Search Results (610)

Stroke is characterized by a sudden onset of neurological deficit attributed to a focal brain injury. The main treatments for patients with an acute ischemic stroke are intravenous thrombolysis and mechanical thrombectomy. Recanalization therapies have significantly improved patient outcomes; however, their effectiveness depends on a range of pathophysiological factors. This prospective observational study included 60 patients with acute ischemic stroke. The control group consisted of 20 healthy blood donors. Patients were divided into three groups based on whether they received intravenous thrombolysis, mechanical thrombectomy, or combination therapy. We investigated differences between recanalization therapies in patients with ischemic stroke with respect to peripheral blood concentrations of the proinflammatory cytokine interleukin (IL)-18 and endothelial glycocalyx degradation products: syndecan-1, heparan sulphate, and hyaluronic acid, measured by enzyme-linked immunosorbent assay. The blood samples were collected before, 24, and 48 h after recanalization therapy. The concentration of IL-18, syndecan-1, and heparan sulphate increased statistically significantly in patients treated with mechanical thrombectomy. The concentration of hyaluronic acid increased statistically significantly in patients treated with intravenous thrombolysis. The findings primarily reflect between-group differences. Our findings indicate that IL-18 has a significant role in the early inflammatory response. IL-18 and EG degradation products represent potential biomarkers for identifying high-risk patients. Their measurement could help improve the treatment, recovery, and outcomes in patients with acute ischemic stroke. The aforementioned observations underscore their potential value as biomarkers for future research. Full article

Two accelerated magnetic resonance imaging (MRI) protocols for pediatric brain imaging, GOBrain and Deep Resolve Swift Brain, developed by Siemens Healthineers (Erlangen, Germany), were evaluated in a series of clinically relevant pediatric cases at 3 Tesla. Pediatric patients are particularly prone to motion, may be uncooperative, and often require sedation, especially in emergency settings. Consequently, there is a persistent clinical demand for fast brain MRI protocols that provide diagnostically sufficient image quality while minimizing examination time. Contemporary turbo spin-echo (TSE)-based clinical protocols commonly integrate parallel imaging (PI) and simultaneous multi-slice (SMS) techniques to achieve substantial reductions in scan time. Recent advances in three-dimensional volumetric encoding, compressed sensing, and deep learning (DL)-based reconstruction have further mitigated geometry-factor-related noise amplification, enabling higher acceleration factors (GOBrain). In parallel, echo-planar imaging (EPI) has emerged as a promising approach for ultrafast multi-contrast imaging. To overcome the limitations of single-shot EPI, a multi-shot EPI-based brain MRI protocol combined with the DL-based reconstruction method Deep Resolve Swift Brain has been developed. This approach leverages the efficiency of EPI while improving image quality. Using these accelerated protocols, a comprehensive diagnostic multi-contrast brain MRI examination, particularly suited to triage and emergency imaging, can be completed in minutes. This case overview, including therapy-related leukencephalopathy in acute lymphoblastic leukemia (ALL), a brain abscess, traumatic diffuse axonal injury (DAI), a posterior circulation infarction due to vertebral artery dissection, leuokostasis syndrome, and a posterior fossa tumor with obstructive hydrocephalus, demonstrates the potential clinical feasibility of both protocols in pediatric neuroimaging. Both protocols position them as supplementary options alongside established imaging protocols, while dedicated high-resolution protocols might remain necessary for subtle pathological findings, such as focal cortical dysplasia, and for neuronavigation until larger comparative studies are available. Full article

