Characterization of fetal microchimeric immune cells in mouse maternal hearts during physiologic and pathologic pregnancies.

Introduction: During pregnancy, fetal cells can be incorporated into maternal tissues (fetal microchimerism), where they can persist postpartum. Whether these fetal cells are beneficial or detrimental to maternal health is unknown. This study aimed to characterize fetal microchimeric immune cells in the maternal heart during pregnancy and postpartum, and to identify differences in these fetal microchimeric subpopulations between normal and pregnancies complicated by spontaneous preterm induced by ascending infection. Methods: A Cre reporter mouse model, which when mated with wild-type C57BL/6J females resulted in cells and tissues of progeny expressing red fluorescent protein tandem dimer Tomato (mT+), was used to detect fetal microchimeric cells. On embryonic day (E)15, 104 colony-forming units (CFU) E. coli was administered intravaginally to mimic ascending infection, with delivery on or before E18.5 considered as preterm delivery. A subset of pregnant mice was sacrificed at E16 and postpartum day 28 to harvest maternal hearts. Heart tissues were processed for immunofluorescence microscopy and high-dimensional mass cytometry by time-of-flight (CyTOF) using an antibody panel of immune cell markers. Changes in cardiac physiologic parameters were measured up to 60 days postpartum via two-dimensional echocardiography. Results: Intravaginal E. coli administration resulted in preterm delivery of live pups in 70% of the cases. mT + expressing cells were detected in maternal uterus and heart, implying that fetal cells can migrate to different maternal compartments. During ascending infection, more fetal antigen-presenting cells (APCs) and less fetal hematopoietic stem cells (HSCs) and fetal double-positive (DP) thymocytes were observed in maternal hearts at E16 compared to normal pregnancy. These HSCs were cleared while DP thymocytes persisted 28 days postpartum following an ascending infection. No significant changes in cardiac physiologic parameters were observed postpartum except a trend in lowering the ejection fraction rate in preterm delivered mothers. Conclusion: Both normal pregnancy and ascending infection revealed distinct compositions of fetal microchimeric immune cells within the maternal heart, which could potentially influence the maternal cardiac microenvironment via (1) modulation of cardiac reverse modeling processes by fetal stem cells, and (2) differential responses to recognition of fetal APCs by maternal T cells.

Haemophilia B in Algeria: Realities and therapeutic perspectives.

INTRODUCTION: Haemophilia B is a debilitating hereditary coagulation disorder characterized by prolonged or spontaneous episodes of bleeding caused by a deficiency of endogenous factor IX. In Algeria, even though many studies are being carried out to evaluate the prevalence and management of haemophilia B, there is a paucity of locally published literature that can be used to understand the most recent information on the disease's epidemiology, diagnostic techniques and treatment options. AIMS: The aim of this manuscript is to raise awareness among patients and family clinicians about current practices, recent developments and unmet needs related to haemophilia B in Algeria. METHODS: A comprehensive literature search was conducted through online scientific databases to review publications regarding haemophilia B in Algeria. Exclusions of the review include case studies, interregional comparisons, abstract-only papers and studies outside the range of 2012-2022. RESULTS: The findings discussed relate to the epidemiology of haemophilia B in Algeria, the clinical diagnostic process, disease symptoms, the benefits of molecular and genetic testing, advancements in prophylactic care, as well as unmet needs hindering the progression of optimal haemophilia B management. CONCLUSION: These findings are crucial to encourage the maintenance of national registries with updated epidemiological data, facilitate early and timely detection of disease symptoms, improve the provision of diagnostic facilities and enhance the overall treatment landscape for better patient outcomes.

Cost-effectiveness of Apixaban for Stroke Prevention in Patients with Atrial Fibrillation in Algeria.

Background: Atrial fibrillation (AF) is a chronic sustained heart rhythm disorder associated with an increased risk of stroke. Apixaban, a new oral anticoagulant, was approved by the European Medicines Agency for prevention of stroke in patients with AF. The efficacy of apixaban has been investigated in randomised controlled trials. Objectives: The objective of this study was to estimate the economic implications of using apixaban compared to other anti-coagulations to reduce the risk of stroke in patients with AF from the perspective of the Algerian payer. Methods: A previously published Markov model was adapted to the Algerian setting. The model included patients for whom vitamin K antagonist (VKA) treatment is suitable and could initiate on acenocoumarol, rivaroxaban or apixaban, and those unsuitable for VKA treatment who could initiate on aspirin or apixaban. Over a lifetime time horizon, costs were estimated in Algerian dinars (DZD) and outcomes included life-years (LYs), quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratios (ICERs). Results: In the VKA suitable population, apixaban was estimated to be a dominant treatment option over rivaroxaban, providing a higher number of QALYs at lower costs, while when compared with acenocoumarol, an ICER of 3 672 059 DZD per QALY gained was estimated. Amongst those unsuitable for VKA therapy, the ICER was 2 061 863 DZD per QALY gained. Conclusion: Apixaban was found to be a cost-effective choice for stroke prevention in patients with AF in Algeria compared to acenocoumarol and rivaroxaban in the VKA suitable population and compared to aspirin in the VKA unsuitable population.