Search Results (570)

Background/Objectives: Cardiovascular disease (CVD) contributes to stroke and dementia. Individuals with CVD have high risk for adverse cognitive outcomes and stroke, possibly due to shared risk factors between CVD, stroke, and dementia, which may be attributed to cerebral small vessel disease (CSVD). We aim to determine the association between prevalent CVD and atrial fibrillation (AF) with CSVD. Methods: Composite of CVD [coronary heart disease, heart failure (HF)], its individual components, and AF were assessed. Multi-marker CSVD score was used to reflect increasing CSVD burden (cerebral microbleeds (CMBs), high-burden perivascular spaces, extensive white matter hyperintensity, cortical superficial siderosis, or covert brain infarcts were assigned 1 point each, with a range of 0–5). We related prevalent CVD, its individual components, and AF to multi-marker CSVD score and individual CSVD markers using logistic regression analyses adjusted for age, sex, FHS cohort, time between MRI and clinic exam (model-1), and vascular risk factors (model-2). Results: In 3413 participants (mean age: 59 ± 14 years, 53.4% women), 11% had prevalent CVD or AF, 8% had prevalent CVD, and 4% had prevalent AF. One CSVD marker was seen in 23% participants, and 9% had ≥ 2 markers. In multivariable-adjusted analyses, composite prevalent CVD and AF was associated with the presence of one CSVD marker (OR: 1.38, 95% confidence interval [CI]: 1.05–1.84). The association with ≥2 CSVD markers was not significant. Only CMBs were associated with components of CVD and AF, with the highest odds of association with HF. Conclusions: Prevalent CVD (including AF) is associated with the presence of CSVD, with all components associated with CMBs. Full article

Background: Vascular risk factors (VRFs) are known to influence cerebral small vessel disease (cSVD) burden and progression. However, their specific impact on the presence and distribution of each cSVD imaging marker (white matter hyperintensity [WMH], perivascular spaces [PVSs], lacunes, and cerebral microbleeds [CMBs]) and their spatial distribution remains unclear. Methods: We conducted a retrospective analysis of 93 patients with lacunar stroke with a standardized investigational magnetic resonance imaging protocol using a 3T scanner. WMH and PVSs were segmented semi-automatically, and lacunes and CMBs were manually segmented. We assessed the univariable associations of four common VRFs (hypertension, hyperlipidemia, diabetes, and smoking) with the load of each cSVD marker. Then, we assessed the independent associations of these VRFs in multivariable regression models adjusted for age and sex. Spatial lesion patterns were explored with regional volumetric comparisons using Pearson’s coefficient analysis, which was adjusted for multiple comparisons, and by visually examining heatmap lesion distributions. Results: Hypertension was the VRF that exhibited stronger associations with the cSVD markers in the univariable analysis. In the multivariable analysis, only lacunes (p = 0.009) and PVSs in the basal ganglia (p = 0.014) and white matter (p = 0.016) were still associated with hypertension. In the regional analysis, hypertension showed a higher WMH load in deep structures and white matter, particularly in the posterior periventricular regions. In patients with hyperlipidemia, WMH was preferentially found in hippocampal regions. Conclusions: Hypertension was confirmed to be the VRF with the most impact on cSVD load, especially for lacunes and PVSs, while the lesion topography was variable for each VRF. These findings shed light on the complexity of cSVD expression in relation to factors detrimental to vascular health. Full article

Background/Objectives: Medulloblastoma (MB) is the second leading cause of cancer-related death in children. Its tumor microenvironment (TME) includes endothelial, glial, and immune cells that influence tumor architecture and progression. Neuropilin-1 (NRP1), a co-receptor for semaphorins and vascular endothelial growth factor (VEGF), is expressed in various cell types during oncogenesis, yet its role in MB progression remains unclear. This study aimed to evaluate the expression and localization of NRP1 and glial fibrillary acidic protein (GFAP) in MB tissue. Methods: We analyzed MB tissue samples using immunohistochemistry, immunofluorescence, and quantitative PCR. Samples were stratified by molecular subgroup (WNT, SHH, non-WNT/non-SHH). We assessed NRP1 expression in tumor-associated microglia/macrophages (TAMs) and endothelial cells, as well as GFAP expression in astrocytes and tumor cells. Histopathological correlations and survival analyses were also conducted. Results: NRP1 was consistently expressed by TAMs across all MB molecular subgroups. Tumor vasculature showed strong endothelial NRP1 expression, while perivascular astrocytic coverage was frequently absent. Astrocytic processes exhibited spatial differences according to tumor histology. In SHH-MBs, a subset of tumor cells showed aberrant GFAP expression, which correlated with tumor recurrence or progression. Conclusions: NRP1 and GFAP display distinct expression patterns within the MB microenvironment, reflecting subgroup-specific biological behavior. Endothelial NRP1 positivity combined with limited vascular-astrocytic interaction and aberrant GFAP expression in SHH-MB may contribute to dysregulated angiogenesis and tumor progression. These findings warrant further investigation to explore their prognostic and therapeutic implications. Full article