Extracellular matrix (ECM) stiffening is a defining biophysical feature of solid tumors that reshape gene regulation through mechanotransduction. Increased collagen crosslinking and stromal remodeling enhance integrin engagement, focal-adhesion signaling and force transmission to the nucleus, where key hubs such as lysyl oxidase (LOX), focal adhesion kinase (FAK) and the Hippo co-activators YAP1 and TAZ (WWTR1) promote proliferation, invasion, stemness and therapy resistance. Here, we synthesize evidence that quantitative changes in matrix stiffness remodel the miRNome and lncRNome in both tumor and stromal compartments, including extracellular vesicle cargo that reprograms metastatic niches. To address heterogeneity in experimental support, we classify mechanosensitive ncRNAs into studies directly validated by stiffness manipulation (e.g., tunable hydrogels/AFM) versus indirect associations based on mechanosensitive signaling, and we summarize physiological versus pathophysiological stiffness ranges across tissues discussed. We further review competing endogenous RNA (ceRNA) networks converging on mechanotransduction nodes and ECM remodeling enzymes, and discuss translational opportunities and challenges, including targeting mechanosensitive ncRNAs, combining ncRNA modulation with anti-stiffening strategies, delivery barriers in dense tumors, and the potential of circulating/exosomal ncRNAs as biomarkers. Overall, integrating ECM mechanics with ncRNA regulatory circuits provides a framework to identify feed-forward loops sustaining aggressive phenotypes in rigid microenvironments and highlights priorities for validation in physiologically relevant models. Full article

Heart transplantation remains the definitive therapy for end-stage heart failure, but donor coronary artery disease (CAD) is a common reason for allograft refusal, limiting organ availability. We describe a case of orthotopic heart transplantation using a donor heart with isolated coronary artery disease managed with concurrent surgical revascularization. A 66-year-old male with end-stage non-ischemic cardiomyopathy requiring temporary mechanical circulatory support underwent heart transplantation using a donor allograft with a focal lesion in a large first diagonal artery. Following standard implantation, a left internal mammary artery–to–first diagonal artery bypass was performed prior to reperfusion. The patient was successfully weaned from cardiopulmonary bypass with improving left ventricular function and had an uncomplicated postoperative course aside from transient delirium and dysphagia. Echocardiography demonstrated recovery of normal left ventricular function, and the patient remained clinically well with preserved biventricular function at 7-month follow-up. This case demonstrates the feasibility of orthotopic heart transplantation with concurrent coronary artery bypass grafting using an arterial conduit and supports surgical optimization of select donor hearts, with focal coronary disease as a potential strategy to expand the donor pool without compromising short-term outcomes. Full article

Background: The clinical presentation of temporal lobe epilepsy (TLE) and panic disorder can sometimes overlap, particularly when the seizure symptoms include paroxysmal episodes of intense fear and autonomic symptoms. As a result, patients with TLE can be misdiagnosed with a primary psychiatric illness, which leads to inappropriate treatment, worsening of the underlying condition and decreased function and quality of life. Clinical case: We present the case of a 46-year-old woman, known for a 20-year history of generalized epilepsy and major depressive disorder with panic attacks that were refractory and persistent despite trials of SSRIs, benzodiazepines and cognitive behavioral therapy (CBT). While hospitalized for video-EEG monitoring in the context of worsening epilepsy, she was found to have TLE seizures presenting as what the patient had described as panic attacks, and that sometimes progressed to secondarily generalized seizures. Following a transition from a medication regimen targeting generalized epilepsy to one more appropriate for focal seizures, the patient experienced clinical improvement with a decrease in the magnitude and frequency of panic symptoms. Conclusions: This case, in combination with other case reports in the literature, demonstrates the need for clinical suspicion of TLE in patients presenting with atypical panic-like episodes or a refractory panic disorder, especially in cases known for epilepsy or having risk factors for seizure disorder. It also highlights the importance of comprehensive diagnostic evaluation in neuropsychiatric presentations, including EEG and brain imaging, to ensure accurate diagnosis and appropriate management. Full article

Cardiac fibrosis is a pathological phenomenon caused by tissue remodeling and excessive matrix proliferation under stress conditions. CHIR99021 is a selective glycogen synthase kinase-3 inhibitor that has shown potential in cardiovascular regeneration therapy. Fibroblast growth factor 2 (FGF2) has a protective effect on ischemic myocardium. However, the effect and underlying mechanism of the combined use of CHIR99021 and FGF2 on myocardial fibrosis remains unclear. In this study, we found that the combination of CHIR99021 and FGF2 could significantly inhibit the activation of cardiac fibroblasts (CFs) and alleviate the formation of collagen scars in mouse myocardium. By analyzing the expression levels of fibrotic proteins, such as ColI, ColIII and alpha smooth muscle actin (α-SMA) in fibroblasts in vitro and in vivo, we confirmed the inhibitory effect of CHIR99021 combined with FGF2 on the activation of fibroblasts. Transcriptome sequencing showed that CHIR99021 and FGF2 inhibited the expression level of Serpine1 through the transforming growth factor-β (TGF-β) and Focal Adhesion Kinase (FAK) signaling pathways. By analyzing the regulatory effect of overexpressed and knocked-down Serpine1 on fibrotic pathway-related proteins in CFs, we verified that Serpine1 is a key target for inhibiting fibrosis. In conclusion, this study provides evidence that Serpine1 may be a potential mechanism that enables CHIR99021 combined with FGF2 to improve myocardial fibrosis. Full article

