Peripheral nerve injury and oxidative stress can severely impair Schwann cell function by disrupting the expression of key myelin proteins, promoting intracellular lipid accumulation, and damaging mitochondrial integrity. These pathological changes are central to various neurodegenerative disorders and chemotherapy-induced peripheral neuropathy, yet effective therapeutic approaches remain limited. Clemastine, an FDA-approved antihistamine with known remyelination-enhancing effects in the central nervous system, has not been thoroughly explored for its protective role in peripheral myelinating cells under oxidative stress. In this study, we investigated the time-dependent protective effects of Clemastine in S16 Schwann cells exposed to hydrogen peroxide (H2O2) as a model of oxidative injury. Treatment with Clemastine significantly increased the expression of myelin-related proteins such as myelin protein zero (MPZ), alongside in increase in AMPK phosphorylation at Thr172. However, co-treatment with H2O2 ensued oxidative damage, leading to reduced pAMPK(T172) and MPZ expression, elevated ROS levels, and increased lipid accumulation. These results suggest that oxidative stress can attenuate Clemastine’s effects in association with disrupted redox balance and energy metabolism. Subsequent treatment with Metformin (Met), a pharmacological activator of AMPK, was associated with partial recovery from H2O2-induced oxidative damage. Overall, our findings support the potential of a combinatorial approach using Clemastine and Met to promote myelin-related protein expression and lipid metabolic balance in Schwann cells under oxidative stress, rather than establishing a definitive synergistic or causal mechanism.

Immunosenescence, an age-associated decline in immune function, is increasingly recognized as a central determinant of health and disease in older adults. Characterized by thymic involution, loss of naïve T cells, contraction of T cell receptor diversity, accumulation of senescent and exhausted lymphocytes, and a chronic inflammatory state known as inflammaging, immunosenescence compromises both innate and adaptive immune responses. Immunosenescence contributes to the pathogenesis of diverse age-related diseases. In autoimmune and metabolic diseases, premature accumulation of senescent T cells and impaired regulatory T cell function drive chronic inflammation and tissue damage, while in neurodegenerative diseases, microglial aging and sustained neuroinflammation exacerbate neuronal loss. These findings highlight immunosenescence as a unifying mechanism linking aging to systemic and organ-specific pathologies. Advances in biomarker discovery, including phenotypic markers, telomere attrition, and epigenetic signatures, have enabled the quantitative assessment of immune aging, while emerging therapeutic strategies, such as cytokine modulation, mTOR inhibition, senolytics, and epigenetic reprogramming, show promise in restoring immune competence. Here, we summarize recent research on immunosenescence in various diseases, particularly chronic inflammatory, metabolic, and neurodegenerative diseases, and suggest novel strategies for the development of senolytic drugs.

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: Low-dose chest computed tomography (LDCT) is recommended for surveillance 2–3 years after curative resection of non-small cell lung cancer (NSCLC); however, supporting clinical evidence is limited. This study compared LDCT with contrast-enhanced chest computed tomography (CECT) in terms of recurrence detection and overall survival (OS) in patients 2 years after curative resection of NSCLC. Materials and Methods: Among patients who underwent curative resection for NSCLC between January 2011 and December 2017 and survived for 2 years without recurrence, 2,083 patients were included. Comparisons between the LDCT and CECT groups were performed in both the entire cohort and propensity score-matched cohort. The primary outcome was the difference in overall survival. Secondary outcomes included time-to-recurrence, recurrence-free survival, and post-recurrence survival in each group. Results: In the propensity score-matched population, the 5-year OS (96.0% for LDCT, 98.0% for CECT, p=0.097) and recurrence-free survival (RFS) (95.4% for LDCT, 96.0% for CECT, p=0.761) did not differ. The OS and RFS did not differ in subgroup analyses stratified by pathologic stage and histologic type. In the competing risk analysis, the overall 5-year cumulative incidence of recurrence did not differ between the two groups (4.56% for LDCT, 3.93% for CECT, p=0.765). When stratified by pathologic stage and histologic type, there was no significant difference in the cumulative incidence of recurrence. The distribution of recurrence sites did not differ between groups. Conclusion Similar OS and RFS were observed in LDCT and CECT surveillance in patients who achieved a 2-year disease-free status after curative resection for NSCLC.

Purpose: The aim of this study is to compare the detection ability of quality of life (QoL) changes and responsiveness of the KOrean QUality of life in Stomach cancer patients Study group (KOQUSS)-40 and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ). Materials and Methods: A multicenter prospective observational study was conducted to evaluate QoL changes after various gastrectomies between January 2021 and April 2022. Participants were instructed to complete the KOQUSS-40 and EORTC QLQ-C30/STO22 preoperatively and at 1, 3, 6, and 12 months postoperatively. QoL changes over time and QoL responsiveness were assessed for each questionnaire. Results: Data from 491 patients who underwent curative gastrectomy for gastric cancer at 22 institutions were analyzed. The summary scores of the KOQUSS-40 and EORTC QLQ-STO22 showed significant differences between the total and proximal gastrectomy groups (p=0.044 and p=0.038, respectively), but no difference was observed for the EORTC QLQ-C30. Dysphagia on the KOQUSS-40 was significantly different between the total and proximal gastrectomy groups (p=0.031); however, dysphagia on the EORTC QLQ-STO22 did not differ. The responsiveness of the KOQUSS-40 was similar to that of the EORTC QLQ in patients who experienced ≥ 10% body weight loss, but approximately 10% less in patients receiving adjuvant chemotherapy than the EORTC QLQ. Conclusion KOQUSS-40 has several advantages over EORTC QLQ-C30/STO22 when comparing QoL between the total and proximal gastrectomy groups. The findings provide information for researchers investigating the QoL of patients who have undergone curative gastrectomy for gastric cancer.

