Search Results (78,326)

Background: The characteristics and prognosis of HIV-associated Kaposi sarcoma (KS) among people living with HIV (PLWH), and their association with HHV-8 viral load are not well understood in Japan. Methods: We conducted a retrospective study of PLWH diagnosed with KS at Tokyo Medical University from 2000 to 2023. Results: Seventy cases of KS were identified; HHV-8 viral load data were available for twenty-three of these cases. The median age was 43 years (interquartile range [IQR], 11 years). The median HIV viral load at diagnosis was 150,000 copies/mL (IQR, 560,000 copies/mL). The median CD4 count was 76.0/μL (IQR, 157/μL). Lesions other than those of the skin were observed in the gastrointestinal tract (nine cases, 39.1%), oropharynx (three cases, 13.0%), and bronchial/lung (two cases, 8.7%). The median HHV-8 viral load was 0.0 copies/10⁶ WBC (IQR, 1500 copies/10⁶ WBC). Among the nine deceased PLWH, KS inflammatory cytokine syndrome (KICS) was diagnosed in five PLWH. Older age (≥50 years) and a high HHV-8 viral load (>615 copies/10⁶ WBCs) were significantly associated with worse survival. Conclusion: A high HHV-8 viral load may be a risk factor for mortality in PLWH with KS. Notably, all PLWH diagnosed with KICS in this study died, underscoring the poor prognosis associated with this condition. Full article

Background: Altered lipid metabolism has been reported in several malignancies, but its clinical relevance in non-small cell lung cancer (NSCLC) remains uncertain. This study aimed to compare serum lipid parameters between NSCLC patients and healthy controls and to explore their association with histological subtype and selected driver mutations. Methods: We retrospectively analyzed serum total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL), and triglycerides (TG) in patients diagnosed with adenocarcinoma or squamous cell carcinoma from 2021 to 2024, alongside a control group of 100 healthy individuals. Statistical comparisons were performed using appropriate parametric or nonparametric tests after normality assessment (Shapiro–Wilk), and p-values were adjusted using the Benjamini–Hochberg false discovery rate (FDR). Results: A total of 160 NSCLC patients were included. Most were male (75.5%) and current or former smokers (96.1%), with a mean age of 70.4 ± 10.3 years. Squamous cell carcinoma was the predominant subtype (64.4%). Hypocholesterolemia was observed in 59.9% of patients, while hypercholesterolemia was less frequent (40.1%). Compared with controls, patients had significantly lower HDL levels (p = 0.007, FDR-adjusted p = 0.024), while other lipid markers showed no statistically significant differences after correction for multiple testing. Differences between adenocarcinoma and squamous cell carcinoma were not statistically significant. Squamous cell carcinoma patients had higher TG but lower TC, LDL, and HDL levels compared with adenocarcinoma. A negative correlation between TG and ROS1 expression remained significant (r = −0.223, FDR-adjusted p = 0.004). Conclusions: In this retrospective, real-world cohort, only HDL levels demonstrated a robust difference between NSCLC patients and controls. Observed associations should be interpreted cautiously due to potential confounding factors and incomplete clinical data inherent to retrospective analyses. Prospective studies are needed to clarify whether lipid alterations play a biological or prognostic role in NSCLC. Full article

In this study, we propose a YOLO-based object detection algorithm for the automated and accurate identification of the fifth wave (Wave V) in auditory brainstem response (ABR) graphs. The ABR test plays a critical role in the diagnosis of hearing disorders, with the fifth wave serving as a key marker for clinical assessment. However, conventional manual detection is time-consuming and subject to variability depending on the examiner’s expertise. To address these limitations, we developed a real-time detection method that utilizes a YOLO object detection model applied to ABR graph images. Prior to YOLO training, we employed a U-Net-based preprocessing algorithm to automatically remove existing annotated peaks from the ABR images, thereby generating training data suitable for peak detection. The proposed model was evaluated in terms of precision, recall, and mean average precision (mAP). The experimental results demonstrate that the YOLO-based approach achieves high detection performance across these metrics, indicating its potential as an effective tool for reliable Wave V peak localization in audiological applications. Full article

