New Approaches for Basophil Activation Tests Employing Dendrimeric Antigen-Silica Nanoparticle Composites.

In vitro cell activation through specific IgE bound to high-affinity receptors on the basophil surface is a widely used strategy for the evaluation of IgE-mediated immediate hypersensitivity reactions to betalactams. Cellular activation requires drug conjugation to a protein to form a large enough structure displaying a certain distance between haptens to allow the cross-linking of two IgE antibodies bound to the basophil's surface, triggering their degranulation. However, no information about the size and composition of these conjugates is available.

Traumatic scalp arteriovenous fistula post capillary implantation successfully treated using PHIL embolic agent.

Background: A traumatic arteriovenous fistula of the scalp due to hair transplantation (AVFHT) is a rare fistulous communication between branches of the arteries and draining veins in the scalp's subcutaneous tissue. Its incidence is unknown and its clinical manifestations may range from a pulsatile mass to seldom epilepsy. Surgery and interventional approaches (percutaneous and endovascular embolization) using coils and embolic agents such as Onyx have been used as treatment options.

Synthetic antigenic determinants of clavulanic acid induce dendritic cell maturation and specific T cell proliferation in patients with immediate hypersensitivity reactions.

Background: Immediate drug hypersensitivity reactions (IDHRs) to clavulanic acid (CLV) have increased in the last decades due to a higher consumption alongside amoxicillin (AX). Due to its chemical instability, diagnostic procedures to evaluate IDHRs to CLV are difficult, and current in vitro assays do not have an optimal sensitivity. The inclusion of the specific metabolites after CLV degradation, which are efficiently recognised by the immune system, could help to improve sensitivity of in vitro tests.

Addition of intermittently scanned continuous glucose monitoring to standard care in a cohort of pregnant women with type 1 diabetes: effect on glycaemic control and pregnancy outcomes.

Aims/hypothesis: The aim of this study was to assess whether the addition of intermittently scanned continuous glucose monitoring (isCGM) to standard care (self-monitoring of blood glucose [SMBG] alone) improves glycaemic control and pregnancy outcomes in women with type 1 diabetes and multiple daily injections.

Methods: This was a multicentre observational cohort study of 300 pregnant women with type 1 diabetes in Spain, including 168 women using SMBG (standard care) and 132 women using isCGM in addition to standard care. In addition to HbA, the time in range (TIR), time below range (TBR) and time above range (TAR) with regard to the pregnancy glucose target range (3.

Amoxicillin Haptenation of -Enolase is Modulated by Active Site Occupancy and Acetylation.

Allergic reactions to antibiotics are a major concern in the clinic. -lactam antibiotics are the class most frequently reported to cause hypersensitivity reactions. One of the mechanisms involved in this outcome is the modification of proteins by covalent binding of the drug (haptenation).

Multiepitope Dendrimeric Antigen-Silica Particle Composites as Nano-Based Platforms for Specific Recognition of IgEs.

β-lactam antibiotics (BLs) are the drugs most frequently involved in drug hypersensitivity reactions. However, current diagnostic tests have limited sensitivity, partly due to a poor understanding of drug-protein conjugates that both induce the reactions and are immunologically recognized. Dendrimeric Antigen-Silica particle composites (DeAn@SiO), consisting on nanoparticles decorated with BL-DeAns are promising candidates for improving the clinical diagnostic practice.

Diagnostic Approach of Hypersensitivity Reactions to Cefazolin in a Large Prospective Cohort.

Background: Cefazolin is a common trigger of perioperative anaphylaxis. The diagnostic approach is controversial because the optimal concentration for skin testing is uncertain, drug provocation tests (DPTs) are contraindicated in severe reactions, and in vitro tests are not thoroughly validated.

Objective: We aimed to characterize a large number of patients reporting cefazolin allergic reactions and to analyze the diagnostic role of in vivo and in vitro tests.

Nanoarchitectures for efficient IgE cross-linking on effector cells to study amoxicillin allergy.

Background: Amoxicillin (AX) is nowadays the β-lactam that more frequently induces immediate allergic reactions. Nevertheless, diagnosis of AX allergy is occasionally challenging due to risky in vivo tests and non-optimal sensitivity of in vitro tests. AX requires protein haptenation to form multivalent conjugates with increased size to be immunogenic.

The Role of Benzylpenicilloyl Epimers in Specific IgE Recognition.

The high prevalence of allergy to β-lactam antibiotics is a worldwide issue. Accuracy of diagnostic methods is important to prove tolerance or allergy, with skin test considered the best validated method for diagnosing immediate reactions to β-lactams. Although drug provocation test is the reference standard, it cannot be performed in highly risk reactions or in those with positive skin tests.