Purpose: Considering the current lack of consensus on post–poly(adenosine diphosphate-ribose) polymerase inhibitor (PARPi) treatment strategies, this study aimed to evaluate the efficacy of subsequent therapy and compare the outcomes of regimes in patients with recurrent ovarian cancer after PARPi treatment. Materials and Methods: This multi-center retrospective cohort study analyzed data on patients diagnosed with ovarian cancer between January 2012 and June 2023 who had previously used PARPi after first- to fourth-line platinum-based chemotherapy. The primary endpoint was progression-free survival (PFS), which was the interval between recurrence after using PARPi and subsequent recurrence in the case of recurrence. Results: Of 318 patients, 147/318 (46.2%) recurred after the PARPi maintenance. Patients were categorized into groups based on subsequent therapy except non-treated (11/147, 7.5%): platinum-based chemotherapy (89/147, 60.5%), non-platinum-based chemotherapy (21/147, 14.3%), other treatments (26/147, 17.7%), and the median PFS (mPFS) for each group were 7.3, 4.8, and 11.4 months, respectively. Among the platinum-based chemotherapy group, the gemcitabine+carboplatin regimen demonstrated a longer mPFS (10.1 months) than the other regimens (6.6 months, p=0.019). In non-platinum-based chemotherapy, no statistically significant differences were observed among the regimens. And, in the other therapy group, where the proportion of patients with oligometastasis was as high as 88.5%, no significant differences were observed among the therapies, including other modalities. Conclusion In the subsequent chemotherapy of recurrent ovarian cancer after platinum-based chemotherapy and PARPi, the gemcitabine+carboplatin regimen demonstrated a potential to delay recurrence more effectively compared to other therapies.

Background: and Purpose The relationship between thrombus histology and long-term stroke patient outcomes remains unexplored. We aimed to determine whether the histological characteristics of thrombi are associated with long-term outcomes in stroke patients and to identify the thrombus features linked to these outcomes. Methods: This retrospective multicenter cohort study included 512 patients with ischemic stroke who underwent endovascular thrombectomy between July 2017 and July 2023. Patients were followed up for long-term major adverse cardiovascular events occurrence. Thrombus histology was assessed using immunohistochemistry, including the proportion of fibrin, red blood cells, and platelets, as well as the distribution patterns categorized as layered, erythrocytic, diffuse platelet, and mixed. Results: During a median follow-up of 38.1 months, 164 patients experienced major adverse cardiovascular events, with an incidence rate of 3.02 per 100 person-years. Major adverse cardiovascular events occurrence was associated with the diffuse platelet pattern and proportion of platelets and red blood cells within the thrombus. After adjusting for confounders, the diffuse platelet pattern independently predicted major adverse cardiovascular events, including mortality and stroke recurrence. Subgroup analysis also demonstrated that the association between the diffuse platelet pattern and major adverse cardiovascular events was consistent across key clinical subgroups based on age (≥65 vs. <65 yr), atrial fibrillation, cancer status, and discharge medications. Conclusions Thrombus histology could provide predictive value for long-term prognosis. In particular, histological distribution patterns may be more important than simple composition in thrombus research, including in the prediction of prognosis.

Limb salvage surgery using a tumor prosthesis for the treatment of malignant bone tumors in the proximal femur is an effective method for preserving hip joint function. On the other hand, maintaining hip joint stability can be challenging because of the extensive resection of the bone and surrounding soft tissue. This paper reports an unusual case of hip dislocation in a patient with a proximal femoral osteosarcoma who underwent limb salvage surgery. Over six years, the tumor prosthesis gradually migrated posterosuperiorly above the iliac crest, resulting in 14 cm of lower limb shortening. The acetabular reconstruction was performed using an allograft, and the middle segment of the tumor prosthesis was removed to allow for hip reduction. Concurrent reconstruction of the hip abductor muscles was also carried out. No recurrence of the dislocation was observed during follow-up, and the patient could walk independently with the aid of an orthopedic brace, despite an 8 cm leg length discrepancy.

Rectal cancer, which accounts for approximately 40% of colorectal cancers, remains a major clinical concern. Recent advances in diagnostic imaging, surgical techniques, radiotherapy, and systemic treatment have steadily improved rectal cancer outcomes. Considering this, the Korean Rectal Cancer Multidisciplinary (KRCM) Committee has aimed to provide clinicians and policymakers with up-to-date, evidence-based clinical practice guidelines to support optimal decision-making, reflecting current evidence, the Korean healthcare context, and patient values and preferences. The Clinical Practice Guidelines for Rectal Cancer version 2.0 were developed through multidisciplinary collaboration with related academic societies, building upon and updating the KRCM Clinical Practice Guidelines version 1.0 (titled “Multidisciplinary guidelines for the management of rectal cancer”). These consensus guidelines of the KRCM were established based on a comprehensive literature review, evidence synthesis, with recommendation development guided by the GRADE (Grading of Recommendations Assessment, Development and Evaluation) methodology, and consideration of applicability in real-world clinical practice under the national health insurance system. Each recommendation has been presented with its strength and level of evidence.