Background/Objectives: Epilepsy represents one of the most common chronic neurological disorders in children, with a considerable proportion of patients exhibiting resistance to pharmacotherapy despite the advent of novel antiseizure medications (ASMs) in recent decades. This retrospective study assesses the off-label administration of cenobamate—a newly approved antiseizure medication (ASM) for focal seizures in adults—in a cohort of paediatric patients with drug-resistant epilepsy at a single neurology centre. Methods: Clinical outcomes were reviewed retrospectively for 18 children who received cenobamate for at least 6 months. Results: Eighteen paediatric patients with drug-resistant epilepsy received cenobamate therapy at a neurology centre. The mean age was 164.6 months, and each patient had previously trialled an average of 8.7 antiseizure medications. During a follow-up period of up to 29 months, 39% of participants achieved complete seizure freedom, while five additional patients experienced a seizure reduction exceeding 80%. Concomitant clobazam use was common among the cohort. Adverse events were reported in 78% of patients, predominantly somnolence, though these were generally transient or manageable. One patient developed a temporary exacerbation of seizures, which resolved following a dosage adjustment. Many patients were able to reduce or discontinue other ASMs during the observation period. Conclusions: Cenobamate demonstrated acceptable tolerability in this paediatric cohort, and seizure improvements were observed in a subset of patients. Further clinical trials are warranted to comprehensively evaluate the efficacy and safety profile of cenobamate in this patient population. Full article

Background/Objectives: Stereotactic Body Radiation Therapy (SBRT) is increasingly used for localized prostate cancer (PCa), but evidence supporting its use in high-risk PCa (HRPC) remains limited. Standard management continues to favor conventional or moderately hypofractionated radiotherapy combined with long-course androgen deprivation therapy (ADT). This systematic review aimed to synthesize current data on SBRT biochemical outcomes, toxicity, and technical aspects in localized HRPC. Methods: A systematic PubMed search was conducted on 1 May 2024, following PRISMA 2020 guidelines (PROSPERO ID CRD420251235649). Studies reporting biochemical control (BC) for HRPC treated definitively with SBRT, with or without ADT, were included. Studies not meeting these criteria or including ≤10 HRPC patients were excluded. Risk of bias was assessed through qualitative appraisal of study methodology. Substantial heterogeneity across study design, SBRT schedules, cohort composition, and ADT integration precluded a meta-analysis; data were synthesized descriptively. Results: Thirty studies contributed biochemical control data after prostate SBRT for 1354 patients meeting inclusion criteria. SBRT was delivered using diverse platforms and dose-fractionation schemes, frequently in combination with ADT. Across studies, BC was generally favorable, though follow-up duration varied widely. Toxicity profiles were acceptable, with most reports describing predominantly grade 1–2 events and low rates of severe toxicity. Marked variability was observed in target volume definition, focal-boost strategies, urethra-sparing techniques, and the use of rectal spacers. Conclusions: Although current evidence is heterogeneous and largely derived from non-randomized studies, BC and toxicity outcomes are consistently promising, supporting SBRT as a potentially effective strategy for localized HRPC. Randomized prospective trials are needed to confirm these findings and refine optimal SBRT regimens and the role of ADT. This review received no funding. Full article

