Bimekizumab in the Treatment of Axial Spondyloarthritis and Psoriatic Arthritis: A New Kid on the Block.

The interleukin (IL)-17 family encompasses six structurally related pro-inflammatory cystine knot proteins, designated as IL-17A to IL-17F. Over the last decades, evidence has pointed to its role as a critical player in the development of inflammatory diseases such as psoriasis (PsO), axial spondyloarthritis (axSpA), and psoriatic arthritis (PsA). More specifically, IL-17A and IL-17F are overexpressed in the skin and synovial tissues of patients with these diseases, and recent studies suggest their involvement in promoting inflammation and tissue damage in axSpA and PsA.

Low thrombin generation in postmenopausal women using estetrol.

Objective: Estetrol (E4) represents a novel estrogen of interest to relieve vasomotor symptoms. E4 activates the nuclear estrogen receptor α (ERα) but antagonizes the estradiol ERα-dependent membrane-initiated steroid signaling pathway. The distinct pharmacological properties of E4 could explain its low impact on hemostasis.

Evaluation of Activated Protein C Resistance Using Thrombin Generation Test.

Activated protein C (APC) resistance (APCR) has been identified as a risk factor of venous thromboembolism (VTE). A mutation at the level of factor (F) V has at first permitted the description of this phenotypic pattern and corresponded to a transition (guanine to adenine) at nucleotide 1691 in the gene coding for factor V, resulting in the replacement of arginine at position 506 by a glutamine. This confers to this mutated FV a resistance toward the proteolytic action of the complex formed by activated protein C with protein S.

[Neurology: what's new in 2022].

The year 2022 was marked by the development of numerous new treatments for refractory myasthenia gravis. The link between epilepsy and cerebrovascular disorder was studied and lamotrigine discovered to be the optimal treatment choice for epilepsy secondary to stroke to prevent mortality on patient of 45 years and older. New randomized study finally demonstrated the utility of thrombectomy in selected patients with basilar artery occlusion.

Impact of estetrol (E4) on hemostasis, metabolism and bone turnover in postmenopausal women.

Objective: This study aimed to determine the effects of estetrol (E4) on hemostasis, lipids, carbohydrate metabolism and bone turnover in postmenopausal women.

Methods: This study was a multicenter, randomized, double-blind placebo-controlled phase 2 trial. Participants ( = 180, age 43-64 years) received E4 2.

Comparison of analytical performances between clot waveform analysis and FibWave in edoxaban-treated patients and healthy controls.

Introduction: The activated partial thromboplastin time (aPTT) and the prothrombin time (PT) are widely available coagulation parameters which are however poor predictors of the anticoagulant effect of direct oral anticoagulants (DOACs). Some coagulometers use the clot waveform analysis (CWA) to assess the clotting time but mainly based on a unique parameter. The improvement of these methodologies and the evaluation of the other waveform parameters may increase the sensitivity to DOACs.

Laboratory Testing for the Evaluation of Phenotypic Activated Protein C Resistance.

Activated protein C (APC) resistance (APCR) is considered a risk factor of venous thromboembolism (VTE). The most common genetic disorder conferring APCR is a factor (F) V Leiden mutation, but many other factors are also implicated, such as other mutations (e.g.

Laboratory Testing for the Evaluation of Phenotypic Activated Protein C Resistance.

Activated protein C (APC) resistance (APCR) is considered a risk factor of venous thromboembolism (VTE). The most common genetic disorder conferring APCR is a factor (F) V Leiden mutation, but many other factors are also implicated, such as other mutations (e.g.

NETosis and Nucleosome Biomarkers in Septic Shock and Critical COVID-19 Patients: An Observational Study.

Background: Neutrophil extracellular traps’ (NETs’) formation is a mechanism of defense that neutrophils deploy as an alternative to phagocytosis, to constrain the spread of microorganisms. Aim: The aim was to evaluate biomarkers of NETs’ formation in a patient cohort admitted to intensive care unit (ICU) due to infection. Methods: Forty-six septic shock patients, 22 critical COVID-19 patients and 48 matched control subjects were recruited.

The edoxaban-M4 metabolite and measurement of edoxaban by chromogenic assays in human plasma.

Introduction: Edoxaban is the only anti-Xa inhibitor metabolized in pharmacologically active moiety that could interfere with chromogenic anti-Xa assays, especially in case of drug-drug interactions or physiological disorders.

Materials And Methods: We evaluated the contribution of the main metabolite of edoxaban, edoxaban-M4 (M4), in 79 plasma samples from patients taking edoxaban. The total anti-Xa activity was evaluated on three different chromogenic factor Xa-based assays.

Interlaboratory variability of activated protein C resistance using the ETP-based APC resistance assay.

Background And Objective: Although the endogenous thrombin potential (ETP)-based activated protein C (APC) resistance is recommended for the development of steroid contraceptive agents, one of the main limitations of this technique was its lack of standardization, which hampered study-to-study comparison. A validated methodology that meets all the regulatory requirements in terms of analytical performances has been developed recently. To ensure a wide implementation of this test, the assessment of the interlaboratory variability was needed.

Impact of centrifugation on thrombin generation in healthy subjects and in patients treated with direct oral anticoagulants.

Introduction: Double centrifugation before freezing is recommended before thrombin generation assays (TGA). However, this procedure is not mandatory for routine hemostasis tests, precluding the use of these samples for TGA. The aim of this study is to assess the impact of single and double centrifugation on TGA performed on frozen samples from healthy volunteers (HVs) and patients receiving direct oral anticoagulants (DOACs).