Epidemiological studies identified insufficient and poor-quality sleep as independent risk factors for multiple sclerosis (MS). The glymphatic system, active during slow-wave sleep, clears brain waste through perivascular astrocytic aquaporin-4 (AQP4) channels. The presence of antigens induces a transient, physiological lowering of glymphatic flux as a first step of an inflammatory response. A possible hypothesis linking infection with the Epstein–Barr virus, a well identified causal step in MS, and the development of the disease is that mechanisms such as poor sleep or less functional AQP4 polymorphisms may sustain glymphatic flow reduction. Such chronic glymphatic reduction would trigger a vicious circle in which the persistence of antigens and an inflammatory response maintains glymphatic dysfunction. In addition, viral proteins that persist in demyelinated plaques can depolarize AQP4, further restricting waste elimination and sustaining local inflammation. This review examines the epidemiological evidence connecting sleep and MS risk, and the mechanistic findings showing how poor sleep and other glymphatic modulators heighten inflammatory signaling implicated in MS pathogenesis. Deepening knowledge of glymphatic functioning in MS could open new avenues for personalized prevention and therapy. Full article

Background/Objectives: The glymphatic system plays a crucial role in clearing brain metabolic waste, and its dysfunction has been correlated to various neurological disorders. The Diffusion Tensor Imaging Analysis Along the Perivascular Space (DTI-ALPS) index has been proposed as a non-invasive marker of glymphatic function by measuring diffusivity along perivascular spaces; however, its sensitivity to sleep-related changes in glymphatic activity has not yet been validated. This study aimed to evaluate the feasibility of using the DTI-ALPS index as a quantitative marker of dynamic glymphatic activity during sleep. Methods: Diffusion tensor imaging (DTI) data were obtained from 12 healthy male participants (age = 24.44 ± 2.5 years; Pittsburgh Sleep Quality Index (PSQI) < 5), once while awake and 16 times during sleep, following 24 h sleep deprivation and administration of 10 mg zolpidem. Simultaneous MR-compatible electroencephalography was used to determine whether the subject was asleep or awake. DTI preprocessing included eddy current correction and tensor fitting. The DTI-ALPS index was calculated from nine regions of interest in projection and association areas aligned to standard space. The final analysis included nine participants (age = 24.56 ± 2.74 years; PSQI < 5) who maintained a continuous sleep state for 1 h without awakening. Results: Among nine ROI pairs, three showed significant increases in the DTI-ALPS index during sleep compared to wakefulness (Friedman test; p = 0.027, 0.029, 0.034). These ROIs showed changes at 14, 19, and 25 min after sleep induction, with FDR-corrected p-values of 0.024, 0.018, and 0.018, respectively. Conclusions: This study demonstrated a statistically significant increase in the DTI-ALPS index within 30 min after sleep induction through time-series DTI analysis during wakefulness and sleep, supporting its potential as a biomarker reflecting glymphatic activity. Full article

Background: Perivascular epithelioid cell tumors (PEComas) are a rare group of mesenchymal neoplasms with distinctive histological and immunohistochemical features. This systematic review aims to characterize the clinical presentation, diagnostic approach, treatment, and outcomes of adult patients with hepatic PEComa. Methods: We performed a systematic literature search for English-language articles regarding hepatic PEComas using the terms (perivascular epithelioid cell tumor) OR (PEComa) AND (liver) OR (hepatic), up to 25 May 2025. Results: A total of 145 studies encompassing 281 patients were included in the analysis. Most studies originated from Asia. The mean age at diagnosis was 46 years (IQR: 35.25–53.75) with a female predominance. The underlying comorbidities were uncommon among the reported cases, and more than half were asymptomatic at presentation. The tumor presented as a single liver lesion in almost 9 out of 10 patients. Surgical excision was the primary treatment, and diagnosis in 74% of patients was made with positive immunohistochemistry for markers such as HMB-45 and smooth muscle actin. A malignant phenotype was reported in 30 cases. The median follow-up duration was 24 months (IQR: 12–48); recurrence occurred in 17 patients, and disease-related mortality occurred in 8 patients. Conclusions: Primary hepatic PEComa is a rare liver tumor with mostly benign clinical behavior and non-specific presentation. Future studies are needed to support clinician decisions regarding this entity and improve patient care. Full article