Background/Objectives: This study aimed to investigate whether therapy with perampanel is associated with the development of psychosis or psychosis-like symptoms in patients with epilepsy. Methods: We conducted systematic electronic searches in PubMed, Google Scholar, ScienceDirect, and Scindex databases. We included articles published as case reports/case series, as well as conference abstracts and letters from the editor, if they contained enough data for analysis and quality assessment. The main inclusion criteria relate to patients who experienced psychosis or psychosis-like symptoms described by the authors during perampanel therapy or during its recent use. Results: Publications (n = 17) describing a total of 33 patients who met the inclusion criteria were included. Patient ages ranged from 11 to 70 years, and the majority of them were female (66.67%). A confirmed personal psychiatric history was identified in 60.61% of patients. The time interval between the initiation of perampanel and the onset of adverse events varied significantly across cases. The most frequently reported symptom was aggression (75.75%), followed by irritability (30.30%), while delusions or hallucinations were observed in 8 patients (24.24%). Conclusions: Clinicians should be aware that psychosis or psychosis-like symptoms may represent dose-dependent adverse effects of perampanel with a satisfactory prognosis. Identified risk factors for these developments were positive personal psychiatric history, antiseizure polytherapy at high doses, women’s gender, and focal epilepsies with secondary generalization, mainly manifested as tonic–clonic seizures. Early recognition of symptoms, followed by drug discontinuation, dose reduction, symptomatic treatment, or a combination of the mentioned strategies, is crucial for achieving better outcomes. Full article

Chronic atrophic gastritis (CAG) is a key precursor in the Correa cascade leading to gastric cancer and is driven by long-standing Helicobacter pylori infection, autoimmune reactions, environmental exposures, and persistent inflammation. Emerging evidence indicates that mild to moderate atrophy and part of intestinal metaplasia exhibit a degree of reversibility when etiological eradication, microenvironmental optimization, and regenerative stimulation are achieved. This review summarizes recent advances in the pathological basis, evaluation systems, therapeutic mechanisms, and clinical management strategies of CAG. Reversibility is closely related to residual glandular reserve, stem-cell plasticity, and effective mitigation of chronic inflammation. Current assessment tools integrate OLGA/OLGIM histological staging, high-quality endoscopy with AI assistance, and serological biomarkers. Fundamental interventions include early H. pylori eradication, mucosal protective agents, micronutrients, and small-molecule drugs targeting inflammation, oxidative stress, and epithelial regeneration. Novel strategies such as mesenchymal stem cells, exosomes, and focal endoscopic therapies demonstrate regenerative potential in preclinical studies. Traditional Chinese medicine provides multi-target regulation of inflammation, apoptosis, microecology, and stem-cell-related pathways, contributing to histological improvement. Contemporary guidelines emphasize early eradication, risk-stratified surveillance, and comprehensive intervention. Future directions focus on unified evaluation criteria, long-term prospective studies, multimodal combination regimens, and integration of AI-based risk modeling to achieve precise, cancer-preventive CAG management. Full article

DEAD-box (DDX) RNA helicases are essential regulators of RNA metabolism and gene expression. Among them, DDX10 remains poorly characterized despite growing evidence supporting its involvement in human diseases. This review provides a comprehensive analysis of DDX10, from its structural and functional features to its emerging roles in solid tumors and hematologic malignancies. We discuss how DDX10, through its conserved domains, contributes to pre-rRNA processing, ribosome biogenesis, and cell proliferation, and explore potential links between DDX10 and processes such as liquid–liquid phase separation (LLPS) and epigenetic regulation, which may underlie its roles in cancer cell plasticity and stress response. We argue that the dysregulation of these fundamental cellular processes positions DDX10 as a focal point where aberrant RNA metabolism and altered molecular condensates converge to disrupt transcriptional homeostasis and drive oncogenic transformation. Aberrant DDX10 expression is a recurrent feature across multiple cancers, where it promotes tumor progression, therapy resistance, and poor prognosis. Moreover, DDX10 participates in oncogenic fusion events, most notably the NUP98::DDX10 fusion identified in a subset of acute myeloid leukemias, which drives leukemogenesis by disrupting transcriptional regulation and cellular differentiation. Given its tumor-associated expression and diverse biological functions, DDX10 is increasingly recognized as a potential diagnostic biomarker and a promising target for therapeutic strategies. By consolidating current knowledge under this unifying framework, this review highlights the multifaceted roles of DDX10 in cancer biology, advocating further research into its molecular functions and translational potential. 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

