Search Results (19)

Background and Clinical Significance: Cerebral amyloid angiopathy (CAA) is a neurovascular disorder characterized by the deposition of amyloid beta (Aβ) peptides within the walls of small-to-medium-sized cerebral vessels, leading to vascular fragility and an increased risk of lobar intracerebral hemorrhage (ICH), cognitive decline, and recurrent stroke. CAA is an important cause of spontaneous ICH in elderly patients and may be underrecognized, particularly when presenting with acute neurologic symptoms that mimic ischemic stroke. Early identification has significant implications for management, prognosis, and secondary prevention. Case Presentation: An 80-year-old male presented to the emergency department with incoherent speech, rambling, and severe headache concerning for acute stroke. His medical history was notable for a prior cerebrovascular accident, hypertension, diabetes mellitus, benign prostatic hyperplasia, and recent evaluation for dementia-like symptoms. Initial neuroimaging revealed a 3.2 cm intraparenchymal hemorrhage in the left occipital lobe with surrounding edema. Subsequent MRI demonstrated a lobar hemorrhage pattern suggestive of CAA based on imaging findings and clinical context. The patient was admitted to the intensive care unit (ICU) for close neurologic monitoring. He remained hemodynamically stable with no new motor or sensory deficits. Over a three-day hospital course, his speech and visual deficits improved. Blood pressure was carefully controlled, and repeat imaging demonstrated stable hemorrhage without progression. He was diagnosed with probable CAA and discharged home with supportive services. Conclusions: This case highlights the importance of considering cerebral amyloid angiopathy in elderly patients presenting with spontaneous lobar intracerebral hemorrhage and cognitive symptoms. Prompt recognition and appropriate neuroimaging are critical for diagnosis, risk stratification, and guiding management. Full article

One of the most common and severe complications of diabetes mellitus is diabetic foot, making early detection a public health priority. Infrared thermography is a promising noninvasive technique for identifying abnormal thermal patterns associated with inflammation, neuropathy, angiopathy, and tissue damage. This technique involves acquiring infrared radiation emitted by the skin and processing it to generate thermal maps that reflect underlying physiological changes. However, the reliability of thermographic assessments depends on strict technical conditions, including sensor performance, environmental control, and reproducible measurements. Despite its advantages, the clinical adoption of thermography is limited by the absence of standardized acquisition protocols and the influence of external and physiological factors on temperature measurements. Addressing these challenges is essential to ensure the accurate interpretation and validation of results. Recent advances, such as the incorporation of artificial intelligence algorithms and the development of portable, low-cost devices, offer new opportunities to enhance thermography’s applicability in clinical settings and home monitoring. Full article

Background/Objectives: Intracerebral hemorrhage (ICH) is primarily a disease of older adults, commonly linked to chronic hypertension and cerebral amyloid angiopathy. In young adults, however, ICH is rare and often driven by distinct structural, hematologic, or vascular causes. Methods: Using the National Inpatient Sample (2016–2022), we identified hospitalizations with a primary diagnosis of ICH (ICD-10-CM: I61.x). Patients younger than 18 years were excluded. Patients were stratified into 18–39 vs. ≥40 years. Comorbidities were defined using validated ICD-10 codes (E08–E13 for diabetes mellitus, I10–I15 for hypertension), excluding transient hyperglycemia (R73.x). Weighted analyses using NIS discharge weights compared demographics, comorbidities, rare etiologies, and outcomes, including in-hospital mortality, length of stay (LOS), and total hospital charges. Survey-weighted multivariable logistic regression identified independent predictors of mortality. Results: Among 76,264 ICH hospitalizations, 4012 (5.3%) occurred in patients < 40 years. Compared with older adults, younger patients had lower prevalence of hypertension (47.8% vs. 84.1%) and diabetes (10.2% vs. 60.4%) but higher rates of substance use (27.7% vs. 15.6%). Rare etiologies were more frequent, including arteriovenous malformation/aneurysm (14.0% vs. 3.6%), Moyamoya disease (1.4% vs. 0.2%), sickle cell disease (1.1% vs. 0.1%), and pregnancy-related ICH (0.05%). In-hospital mortality was lower among young adults (15.7% vs. 21.7%, p < 0.001), though LOS was longer (12.1 vs. 8.7 days, p < 0.001), and mean hospital charges were higher ($228,000 vs. $125,000, p < 0.001). Conclusions: Young-adult ICH is uncommon but etiologically distinct, often associated with vascular malformations, hemoglobinopathies, and substance use. Despite lower mortality, these patients experience longer and more resource-intensive hospitalizations, underscoring a substantial clinical and economic burden. Full article