Background and Objectives: Patients with type 2 diabetes mellitus (T2DM) and ischemic stroke present with endothelial, vascular and left ventricular (LV) myocardial dysfunction. We investigated the effects of treatment with either glucagon-like peptide-1 receptor agonists (GLP-1RA) or sodium-glucose contrasporter-2 inhibitors (SGLT-2i) on endothelial glycocalyx, arterial stiffness, and LV myocardial strain in patients with metformin-treated T2DM and a prior ischemic stroke. Materials and Methods: A total of 54 consecutive patients with T2DM and ischemic stroke who attended a cardiometabolic outpatient clinic in Athens, Greece, and received either GLP-1RA (dulaglutide; n = 27) or SGLT-2i (empagliflozin; n = 27) were enrolled in the study. We measured the perfused boundary region (PBR) of the sublingual microvessels, a marker of glycocalyx thickness, as well as carotid-femoral pulse wave velocity (PWV) and LV global longitudinal strain (GLS), at baseline and at 4 and 12 months of treatment. Results: Twelve months after treatment, all patients had reduced glycosylated hemoglobin and body mass index (BMI) (p < 0.001). Patients treated with dulaglutide showed a greater reduction in BMI (−11.8% vs. −4.8%, p < 0.001) compared to those treated with empagliflozin. Compared to baseline, all patients had reduced PBR, PWV and GLS (p < 0.001) after 12 months of treatment. However, empagliflozin presented a greater decrease in PWV (−14% vs. −10.9%, p = 0.041), while dulaglutide resulted in a greater increase in GLS (14.7% vs. 8.3%, p = 0.024) compared to empagliflozin. In all patients, the reduction in PBR at 12 months was correlated with a decrease in PWV and with an increase in GLS (p < 0.05). Conclusions: Both dulaglutide and empagliflozin improve cardiovascular function in T2DM patients with ischemic stroke. Dulaglutide appears to be more effective in the improvement of LV myocardial strain, whereas empagliflozin is more effective in reducing arterial stiffness. Full article

Cervical dystonia (CD), blepharospasm (BSP), and idiopathic hemifacial spasm (HFS) are focal hyperkinetic movement disorders with distinct underlying mechanisms. While CD and BSP involve central network dysfunctions within the basal ganglia-thalamo-cortical and cerebellar circuits, HFS primarily results from peripheral facial nerve hyperexcitability. Still, people living with all three conditions often struggle with mood issues like depression and anxiety, which can originate from both the burden of illness and changes in brain biology. We studied 61 patients (CD, n = 30; BSP, n = 9; HFS, n = 22) and assessed depression and anxiety before and three weeks after botulinum neurotoxin type A (BoNT-A) therapy, considering injection site and dose. BoNT-A significantly reduced depressive and anxiety symptoms across all groups, regardless of disease type, dose, or glabellar injection. These psychiatric improvements were not associated with the degree of motor symptom reduction, suggesting a partially independent mechanism of mood modulation. Our findings indicate that BoNT-A’s mood benefits may extend beyond local motor effects, possibly involving broader sensorimotor-limbic interactions. These results highlight the therapeutic potential of BoNT-A for addressing non-motor symptoms in both dystonic and non-dystonic hyperkinetic disorders. Future studies employing imaging and neurophysiological methods are necessary to explain the neural pathways underlying these effects. Full article