Role of nanostructures in allergy: Diagnostics, treatments and safety.

Nanotechnology is science, engineering and technology conducted at the nanoscale, which is about 1-100 nm. It has led to the development of nanomaterials, which behave very differently from materials with larger scales and can have a wide range of applications in biomedicine. The physical and chemical properties of materials of such small compounds depend mainly on the size, shape, composition and functionalization of the system.

Biotin-Labelled Clavulanic Acid to Identify Proteins Target for Haptenation in Serum: Implications in Allergy Studies.

Clavulanic acid (CLV) and amoxicillin, frequently administered in combination, can be independently involved in allergic reactions. Protein haptenation with β-lactams is considered necessary to activate the immune system. The aim of this study was to assess the suitability of biotinylated analogues of CLV as probes to study protein haptenation by this β-lactam.

Penicillin and cephalosporin cross-reactivity: role of side chain and synthetic cefadroxil epitopes.

Background: Analysis of cross-reactivity is necessary for prescribing safe cephalosporins for penicillin allergic patients. Amoxicillin (AX) is the betalactam most often involved in immediate hypersensitivity reactions (IHRs), and cefadroxil (CX) the most likely cephalosporin to cross-react with AX, since they share the same R1 side chain, unlike cefuroxime (CO), with a structurally different R1. We aimed to analyse cross-reactivity with CX and CO in patients with confirmed IHRs to AX, including sIgE recognition to AX, CX, CO, and novel synthetic determinants of CX.

Risk Factors in Adolescence for the Development of Elevated Blood Pressure and Hypertension in American Indian and Alaskan Native Adults.

To examine risk factors for elevated blood pressure and hypertension in American Indians and Alaska Natives (AI/ANs), compared to three other ethnic groups in the US. Weighted relative risk regression models, stratified by race/ethnicity, were used to measure the associations between risk factors and elevated blood pressure and hypertension in AI/ANs, compared to non-Hispanic Whites, non-Hispanic Blacks and Hispanics, with data from the National Longitudinal Study of Adolescent to Adult Health. In all groups, females had a lower risk of both elevated blood pressure and hypertension than males.

SARS-CoV-2 in pregnancy: characteristics and outcomes of hospitalized and non-hospitalized women due to COVID-19.

Background: There is little evidence about how novel coronavirus (SARS-CoV-2) affects pregnant women and their newborns. Comparisons with other members of the coronavirus family responsible for severe acute respiratory syndrome (SARS) have been done to predict maternal and neonatal outcomes; however, more information is required to establish clinical patterns, disease evolution and pregnancy prognosis in this group of patients.

Methods: This paper is reporting a series of 91 women diagnosed with SARS-CoV-2 infection during pregnancy and puerperium.

Consumption of fat-free dairy products is not associated with a lower risk of maternofetal adverse events.

Background: The consumption of dairy products in pregnancy is widely extended. However, whether the consumption of low or high fat dairy produce is more beneficial for maternofetal health has yet to be established.

Research Design And Methods: This prospective cohort study evaluated the effect of consumption of dairy products during pregnancy on the frequency of gestational diabetes mellitus (GDM) and a composite of adverse maternofetal outcomes (CMFO).

Amoxicillin Inactivation by Thiol-Catalyzed Cyclization Reduces Protein Haptenation and Antibacterial Potency.

Serum and cellular proteins are targets for the formation of adducts with the β-lactam antibiotic amoxicillin. This process could be important for the development of adverse, and in particular, allergic reactions to this antibiotic. In studies exploring protein haptenation by amoxicillin, we observed that reducing agents influenced the extent of amoxicillin-protein adducts formation.

An Update on the Immunological, Metabolic and Genetic Mechanisms in Drug Hypersensitivity Reactions.

Drug hypersensitivity reactions (DHRs) represent a major burden on the healthcare system since their diagnostic and management are complex. As they can be influenced by individual genetic background, it is conceivable that the identification of variants in genes potentially involved could be used in genetic testing for the prevention of adverse effects during drug administration. Most genetic studies on severe DHRs have documented HLA alleles as risk factors and some mechanistic models support these associations, which try to shed light on the interaction between drugs and the immune system during lymphocyte presentation.

Identification of an antigenic determinant of clavulanic acid responsible for IgE-mediated reactions.

Background: Selective reactions to clavulanic acid (CLV) account for around 30% of immediate reactions after administration of amoxicillin-CLV. Currently, no immunoassay is available for detecting specific IgE to CLV, and its specific recognition in patients with immediate reactions has only been demonstrated by basophil activation testing, however with suboptimal sensitivity. The lack of knowledge regarding the structure of the drug that remains bound to proteins (antigenic determinant) is hampering the development of in vitro diagnostics.