Endothelial dysfunction appears early in type 1 diabetes (T1D). The detection of the first vascular disturbances in T1D patients is crucial, and the introduction of novel techniques, such as flow-mediated skin fluorescence (FMSF) and adaptive optics retinal camera (Rtx) imaging, gives hope for better detection and prevention of angiopathies in the future. In this study, we aimed to investigate microcirculation disturbances in pediatric patients with T1D with the use of FMSF and Rtx imaging. This research focused especially on the relationship between microvascular parameters obtained in FMSF and Rtx measurements, and the glycemic control evaluated in continuous glucose monitoring (CGM) reports. We observed significantly increased wall thickness (WT) and wall-to-lumen ratio (WLR) values in T1D patients in comparison to the control group. Although we did not observe significant differences between the T1D and control groups in the FMSF results, a trend toward significance between the time in range (TIR) and hyperemic response (HR_max) and an interesting correlation between the carotid intima-media thickness (cIMT_max) and HR_max. were observed. In conclusion, FMSF and Rtx measurments are innovative techniques enabling the detection of early microvascular disturbances. Full article

Photocatalysis and photodynamic therapy have been increasingly used in the management of diabetic foot ulcers (DFUs), and their integration into increasingly innovative treatment protocols enables effective infection control. Advanced techniques such as antibacterial photodynamic therapy (aPDT), liposomal photocatalytic carriers, nanoparticles, and nanomotors—used alone, in combination, or with the addition of antibiotics, lysozyme, or phage enzymes—offer promising solutions for wound treatment. These approaches are particularly effective even in the presence of comorbidities such as angiopathies, neuropathies, and immune system disorders, which are common among diabetic patients. Notably, the use of combination therapies holds great potential for addressing challenges within diabetic foot ulcers, including hypoxia, poor circulation, high glucose levels, increased oxidative stress, and rapid biofilm formation—factors that significantly hinder wound healing in diabetic patients. The integration of modern therapeutic strategies is essential for effective clinical practice, starting with halting infection progression, ensuring its effective eradication, and promoting proper tissue regeneration, especially considering that, according to the WHO, 830 million people worldwide suffer from diabetes. Full article

Many clinico-pathological studies point to the presence of multiple comorbidities/co-pathologies in the course of Parkinson disease (PD). Lewy body pathology, the morphological hallmark of PD, rarely exists in isolation, but is usually associated with other concomitant pathologies, in particular Alzheimer disease-related changes (ADNC), cerebrovascular pathologies (macro- and microinfarcts, cerebral small vessel disease, cerebral amyloid angiopathy), TDP-43 pathology as well as multiple pathological combinations. These include cardiovascular disorders, metabolic syndrome, diabetes mellitus, autoimmune and rheumatic diseases, myasthenia gravis, Sjögren’s syndrome, restless leg syndrome or other rare disorders, like Fabry disease. A combination of PD and multiple sclerosis (MS) may be due to the immune function of LRRK2 and its interrelation with α-synuclein. COVID-19 and HIV posed considerable impacts on patients with PD. Epidemiological evidence points to a decreased risk for the majority of neoplasms, except melanoma and other skin cancers, while some tumors (breast, brain) are increased. On the other hand, a lower frequency of malignancies preceding early PD markers may argue for their protective effect on PD risk. Possible pathogenetic factors for the association between PD and cancer are discussed. The tremendous heterogeneity of concomitant pathologies and comorbidities observed across the PD spectrum is most likely caused by the complex interplay between genetic, pathogenic and other risk factors, and further research should provide increasing insight into their relationship with idiopathic PD (and other parkinsonian disorders) in order to find better diagnostic tools and probable disease-modifying therapies. Full article

The microvessel neurovascular unit, with its brain endothelial cells (BEC) and blood–brain barrier remodeling, is important in the development of impaired cognition in sporadic or late-onset Alzheimer’s disease (LOAD), which is associated with aging and is highly prevalent in older populations (≥65 years of age). It is also linked with vascular dementia and vascular contributions to cognitive impairment and dementia, including cerebral amyloid angiopathy in neurodegeneration. LOAD is considered to be the number one cause of dementia globally; however, when one considers the role of mixed dementia (MD)—the combination of both the amyloid cascade hypothesis and the vascular hypothesis of LOAD—it becomes apparent that MD is the number one cause. Microvessel BECs are the first cells in the brain to be exposed to peripheral neurotoxins from the systemic circulation and are therefore the brain cells at the highest risk for early and chronic injury. Therefore, these cells are the first to undergo injury, followed by excessive and recurrent wound healing and remodeling processes in aging and other age-related diseases such as cerebrocardiovascular disease, hypertension, type 2 diabetes mellitus, and Parkinson’s disease. This narrative review explores the intricate relationship between microvessel remodeling, cerebral small vessel disease (SVD), and neurodegeneration in LOAD. It also discusses the current understanding of how microvessel dysfunction, disruption, and pathology contribute to the pathogenesis of LOAD and highlights potential avenues for therapeutic intervention. Full article

