Phase 2 study of efgartigimod,a novel FcRn antagonist,in adult patients with primary immune thrombocytopenia

Primary immune thrombocytopenia (ITP) is an acquired autoimmune bleeding disorder, characterized by a low platelet count (<100 × 10⁹/L) in the absence of other causes associated with thrombocytopenia. In most patients, IgG autoantibodies directed against platelet receptors can be detected. They accelerate platelet clearance and destruction, inhibit platelet production, and impair platelet function, resulting in increased risk of bleeding and impaired quality of life. Efgartigimod is a human IgG1 antibody Fc-fragment, a natural ligand of the neonatal Fc receptor (FcRn), engineered for increased affinity to FcRn, while preserving its characteristic pH-dependent binding. Efgartigimod blocks FcRn, preventing IgG recycling, and causing targeted IgG degradation. In this Phase 2 study, 38 patients were randomized 1:1:1 to receive four weekly intravenous infusions of either placebo (N = 12) or efgartigimod at a dose of 5 mg/kg (N = 13) or 10 mg/kg (N = 13). This short treatment cycle of efgartigimod in patients with ITP, predominantly refractory to previous lines of therapy, was shown to be well tolerated, and demonstrated a favorable safety profile consistent with Phase 1 data. Efgartigimod induced a rapid reduction of total IgG levels (up to 63.7% mean change from baseline), which was associated with clinically relevant increases in platelet counts (46% patients on efgartigimod vs 25% on placebo achieved a platelet count of ≥50 × 10⁹/L on at least two occasions, and 38% vs 0% achieved ≥50 × 10⁹/L for at least 10 cumulative days), and a reduced proportion of patients with bleeding. Taken together, these data warrant further evaluation of FcRn antagonism as a novel therapeutic approach in ITP.     

Ovarian hyperstimulation syndrome after gonadotropin-releasing hormone agonist triggering and “freeze-all”: in-depth analysis of genetic predisposition

PurposeWe report on the results of the whole-genome analysis performed in a patient who developed severe ovarian hyperstimulation syndrome (OHSS) following gonadotropin-releasing hormone (GnRH) agonist triggering in a “freeze-all” protocol.MethodsA 30-year-old patient with polycystic ovary syndrome who developed severe early-onset OHSS with clinical ascites, and slight renal and hepatic dysfunction was admitted for monitoring and treatment with cabergoline and intravenous albumin. Exome sequencing to assess for any known genetic predisposition for OHSS was performed.ResultsNo known genetic variants associated with OHSS predisposition were found.ConclusionsCase reports of severe OHSS following a “freeze-all” strategy are starting to arise, showing that OHSS has not been completely eliminated with this approach. Further studies should be conducted to confirm if such cases may be due to genetic predisposition or not.     

Improving tetanus prophylaxis in the emergency department: a prospective, double-blind cost-effectiveness study

Background

The choice of tetanus prophylaxis for patients with wounds depends on obtaining their vaccination history, which has been demonstrated to be unreliable. Use of a rapid immunoassay (Tétanos Quick Stick, the TQS), combined with knowledge of certain demographic characteristics, may improve the evaluation of tetanus immunity and thus help to avoid inadequate prophylactic measures and reduce costs.

Objectives

To evaluate the contribution of the TQS in the choice of tetanus prophylaxis and to perform a cost‐effectiveness analysis. The final aim was to define the place of the TQS in a modified algorithm for assessment of tetanus immunity in the emergency department.

Method

In this Belgian prospective, double‐blind, multicentre study, 611 adult patients with a wound were included; 498 (81.5%) records were valid. The TQS test was performed by a nurse before the vaccination history was taken and the choice of prophylaxis was made, using the official algorithm (Belgian Superior Health Council), by a doctor who was unaware of the TQS result.

Results

The prevalence of protective anti‐tetanus immunity was 74.1%. Immunity was lower in older patients and in female patients. The TQS was a cost‐effective tool for patients presenting with a tetanus‐prone wound and considered from the vaccination history to be unprotected. Use of the TQS would have improved management in 56.9% (95% CI 47.7% to 65.7%) of patients by avoiding unnecessary treatments, leading to a reduction in the mean cost per patient (€10.58/patient with the TQS versus €11.34/patient without). The benefits of the TQS use were significantly greater in patients <61 years old: unnecessary treatment would have been avoided in 76.9% (95% CI 65.8% to 85.4%) of cases and the mean cost per patient reduced to €8.31.

