ROS-induced modifications of fibrin clots connect immune responses to atherothrombosis in systemic lupus erythematosus.

Objective: Cardiovascular events are major determinants of morbidity and mortality in systemic lupus erythematosus (SLE), particularly in patients with renal involvement. While oxidative stress has been implicated in driving vascular and renal damage in SLE, the specific mechanisms remain unclear. This study investigated the potential role of oxidative stress-induced alterations in fibrinogen structure and function in the pathogenesis of atherothrombosis in SLE.

Reactive Nitrogen Species and Fibrinogen: Exploring the Effects of Nitration on Blood Clots.

Reactive nitrogen species (RNS), particularly peroxynitrite (ONOO), play a central role in post-translational modifications (PTMs) of proteins, including fibrinogen, a key component of the coagulation cascade. This review explores the structural and functional consequences of fibrinogen nitration, with a focus on its impact on clot formation, morphology, mechanical stability, and fibrinolysis. Nitration, primarily targeting tyrosine residues within functional domains of the Aα, Bβ, and γ chains, induces conformational changes, dityrosine crosslinking, and aggregation into high molecular weight species.

Homocysteinylation of Fibrinogen: A Post-Translational Link to Thrombosis.

Homocysteinylation, a post-translational modification involving the covalent attachment of homocysteine to proteins, has emerged as a critical mechanism linking hyperhomocysteinemia to thrombotic disease. This review focuses on the homocysteinylation of fibrinogen, a key coagulation factor, and its impact on clot structure and function. Evidence indicates that elevated homocysteine levels can induce significant changes in fibrin architecture, promoting the formation of dense, rigid clots with reduced permeability and impaired fibrinolytic susceptibility, thus fostering a prothrombotic environment.

The Erythrocyte-ROS Axis in Thrombosis and Hemostasis.

Thrombosis and hemostasis are critical processes that maintain vascular integrity, yet imbalances can lead to life-threatening cardiovascular events. Traditionally, erythrocytes were considered passive bystanders in coagulation, but emerging evidence highlights their active role in thrombogenesis, particularly through redox biology. Erythrocytes generate reactive oxygen and nitrogen species (RONS) via Hb autoxidation, NADPH oxidase activation, and external uptake from other blood components.

Fibrinogen Oxidation and Thrombosis: Shaping Structure and Function.

Fibrinogen, a pivotal plasma glycoprotein, plays an essential role in hemostasis by serving as the precursor to fibrin, which forms the structural framework of blood clots. Beyond coagulation, fibrinogen influences immune responses, inflammation, and tissue repair. Oxidative stress, characterized by an imbalance between reactive oxygen species (ROS) and antioxidants, induces fibrinogen oxidation, significantly altering its structure and function.

Complete blood count in neonatal Intensive care Unit (NICU): Performance comparison between POCT Sight OLO® and Sysmex XN-9100™ hematology analyzers.

Background And Aims: The use of a POCT (Point Of Care Test) could help in reducing the impact of pre-analytical errors in particular in challenging newborn samples.The study purpose is to compare the POCT Sight OLO® hematology analyzer, validated for >3 months patients, with the reference system Sysmex XN-9100™ in Neonatal Intensive Care Unit (NICU).

Material And Methods: The two analyzers were compared through Passing-Bablok regression analysis and Bland-Altman plot.

Fibrinogen Structural Changes and Their Potential Role in Endometriosis-Related Thrombosis.

Endometriosis (EM), a chronic inflammatory condition predominantly affecting women of reproductive age, has been linked to an elevated risk of thrombosis, though its underlying molecular mechanisms remain incompletely understood. In this case-control study, involving 71 EM patients and 71 matched controls, we explored the structural and functional changes in fibrinogen and their potential role in thrombosis. Key oxidative stress markers, such as reactive oxygen species (ROS) levels in blood lymphocytes, monocytes, and granulocytes, along with plasma lipid peroxidation markers and total antioxidant capacity, were measured.

Dietary Antioxidants and Natural Compounds in Preventing Thrombosis and Cardiovascular Disease.