Diabetes Mellitus (DM) is a significant global concern. Many diabetic patients will experience complications due to angiopathy, neuropathy, and immune dysfunction, namely diabetic foot ulcers (DFU) and diabetic foot infections (DFI), which can result in lower limb amputation and potentially death. The prevalence of common superficial fungal infections, such as tinea pedis and onychomycosis, can directly increase a diabetic patient’s risk of developing both DFU and DFI. In this review article, we discuss the etiology of diabetic foot complications as well as considerations for both screening and management. We also discuss the role of the dermatologist within a multidisciplinary care team in prescribing and managing treatments for tinea pedis and onychomycosis infections within this patient population. We believe that reducing the burden of these fungal infections in the context of the diabetic foot will help reduce DFU and DFI complications and their associated morbidity and mortality. Full article

Type 1 diabetes (T1D) is a progressive disorder leading to the development of microangiopathies and macroangiopathies. Numerous cytokines and chemokines are involved in the pathogenesis of T1D complications. The study aimed to assess the presence of complications in patients with long-standing T1D and its relationship with serum biomarker concentrations. We examined 52 T1D subjects, with a disease duration ≥4 years and 39 healthy controls. The group of T1D patients was further divided into subgroups based on the duration of the disease (<7 years and ≥7 years) and the metabolic control assessed by the HbAlc level (<8% and ≥8%). We used Luminex Technology to assess a wide range of biomarker concentrations. A 24 h urine test was done to evaluate the rate of albuminuria. Optical coherence tomography (OCT) was conducted to detect early retinopathic changes. Subclinical atherosclerosis was assessed by measuring the carotid intima–media thickness (IMT). T1D patients showed remarkably higher concentrations of EGF, eotaxin/CCL11, MDC/CCL22, sCD40L, TGF-α, and TNF-α. Moreover, we reported statistically significant correlations between cytokines and IMT. Biomarker concentrations depend on numerous factors such as disease duration, metabolic control, and the presence of complications. Although the majority of pediatric T1D patients do not present signs of overt complications, it is indispensable to conduct the screening for angiopathies already in childhood, as its early recognition may attenuate the further progression of complications. Full article

Diabetes mellitus (DM) is a chronic illness with an increasing global prevalence. More than 537 million cases of diabetes were reported worldwide in 2021, and the number is steadily increasing. The worldwide number of people suffering from DM is projected to reach 783 million in 2045. In 2021 alone, more than USD 966 billion was spent on the management of DM. Reduced physical activity due to urbanization is believed to be the major cause of the increase in the incidence of the disease, as it is associated with higher rates of obesity. Diabetes poses a risk for chronic complications such as nephropathy, angiopathy, neuropathy and retinopathy. Hence, the successful management of blood glucose is the cornerstone of DM therapy. The effective management of the hyperglycemia associated with type 2 diabetes includes physical exercise, diet and therapeutic interventions (insulin, biguanides, second generation sulfonylureas, glucagon-like peptide 1 agonists, dipeptidyl-peptidase 4 inhibitors, thiazolidinediones, amylin mimetics, meglitinides, α-glucosidase inhibitors, sodium-glucose cotransporter-2 inhibitors and bile acid sequestrants). The optimal and timely treatment of DM improves the quality of life and reduces the severe burden of the disease for patients. Genetic testing, examining the roles of different genes involved in the pathogenesis of DM, may also help to achieve optimal DM management in the future by reducing the incidence of DM and by enhancing the use of individualized treatment regimens. Full article

Single nucleotide polymorphisms (SNP) in the RAC1 (Rac family small GTPase 1) gene have recently been linked to type 2 diabetes (T2D) and hyperglycemia due to their contribution to impaired redox homeostasis. The present study was designed to determine whether the common SNPs of the RAC1 gene are associated with diabetic complications such as neuropathy (DN), retinopathy (DR), nephropathy, angiopathy of the lower extremities (DA), and diabetic foot syndrome. A total of 1470 DNA samples from T2D patients were genotyped for six common SNPs by the MassArray Analyzer-4 system. The genotype rs7784465-T/C of RAC1 was associated with an increased risk of DR (p = 0.016) and DA (p = 0.03) in males, as well as with DR in females (p = 0.01). Furthermore, the SNP rs836478 showed an association with DR (p = 0.005) and DN (p = 0.025) in males, whereas the SNP rs10238136 was associated with DA in females (p = 0.002). In total, three RAC1 haplotypes showed significant associations (FDR < 0.05) with T2D complications in a sex-specific manner. The study’s findings demonstrate, for the first time, that the RAC1 gene’s polymorphisms represent novel and sex-specific markers of neuropathy and microvascular complications in type 2 diabetes, and that the gene could be a new target for the pharmacological inhibition of oxidative stress as a means of preventing diabetic complications. Full article