Conclusion

In selected patients, the TQS is a cost‐effective tool to evaluate tetanus immunity. An algorithm is proposed for ED assessment of tetanus immunity integrating age and the TQS result.     

Rapidly fatal Acanthamoeba encephalitis and treatment of cryoglobulinemia

We describe a 66-year-old woman with therapy-refractory cryoglobulinemia treated with rituximab, plasmapheresis, and steroids; a case of fatal meningoencephalitis caused by Acanthamoeba spp. then developed. Such infections are rare and show an unusually rapid course (possibly related to rituximab).     

COVID-19–related laboratory coagulation findings

The alterations in the hemostatic balance in COVID-19 patients are strongly disturbed and contribute to a high prothrombotic status. The high rate of venous thromboembolism in COVID-19 patients goes along with derangements in coagulation laboratory parameters. Hemostasis testing has an important role in diagnosed COVID-19 patients. Elevated D-dimer levels were found to be a crucial laboratory marker in the risk assessment of thrombosis in COVID-19 patients. The diagnostic approach also includes prothrombin time and platelet count. Fibrinogen might give an indication for worsening coagulopathy. Other markers (activated partial thromboplastin time (aPTT), fibrinolysis parameters, coagulation factors, natural anticoagulants, antiphospholipid antibodies and parameters obtained by thromboelastography or thrombin generation assays) have been described as being deranged. These may help to understand the pathophysiology of thrombosis in COVID-19 patients but have currently no place in diagnosis or management in COVID-19 patients. For monitoring the heparin anticoagulant therapy, the anti-Xa assay is suggested, because the severe acute-phase reaction (high fibrinogen and high factor VIII) shortens the aPTT.     

Non‐Suicidal Self‐Injury in Patients with Eating Disorder: Associations with Identity Formation Above and Beyond Anxiety and Depression

In the present study, we investigated the association between non‐suicidal self‐injury (NSSI) and problems in identity formation among patients with eating disorder (ED). NSSI is highly prevalent in ED, and problems with identity formation are characteristic of both NSSI and ED. Few studies, however, have investigated identity formation in patients with ED with and without NSSI while taking into account comorbid psychopathology (e.g. anxiety and depression). Therefore, we investigated the relationships between NSSI characteristics, identity confusion/synthesis, and anxiety/depression in 99 female patients with ED by means of self‐report questionnaires. The results showed that 58.6% of the patients with ED engaged in at least one type of NSSI (most frequently cutting), with no significant differences in rates of NSSI or identity problems among ED subtypes. Presence, versatility and automatic negative reinforcement functions of NSSI were each significantly and positively related to identity confusion and negatively related to identity synthesis. Even after controlling for age, anxiety, and depression, lack of identity synthesis remained a significant predictor of NSSI in patients with ED. Given that NSSI may constitute an effort to deal with identity confusion/synthesis in patients with ED, therapists should take this developmental task into account while treating patients with ED with NSSI. Copyright © 2014 John Wiley & Sons, Ltd and Eating Disorders Association.     

Cripto regulates skeletal muscle regeneration and modulates satellite cell determination by antagonizing myostatin

Skeletal muscle regeneration mainly depends on satellite cells, a population of resident muscle stem cells. However, our understanding of the molecular mechanisms underlying satellite cell activation is still largely undefined. Here, we show that Cripto, a regulator of early embryogenesis, is a novel regulator of muscle regeneration and satellite cell progression toward the myogenic lineage. Conditional inactivation of cripto in adult satellite cells compromises skeletal muscle regeneration, whereas gain of function of Cripto accelerates regeneration, leading to muscle hypertrophy. Moreover, we provide evidence that Cripto modulates myogenic cell determination and promotes proliferation by antagonizing the TGF-β ligand myostatin. Our data provide unique insights into the molecular and cellular basis of Cripto activity in skeletal muscle regeneration and raise previously undescribed implications for stem cell biology and regenerative medicine.