Search Results (1,073)

Rituximab has been increasingly used as a choice of treatment in various forms of glomerulonephritis. Recent evidence and the KDIGO guideline establish Rituximab as the first-line treatment for Primary Membranous Nephropathy and ANCA-associated vasculitis. It is also recommended in cases of steroid-dependent or frequently relapsing Minimal Change Disease and Focal Segmental Glomerulosclerosis, as well as in refractory Lupus Nephritis. In this review, we set out to analyze the evidence behind its use and some of its shortfalls, including gaps in understanding the dosing and redosing schedule, as well as long-term safety, which advocate for further research. Finally, we also provide some practical tips on patient use. Full article

Objectives: There is a critical need for effective focal therapies for patients with inoperable or anatomically complex tumors where conventional ablation techniques pose high risk or are ineffective. Integrated Nanosecond Pulsed Irreversible Electroporation (INSPIRE) is a novel non-thermal ablation modality which uses real time temperature feedback during pulse delivery to safely treat tumors near critical structures. This study evaluated the impact of exposed electrode length on ablation zone size, reproducibility, and cardiac safety in a large animal model. Methods: INSPIRE treatments were performed in an in vivo healthy porcine liver model. All treatments administered 6000 V 1000 ns pulses with a 45 °C temperature set point. Treatments were administered percutaneously via an electrode and grounding pad approach using an internally cooled electrode applicator. The exposed electrode region at the distal end of the applicator was set to either 0.5, 1.0, 1.5, or 2.0 cm. Ablation zones were assessed via ultrasound, contrast-enhanced CT, and gross pathology one week post-treatment. Cardiac safety was evaluated by measuring pre- and post-treatment serum Troponin levels. Results: All treatments were completed without adverse events. Troponin levels remained stable (pre: 0.249 ng/mL; post: 0.224 ng/mL), indicating no measurable cardiac injury. The 1.5 cm exposure length produced the largest and most consistent ablation volumes, with a mean volume of 12.8 ± 2.6 cm³ and average dimensions of 3.7 × 2.7 cm in under 6 min. Increasing exposure length beyond 1.5 cm introduced greater variability and reduced treatment volumes. Conclusions: INSPIRE enables safe, large-volume, single-applicator ablation without a need for electrical pulse synchronization with R wave in cardiac rhythm. The 1.5 cm exposure length offers optimal balance between energy delivery and treatment consistency. These findings support further clinical investigation of INSPIRE for non-thermal ablation of inoperable tumors. Full article

Background: Epilepsy and cognitive impairment frequently coexist, yet their relationship remains complex and insufficiently understood. This study aims to explore the clinical and electrophysiological features of patients presenting with both conditions in order to identify patterns that may inform more accurate diagnosis and effective management within a personalized medicine framework. Methods: We retrospectively analyzed 14 patients with late-onset epilepsy and coexisting cognitive impairment, including mild cognitive impairment and Alzheimer’s disease. Clinical history, cognitive assessments, neuroimaging, and electroencephalographic recordings were reviewed. EEG abnormalities, seizure types, and treatment responses were systematically documented. Results: Patients were categorized into two groups: (1) those with established Alzheimer’s disease who later developed epilepsy and (2) those in whom epilepsy preceded cognitive impairment. Temporal lobe involvement was a key feature, with EEG abnormalities frequently localizing to the frontal–temporal electrodes and manifesting as background slowing, focal multiform slow waves, and epileptiform discharges. Levetiracetam was the most commonly used antiseizure medication, and it was effective across both groups. Conclusions: This case series highlights the value of EEG in characterizing patients with subclinical and overt epileptic activity and cognitive impairment comorbidity. The inclusion of a substantial number of cases with documented EEG abnormalities provides valuable insight into the interplay between epilepsy and neurodegenerative diseases. By integrating neurophysiological data with clinical and cognitive trajectories, this work aligns with the principles of precision medicine, facilitating a more comprehensive evaluation and tailored management approach. Further longitudinal studies are required to validate prognostic markers and guide optimal therapeutic strategies. Full article