People at risk for diabetic foot ulcer (DFU) often misunderstand why foot ulcers develop and what self-care strategies may help prevent them. The etiology of DFU is complex and difficult to communicate to patients, which may hinder effective self-care. Thus, we propose a simplified model of DFU etiology and prevention to aid communication with patients. The Fragile Feet & Trivial Trauma model focuses on two broad sets of risk factors: predisposing and precipitating. Predisposing risk factors (eg, neuropathy, angiopathy, and foot deformity) are usually lifelong and result in “fragile feet.” Precipitating risk factors are usually different forms of everyday trauma (eg, mechanical, thermal, and chemical) and can be summarized as “trivial trauma.” We suggest that the clinician consider discussing this model with their patient in three steps: 1) explain how a patient’s specific predisposing risk factors result in fragile feet for the rest of life, 2) explain how specific risk factors in a patient’s environment can be the trivial trauma that triggers development of a DFU, and 3) discuss and agree on with the patient measures to reduce the fragility of the feet (eg, vascular surgery) and prevent trivial trauma (eg, wear therapeutic footwear). By this, the model supports the communication of two essential messages: that patients may have a lifelong risk of ulceration but that there are health-care interventions and self-care practices that can reduce these risks. The Fragile Feet & Trivial Trauma model is a promising tool for aiding communication of foot ulcer etiology to patients. Future studies should investigate whether using the model results in improved patient understanding and self-care and, in turn, contributes to lower ulceration rates. Full article

Angiopathy is a common complication of diabetes mellitus. Vascular endothelium is among the first targets to experience blood-borne metabolic alterations, such as hyperglycemia and hyperlipidemia, the hallmarks of type 2 diabetes. To explore mechanisms of vascular dysfunction and eventual damage brought by these pathologic conditions and to find ways to protect vasculature in diabetic patients, various research approaches are used including in vitro endothelial cell-based models. We present an analysis of the data available from these models that identifies early endothelial cell apoptosis associated with oxidative stress as the major outcome of mimicking hyperglycemia and hyperlipidemia in vitro. However, the fate of endothelial cells observed in these studies does not closely follow it in vivo where massive endothelial damage occurs mainly in the terminal stages of diabetes and in conjunction with comorbidities. We propose that the discrepancy is likely in missing essentials that should be available to cultured endothelial cells to adjust the metabolic state and withstand the immediate apoptosis. We discuss the role of carnitine, creatine, and AMP-activated protein kinase (AMPK) in suiting the endothelial metabolism for long-term function in diabetic type milieu in vitro. Engagement of these essentials is anticipated to expand diabetes research options when using endothelial cell-based models. Full article

Diabetes mellitus (DM) is a frequent medical problem, affecting more than 4% of the population in most countries. In the context of diabetes, the vascular endothelium can play a crucial pathophysiological role. If a healthy endothelium—which is a dynamic endocrine organ with autocrine and paracrine activity—regulates vascular tone and permeability and assures a proper balance between coagulation and fibrinolysis, and vasodilation and vasoconstriction, then, in contrast, a dysfunctional endothelium has received increasing attention as a potential contributor to the pathogenesis of vascular disease in diabetes. Hyperglycemia is indicated to be the major causative factor in the development of endothelial dysfunction. Furthermore, many shreds of evidence suggest that the progression of insulin resistance in type 2 diabetes is parallel to the advancement of endothelial dysfunction in atherosclerosis. To present the state-of-the-art data regarding endothelial dysfunction in diabetic micro- and macroangiopathy, we constructed this literature review based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). We interrogated five medical databases: Elsevier, PubMed, PMC, PEDro, and ISI Web of Science. Full article

Protein glycation is an important protein post-translational modification and is one of the main pathogenesis of diabetic angiopathy. Other than glycated hemoglobin, the protein glycation of other globins such as myoglobin (Mb) is less studied. The protein glycation of human Mb with ribose has not been reported, and the glycation sites in the Mb remain unknown. This article reports that d-ribose undergoes rapid protein glycation of human myoglobin (HMb) at lysine residues (K34, K87, K56, and K147) on the protein surface, as identified by ultra-high performance liquid chromatography-mass spectrometry (UHPLC-MS) and electrospray ionization tandem mass spectrometry (ESI-MS/MS). Moreover, glycation by d-ribose at these sites slightly decreased the rate of the met heme (Fe^III) in reaction with H₂O₂ to form a ferryl heme (Fe^IV=O). This study provides valuable insight into the protein glycation by d-ribose and provides a foundation for studying the structure and function of glycated heme proteins. Full article