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Background/aim: Behçet's Disease is a systemic vasculitis affecting both venous and arterial vessels, characterized by painful oral and genital ulcers. Primary Sjögren's Syndrome is an autoimmune disorder mainly targeting exocrine glands, especially the salivary and lacrimal glands, with possible systemic involvement. Molecular hydrogen has emerged as a potential adjuvant therapy due to its antioxidant and immunomodulatory effects. This report evaluates the efficacy of molecular hydrogen as adjunctive therapy for refractory oral ulcers in a patient with Behçet's disease and primary Sjögren's syndrome.

Case report: A 67-year-old Taiwanese woman with Behçet's disease and primary Sjögren's syndrome had recurrent painful oral ulcers and mucosal atrophy since 2018, meeting the International Study Group (ISG) criteria. In 2020, she fulfilled the 2016 European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) criteria for Sjögren's syndrome based on Schirmer's test (0/0 mm), positive anti-Ro antibody (29 U/ml), and labial salivary gland biopsy findings. Despite long-term, hydroxychloroquine, colchicine, and monthly high-dose intravenous vitamin C and glutathione, her oral ulcers recurred with petechiae and bleeding. In January 2024, oral molecular hydrogen capsules were added as adjunctive therapy. Over several months, she showed marked clinical improvement, with less mucosal bleeding and decreased anti-Ro antibody levels. Immunophenotyping revealed increased naïve T helper Fas cell surface death receptor-positive (Fas⁺) and cytotoxic T cell programmed death-1-positive (PD-1⁺) subsets, suggesting immunomodulatory effects. The therapy was well tolerated, with no major adverse events. By August 2025, oral ulcers had markedly improved, and systemic disease remained stable on maintenance with hydroxychloroquine, azathioprine, corticosteroid infusions, and hydrogen therapy.

Conclusion: Molecular hydrogen may aid refractory oral ulcers in Behçet's and primary Sjögren's syndromes, with clinical and immunologic benefits.

Background/aim: The incidence of positive microscopic margins after gastrectomy for gastric cancer (GC) has been reported between 1% to 5%. The aim of the present study was to identify risk factors associated with positive microscopic resection margin in GC patients undergoing gastrectomy, and to assess the survival outcomes and prognostic factors in these patients.

Patients and methods: The patients were selected from the consecutive database of Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Department of Gastric Surgery, according to the following criteria: (i) histologically proven gastric adenocarcinoma (ii) patients who underwent curative gastrectomy for gastric cancer as a primary treatment and archived R0 or R1 resection between 2005 and 2025. Positive microscopic resection margin was defined as disease present at the line of luminal transaction in mucosa, submucosa, or serosa on final pathology. Univariate and multivariate logistic regression analyses were performed to identify risk factors for resection margin positivity.

Results: A total of 1,996 patients were eligible for the present study. Among these patients, 35 patients (1.8%) had positive microscopic resection margin. Pathological type, macroscopic tumor type, and tumor size were identified as independent risk factors for positive resection margin in multivariate analysis. Moreover, positive peritoneal lavage cytology was identified as an independent predictor of poor overall survival prognostic factor in margin-positive GC patients.

Conclusion: Microscopic resection margin positivity after gastrectomy for GC was linked to specific tumor characteristics, while positive peritoneal lavage cytology independently predicted poorer survival. To minimize the occurrence of resection margin-positive GC after gastrectomy, it is essential to identify risk factors during perioperative evaluation. Furthermore, treatment strategies based on lavage cytology status could improve prognosis in high-risk patients.

Background/aim: Aortic valve calcification is a key determinant of aortic stenosis severity. Whether AI-derived thoracic aortic calcium volume reflects valvular calcification remains unclear. This study examined the association between aortic valve calcification quantified using Agatston, volume and mass scores, and total aortic calcium volume measured with an automated AI tool.

Patients and methods: This retrospective single-center study included 32 patients undergoing computed tomography (CT) for transcatheter aortic valve implantation planning. Aortic valve calcification was quantified on noncontrast CT using Agatston, volume and mass scores. Total aortic calcium volume was derived from contrast-enhanced CT using the AI-Rad Companion Chest CT. Correlation analyses and simple linear regression assessed associations between aortic and valvular calcification metrics.

