Prediction of the chance of successful immune tolerance induction in persons with severe hemophilia A and inhibitors: a clinical prediction model.

Background: Inhibitor eradication to restore factor (F)VIII efficacy is the treatment goal for persons with severe hemophilia A (HA) and inhibitors. Immune tolerance induction (ITI) is demanding and successful in about 70% of people. Until now, it has remained difficult to quantify the probability of ITI success or failure, complicating the decision to initiate or not initiate ITI.

Warming, stochastic diel thermal fluctuations affect physiological performance and gill plasticity in an amphibious mangrove fish.

Natural temperature variation in many marine ecosystems is stochastic and unpredictable, and climate change models indicate that this thermal irregularity is likely to increase. Temperature acclimation may be more challenging when conditions are highly variable and stochastic, and there is a need for empirical physiological data in these thermal environments. Using the hermaphroditic, amphibious mangrove rivulus (Kryptolebias marmoratus), we hypothesized that compared with regular, warming diel thermal fluctuations, stochastic warm fluctuations would negatively affect physiological performance.

Measurement invariance of the Personality Inventory for DSM-5 across sex.

Introduction: There has been an international movement towards dimensional models of personality disorders (PDs) in the last decades, which culminated in the publication of the Alternative Model of Personality Disorders (AMPD) in the Emerging Measures and Models section of the DSM-5. This model was accompanied by a APA-sanctioned Personality Inventory for DSM-5 (PID-5) for the assessment of the AMPD pathological personality traits. One major issue with the assessment of personality disorders pertains to sex differences, and measurement invariance across sex in assessment instruments for PDs is necessary in order to ensure non-biased evaluations and to make valid comparisons between men and women.

Inhibitor development according to concentrate in severe hemophilia: reporting on 1392 Previously Untreated Patients from Europe and Canada.

Background: Clotting factor concentrates have been the mainstay of severe hemophilia treatment over the last 50 years. Differences in risk of neutralizing antibody (inhibitor) formation according to concentrate used remain clinically relevant.

Objectives: To assess inhibitor development according to type of clotting factor concentrate in previously untreated patients (PUPs) with severe hemophilia A and B.

Prevalence of the alternative model of personality disorders diagnoses in populational and at-risk samples, gender and age groups comparisons, and normative data for the LPFS-SR and PID-5.

The Alternative Model of Personality Disorders (AMPD), introduced in Section III of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5; American Psychiatric Association, 2013), was proposed as a new operationalization of personality disorders (PDs) aiming to overcome the several limitations of the traditional symptom-based model (Waugh et al., 2017; Zimmerman et al., 2019).

Incidence of thrombotic microangiopathies in Quebec: insight from a laboratory centralizing ADAMTS-13 testing.

Background: Thrombotic microangiopathies (TMA) are serious medical conditions requiring a prompt diagnosis to adapt treatment. The determination of ADAMTS-13 activity enables discriminating thrombotic thrombocytopenic purpura (TTP) from other forms of TMA. The purpose of this study was to provide an estimate of the incidence of TTP and TMA in the Canadian Quebec province using data collected from a laboratory centralizing ADAMTS-13 testing for the whole province.

Intravenous Immunoglobulins Tapering and Withdrawal in Systemic Capillary Leak Syndrome (Clarkson Disease).

Background: The systemic capillary leak syndrome (SCLS), also known as Clarkson disease, is a very rare condition characterized by recurrent life-threatening episodes of vascular hyperpermeability in the presence of a monoclonal gammopathy. Extended intravenous immunoglobulin (IVIG) treatment is associated with fewer recurrences and improved survival, but the optimal treatment dosage and duration remain unknown.

Objective: We aim to evaluate the safety of IVIG tapering and withdrawal in patients with SCLS.

Picomolar Sensitivity Analysis of Multiple Bradykinin-Related Peptides in the Blood Plasma of Patients With Hereditary Angioedema in Remission: A Pilot Study.

Background: Hereditary angioedema (HAE) is a rare autosomal dominant disease; the most well understood forms concern the haplodeficiency of C1 esterase inhibitor (C1INH) and a gain of function mutation of factor XII (FXII). The acute forms of these conditions are mediated by an excessive bradykinin (BK) formation by plasma kallikrein.

Methods: A validated LC-MS/MS platform of picomolar sensitivity developed for the analysis of eleven bradykinin-related peptides was applied to the plasma of HAE-C1INH and HAE-FXII sampled during remission.

Opioids for Cesarean delivery under general anesthesia and neonatal outcome: a historical cohort study.

