% of cases, respectively. When analyzing inhaler prescription patterns according to both subgroups and considering the Korean 2018, GOLD 2019, and GOLD 2023 guidelines concurrently, the adherence rates were as follows: (56.6%, 37.8%, 24.0%) and (57.7%, 14.0%, 38.6%). Conclusion Adherence rates were higher for the Korean guideline compared to the GOLD recommendations. Furthermore, alignment with both the Korean 2018 and GOLD 2023 guidelines increased among patients enrolled after 2019, compared to those registered earlier. These findings suggest that physicians are modifying their therapeutic strategies to align with both domestic and recent international guidelines.

Background: Skipping breakfast is associated with an increased risk of chronic inflammatory diseases. This study aimed to examine the association between breakfast-eating habits and inflammation, using high-sensitivity C-reactive protein (hs-CRP) as a marker. Methods: A total of 4,000 Korean adult males with no history of myocardial infarction, angina, stroke, diabetes, rheumatoid arthritis, cancer, or current smoking were included. Data from the 2016–2018 Korea National Health and Nutrition Examination Survey were used for analysis. The frequency of breakfast consumption was assessed through a questionnaire item in the dietary survey section asking participants about their weekly breakfast consumption routines over the past year. Participants were categorized into two groups, namely “0–2 breakfasts per week” and “3–7 breakfasts per week”; hs-CRP concentrations were measured through blood tests. Results: Comparing between the “infrequent breakfast consumption (0–2 breakfasts per week)” and “frequent breakfast consumption (3–7 breakfasts per week)” groups, the mean hs-CRP was found to be significantly higher in the “infrequent breakfast consumption” group, even after adjusting for age, body mass index, physical activity, alcohol consumption, systolic blood pressure, blood pressure medication, fasting blood glucose, and triglycerides (mean hs-CRP: frequent breakfast consumption, 1.36±0.09 mg/L; infrequent breakfast consumption, 1.17±0.05 mg/L; P-value=0.036). Conclusion Less frequent breakfast consumption was associated with elevated hs-CRP levels. Further large-scale studies incorporating adjusted measures of daily eating patterns as well as food quality and quantity are required for a deeper understanding of the role of breakfast in the primary prevention of chronic inflammatory diseases.

Background: Hearing level reference values based on the results of recent audiometry have not been established for the general population of South Korea. This study aimed to evaluate the mean hearing levels of each age group and to measure the annual progression of hearing loss. Methods: We used the database of the eighth and ninth Korea National Health and Nutrition Examination Survey from 2020 to 2022, and included participants with normal tympanic membranes and without occupational noise exposure. Mean hearing levels were calculated by averaging hearing levels at 0.5 kHz, 1 kHz, 2 kHz, and 4 kHz. Hearing loss was defined as a hearing level exceeding 25 dB in the better ear, and severity of hearing loss was classified as moderate, moderately severe, severe, and profound, following the World Health Organization classification. Results: Hearing levels and the proportions of patients with hearing loss increased with age. Hearing levels were 9.11 ± 6.28 dB, 13.33 ± 7.85 dB, 19.90 ± 10.30 dB, and 31.95 ± 13.37 dB in those in their 40s, 50s, 60s, and 70s, respectively, and the proportions of patients with hearing loss were 1.81%, 7.51%, 25.32%, and 63.94%, respectively. The annual increase in hearing level was 0.71 dB, and increases were greater at higher frequencies. Hearing loss was also worse in men. Conclusion The present study provides reference values for normal hearing levels by age group, and indirectly reveals the progression of age-related hearing loss. Based on the results, physicians will be able to provide appropriate advice regarding hearing levels and the need for monitoring in the elderly.