Oral tongue squamous cell carcinoma (OTSCC) is a common type of oral cancer influenced by genetic, epigenetic, and environmental factors like exposure to environmental toxins. These environmental toxins can decrease the effectiveness of established chemotherapy drugs, such as Irinotecan, used in OTSCC treatment. Bioinformatics, drug discovery, and machine learning techniques were employed to investigate the impact of Irinotecan on OTSCC patients by identifying targets and signaling pathways, including those that positively influence protein phosphorylation, protein tyrosine kinase activity, the PI3K-Akt (Phosphatidylinositol 3-kinase- Protein Kinase B) signaling system, cancer pathways, focal adhesion, and the HIF-1 (Hypoxia-Inducible Factor 1) signaling pathway. Later, the protein–protein interactions (PPIs) network, along with twelve cytoHubba approaches to finding the most interacting molecule, was employed to find the important proteins BCL2 and EGFR. Drugs related to BCL2 and EGFR were extracted from the DGIdb database for further molecular docking. Molecular docking revealed that Docetaxel, Paclitaxel, Imatinib, Ponatinib, Ibrutinib, Sorafenib, and Etoposide showed more binding affinity than Irinotecan (i.e., −9.8, −9.6). Of these, Paclitaxel (−10.3, −11.4) and Imatinib (−9.9, −10.4) are common in targeting BCL2 and EGFR. Using these identified candidate genes and pathways, we may be able to uncover new therapeutic targets for the treatment of OTSCC. Furthermore, molecular dynamics (MD) simulations were performed for selected ligand–receptor complexes, revealing stable binding interactions and favorable energetic profiles that supported the docking results and strengthened the reliability of the proposed drug repurposing strategy. Full article

WWOX and HIF1α proteins are involved in cancer progression; their functions are closely related. WWOX binds HIF1α through its WW domains, sequestering it in the cytoplasm and inhibiting its transcriptional activity. This study evaluates the prognostic significance of the WWOX/HIF1A interaction across cancers, breast cancer subtypes, glioblastoma (GBM), low-grade glioma (LGG), and hepatocellular carcinoma (HCC) through gene expression and pathway analysis focused on metabolism, ECM, and epithelial–mesenchymal transition. In breast cancer, metabolic pathways correlated with good prognosis in basal subtypes. HER2 subtypes showed enrichment in DNA replication pathways. Luminal A subtypes showed favourable prognosis via TNF and PI3K/AKT signalling, while luminal B subtypes had poor prognosis tied to metabolic activity; genes associated with good prognosis mirrored those tied to poor prognosis in luminal A. In HCC, enhanced metabolic activity was associated with good prognosis. In contrast, poor prognosis involved TNF signalling and cytoskeleton-related pathways, indicating more aggressive tumour behaviour. In LGG, good prognosis was linked to metabolic and cAMP pathways, while poor outcomes involved TNF, cell cycle, apoptosis, and focal adhesion pathways. GBM showed similar patterns: metabolic and cAMP pathways indicated better outcomes, while NFKB, TNF, JAK-STAT, and PI3K/AKT pathways marked poor prognosis. These findings suggest the WWOX/HIF1A ratio is a robust prognostic marker and a possible guide for developing targeted treatments. Full article