Purpose: The lack of evidence-based recommendations for Cesarean delivery under general anesthesia can lead to practice variability and morbidity, particularly concerning the use of opioids. The goal of this study was to describe the practice for Cesarean delivery performed under general anesthesia and identify predictive factors for opioid use at anesthesia induction and the need for neonatal resuscitation.

Methods: We conducted a single-center historical cohort study.

Quantitation of a plasma biomarker profile for the early detection of Gaucher disease type 1 patients.

Gaucher disease (GD) is caused by a deficiency of the lysosomal enzyme acid β-glucocerebrosidase. Recent metabolomic studies highlighted several new metabolites increased in the plasma of GD patients. We aimed to develop and validate a UPLC-MS/MS method allowing a relative quantitation of lyso-Gb and lyso-Gb analogs -28, -12, -2, +14, +16 and +18 Da in addition to sphingosylphosphorylcholine, -palmitoyl--phosphocholine to study potential correlations with clinical manifestations.

Magnetic resonance imaging in boys with severe hemophilia A: Serial and end-of-study findings from the Canadian Hemophilia Primary Prophylaxis Study.

Background: This study examined the structural outcomes for joints of boys with severe hemophilia A receiving frequency/dose-escalated primary prophylaxis using magnetic resonance imaging (MRI), and the importance of interval MRI changes.

Methods: Forty-six subjects (27 with interval studies) were evaluated by radiographs (X-rays) and mid- and end-of-study MRIs (using the International Prophylaxis Study Group scale), as part of the Canadian Hemophilia Prophylaxis Study. The primary outcome was the presence of MRI osteochondral findings.

Predictive significance of anti-FVIII immunoglobulin patterns on bleeding phenotype and outcomes in acquired hemophilia A: Results from the Quebec Reference Center for Inhibitors.

Background: Acquired hemophilia A (AHA) is a potentially life-threatening bleeding disorder caused by factor VIII (FVIII) autoantibodies, involving various immunoglobulin (Ig) isotypes and IgG subclasses.

Objectives: We analyzed the profile of Ig against FVIII in patients with AHA to identify Ig patterns predictive of bleeding phenotype and outcomes.

Patients/methods: Ig detection and titration were determined by enzyme-linked immunosorbent assay (ELISA) at disease presentation in a cohort of 66 subjects from the Quebec Reference Centre for Inhibitors registry.

Glanzmann Thrombasthenia: Perspectives from Clinical Practice on Accurate Diagnosis and Optimal Treatment Strategies.

Glanzmann thrombasthenia (GT) is a rare autosomal recessive disorder of fibrinogen-mediated platelet aggregation due to a quantitative or qualitative deficit of the αβ integrin at the platelet surface membrane resulting from mutation(s) in and/or . Patients tend to present in early childhood with easy bruising and mucocutaneous bleeding. The diagnostic process requires consideration of more common disorders of haemostasis and coagulation prior to confirming the disorder with platelet light transmission aggregation, flow cytometry of CD41 and CD61 expression, and/or exon sequencing of and .

Patterns of joint damage in severe haemophilia A treated with prophylaxis.

Objective: The primary objective of this study was to assess whether there are different patterns (classes) of joint health in young boys with severe haemophilia A (SHA) prescribed primary tailored prophylaxis. We also assessed whether age at first index joint bleed, blood group, FVIII gene abnormality variant, factor VIII trough level, first-year bleeding rate and adherence to the prescribed prophylaxis regimen significantly predicted joint damage trajectory, and thus class membership.

Methods: Using data collected prospectively as part of the Canadian Hemophilia Primary Prophylaxis Study (CHPS), we implemented a latent class growth mixture model technique to determine how many joint damage classes existed within the cohort.

Identification of a Reliable Biomarker Profile for the Diagnosis of Gaucher Disease Type 1 Patients Using a Mass Spectrometry-Based Metabolomic Approach.

Gaucher disease (GD) is a rare autosomal recessive multisystemic lysosomal storage disorder presenting a marked phenotypic and genotypic variability. GD is caused by a deficiency in the glucocerebrosidase enzyme. The diagnosis of GD remains challenging because of the large clinical spectrum associated with the disease.

The challenge of genetically unresolved haemophilia A patients: Interest of the combination of whole F8 gene sequencing and functional assays.

Background: The causative variant remains unidentified in 2%-5% of haemophilia A (HA) patients despite an exhaustive sequencing of the full F8 coding sequence, splice consensus sequences, 5'/3' untranslated regions and copy number variant (CNV) analysis. Next-generation sequencing (NGS) has provided significant improvements for a complete F8 analysis.

Aim: The aim of this study was to identify and characterize pathogenic non-coding variants in F8 of 15 French and Canadian HA patients genetically unresolved, through the use of NGS, mRNA sequencing and functional confirmation of aberrant splicing.