1,720,988 research outputs found
Molecular Links and Clinical Effects of Inflammation and Metabolic Background on Ischemic Stroke: An Update Review
Stroke is a major global health concern, with 12.2 million new cases and 6.6 million deaths reported in 2019, making it the second leading cause of death and third leading cause of disability worldwide. Ischemic stroke, caused by blood vessel occlusion, accounts for 87% of stroke cases and results in neuronal death due to oxygen and nutrient deprivation. The rising global stroke burden is linked to aging populations and increased metabolic risk factors like high blood pressure, obesity, and elevated glucose levels, which promote chronic inflammation. This article explores the intricate molecular and clinical interplay between inflammation and metabolic disorders, emphasizing their role in ischemic stroke development, progression, and outcomes
From Circulating Biomarkers to Polymorphic Variants: A Narrative Review of Challenges in Thrombophilia Evaluation
Thrombophilia is characterized by a hypercoagulable state that predisposes individuals to venous and arterial thrombotic events, posing significant challenges for clinical evaluation and management. This narrative review critically examines the current landscape of thrombophilia testing, focusing on the utility and limitations of both circulating and genetic biomarkers. Circulating biomarkers—such as D-dimer, antithrombin, protein C, and protein S—offer dynamic insights into the coagulation process yet often suffer from low specificity in varied clinical settings. In contrast, genetic biomarkers, notably Factor V Leiden and the prothrombin G20210A mutation, provide stable risk stratification but are limited by their low prevalence in the general population. Emerging markers, including selectins, Factor VIII, Factor XI, neutrophil extracellular traps, and extracellular vesicles, are also discussed for their potential to refine thrombotic risk assessment. By integrating evidence-based guidelines from international health organizations, this review underscores the need for a personalized approach to thrombophilia evaluation that balances comprehensive risk assessment with the avoidance of over-testing. Such an approach is crucial for optimizing patient outcomes and informing the duration and intensity of anticoagulant therapy
Challenges and Opportunities of Direct Oral Anticoagulant (DOAC) Therapy in Complex Clinical Scenarios: A Comprehensive Review and Practical Guide
Direct oral anticoagulants (DOACs) have emerged as a preferred alternative to vitamin K antagonists (VKAs) for the prevention and treatment of thromboembolic disorders, offering improved safety, predictable pharmacokinetics, and ease of administration. Despite these advantages, their use in complex clinical scenarios presents significant challenges that necessitate individualized therapeutic strategies. This comprehensive review explores the efficacy, safety, and limitations of DOAC therapy in special populations, including patients with renal or hepatic impairment, obesity, cancer-associated thrombosis, and antiphospholipid syndrome. Additionally, we examine their role in uncommon thrombotic conditions such as superficial venous thrombosis, embolic stroke of undetermined source, upper extremity vein thrombosis, inferior vena cava thrombosis, pelvic vein thrombosis, and cerebral vein thrombosis. The pharmacokinetic variability of DOACs in renal and hepatic dysfunction requires caution to balance the bleeding and thrombotic risks. In obesity, altered drug distribution and metabolism raise concerns regarding appropriate dosing and therapeutic efficacy. Cancer-associated thrombosis presents a complex interplay of prothrombotic mechanisms, necessitating careful selection of anticoagulant therapy. Furthermore, the use of DOACs in antiphospholipid syndrome remains controversial due to concerns about recurrent thrombotic events. Finally, in some unusual scenarios like inferior vena cava, pelvic vein, and cerebral vein thrombosis, the use of DOACs has scarce evidence. This review aims to guide clinicians in optimizing anticoagulation management in challenging patient populations by synthesizing current evidence and providing practical recommendations
Establishing Decisional Cutoff Values of Neurofilament Light Chains in Cerebrospinal Fluid Measured by Fully Automated Chemiluminescent Enzyme Immunoassay
Introduction: Neurofilament light chain (NfL) is one of the most important biomarkers in the field of clinical neurochemistry. Several analytical methods have been developed in the last decade. Recently, Fujirebio introduced a ready-to-use assay kit for measuring NfL levels in the cerebrospinal fluid (CSF) on the fully automated LUMIPULSE G System. In this study, we established the decisional cutoffs for CSF NfL. Materials and Methods: We performed a retrospective observational study including patients with cognitive decline. CSF NfL levels were measured by two analytical methods: the NF-light ELISA kit (UmanDiagnostics) and the Lumipulse G1200 fully automated system (Fujirebio). We calculated the cutoffs for the Lumipulse, starting from the consolidated cutoffs of the ELISA method for each age and using the equation obtained by the regression analysis. Results: The