Background and objective: Minimally invasive interventions, including irreversible electroporation (IRE), cryoablation, and high-intensity focused ultrasound (HIFU), offer promising alternatives for the treatment of low- and intermediate-risk prostate cancer. We aimed to evaluate the oncological efficacy and safety of these treatments. Methods: A systematic search of MEDLINE, Central, and EMBASE was conducted up to 5 January 2025, according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Recurrence, complication, survival, biochemical, and retreatment rates were evaluated, with risk of bias assessed using the Risk of Bias In Non-randomized Studies of Interventions (ROBINS-I) and Risk of Bias 2 (RoB2) tools. Results: 85 studies met the inclusion criteria, comprising 42 prospective cohort studies, 36 retrospective cohort studies, six registries, and one randomized controlled trial. Whole-gland HIFU showed significantly lower recurrence (15%) and postoperative mean PSA levels (0.68 ng/mL) than focal HIFU (24%, 2.81 ng/mL). Recurrence rates were similar for focal vs. extended IRE (30% vs. 26%) and focal vs. whole-gland cryoablation (18% vs. 13%). In-field and out-of-field recurrence rates were similar across treatment modalities (5–15%). Retreatment rates were low, with 6–7% of patients receiving a second ablation and 2–8% progressing to radical or hormonal therapy. Major complications were consistently rare. One-year biochemical recurrence-free survival (BRFS) exceeded 95%, and five-year BRFS approached 80% for HIFU and cryoablation. Conclusions: Minimally invasive focal and whole-gland therapies are safe and effective for treating low- and intermediate-risk prostate cancer, with high survival and low major complication rates. Notably, whole-gland HIFU achieves superior biochemical control and lower recurrence than focal HIFU, emphasizing the clinical importance of treatment extent. Full article

The complex pathological mechanisms of atherosclerosis (AS) involve lipid metabolism disorders, inflammatory responses, and plaque instability, resulting in significant challenges to effective clinical management. Current therapeutic approaches, such as statins and stent implantation, suffer from issues including single-target action, notable side effects, and the risk of restenosis. Nanoparticle-based drug delivery systems have demonstrated considerable promise by enabling the codelivery of multiple agents directly to atherosclerotic lesions, thereby improving therapeutic efficacy and minimizing systemic toxicity. Among various nanomaterials, organic nanoparticles have recently emerged as a research hotspot in the field of AS treatment due to their excellent biocompatibility, degradability, and potential for targeted modification. This review systematically summarizes the recent advances and emerging trends in the application of organic nanoparticles for AS treatment, employing bibliometric analysis to delineate research frontiers. We employed bibliometric tools to analyze 1999 articles on organic nanocarriers for AS therapy indexed in the Web of Science Core Collection. The analysis included co-occurrence and clustering techniques to explore influential keywords and key contributors. Temporal analysis was applied to identify emerging research hotspots and track the evolution of this field. The literature reveals three major current focal areas: (1) the development of engineered biomimetic organic nanoparticles; (2) the design of multifunctional polymer-based organic nanocarriers; and (3) the innovation of organic-coated stents. This article not only provides a comprehensive overview of cutting-edge organic nanotechnologies for AS therapy, but also critically discusses the challenges in clinical translation, offering insights into future directions for the development of safe, effective, and personalized nanomedicine strategies against AS. Full article