Background: The clinical meaning of hip joint synovial cavity thickness (HJSCT) on ultrasound (US) in juvenile idiopathic arthritis (JIA) without effusion is uncertain. Methods: In this cross-sectional study, we analyzed 369 children (187 JIA; 182 controls) undergoing hip US at a referral center in Kraków, Poland. JIA examinations were performed upon initial referral, early in the care pathway. We excluded patients with hip effusion and pre-existing inflammatory, traumatic or degenerative hip pathology. HJSCT was defined as the distance from the outer capsule margin to the femoral neck cortex. We used a Toshiba Aplio 400 system with a 12 MHz probe to measure and derive mean bilateral HJSCT. Bilateral concordance was assessed. Iterative multivariable linear regression modeling was used to compare groups, adjusting for non-linear age effects (natural splines) and WHO height-for-age z-scores (HAZ). Results: Left–right HJSCT agreement was high (ICC 0.947; mean difference 0.03 mm; 95% limits of agreement −0.64–0.70). In unadjusted analysis, mean (SD) HJSCT was similar in JIA versus controls: 5.83 (1.09) vs. 5.95 (0.99) mm, respectively (p = 0.25). In the final model (adj. R2 0.656), HJSCT was strongly associated with age (non-linear, p < 0.001) but not significantly associated with HAZ (β = 0.04; p = 0.11) or JIA status (β = 0.07; p = 0.30). Predicted HJSCT showed a steep increment in childhood and plateau in adolescence. Conclusions: In children without hip effusion, HJSCT mainly reflects physiological growth and does not differ significantly between early JIA patients and healthy controls. These findings suggest that capsular thickening is not a reliable standalone marker for early disease in the absence of effusion. Full article

Background/Objective: This systematic review aims to evaluate ex vivo brain slice models in glioblastoma (GBM) research, with a specific focus on tumour invasion, tumour–microenvironment interactions, and therapeutic response. Methods: A systematic search looking for studies employing ex vivo organotypic brain slice models in GBM research was conducted across multiple databases (January 2010–July 2025) in accordance with PRISMA guidelines. The study was registered in PROSPERO database (CRD420251138341). Inclusion criteria encompassed patient-derived brain slices, hybrid rodent–human slice co-cultures, and microfluidic-integrated ex vivo platforms designed to assess tumour invasion, microenvironmental interactions and therapeutic responses. Exclusion criteria included reviews, abstracts, conference proceedings, in vivo-only studies, purely in vitro models without organotypic integration, and studies not focused on GBM. Results: Twenty-six studies met the inclusion criteria. Among these, 18/26 (69%) investigated GBM invasion, 18/26 (69%) evaluated therapeutic responses, and 5/26 (19%) examined tumour–microenvironment interactions, with several studies spanning multiple domains. Across platforms, organotypic slices consistently recapitulated key features of GBM biology—including perivascular and white-matter-aligned invasion, stromal–immune interactions, and patient-specific drug sensitivity—while engineered systems enhanced perfusion and exposure control. Methodological variability, particularly regarding slice preparation, oxygenation and viability assessment, limits direct comparability between studies. Conclusions: Organotypic brain slice models represent an extremely relevant tool for translational investigations of GBM biology and treatment response. However, substantial methodological heterogeneity together with limited standardisation hamper reproducibility and cross-study validation. Future work should focus on enhancing reproducibility and harmonising protocols to support the development of clinically meaningful precision oncology strategies. Full article

Background: Thymic epithelial tumors (TETs), including thymic carcinomas and thymomas, are rare malignancies originating in the mediastinum. Therapeutic options remain limited for patients experiencing disease progression following platinum-based chemotherapy. High tumor mutational burden (TMB) is uncommon in thymic malignancies but may predict response to immunotherapy. We report a patient with TMB-high TET who participated in the KOSMOS-II study in South Korea and achieved a durable response to atezolizumab without developing immune-related adverse events (irAEs). Case presentation: A 73-year-old woman who had been treated for thymoma 20 years ago presented with a left neck mass. A biopsy of the neck mass confirmed recurrent thymoma, type B3, and her disease progressed despite platinum-based chemotherapy and subsequent pemetrexed treatment. TMB-high thymoma is very rare, but based on the next-generation sequencing (NGS) results, she was diagnosed with TMB-high (20.3 mutations/Mb) thymoma. As TMB-based immunotherapy is not approved in Korea, she was enrolled in the KOSMOS-II study and initiated on atezolizumab following molecular tumor board review. She achieved stable disease after three cycles and has remained progression-free for 14 months, completing 20 cycles without significant irAEs. Notably, her underlying myasthenia gravis did not worsen during treatment. Conclusions: This case demonstrates a favorable outcome with biomarker-directed ICI treatment in recurrent thymoma with limited treatment options, highlighting the importance of appropriate molecular markers to predict drug response. Although TMB-based immunotherapy is FDA-approved in the U.S., it remains unavailable in Korea, underscoring the need to explore flexible access pathways, including the potential use of immunotherapy beyond current indications, to improve treatment options for patients with life-threatening conditions. Full article