Reactive oxygen species (ROS) contribute to endothelial dysfunction, platelet activation, and coagulation abnormalities, promoting thrombus formation. Given the growing interest in non-pharmacological approaches to modulate oxidative stress, we examine the potential of various dietary interventions and antioxidant supplementation in reducing oxidative damage and preventing thrombotic events. Key dietary patterns, such as the Mediterranean, Dietary Approaches to Stop Hypertension (DASH), and ketogenic diets, as well as antioxidant-rich supplements like curcumin, selenium, and polyphenols, demonstrate promising effects in improving oxidative stress markers, lipid profiles, and inflammatory responses.

Rapid complete blood count and C-reactive protein determination with the Horiba Microsemi analyzer: the experience in neonatal intensive care unit of Careggi University Hospital.

Unlabelled: Microsystems represent an alternative but proficient approach of analysis outside the laboratory, and their use could help in reducing the impact of pre-analytical errors, in particular in challenging newborn samples. The study purpose is to compare the Horiba Microsemi CRP LC-767G system for rapid 3-part complete blood count (CBC) and C-reactive protein (CRP) determination with the laboratory reference systems (respectively Sysmex XN-9100™ and Roche Cobas® c702) in samples of adult patients and newborns hospitalized in the neonatal intensive care unit (NICU) samples. The comparison between the analyzers was performed through Passing-Bablok regression analysis and Bland-Altman plot.

Comparison of ELISA with automated ECLIA for IL-6 determination in COVID-19 patients: An Italian real-life experience.

Objectives: Coronavirus disease 2019 (COVID-19) has a wide spectrum of clinical severity. A cytokine storm is associated with COVID-19 severity. Of these, IL-6 is significantly associated with higher mortality and is also a marker for predicting disease prognosis.

Sampling from Extracorporeal Circuit: A Step Forward for Dose Monitoring in Continuous Renal Replacement Therapy.

Introduction: Continuous renal replacement therapies (CRRTs) require constant monitoring and periodic treatment readjustments, being applied to highly complex patients, with rapidly changing clinical needs. To promote precision medicine in the field of renal replacement therapy and encourage dynamic prescription, the Acute Dialysis Quality Initiative (ADQI) recommends periodically measuring the solutes extracorporeal clearance with the aim of assessing the current treatment delivery and the gap from the therapeutic prescription (often intended as effluent dose). To perform this procedure, it is therefore necessary to obtain blood and effluent samples from the extracorporeal circuit to measure the concentrations of a target solute (usually represented by urea) in prefilter, postfilter, and effluent lines.

The anti-IgE monoclonal antibody omalizumab as adjuvant treatment in desensitization to carboplatin in patients with ovarian cancer.

•Ovarian cancer is the most lethal among gynecological cancers.•Carboplatin-based chemotherapy identifies as the main systemic treatment for ovarian cancer patients.•Almost one every three patients treated with carboplatin experiences hypersensitivity reactions.

How to Prevent and Mitigate Hypersensitivity Reactions to Biologicals Induced by Anti-Drug Antibodies?

Biologicals are widely used therapeutic agents for rheumatologic diseases, cancers, and other chronic inflammatory diseases. They are characterized by complex structures and content of variable amounts of foreign regions, which may lead to anti-drug antibodies (ADA) development. ADA onset may limit the clinical usage of biologicals because they may decrease their safety.

Strategies Targeting Type 2 Inflammation: From Monoclonal Antibodies to JAK-Inhibitors.

Bronchial asthma and its frequent comorbidity chronic rhinosinusitis (CRS), are characterized by an inflammatory process at lower and upper respiratory tract, with a variability in terms of clinical presentations (phenotypes) and distinct underpin pathophysiological mechanisms (endotypes). Based on the characteristics of inflammation, bronchial asthma can be distinguished into type 2 (eosinophilic) or nontype 2 (noneosinophilic) endotypes. In type 2 asthma endotype, the pathogenic mechanism is sustained by an inflammatory process driven by Th2 cells, type 2 innate lymphoid cells (ILC2) and type 2 cytokines, which include interleukin (IL)-4, IL-5, IL-9 and IL-13.