Results: Mean total aortic calcium volume was 4.38 ml. Mean aortic valve Agatston score was 3307 units and mean valve calcium volume was 2727 mm³. Correlation between total aortic calcium and aortic valve Agatston score was weak and nonsignificant (Pearson r=0.213, p=0.259). Correlation with valve calcium volume was similarly weak (Pearson r=0.219, p=0.244). Regression models showed minimal explained variance (R²≈4-5 percent), and slopes were not statistically significant. No clinically relevant association between thoracic aortic calcium burden and aortic valve calcification was identified.

Conclusion: AI-derived thoracic aortic calcium volume did not correlate with aortic valve calcification. Valvular calcification appears to progress independently of thoracic aortic wall calcification. Automated aortic calcium measurements cannot substitute for direct quantification of aortic valve calcification in preprocedural assessment.

Background/aim: The management of difficult-to-treat rheumatoid arthritis (D2T-RA) is frequently complicated by the occurrence of severe adverse events (SAEs) that severely restrict therapeutic options. Emerging evidence suggests that refractory disease in seropositive patients may be driven by resilient immune cell subsets, such as T peripheral helper (Tph) cells and age-associated B cells (ABCs), which escape standard immune suppression.

Case report: We present the case of a 33-year-old female with high-titer seropositive RA [Anti-cyclic citrullinated peptide (CCP) >200 U/ml] and Sjogren's syndrome who exhibited sequential resistance to conventional synthetic disease-modifying antirheumatic drugs (DMARDs) and tumor necrosis factor (TNF) inhibitors. Subsequent treatment with the janus kinase (JAK) inhibitor upadacitinib was complicated by multi-dermatomal Herpes Zoster infection and a deep vein thrombosis (DVT) event, necessitating permanent drug withdrawal due to safety concerns. Despite a mechanistic switch to B-cell depletion therapy (rituximab), the patient maintained high disease activity (DAS28: 4.98). Longitudinal deep immunophenotyping revealed a distinct pathogenic cellular signature characterizing this refractory state. We observed a sustained expansion of programmed death-1 -positive (PD-1⁺) effector memory T helper cells (a proxy for Tph cells) and persistent circulating plasmablasts, indicating continuous B-cell differentiation. Furthermore, the B cell compartment showed a progressive accumulation of cluster of differentiation 21 (CD21)-low ABCs. While cluster of differentiation 39 (CD39)⁺Helios⁺ regulatory T cells fluctuated, they failed to suppress the inflammatory drive.

Conclusion: This case highlights the clinical complexity of managing D2T-RA when JAK inhibitors are contraindicated due to thromboembolic and infectious risks. The immunophenotypic data suggests that a resilient Tph-ABC interaction axis underpins the mechanism of therapeutic resistance, pointing towards the need for combination strategies targeting these specific cellular reservoirs.

Background/aim: Ferrochel consists of one ferrous ion chelated with two glycine molecules and is characterized by high bioavailability and physiological activity. However, its potential anti-fibrotic effects and underlying mechanisms remain need clarified. The aim of this study was to determine whether Ferrochel exerts anti-fibrotic activity in renal fibrosis and to clarify the mechanisms by which it may regulate fibrosis and epithelial-mesenchymal transition.

Materials and methods: A mouse renal tubulointerstitial fibrosis model was established by applying unilateral ureteral obstruction (UUO). Renal morphology, collagen deposition, and iron content were evaluated using hematoxylin and eosin (H&E) staining and Masson's trichrome staining. The expression of fibrosis- and epithelial-mesenchymal transition (EMT)-related proteins was assessed using immunohistochemistry (IHC) and immunoblotting. Cytotoxicity and cell motility were examined using the MTT assay and wound healing assay, respectively.

Results: Ferrochel treatment significantly reduced collagen deposition and renal injury in UUO mice without inducing iron accumulation. Moreover, Ferrochel reduced the expression of fibrosis markers (α-SMA and collagen I) and the EMT marker vimentin in the UUO model. In HK2 cells, Ferrochel did not exhibit cytotoxicity. However, it markedly attenuated transforming growth factor-beta1 (TGF-β1)-induced cell motility and decreased the expression of fibrosis markers (α-SMA and collagen I) as well as the EMT marker vimentin in TGF-β1-treated HK2 cells.

