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: 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: and Purpose To compare the epidemiological and clinical features of the rare patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) with age- and sex-matched controls in a nationwide cohort from South Korea. Methods: This observational cohort study analyzed newly diagnosed CADASIL patients aged at least 20 years and matched controls using data from the National Health Information Database for 2004–2022. The cumulative incidence of CADASIL was assessed by age and sex, and compared between regions. Neurologic and systemic diseases were compared between the CADASIL and control groups. Results: The study analyzed 816 CADASIL patients and 816 age- and sex-matched controls aged 56.8±15.2 years (mean±standard deviation), among whom 48.3% were male. The cumulative incidence of CADASIL was 1.86 per 100,000 people (95% confidence interval [CI]=1.85– 1.87 per 100,000), and peaked at 60–69 years of age. In terms of regional distribution, the incidence was highest for Jeju, at 39.67 per 100,000 (95% CI 37.84–41.49 per 100,000). Neurologic diseases were more frequent in CADASIL patients, including Alzheimer’s disease (33.1% vs.20.0%), vascular dementia (84.9% vs. 5.0%), epilepsy (34.6% vs. 15.9%), stroke (70.7% vs. 27.6%), parkinsonism (18.9% vs. 11.0%), and depression (60.8% vs. 44.9%). Systemic diseases such as diabetes mellitus (78.9% vs. 68.9%) were also more common in CADASIL patients, while cancer (27.9% vs. 38.7%) and myocardial infarction (10.0% vs. 13.6%) were less common than in controls. The onset ages of all diseases were lower in CADASIL patients. Conclusions This study has provided a precise nationwide estimate of the CADASIL incidence and its regional distribution in South Korea. CADASIL patients showed higher incidence rates and earlier onsets of diverse clinical manifestations.

Purpose: While the benefit of neoadjuvant chemotherapy (NAC) has been established in human epidermal growth factor receptor 2 (HER2)-positive and triple-negative breast cancers, its effectiveness in achieving pathological complete response (pCR) and optimal patient selection in estrogen receptor (ER)-positive, HER2-negative breast cancers remain less clearly defined. This study aimed to identify immunohistochemistry (IHC)-based predictors of pCR and to develop a scoring model for ER-strong positive/HER2-negative breast cancer. Methods: Data from a prospective cohort were retrospectively analyzed. We included 522 patients with ER-strong positive/HER2-negative tumors who received NAC and surgery between 2008 and 2021. IHC markers including progesterone receptor (PR), Ki-67, epidermal growth factor receptor (EGFR), cytokeratin 5/6 (CK5/6), and p53 were evaluated to identify predictors of pCR. Independent predictors of pCR from multivariate logistic regression were used to develop a weighted 4-point model. Model performance was assessed using receiver operating characteristic analysis. The prognostic impact of pCR was evaluated using KaplanMeier and Cox regression analyses. Results: Independent predictors of pCR included PR-negative status, positivity for basallike markers (EGFR or CK5/6), and Ki-67 ≥ 50%. The scoring model demonstrated good discrimination for pCR (area under the curve = 0.754). pCR rates increased stepwise, with scores of 4.9% (low), 10.7% (intermediate), and 36.2% (high). In the high-score group, pCR was significantly associated with improved disease-free survival (hazard ratio [HR], 0.09; p = 0.023) and distant metastasis-free survival (HR, 0.11; p = 0.035), whereas no significant survival differences according to pCR status were observed in the low and intermediate score groups. Conclusion This IHC-based model predicts pCR and helps identify subgroups in which pCR is associated with meaningful survival benefit following NAC in ER-positive/HER2-negative breast cancers. High-scoring patients may benefit from NAC, while patients with low- or intermediatescores may be better managed with surgery and endocrine therapy. This model may support personalized treatment decisions regarding NAC.