Kidney toxicity remains a major dose-limiting complication of radiation therapy and platinum-based chemotherapy, yet the molecular determinants of renal susceptibility and resilience to these genotoxic treatments are incompletely understood. Podocytes are particularly vulnerable to such insults, and emerging evidence implicates lipid dysregulation in podocyte injury. This study investigated the role of sphingomyelin phosphodiesterase acid-like 3B (SMPDL3B), a podocyte-enriched lipid-modulating enzyme, in radiation- and cisplatin-induced nephrotoxicity. Using a doxycycline-inducible, podocyte-specific SMPDL3B transgenic mouse model, renal injury was assessed following focal kidney irradiation, cisplatin administration, or their combination through functional assays, histopathology, ultrastructural analysis, immunofluorescence, and targeted lipidomics. Combined radiation and cisplatin exposure markedly reduced podocyte SMPDL3B expression, accompanied by podocyte depletion, glomerular basement membrane remodeling, proteinuria, and impaired renal function. These structural and functional abnormalities were associated with the selective accumulation of long-chain ceramide-1-phosphate species. In contrast, podocyte-specific induction of SMPDL3B preserved glomerular architecture, maintained renal function, and prevented pathological ceramide-1-phosphate elevation. Collectively, these findings identify SMPDL3B as a key regulator of podocyte stability and lipid homeostasis during chemoradiation stress. Enhancing SMPDL3B activity may represent a mechanistically grounded strategy to mitigate treatment-induced kidney injury while preserving anticancer efficacy. Full article

Background/Objectives: The diffuse sclerosing variant of papillary thyroid carcinoma (DSV-PTC) is a rare and aggressive subtype characterized by diffuse gland involvement and early cervical lymph node metastasis. Preoperative differentiation from classic papillary thyroid carcinoma and autoimmune thyroid disease remains challenging on B-mode ultrasound. This study aimed to describe the multiparametric ultrasound features of DSV-PTC in a single-center case series and highlight practical imaging insights. Methods: We retrospectively reviewed seven consecutive patients with histologically confirmed DSV-PTC evaluated at a single center between 2013 and 2025. All patients underwent standardized B-mode ultrasound, color Doppler, and two-dimensional shear-wave elastography prior to surgery. Clinical, autoimmune, cytological, surgical, pathological, and follow-up data were analyzed descriptively. Results: The cohort included five females and two males (mean age 28 years). Autoimmune thyroid disease was present in three patients. High-risk ultrasound features were identified in all cases, with microcalcifications in six patients and a diffuse “snowstorm” appearance in five. Elastography demonstrated increased stiffness in six out of seven lesions (Emean 28–173 kPa; Emax 31–300 kPa). Cervical lymph node metastases were confirmed in all patients. In two cases, elastography aided identification of focal malignant involvement within diffusely altered thyroid parenchyma. All patients underwent total thyroidectomy with central neck dissection; lateral neck dissection and radioiodine therapy were performed selectively. No distant metastases were detected. Conclusions: In this case series, DSV-PTC showed a characteristic multiparametric ultrasound pattern combining high-risk B-mode features with frequently increased tissue stiffness. Elastography provided complementary information, particularly in the presence of autoimmune thyroid disease, by helping localize focal malignant involvement within diffusely altered parenchyma. Full article

In the context of advanced BRAF-mutant melanoma, the treatment landscape has undergone a paradigm shift due to the impact of immune checkpoint inhibitors and BRAF/MEK inhibitors. This article presents three clinically illustrative melanoma cases that served as focal points for in-depth discussions during 12 expert meetings held across Spain. These include a treatment-naïve metastatic melanoma patient, a patient experiencing a recurrence while on anti-PD-1 adjuvant therapy, and a third patient whose melanoma relapsed ≥6 months after the end of adjuvant therapy. The discussions revolved around optimal treatment sequencing, emphasizing the challenges and alternatives discussed in each scenario. The common view aligned towards a nuanced approach that involves navigating the complexities of treatment choices. The conclusions underscore the need for personalized therapeutic strategies and highlight the ongoing challenge of refining real-life evidence-based algorithms for the management of metastatic BRAF-mutant melanoma. Full article