The advent of effective antiretroviral therapy in the mid-1990s, which successfully prevented the progression to AIDS in people living with HIV (PLWH), was associated with the appearance of the so-called HIV-associated lipodystrophy. This condition involved subcutaneous fat atrophy; abdominal fat hypertrophy; and, in some cases, lipomatosis. It was also associated with systemic metabolic disturbances, primarily insulin resistance and dyslipidemia. Following the replacement of certain antiretroviral drugs, particularly the thymidine-analog reverse transcriptase inhibitors stavudine and zidovudine, with less toxic alternatives, the incidences of lipoatrophy and lipomatosis significantly declined. However, lipodystrophy resulting from first-generation antiretroviral therapy does not always resolve after switching to newer agents. Although the widespread use of modern antiretroviral drugs—especially integrase strand transfer inhibitors and non-lipoatrophic reverse transcriptase inhibitors such as tenofovir alafenamide—has reduced the incidences of severe forms of lipodystrophy, these regimens are not entirely free of adipose tissue-related effects. Notably, they are associated with weight gain that resembles common obesity and can have adverse cardiometabolic consequences. Recent evidence also suggests the hypertrophy of specific fat depots, such as epicardial and perivascular adipose tissue, in PLWH on last-generation treatments, potentially contributing to increased cardiovascular risk. This evolving landscape underscores the persistent vulnerability of PLWH to adipose tissue alterations. While these morphological changes may not be as pronounced as those seen in classic HIV-associated lipodystrophy, they can still pose significant health risks. The continued optimization of treatment regimens and the vigilant monitoring of adipose tissue alterations and metabolic status remain essential strategies to improve the health of PLWH. Full article

Cardiovascular disease remains the leading global cause of mortality, with inflammation now recognized as a central driver of atherosclerosis and other cardiometabolic conditions. Recent advances have repositioned perivascular adipose tissue from a passive structural element to an active endocrine and immunomodulatory organ, now a key focus in cardiovascular and metabolic research. Among the most promising tools for assessing perivascular adipose tissue inflammation is the fat attenuation index, a non-invasive imaging biomarker derived from coronary computed tomography angiography. This review explores the translational potential of the fat attenuation index for cardiovascular risk stratification and treatment monitoring in both coronary artery disease and systemic inflammatory or metabolic conditions (psoriasis, systemic lupus erythematosus, inflammatory bowel disease, obesity, type 2 diabetes, and non-obstructive coronary syndromes). We summarize evidence linking perivascular adipose tissue dysfunction to vascular inflammation and adverse cardiovascular outcomes. Clinical studies reviewing the fat attenuation index highlight its ability to detect subclinical inflammation and monitor treatment response. As research advances, standardization of measurement protocols and imaging thresholds will be essential for routine clinical implementation. Full article

Gynecologic perivascular epithelioid cell tumors (PEComas) are rare mesenchymal neoplasms characterized by the co-expression of melanocytic markers (HMB-45 and Melan-A) and smooth muscle markers (SMA, desmin, and caldesmon). The uterus is the most common organ affected, with approximately 110 cases reported worldwide, while occurrences in the cervix, vagina, ovary, and other gynecologic locations are exceptionally rare. These tumors typically present with nonspecific symptoms such as abnormal uterine bleeding and pelvic pain, often mimicking other uterine neoplasms. Histopathologically, PEComas exhibit epithelioid and spindle cell morphology with variable nuclear atypia, mitotic activity, and characteristic immunohistochemical profiles. Although most PEComas behave benignly, a subset demonstrates malignant potential, associated with larger tumor sizes, an increased mitotic index, necrosis, and vascular invasion; however, standardized diagnostic criteria remain scarce. Molecular alterations frequently involve the mTOR signaling pathway through tuberous sclerosis complex (TSC) 1 and TSC2 gene mutations, offering potential targets for therapy. Surgical resection with clear margins remains the cornerstone of treatment. For advanced or metastatic cases, mTOR inhibitors have shown promising efficacy, whereas the role of radiotherapy remains uncertain. This review aims to synthesize current knowledge regarding the epidemiology, clinical presentation, histologic features, malignant potential, and treatment of uterine PEComas, emphasizing the importance of accurate histopathological classification and molecular profiling to guide individualized therapeutic strategies. Full article