Background: Protein–energy wasting (PEW) is a major predictor of morbidity and mortality in patients with chronic kidney disease (CKD), even before the initiation of dialysis. Its multifactorial pathogenesis includes reduced dietary intake, chronic inflammation, metabolic acidosis, hormonal disturbances, and dysbiosis of the gut microbiota. Early recognition and targeted management are crucial for preventing muscle loss, functional decline, and adverse outcomes. Methods: This narrative review summarises and integrates current evidence from the literature on nutritional and metabolic interventions to prevent and treat protein–energy wasting in patients with nondialysis chronic kidney disease. Relevant clinical trials, meta-analyses, and experimental studies published up to date were evaluated, focusing on dietary strategies, metabolic modulation, physical exercise, and gut microbiome-targeted therapies. Results: Adequate energy and protein intake remain the cornerstone of PEW management, based on available clinical and observational evidence. Individualised diets emphasising high-quality and plant-based proteins, oral nutritional supplements, and ketoanalogues can attenuate muscle wasting. Correction of metabolic acidosis and inflammation enhances protein anabolism and nitrogen balance. Physical exercise acts synergistically with dietary interventions to preserve muscle mass and function. Novel approaches—such as modulating the gut–kidney axis with pre-, pro-, and postbiotics or supplementing with short-chain fatty acids—show promise in improving metabolic and inflammatory profiles. Conclusions: The management of PEW in nondialysis CKD requires a personalised approach that integrates nutrition, physical activity, metabolic correction and microbiome modulation. Early, coordinated intervention may help to slow the progression of CKD and improve patient survival and quality of life. Full article

This study aimed to elucidate the oncogenic role of FOXA1(forkhead box A1) in ovarian cancer and to evaluate its potential as both a therapeutic target and a diagnostic biomarker. We further investigated whether FOXA1 inhibition could enhance responsiveness to immune checkpoint blockade and overcome chemoresistance. A total of seventy-six ovarian tissue samples were analyzed, including nine normal, thirty-four benign, and thirty-three malignant specimens. IHC (immunohistochemistry) staining was performed to assess FOXA1 expression and its correlation with tumor stage. Functional studies were conducted using FOXA1 siRNA in SK-OV3 and HEYA8 cell lines. Changes in cell proliferation, migration, invasion, and wound-healing ability were evaluated following FOXA1 silencing. Quantitative RT-PCR was used to measure the expression of FOXA1 and EMT (epithelial–mesenchymal transition)-related genes. The effects of FOXA1 inhibition on sensitivity to carboplatin and the immune checkpoint inhibitor atezolizumab were also examined. IHC analysis revealed significant differences in FOXA1 expression among normal, benign, and malignant tissues, with levels correlating with tumor stage. FOXA1 silencing significantly reduced proliferation and decreased migration and invasion by 60–80%, accompanied by marked downregulation of EMT-related genes. Moreover, FOXA1 inhibition enhanced atezolizumab responsiveness and reduced carboplatin resistance in ovarian cancer cells. In summary, FOXA1 acts as an oncogenic driver in ovarian cancer, promoting proliferation, invasion, and EMT activation. Its overexpression correlates with disease progression, supporting its potential as a biomarker and therapeutic target. Targeting FOXA1 could enhance immunotherapy efficacy and help overcome chemoresistance in ovarian cancer. Full article