Purpose: Lobular carcinoma In Situ (LCIS) is a noninvasive lesion associated with an increased risk of invasive cancer. Since its removal from the tumor, node, metastasis classification in the 8th edition of the American Joint Committee on Cancer (AJCC) guidelines, the clinical management of LCIS has shifted from surgery to surveillance. However, studies focusing on the risk and associated factors for invasive cancer development in pure LCIS without ductal carcinoma In Situ (DCIS) or invasive cancer remain limited. Methods: We retrospectively analyzed 106 patients diagnosed with pure LCIS between 2008 and 2018. This study evaluated the effect of tamoxifen use and histologic type on the development of invasive cancer. Results: All 106 patients underwent surgery, and nine (8.5%) developed invasive cancer over a median follow-up of 67.5 months. The incidence of invasive cancer was lower in the tamoxifen group (6.3%, n = 4) than in the non-tamoxifen group (11.9%, n = 5), although this difference was not statistically significant (p = 0.266). Pleomorphic LCIS had a significantly higher incidence of invasive cancer (30.0%, n = 3) than classic LCIS (6.3%, n = 6) (p = 0.045).Multivariable Cox regression analysis showed no significant difference in the risk of invasive cancer according to tamoxifen use (hazard ratio [HR], 2.031; 95% confidence interval [CI], 0.544–7.579; p = 0.292). However, pleomorphic LCIS showed a trend toward an increased risk of invasive cancer compared to classic LCIS (HR, 3.856; 95% CI, 0.922–16.126; p = 0.064). Conclusion Postoperative tamoxifen did not significantly lower invasive cancer development in patients with pure LCIS. Pleomorphic LCIS may carry a higher risk than classic LCIS. These findings require tailored follow-up and treatment strategies based on the histologic subtype of LCIS.

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.

Objective: This study aimed to quantitatively assess abnormalities in the talar dome cartilage using MRI T2 mapping, with additional analyses based on the Lauge-Hansen (LH) classification and anatomical locations. Materials and Methods: This retrospective study analyzed 78 patients who underwent ankle MRI with T2 mapping for acute ankle trauma between January 2021 and October 2022. Patients were classified into the supination (S) and pronation (P) groups based on the LH classification, and then divided into subgroups based on posterior malleolus (PM) involvement. The T2 values for the talar cartilage were quantitatively measured in six anatomical regions defined by the combination of medial vs.lateral and anterior vs. central vs. posterior. The T2 mapping values in each region of the talus were compared between the S and P groups and between the PM and non-PM injury groups using t-tests. The T2 values were also compared between the medial and lateral sides within each group. Results: Among the 78 patients (mean age, 38.62 ± 14.82 years; 47 male), 53 and 25 were in the S and P groups, respectively, and 53 patients showed PM involvement. In comparison with the P group, the S group exhibited higher T2 values in the medial portion (61.27 ± 8.30 vs. 54.03 ± 6.96; P < 0.001) and lower T2 values in the lateral talus (54.95 ± 8.47 vs. 64.15 ± 7.31; P < 0.001). The PM injury group showed higher T2 values in the posterior region than the non-PM injury group (P ≤ 0.011). Within the PM injury group, T2 values were higher in the anteromedial and posterolateral regions than on the opposite sides (P= 0.037 and 0.011, respectively). Conclusion MRI T2 values demonstrated significant regional variations in the talar dome cartilage in acute ankle trauma, and the T2 values may reflect different ankle trauma mechanisms and PM involvement. Thus, T2 mapping can facilitate evaluation of talar cartilage alterations.

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.

Objective: This study aimed to quantitatively assess abnormalities in the talar dome cartilage using MRI T2 mapping, with additional analyses based on the Lauge-Hansen (LH) classification and anatomical locations. Materials and Methods: This retrospective study analyzed 78 patients who underwent ankle MRI with T2 mapping for acute ankle trauma between January 2021 and October 2022. Patients were classified into the supination (S) and pronation (P) groups based on the LH classification, and then divided into subgroups based on posterior malleolus (PM) involvement. The T2 values for the talar cartilage were quantitatively measured in six anatomical regions defined by the combination of medial vs.lateral and anterior vs. central vs. posterior. The T2 mapping values in each region of the talus were compared between the S and P groups and between the PM and non-PM injury groups using t-tests. The T2 values were also compared between the medial and lateral sides within each group. Results: Among the 78 patients (mean age, 38.62 ± 14.82 years; 47 male), 53 and 25 were in the S and P groups, respectively, and 53 patients showed PM involvement. In comparison with the P group, the S group exhibited higher T2 values in the medial portion (61.27 ± 8.30 vs. 54.03 ± 6.96; P < 0.001) and lower T2 values in the lateral talus (54.95 ± 8.47 vs. 64.15 ± 7.31; P < 0.001). The PM injury group showed higher T2 values in the posterior region than the non-PM injury group (P ≤ 0.011). Within the PM injury group, T2 values were higher in the anteromedial and posterolateral regions than on the opposite sides (P= 0.037 and 0.011, respectively). Conclusion MRI T2 values demonstrated significant regional variations in the talar dome cartilage in acute ankle trauma, and the T2 values may reflect different ankle trauma mechanisms and PM involvement. Thus, T2 mapping can facilitate evaluation of talar cartilage alterations.