Drug-specific Treg cells are induced during desensitization procedure for rituximab and tocilizumab in patients with anaphylaxis.

Biologic agents (BA) are able to induce an adaptive immune response in a proportion of exposed patients with the onset of anti-drug antibodies (ADA), which are usually responsible for hypersensitivity reactions (HR). Drug desensitization (DD) for BA allows transient clinical tolerance to the drug in reactive patients. The paper aimed to analyse the modification of drug-specific immune responses along DD in two patients with previous ADA-mediated HR (anaphylaxis) to rituximab and tocilizumab.

Asthma and Chronic Rhinosinusitis: How Similar Are They in Pathogenesis and Treatment Responses?

Severe asthma and rhinosinusitis represent frequent comorbidities, complicating the overall management of the disease. Both asthma and chronic rhinosinusitis (CRS) can be differentiated into endotypes: those with type 2 eosinophilic inflammation and those with a non-type 2 inflammation. A correct definition of phenotype/endotype for these diseases is crucial, taking into account the availability of novel biological therapies.

Mechanisms of Drug Desensitization: Not Only Mast Cells.

Drug desensitization (DD) allows transient clinical tolerance to the drug in reactive patients and it is frequently and successfully used in the management of both IgE and non IgE-mediated hypersensitivity reactions (HRs). The underlying mechanisms behind this process is not well understood. The desensitization procedure is associated with the inhibition of mast cells degranulation and cytokine production, that, is attributable, at least partially, to the abrogation of Ca2+ mobilization; findings and mouse models of rapid desensitization show that the organization and spatial distribution of actin is critical for Ca2+ mobilization.

The emerging role of type 2 inflammation in asthma.

: Bronchial asthma (BA) is a chronic airways inflammatory disease. Based on the biological mechanisms that underline the disease, asthma has been classified as type 2 or non-type 2 phenotype.: An emerging role has been identified for group 2 innate lymphoid cells (ILC2s) able to produce the classical type 2 cytokines.

Low-Dose Mepolizumab Effectiveness in Patients Suffering From Eosinophilic Granulomatosis With Polyangiitis.

Eosinophilic granulomatosis with polyangiitis (EGPA) is a vasculitis characterized by multisystemic manifestations including asthma. Mepolizumab (300 mg/4 weeks) has recently been approved for EGPA. However, real-life data are scarce and report experiences with high doses of mepolizumab intravenously administered (750 mg/4 weeks).

Anaphylactic reactions to biological drugs.

Purpose Of Review: This review summarizes the current knowledge of the pathogenic mechanisms of biologics-induced anaphylaxis, and the diagnostic and prophylactic strategies in the management of potentially reactive patients, to improve the safety profile of biologics.

Recent Findings: The recent knowledge on the topic highlights the involvement of both effector and regulatory mechanisms in the immune response to biological agents. In addition, the impact of biological's immunogenicity on hypersensitivity reactions has been confirmed in a wider number of studies, defining some details about the kinetics of antidrug antibodies development, specifically immunoglobulin G (IgG) and immunoglobulin E (IgE).

Prompt Predicting of Early Clinical Deterioration of Moderate-to-Severe COVID-19 Patients: Usefulness of a Combined Score Using IL-6 in a Preliminary Study.

Background: The early identification of patients at risk of clinical deterioration is of interest considering the timeline of COVID-19 after the onset of symptoms.

Objective: The aim of our study was to evaluate the usefulness of testing serum IL-6 and other serological and clinical biomarkers, to predict a short-term negative clinical course of patients with noncritical COVID-19.

Methods: A total of 208 patients with noncritical COVID-19 pneumonia at admission were consecutively enrolled.

Immunogenicity-unwanted immune responses to biological drugs - can we predict them?

Introduction: Biological agents (BAs) target molecules involved in disease mechanisms and have modified the natural history of several immune-mediated disorders. All BAs are immunogenic, resulting in the formation of antidrug antibodies (ADAs), which can neutralize drug activity leading to loss of response and potential relapse, or serious adverse events such as infusion hypersensitivity reactions. The production of ADAs is the result of a specific adaptive immune response in which T and B cells are involved.