Despite tremendous scientific efforts aimed at glioblastoma’s (GB) ability to escape therapeutic attempts, the concern remains unsolved. Postbiotics, metabolites, and macromolecules of probiotic bacteria could become adjuvant therapeutics both dealing with cellular events constituting tumor therapy escape mechanisms and protecting normal cells from therapy-induced damage. The study aims to evaluate the dual potential of postbiotics obtained from lactic acid bacteria, L. plantarum and L. rhamnosus, on patient-derived and commercially available GB and normal cells alone and in combination with chemotherapeutic and irradiation oncotreatment regimens. Postbiotic mixtures (PMs) show cytoprotective potential against a new anti-cancer agent—ARA12—on astrocytes and cytoprotective action to irradiated normal fibroblast cells. Although GB cells’ apoptotic response varied between patient-derived cells, both PMs exert cytotoxic or cytostatic effects alone and, in most of the studied therapeutic combinations, on all tested GB cell lines. In particular, L. plantarum PM alleviates treatment escape, possibly shifting the tumor drug response from senescence to apoptosis. The results suggest that postbiotic-based adjunctive treatment could potentiate the therapeutic effect toward neoplastic cells, while alleviating chemotherapy’s adverse effects, helping clinicians to tackle the issue of therapy resistance and improve patients’ comfort. Full article

Postpericardiotomy syndrome (PPS) is the most frequent inflammatory after-effect of cardiac surgery and is characterized by high morbidity, delayed hospitalization, and increased long-term mortality rates. Although PPS is common, empirical anti-inflammatory therapy has historically been employed for its prevention, and mechanism-based approaches have not yet been standardized. In this literature review, which was conducted on the basis of randomized controlled trials, meta-analyses, cohort studies, and mechanistic research regarding pharmacologic interventions, surgical modalities, and biomarker-based preventive strategies, the deficiencies of a critical synthesis of existing preventive strategies and emerging risk stratification instruments for PPS are addressed. The review affirms that the most evidence-based pharmacologic intervention is colchicine, which demonstrates a consistent reduction in PPS incidence across a range of randomized trials. Nonsteroidal anti-inflammatory drugs show variable responses, whereas corticosteroids are no longer recommended for routine prophylaxis due to relapse. Specific anti–interleukin-1 therapies represent a promising novel approach for high-risk patients. Surgical interventions, such as pericardial closure using biomaterials and posterior pericardiotomy, are important and do not lead to increased hemodynamic complications, while postoperative effusions, atrial fibrillation, and tamponade are reduced. Less invasive methods may also be employed to mitigate inflammatory causes, particularly in valve-sparing procedures and congenital operations. Emerging biomarker data, including postoperative neutrophil-to-lymphocyte ratios, C-reactive protein levels, and pericardial fluid cytokines, enable the identification of high-risk patients and form the basis for a personalized prevention approach. In summary, pharmacologic prophylaxis, innovative surgical techniques, and biomarker-based risk stratification represent a pathway toward reducing the incidence and burden of PPS in modern cardiac surgery. Full article

The escalating incidence of colorectal cancer (CRC), particularly the alarming rise in early-onset cases, necessitates a paradigm shift from a purely genetic perspective to a broader investigation of promising pathways. This review explores the “nutri-epigenetic” interface, positioning liquid biopsy as a critical technology for translating dietary impacts into actionable clinical biomarkers. We contrast the molecular consequences of the Western dietary pattern, characterized by methyl-donor deficiency and pro-inflammatory metabolites, with the protective mechanisms of the Mediterranean diet. Mechanistically, we detail how Western-style diets drive a specific “epigenetic double-hit”: promoting global DNA hypomethylation (destabilizing LINE-1) while paradoxically inducing promoter hypermethylation of critical tumour suppressors (MLH1, APC, MGMT) and silencing tumour-suppressive microRNAs (miR-34b/c, miR-137) via methylation of their encoding genes. Conversely, we highlight the capacity of Mediterranean bioactive compounds (e.g., resveratrol, curcumin, butyrate) to inhibit DNA methyltransferases and restore epigenetic homeostasis. Bridging molecular biology and clinical utility, we demonstrate how these diet-sensitive signatures, specifically circulating methylated DNA and dysregulated microRNAs, can be captured via liquid biopsy. We propose that these circulating analytes serve as dynamic, accessible biomarkers for monitoring the molecular progression toward a carcinogenic state, thereby establishing a novel framework for personalized risk stratification and validating the efficacy of preventive nutritional strategies. Full article