Multiple sclerosis (MS) is a chronic disease of the central nervous system that significantly impairs gait and mobility, contributing to a high risk of falls, reduced participation in daily activities, and diminished quality of life. Despite existing interventions such as exercise programs and pharmacological treatments, challenges such as fatigue, pain, and limited accessibility underscore the need for alternative therapies. Focal vibration therapy (FVT) has shown promise in improving gait, reducing spasticity, and enhancing mobility in people with MS (PwMS). However, further research is required to evaluate its long-term feasibility and optimize its parameters. This study examined the feasibility and preliminary efficacy of a home-based four-week wearable FVT device on gait and explored how FVT parameters impact gait and mobility outcomes. In this pilot double-blind randomized controlled trial, 22 PwMS were randomized into control and vibration groups (four FVT groups with varying vibration intensities/durations). Participants wore Myovolt^® vibrators on distal quadricep muscles near the rectus femoris insertion (approximately 2 cm from the medial edge of the patella), gastrocnemius/soleus, and tibialis anterior muscles (10 min/muscle, 3 days/week, 4 weeks). Feasibility was evaluated via adherence and satisfaction (QUEST 2.0, interviews). Gait (3D motion analysis) and mobility (T25FW) were assessed at baseline and post-intervention. Data were analyzed using descriptive/inferential statistics and thematic analysis. Of 22 participants, 17 completed post-intervention (16 intervention, 1 control). Wearable FVT showed promising feasibility, with high satisfaction despite minor adjustability issues. Intervention groups improved gait speed (p = 0.014), stride length (p = 0.004), and ankle angle (p = 0.043), but T25FW was unchanged (p > 0.05). High-intensity FVT enhanced knee/hip moments. This study’s results support the feasibility of wearable FVT for home-based management of mobility symptoms in MS with high participant satisfaction and acceptance. Notable gains in gait parameters suggest FVT’s potential to enhance neuromuscular control and proprioception but may be insufficient to lead to mobility improvements. Subgroup analyses highlighted the impact of vibration intensity and duration on knee joint mechanics, emphasizing the need for personalized dosing strategies. Challenges included participant retention in the control group and burdensome biomechanical assessments, which will be addressed in future studies through improved sham devices and a larger sample size. Full article

Introduction: Patients with generalized epilepsy are rarely referred for advanced diagnostics like magnetoencephalography (MEG). This is due to the assumption that generalized seizures cannot be localized noninvasively. Methods: We present simultaneous MEG (306 channels) and EEG (64 channels) data from seven patients with drug-resistant generalized epilepsy. Three patients experienced typical generalized seizures during their MEG clinical evaluation. In total, 38 epileptiform events (three seizures, 35 interictal discharges) were analyzed using two software platforms and three localization methods: equivalent current dipole (ECD), sLORETA (via SWARM), and dynamic statistical parametric mapping (dSPM). Individual head models were created from each patient’s MRI. Results: MEG successfully localized seizure onset zones, showing distinct hypersynchronous discharges on all sensors as well as alternately during interictal discharges. Localization was consistent across methods and generalized events within subjects, revealing cortical sources in all cases, with rapid propagation (27–60 ms) across networks. Conclusions: This study demonstrates that MEG can meaningfully localize both seizures and interictal discharges in generalized epilepsy. This supports a broader use for MEG beyond focal epilepsy. Incorporating MEG in drug-resistant cases including generalized epilepsies may improve diagnosis and guide treatments including non-surgical options. Full article

Background: The COVID-19 pandemic has claimed thousands of lives worldwide. While infection rates have declined in recent years, emerging variants remain a deadly threat. Accurate diagnosis is critical to curbing transmission and improving treatment outcomes. However, the similarity of COVID-19 symptoms to those of the common cold and flu has spurred the development of automated diagnostic methods, particularly through lung computed-tomography (CT) scan analysis. Methodology: This paper proposes a novel deep learning-based approach for detecting diverse COVID-19 variants using advanced textural feature extraction. The framework employs a dual-channel convolutional neural network (CNN), where one channel processes texture-based features and the other analyzes spatial information. Unlike existing methods, our model dynamically learns textural patterns during training, eliminating reliance on predefined features. A modified local binary pattern (LBP) technique extracts texture data in matrix form, while the CNN’s adaptable internal architecture optimizes the balance between accuracy and computational efficiency. To enhance performance, hyperparameters are fine-tuned using the Adam optimizer and focal loss function. Results: The proposed method is evaluated on two benchmark datasets, COVID-349 and Italian COVID-Set, which include diverse COVID-19 variants. Conclusions: The results demonstrate its superior accuracy (94.63% and 95.47%, respectively), outperforming competing approaches in precision, recall, and overall diagnostic reliability. Full article