Conclusion: Ferrochel attenuated renal fibrogenesis and EMT in vitro and in vivo, indicating anti-fibrotic activity. These results suggest that Ferrochel may serve as a potential therapeutic agent for renal tubulointerstitial fibrosis.

Background/aim: Age-related cerebral microvascular loss is associated with reduced angiogenesis and leads to inadequate tissue perfusion in the brain. Vascular endothelial growth factor (VEGF), crucial for angiogenesis, declines with age. Exercise enhances microvascular density and blood flow, promoting brain health. The specific mechanisms underlying exercise-induced angiogenesis in aging brains remain unclear. This study investigated the impact of exercise on microvessel density, tissue perfusion, and VEGF-angiogenic signaling in aging brains.

Materials and methods: Male rats were divided into three groups: an age-matched control, a sedentary control, and an exercise-trained group, which underwent swimming exercise. Regional cerebral tissue perfusion (CTP) was assessed in an in vivo study. Brain immunohistochemical staining of glucose transporter-1 (GLUT1) was used to determine microvessel density and endothelial metabolic state. Immunoassays of VEGF angiogenic proteins in isolated brain microvessels were conducted to reveal microvascular signaling mechanisms.

Results: Microvessel density and regional CTP in the sedentary control group were significantly reduced compared to the age-matched control group. The exercise-trained group demonstrated substantial increases in microvessel density and regional CTP compared to the sedentary control group. An increase in GLUT1 in the exercise group indicates microvascular metabolic restoration. VEGF angiogenic protein levels were significantly decreased in the sedentary control group compared to the age-matched control group; however, exercise training significantly increased these protein levels relative to the sedentary control group. Furthermore, we discovered a strong and significant positive correlation among the microvessel density, regional CTP, and VEGF angiogenic proteins across the three groups.

Conclusion: Swimming exercise training may protect against age-induced cerebral microvascular loss and insufficient brain tissue perfusion through the VEGF-mediated angiogenic signaling cascade. The increase in GLUT1 indicates restored structural and metabolic endothelial function in the aging brain.

Background/aim: Anaplastic thyroid cancer (ATC) is a highly aggressive malignancy associated with a limited prognosis. Recent advances in targeted therapies and improved systemic therapy options have led to an increasing number of patients experiencing isolated or limited metastatic progression. Stereotactic radiosurgery (SRS) and stereotactic body radiotherapy (SBRT) have emerged as potential treatment options for metastatic ATC. This prospective observational study aimed to evaluate the role of SBRT and SRS in treating ATC metastases.

Patients and methods: Patients with histologically confirmed ATC and an indication for radiotherapy were enrolled at a tertiary care hospital in Munich, Germany from 12/2020 to 01/2025. Treatment-related toxicity was assessed using CTCAE v3, and follow-ups occurred every three months post-radiotherapy. A systematic literature review was conducted using PubMed/Medline, Scopus and Cochrane databases, analyzing studies on SRS and SBRT for ATC metastases.

Results: Our prospective patient cohort enrolled 31 patients, with four (12.9%) receiving SBRT/SRS for metastatic disease. The systematic review identified 11 studies that met the inclusion criteria, of which two were selected for further analysis. Reported overall survival ranged between 2.1 and 3.6 months. Our prospective study demonstrated efficacy of SBRT/SRS in providing symptom relief, accompanied by manageable adverse effects.

Conclusion: SBRT and SRS are viable treatment options for metastatic ATC, providing local tumor control and symptom relief with low toxicity, particularly for bone and brain metastases. However, given the poor prognosis associated with ATC, further research is required to refine patient selection criteria and optimize treatment regimens, particularly in combination with systemic therapy.