Posterior pituitary tumors (PPTs) are rare, non-neuroendocrine neoplasms derived from pituicytes of the neurohypophysis or infundibulum. According to the 2025 WHO classification, PPTs comprise four distinct but related low-grade entities: pituicytoma, granular cell tumor of the sellar region, spindle cell oncocytoma, and ependymal pituicytoma. All share nuclear TTF-1 expression, confirming their common origin, but differ in morphology, immunophenotype, and ultrastructure. Histologically, pituicytomas consist of bipolar spindle cells in fascicles; granular cell tumors show polygonal cells with PAS-positive, diastase-resistant cytoplasmic granules; spindle cell oncocytomas display oncocytic change and abundant mitochondria; and ependymal pituicytomas exhibit perivascular pseudorosettes and EMA positivity in apical or dot-like patterns. Immunohistochemically, all are S100 and vimentin positive, and negative for pituitary hormones and lineage-specific transcription factors. Clinically, PPTs are typically non-functioning but may be associated with corticotroph or somatotroph hyperfunction. Imaging features are nonspecific. Surgical resection is the treatment of choice, although hypervascularity and adherence—especially in spindle cell oncocytomas—can hinder complete excision. Radiotherapy is reserved for recurrences. Molecular analyses reveal recurrent alterations in MAPK/PI3K pathways (e.g., HRAS, BRAF, FGFR1, NF1, TSC1) and suggest a shared histogenesis. Copy number imbalances correlate with reduced progression-free survival in some subtypes. Despite a generally favorable prognosis, recurrence—particularly in spindle cell oncocytomas—necessitates long-term follow-up. The WHO 2025 update provides a unified framework for classification, diagnosis, and prognostic stratification of these rare tumors. Full article

SARS-CoV-2, a β-coronavirus, primarily affects the lungs, with non-specific lesions and no cytopathic viral effect in the skin. Cutaneous antiviral mechanisms include activation of TLR/IRF pathways and production of type I IFN. We evaluated the antiviral mechanisms involved in the skin of COVID-19 patients, including skin samples from 35 deceased patients who had contracted COVID-19 before the launch of the vaccine. Detection of SARS-CoV-2 in the skin was performed using transmission electron microscopy and RT-qPCR. Microscopic and molecular effects of the virus in skin were evaluated by histopathology, RT-qPCR, and immunohistochemistry (IHC). The results revealed the presence of SARS-CoV-2 and microscopic changes, including microvascular hyaline thrombi, perivascular dermatitis, and eccrine gland necrosis. There was increased transcription of TBK1 and a reduction in transcription of TNFα by RT-qPCR in the COVID-19 group. IHC revealed reduced expression of ACE2, TLR7, and IL-6, and elevated expression of IFN-β by epidermal cells. In the dermis, there was decreased expression of STING, IFN-β, and TNF-α and increased expression of IL-6 in sweat glands. Our results highlight the role of type I IFN in the skin of COVID-19 patients, which may modulate the cutaneous response to SARS-CoV-2. Full article

Background/Objectives: In preclinical research of airway inflammation, the endotoxin (lipopolysaccharide: LPS)–induced acute interstitial pneumonitis is the most commonly used mechanism model. However, studies apply different LPS serotypes, doses, administration routes, and reference compounds, making result interpretation challenging and drawing conclusions difficult. Therefore, here we aimed to optimize, characterize, and validate this model with dexamethasone in mice. Methods: Pneumonitis was induced by intratracheal LPS (0.25, 1, 2.5, 5 mg/kg; E. coli O111:B4) in C57BL/6J and NMRI mice; controls received phosphate-buffered saline (PBS). Dexamethasone (5 mg/kg i.p.) was used as a positive control. Respiratory functions were measured by restrained plethysmography 24 h after induction, and core body temperature was monitored. Lungs were excised and weighed, and then myeloperoxidase (MPO) activity and histopathological analysis were performed to assess pulmonary inflammation. Results: LPS-induced significant body weight loss, perivascular pulmonary edema, MPO activity increase, neutrophil infiltration, and respiratory function impairment in a dose-independent manner. However, LPS-induced hypothermia dynamics and duration were dose-dependent. The inhibitory effects of the reference compound dexamethasone were only detectable in the case of the 0.25 mg/kg LPS dose on most inflammatory parameters. These results did not differ substantially between C57BL/6J and NMRI mouse strains. Conclusions: Very low doses of LPS induce characteristic functional and morphological inflammatory alterations in the lung, which do not worsen in response to even 20 times higher doses. Since the effect of pharmacological interventions is likely to be detectable in the case of the 0.25 mg/kg LPS dose, we suggest this protocol for testing novel anti-inflammatory agents. Full article