study population consisted of 100 patients with cognitive decline. The median levels of CSF NfL measured by Lumipulse and ELISA were 776.5 ± 772.6 pg/mL and 473.5 ± 443.5 pg/mL, respectively, significantly different (p < 0.001). The Spearman's rank correlation coefficient was 0.962, indicating a robust positive correlation between the two measurement methods. The equation derived from the Passing–Bablok regression analysis was CSF CLEIA = −61.16 + 1.83 × CSF ELISA. Based on this equation, we defined the decisional cutoff values. Conclusions: Decisional cutoffs are fundamental tools for guiding clinicians to use biomarkers' results and interpretation appropriately. This is the first study establishing the decisional cutoff value of NfL measured by Lumipulse, a fully automated platform widely used in clinical laboratories
Longitudinal analysis of anti-SARS-CoV-2 S-RBD IgG antibodies before and after the third dose of the BNT162b2 vaccine
Immunosurveillance by evaluating anti-spike protein receptor-binding domain (S-RBD) antibodies represents a useful tool to estimate the long immunity against Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2) infection. The aim of this study was to evaluate the kinetics of antibody response in vaccine recipients. We measured anti-S-RBD IgG levels by indirect chemiluminescence immunoassay on Maglumi 800 (SNIBE, California) in 1013 healthy individuals naïve to SARS-CoV2 infection after two and three COVID-19 vaccine doses. We found that anti-S-RBD IgG levels are higher in females than males. Antibody levels gradually decrease to a steady state after four months since the peak, and the decay is independent of age, sex, vaccine doses, and baseline antibodies titer. The third dose induces a high anti-S-RBD IgG reactivity in individuals with previous high responses and triggers a moderate-high anti-S-RBD IgG reactivity. The assessment of anti-S-RBD IgG levels is essential for monitoring long-term antibody response. A third SARS-CoV-2 vaccine dose is associated with a significant immunological response. Thus, our results support the efficacy of the vaccine programs and the usefulness of the third dose
Comparison of a Fully Automated Platform and an Established ELISA for the Quantification of Neurofilament Light Chain in Patients With Cognitive Decline
BACKGROUND: Enzyme-linked immunosorbent assay (ELISA) is the most-used method for neurofilament light chain (NfL) quantification in cerebrospinal fluid (CSF). Recently, fully automated immunoassays for NfL measurement in CSF and blood have allowed high reproducibility among laboratories, making NfLs suitable for routine use in clinical practice. In this study, we compared the Uman Diagnostics NF-light ELISA with the fully automated platform Lumipulse. METHODS: We enrolled 60 patients with cognitive decline, including Alzheimer disease (AD). CSF NfL levels were measured by a NF-light ELISA kit (UmanDiagnostics), and chemiluminescent enzyme immunoassay (CLEIA) on the Lumipulse G1200 platform (Fujirebio Diagnostics). Serum NfLs levels were measured by CLEIA on the Lumipulse G1200. RESULTS: We found a significant, very strong correlation [Spearman rho = 0.94 (0.90-0.96)] between CLEIA and ELISA in CSF, and a significant moderate correlation between CSF and serum with both analytical methods [CLEIA vs serum CLEIA 0.41 (0.16-0.61); ELISA vs serum CLEIA 0.40 (0.15-0.60)]. It is worth noting that CSF CLEIA measurements were approximately 136.12 times higher than the serum measurements. CONCLUSIONS: Our findings show a robust correlation between ELISA Uman Diagnostic and the standardized Lumipulse G1200 platform for CSF NfL measurements
Vitamin D and Multiple Sclerosis: An Open-Ended Story
Multiple Sclerosis (MS) is a chronic inflammatory autoimmune disease of the Central Nervous System (CNS). Genetic, epigenetic and environmental factors interact together, contributing to the complex pathogenesis of the disease. In the last decades, the role of hypovitaminosis D on MS risk was hypothesised. Several factors drive the regulation of vitamin D status, including genetics. The current review summarises the literature evidence on the association between vitamin D and MS, with a focus on the genetic polymorphisms in vitamin D-related genes. The variants of the genes codifying Vitamin D Receptor (VDR), Vitamin D Binding Protein (VDBP) and CYP enzymes have been investigated, but the findings are controversial. Only a few studies have addressed the role of DHCR7 polymorphisms in MS risk
Prostate health index (PHI) as a reliable biomarker for prostate cancer: a systematic review and meta-analysis
Prostate cancer (PCa) represents the second most common solid cancer in men worldwide. In the last decades, the prostate health index (PHI) emerged as a reliable biomarker for detecting PCa and differentiating between non-aggressive and aggressive forms. However, before introducing it in clinical practice, more evidence is required. Thus, we performed a systematic review and meta-analysis for assessing the diagnostic performance of PHI for PCa and for detecting clinically significant PCa (csPCa)
Going Beyond Counting First Authors in Author Co-citation Analysis
The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
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