Chondromyxoid fibroma (CMF) is a rare benign cartilaginous neoplasm that most frequently occurs in the metaphysis of long bones in adolescents and young adults. The most common symptom is pain and/or swelling in the affected area. Radiographs typically show a well-defined, eccentric lytic lesion with sclerotic margins and scalloped or lobulated borders. Unlike other cartilaginous neoplasms, matrix calcification is uncommon. On magnetic resonance imaging (MRI), CMF usually exhibits low to intermediate signal intensity on T1-weighted sequences and heterogenous high signal intensity on T2-weighted sequences. Contrast-enhanced MRI demonstrates intense homogeneous, heterogeneous or peripheral enhancement. Histologically, CMF is composed of lobules of stellate to spindle-shaped cells in a myxoid background. The periphery of the lobules is generally hypercellular, imparting a characteristic zonal architecture. Recent molecular studies have identified alteration of glutamate metabotropic receptor 1 (GRM1) gene, and GRM1 positivity by immunohistochemistry has emerged as a reliable surrogate marker for this molecular event. Curettage or en bloc resection is the treatment of choice, with a non-negligible risk for local recurrence. This review provides an updated overview of the clinical, radiological, histological, immunohistochemical and molecular genetic features of CMF and discusses the differential diagnosis of this unusual neoplasm.

Background/aim: The transition from compensated to decompensated cirrhosis indicates a poor prognosis, and decompensated symptoms are subclassified as bleeding and non-bleeding. This study aimed to investigate the association between serum systemic inflammation marker levels and the development of the first bleeding and non-bleeding decompensation in patients with compensated cirrhosis.

Patients and methods: This retrospective study included 214 patients with compensated liver cirrhosis. The baseline serum C-reactive protein, interleukin 6, procalcitonin, and serum amyloid A protein levels were measured. Factors associated with the first decompensation were assessed using the Cox proportional hazards model. The probability of first decompensation was evaluated using Kaplan-Meier analysis and the log-rank test.

Results: In the study cohort, 167 (78%) patients showed elevation of one or more systemic inflammation markers. During a median follow-up of 3.6 years, 28 and 35 patients developed first bleeding and non-bleeding decompensation, respectively. The multivariate Cox proportional hazards model identified that nonviral etiology and low platelet count were significantly associated with bleeding decompensation and nonviral etiology, albumin-bilirubin grade, and serum interleukin 6 level with non-bleeding decompensation. Kaplan-Meier analyses showed that patients with high serum interleukin 6 levels (≥10 pg/ml) showed significantly higher probability of first non-bleeding decompensation than those with low serum interleukin 6 levels, but probability of bleeding decompensation was not different between them.

Conclusion: Serum pro-inflammatory cytokine interleukin 6 predicts the risk of first non-bleeding decompensation but not bleeding decompensation in patients with compensated cirrhosis.

Background/aim: Glioblastoma multiforme (GBM) is the most common and aggressive primary malignant brain tumor, with a poor prognosis despite standardized multimodal treatment. Recent research has explored the prognostic value of systemic inflammatory markers, which could provide accessible and cost-effective indicators of patient outcomes.

Patients and methods: This retrospective single-center study analyzed patients with GBM treated between 2014 and 2024. Eligible patients underwent radiotherapy with concurrent and adjuvant temozolomide. Hematological parameters, including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), systemic immune-inflammation index (SII), and systemic inflammatory response index (SIRI), were assessed for prognostic significance. Overall survival (OS) was analyzed using Kaplan-Meier curves and Cox regression models.

Results: A total of 74 newly diagnosed patients with GBM were included, with a median follow-up of 18 months. ROC curve analysis identified significant cutoff values for NLR, MLR, SII, and SIRI, which were associated with OS. Patients with elevated inflammatory markers had significantly worse OS. Median OS was significantly shorter in patients with elevated NLR (14 months vs. 21 months, p=0.01), MLR (13 months vs. 16 months, p=0.006), SII (14 months vs. 20 months, p=0.04) and SIRI (13 months vs. 20 months, p=0.001). No statistically significant correlation was found between inflammatory markers and MGMT promoter methylation status.

Conclusion: This study confirms the prognostic relevance of systemic inflammatory markers, particularly NLR, MLR, SII, and SIRI, in patients with GBM. These easily obtainable parameters could complement molecular profiling in risk stratification and treatment planning, pending validation in prospective studies, and contribute to more personalized patient management.