Background: In the evolving landscape of localized prostate cancer management, focal therapies such as high-intensity focused ultrasound (HIFU) and prostate gland cryoablation (PGC) have emerged as organ-sparing alternatives for patients with low- to intermediate-risk disease. While these strategies aim to preserve functional outcomes, comparative data against robot-assisted radical prostatectomy (RARP) remain scarce and heterogeneous. Methods: We conducted a prospective, single-center study evaluating oncologic and functional outcomes in patients with organ-confined prostate cancer (Grade Group ≤ 2) treated with HIFU (n = 49), PGC (n = 114), or RARP (n = 109). Outcomes were assessed using standardized definitions at a median follow-up of 22 months. Treatment failure was defined according to EAU guidelines, and Kaplan–Meier analysis was applied to time-to-event outcomes. Results: Focal therapy patients were older, more comorbid, and had lower baseline erectile function (each p < 0.001). RARP was associated with the longest operative time but yielded the lowest complication rate (2.75% vs. 20.4% for HIFU and 31.5% for PGC; p < 0.001). Catheter-related morbidity was disproportionately higher in the PGC group. RARP conferred a longer time to treatment failure (p < 0.001), although continence and potency recovery at follow-up were comparable across groups. Notably, erectile function returned earlier among HIFU patients. Conclusions: While focal therapies offer promising early functional results with minimal perioperative risk, they are associated with earlier treatment failure and higher catheter-related morbidity, particularly after cryoablation. These findings underscore the need for individualized treatment strategies guided by standardized, comparative outcome frameworks. Full article

Background/Objectives: Spasticity is a common and disabling sequela of stroke that limits voluntary movement and functional recovery. Vibration therapy (VT) has been proposed as a non-invasive neuromodulatory intervention, but the existing studies report inconsistent outcomes due to methodological heterogeneity. This study aimed to evaluate the overall effectiveness of VT in reducing post-stroke spasticity and to identify optimal stimulation parameters via meta-analytic and meta-regression approaches. Methods: A systematic review and meta-analysis were conducted following the PRISMA 2020 guidelines. Standardized effect sizes (Hedges’ g) were calculated based on the within-group pre–post changes and compared across the groups. Meta-regression and subgroup analyses explored seven potential moderators, including the vibration frequency, amplitude, and time since stroke onset. Results: Thirteen randomized controlled trials (RCTs) involving whole-body or focal vibration interventions in stroke populations were included. Vibration therapy significantly reduced spasticity, yielding a moderate overall effect size (Hedges’ g = −0.50; 95% CI: −0.65 to −0.34; p < 0.001). The greatest treatment effects were observed when VT was applied during the late subacute to early chronic phase (6–12 months post-stroke), with low-frequency (<20 Hz) and low-amplitude (≤0.5 mm) stimulation. The frequency, amplitude, and stroke onset emerged as significant moderators (p < 0.05). Conclusions: Vibration therapy is an effective and clinically meaningful intervention for post-stroke spasticity, particularly when delivered with low-intensity parameters during the optimal recovery window. These findings support the development of individualized VT protocols and provide evidence to guide future rehabilitation strategies. Full article

Background: Clear cell renal cell carcinoma with rhabdoid features (ccRCC-R) is a highly aggressive variant of renal cell carcinoma that carries a poor prognosis and limited treatment options. Methods: To better define the clinicopathologic and molecular landscape of ccRCC-R, we conducted an integrated clinicopathologic and molecular study of 17 tumors of ccRCC-R, utilizing comprehensive histomorphologic evaluation, immunohistochemistry, and targeted next-generation sequencing (NGS). Results: Histologically, all tumors demonstrated classic clear cell renal cell carcinoma morphology with focal to extensive rhabdoid differentiation, characterized by eccentrically located nuclei, prominent nucleoli, abundant eosinophilic cytoplasm, and paranuclear intracytoplasmic inclusion. Architectural alterations, including solid/sheet-like, alveolar/trabecular, and pseudopapillary growth patterns, were frequently observed. Immunohistochemically, tumors commonly exhibited loss of PAX8 and Claudin4 expression, preserved cytokeratin AE1/AE3 staining, and diffuse membranous CAIX expression. Frequent loss of SMARCA2 with retained SMARCA4 supported aberrations in chromatin remodeling. Unsupervised hierarchical clustering based on pathway-specific somatic mutations identified four distinct molecular subgroups defined by recurrent alterations in (1) DNA damage repair (DDR) genes, (2) chromatin remodeling genes, (3) PI3K/AKT/mTOR signaling components, and (4) MAPK pathway genes. Clinicopathologic correlation revealed that each subgroup was associated with unique biological characteristics and suggested distinct therapeutic vulnerabilities. Conclusions: Our findings underscore the molecular heterogeneity of ccRCC-R and support the utility of pathway-based stratification for guiding precision oncology approaches and biomarker-informed clinical trial design. Full article