Background and Clinical Significance: Fibrolipoma is an uncommon histological variant of lipoma characterized by mature adipose tissue with a significant fibrous component. Intraoral lipomas are rare (only about 1–4% of all lipomas) and lipomas arising in the buccal fat pad (buccal space) are particularly uncommon. Case Presentation: A 47-year-old male presented with a painless, slowly enlarging swelling in the left cheek region. Physical examination revealed a soft, non-tender mass in the buccal space, causing mild bulging of the cheek. Contrast-enhanced computed tomography and magnetic resonance imaging demonstrated a well-circumscribed lesion within the left buccal fat pad suggestive of a lipoma. The tumor was excised entirely via an intraoral approach under general anesthesia. Histopathological examination showed lobules of mature adipocytes interspersed with dense fibrous connective septa consistent with a diagnosis of a fibrolipoma. The postoperative course was uneventful. Conclusions: This case highlights that fibrolipoma, while rare in the maxillofacial region, should be included in the differential diagnosis of buccal space tumors. Imaging studies can aid in identifying the fatty nature and extent of such lesions, but definitive diagnosis relies on histopathology. The buccal fat pad’s anatomy allows an intraoral surgical approach in appropriate cases, providing direct access and excellent cosmetic outcomes. Complete excision is curative in benign fibrolipomas, and careful surgical technique prevents injury to adjacent structures. Full article

Background: Sinonasal undifferentiated carcinoma (SNUC) is an extremely rare, high-grade, and aggressive tumor of the sinonasal tract. Due to the rarity of this malignancy, current treatment guidelines are based on small and often/mainly single-center retrospective datasets. In the absence of a universally accepted standard of care for SNUC, treatment approaches vary across countries and institutions, reflecting real-world clinical practice. The primary aim of this study was to describe real-world treatment and outcomes for patients with confirmed SNUC. Methods: This was an international, multi-center, retrospective, observational cohort study that pooled patients into the largest SNUC dataset to date. Fifteen centers were enrolled to contribute data, including seven from Europe, four from the United States, three from the United Kingdom, and one from Canada. In the absence of a universally accepted standard of care for SNUC, treatment approaches varied across countries and institutions, reflecting real-world clinical practice. Patients included were those with histologically confirmed SNUC who were treated between 1997 and 2021. Results: This study yielded 485 patients treated for SNUC. The median age at diagnosis was 55.6 years (IQR: 44.5–67.6), and 63.7% were male. Most cases presented at advanced stages, with 70.8% as T4a or T4b. Overall survival (OS) outcomes were available for 412 patients, with a median follow-up of 26.0 months. The 5- and 10-year OS were 47.2% (95% CI: 40.8–53.3%) and 39.6% (95% CI: 32.5–46.6%), respectively. Advanced age, dichotomized T-stage (T4a/b vs. T1–3), M-stage, and orbital involvement were significant poor prognostic factors on univariable analysis (p’s < 0.01). On multivariable analysis, orbital involvement (HR: 2.73, 95% CI: 1.42–5.27, p = 0.003) and distance metastasis stage (HR: 3.00, 95% CI: 1.25–7.21, p = 0.014) were both independently associated with worse OS. Conclusions: This observational study presents the largest multi-center cohort analysis of SNUC to date, providing new insights into prognostic factors for a rare cancer treated at global centers of excellence. Orbital involvement and the presence of metastases are candidate independent risk factors associated with poorer OS. Full article