Oral Contraceptives and Venous Thromboembolism: Focus on Testing that May Enable Prediction and Assessment of the Risk.

Combined oral contraceptives (COCs) induce several changes in the levels of coagulation factors. The levels of procoagulant factors are often increased, while levels of anticoagulant factors are decreased. Fibrinolysis is also affected, even if the effect seems to be more counterbalanced by opposite regulation of profibrinolytic and antifibrinolytic factors.

The Risk of Arterial Thrombosis in Patients With Chronic Myeloid Leukemia Treated With Second and Third Generation BCR-ABL Tyrosine Kinase Inhibitors May Be Explained by Their Impact on Endothelial Cells: An In-Vitro Study.

BCR-ABL tyrosine kinase inhibitors (TKIs) revolutionized the treatment of chronic myeloid leukemia, inducing deep molecular responses, largely improving patient survival and rendering treatment-free remission possible. However, three of the five BCR-ABL TKIs, dasatinib, nilotinib, and ponatinib, increase the risk of developing arterial thrombosis. Prior investigations reported that nilotinib and ponatinib affect the endothelium, but the mechanisms by which they exert their toxic effects are still unclear.

Proof of concept of a new scale for the harmonization and the standardization of the ETP-based APC resistance.

Background: The evaluation of the activated protein C resistance (APCr) based on the endogenous thrombin potential (ETP) is recommended during the development of steroid contraceptives. Results are usually expressed as "normalized APC sensitivity ratio" (nAPCsr) using a reference plasma that should achieve an ETP ratio of 0.1 in presence of exogenous APC.

Validation and standardization of the ETP-based activated protein C resistance test for the clinical investigation of steroid contraceptives in women: an unmet clinical and regulatory need.

Background Regulatory bodies recommend the use of an assay based on the assessment of the endogenous thrombin potential (ETP) for the investigation of the activated protein C resistance (APCr) in the development of steroid contraceptives in women. However, the assays described in the literature are home-made and not standardized regarding the method, the reagents, the reference plasma and the quality controls. In the absence of any commercially available method, we aimed at validating the ETP-based APCr assay.

Assessment of the analytical performances and sample stability on ST Genesia system using the STG-DrugScreen application.

Background: Thrombin generation testing has been used to provide information on the coagulation phenotype of patients. The most used technique is the calibrated automated thrombogram (CAT) but it suffers from a lack of standardization, preventing its implementation in routine. The ST Genesia is a new analyzer designed to assess thrombin generation based on the same principle as the CAT.

Optimal wavelength for the clot waveform analysis: Determination of the best resolution with minimal interference of the reagents.

Introduction: Clot waveform analysis (CWA), a new methodology to assess coagulation process, can be usefully applied in various clinical settings. However, its clinical use is limited mainly because of the absence of standardization. No consensus exists regarding the wavelengths at which CWA has to be performed what is crucial for the sensitivity of the CWA.

Development of new methodologies for the chromogenic estimation of betrixaban concentrations in plasma.

Introduction: Chromogenic anti-Xa assays are the most appropriate tests to estimate the amount of betrixaban in plasma but the sensitivity of available tests is limited and improvements are needed to encompass the on-therapy range.

Methods: Betrixaban was spiked at concentrations ranging from 0 to 500 ng/mL in plasma from healthy donors. Three commercial tests were used (Biophen DiXaI , STA Liquid Anti-Xa, and HemosIL Liquid Anti-Xa), and adaptation of their sample dilution scheme was performed.

Locus Coeruleus atrophy doesn't relate to fatigue in Parkinson's disease.

Fatigue is a frequent complaint among healthy population and one of the earliest and most debilitating symptoms in Parkinson's disease (PD). Earlier studies have examined the role of dopamine and serotonin in pathogenesis of fatigue, but the plausible role of noradrenalin (NA) remains underexplored. We investigated the relationship between fatigue in Parkinsonian patients and the extent of degeneration of Locus Coeruleus (LC), the main source of NA in the brain.

Circulating MicroRNAs as Biomarkers in Diffuse Large B-cell Lymphoma: A Pilot Prospective Longitudinal Clinical Study.

Objectives: Diffuse large B-cell lymphoma (DLBCL) is highly heterogeneous in terms of phenotype and treatment response in patients. These characteristics make the prognosis difficult to establish and hinder the use of new personalized treatments in clinical practice. In this context, there is currently a need to define new biomarkers enabling a better definition of DLBCL subtypes, prognosis evaluation, and an overview of the resistance to chemotherapeutics.

Transfer of multidrug resistance among acute myeloid leukemia cells via extracellular vesicles and their microRNA cargo.

The treatment of acute leukemia is still challenging due in part to the development of resistance and relapse. This chemotherapeutics resistance is established by clonal selection of resistant variants of the cancer cells. Recently, a horizontal transfer of chemo-resistance among cancer cells via extracellular vesicles (EVs) has been suggested.

Eculizumab decreases the procoagulant activity of extracellular vesicles in paroxysmal nocturnal hemoglobinuria: A pilot prospective longitudinal clinical study.

Introduction: Paroxysmal nocturnal hemoglobinuria (PNH) is a disease characterized by the susceptibility of blood cells to attack by the complement system, inducing extracellular vesicle (EV) production. Thromboembolism is the leading cause of death in this condition. Eculizumab, a humanized monoclonal antibody which inhibits the C5 protein of the complement, reduces the thrombotic risk in PNH.