Focal therapy for prostate cancer (PCa) provides approaches to treat PCa patients in a less invasive manner than traditional whole-gland surgical or radiation modalities. This manuscript provides a case series of high-intensity focused ultrasound (HIFU), cryoablation, and irreversible electroporation (IRE) for PCa at a single institution and cost analysis with a review of the literature. All patients who underwent HIFU, cryoablation, or IRE for localized PCa were retrospectively reviewed, excluding patients who received whole-gland therapy. Functional outcomes were erectile dysfunction and lower urinary tract symptoms. Cost data were collected. A total of 45 patients were included in the study with focal therapy ranging from 2023 to 2025 (4 HIFU, 20 cryoablation, 21 IRE). A total of 30 patients had focally treated lesions, and 15 patients had hemi-gland treatment. The mean preoperative PSA was 7.7 ng/mL. On the paired sample t-test, there was no significant difference between pre-focal and post-focal therapy PSA. Three patients experienced biochemical recurrence requiring prostate biopsy after focal treatment. Mean cost was USD 3804.50 and not significantly different by focal treatment. No metastatic events occurred nor deaths at a median follow-up of 6 months. Patients in this series had largely unaltered functional outcomes. Cost analysis in contemporary publications is lacking. Although follow-up was short, cancer control was adequate. Full article

Objective: The purpose of this study was to report the clinical characteristics and prognosis of spontaneous isolated abdominal aortic dissection (SIAAD) based on the dissection length. Methods: Between March 2012 and September 2023, 159 of 7572 patients with aortic dissection were diagnosed with SIAAD and enrolled in the retrospective study. We proposed a new morphologic classification: extensive SIAAD (e-SIAAD) and focal SIAAD (f-SIAAD), based on whether the dissection length exceeds 50 mm or not. The clinical baseline, computed tomography angiography (CTA) findings, and long-term follow-up of the two types were compared. Results: SIAAD prevalence was 2.1%. Patients with f-SIAAD were significantly older (63.74 ± 10.97 vs. 50.70 ± 10.10 years, p < 0.001), had more atherosclerosis risk factors, arteriosclerosis, and penetrating aortic ulcers compared to e-SIAAD patients. Conversely, e-SIAAD presented more acutely (72.97% vs. 34.12%, p = 0.001), exhibited more frequent symptoms (85.14% vs. 61.18%, p = 0.0037), larger dissection diameters (31.89 ± 10.99 vs. 24.41 ± 11.28 mm, p = 0.001), and greater involvement of the renal and iliac arteries. Treatment involved medical management (30%), endovascular repair (65%), or surgery (2.5%), without significant differences between groups. In-hospital mortality was higher in f-SIAAD (six deaths vs. one in e-SIAAD). During median follow-up of 48 months (range, 6–148 months), mortality was higher in f-SIAAD (70% vs. 90% estimated 10-year survival). Conclusions: SIAAD classification by dissection length revealed significant differences in clinical presentation, CTA characteristics, and prognosis. Focal dissections correlated with advanced age, severe arteriosclerosis, and poorer long-term outcomes, emphasizing the need for tailored management approaches. Full article