A newly recognized fourth type of perivascular space has recently been described in the radiological literature. Despite its growing relevance, many radiologists are still unfamiliar with its imaging characteristics, often leading to misinterpretation as cystic neoplasms. Due to its potential for diagnostic confusion, further studies are necessary—particularly those incorporating high-quality imaging examples across various presentations—to facilitate accurate recognition and classification. Perivascular spaces (PVSs) of the brain are cystic, fluid-filled structures formed by the pia mater and located alongside cerebral blood vessels, particularly penetrating arterioles, venules, and capillaries. Under normal conditions, these spaces are small (typically <2 mm in diameter), but in rare instances, they may become markedly enlarged (>15 mm), exerting a mass effect on adjacent brain tissue. This newly identified fourth type of PVS is found in association with the M2 and M3 segments of the middle cerebral artery, typically within the anterior temporal lobe white matter. It may mimic low-grade cystic tumors on imaging due to its size and frequent presence of surrounding perifocal edema. We present two adult male patients with this rare PVS variant. The first patient, a 63-year-old, had a brain magnetic resonance imaging scan (MRI) that revealed a cystic lesion in the white matter of the right temporal lobe anterior pole, near the middle cerebral artery M2 segment, with perifocal vasogenic edema. The second patient, a 67-year-old, had a brain MRI that showed a cystic lesion in the white matter and subcortical region of the right temporal lobe anterior pole, with minimal surrounding gliosis or minimal edema. The cystic lesions in both patients remained unchanged over time on follow-up MRI. These cases illustrate the radiological complexity of this under-recognized entity and emphasize the importance of differential diagnosis to avoid unnecessary intervention. Full article

Perivascular epithelioid cell tumors (PEComas) are rare mesenchymal neoplasms characterized by perivascular epithelioid cell proliferation. They can occur in various organs, but colonic PEComas are exceptionally rare, showing diagnostic challenges due to their nonspecific clinical presentation and similar features to those of other colorectal tumors. We present a case of a 61-year-old female with defecation accompanied by blood clots, initially diagnosed with a suspected tumor in the sigmoid colon. Despite initial biopsy yielding non-informative material, repeat colonoscopy and imaging studies revealed a malignant tumor with multinucleated giant (osteoclast-like) cells and probable p53 mutation, most likely of mesenchymal origin. Robotic surgical resection was performed, and ultimately pathological examination refined the diagnosis as a malignant PEComa of the colon. This case demonstrates the importance of considering PEComa in the differential diagnosis of colonic tumors. Further research is needed to ascertain the clinical behavior and optimal treatment for colonic PEComas. Full article

Pericytes (PCs), a heterogeneous population of perivascular supporting cells, are critical regulators of vascular stability, angiogenesis, and blood–tissue barrier integrity. Increasing evidence highlights their active role in the pathophysiology of diabetic microangiopathies, including those affecting the retina, kidney, brain, heart, and peripheral nerves. In diabetes, hyperglycemia-induced PC dysfunction is a major contributor to vascular degeneration, impaired tissue repair, and disease progression across multiple organs. Pericytes also share many characteristics with mesenchymal stem cells (MSCs). They exhibit regenerative capacity, immunomodulatory activities, and multipotent capacities. This review explores the emerging role of PCs as tissue resident MSCs, emphasizing their pathophysiological involvement in diabetes complications, and their potential for utilization in regenerative medicine. We also discuss advances in PC-based therapies, tissue engineering strategies, and clinical applications. Thus, PCs are positioned as promising targets for therapeutic intervention and vascular tissue regeneration. Full article