The quadricuspid truncal valve: Surgical management and outcomes

ObjectiveTo determine the outcomes of patients with a quadricuspid truncal valve (TV) and durability of TV repair.MethodWe reviewed 56 patients with truncus arteriosus and a quadricuspid TV who underwent complete repair between 1979 and 2018.ResultsTV insufficiency was present in 39 patients (mild, n = 22; moderate, n = 14; and severe, n = 3). Fourteen patients had concomitant TV surgery. Early mortality in patients who had concomitant TV surgery was 14% (2 out of 14 patients) and overall survival was 77.1% ± 11.7% at 15 years. Freedom from TV reoperation was 30.3% ± 14.6% at 15 years. Early mortality in patients who did not undergo concomitant TV surgery was 9.5% (4 out of 42 patients) and overall survival was 74.9% ± 6.9% at 15 years. Progression of TV insufficiency requiring TV surgery occurred in 16.7% (7 out of 42 patients). Freedom from TV reoperation was 77.1% ± 7.8% at 15 years. The most common method of repair was tricuspidization of the TV. Freedom from TV reoperation was 64.3% ± 21.0% at 10 years after tricuspidization and 0% at 6 years after other types of TV surgery. Overall follow-up was 97.6% (41 out of 42 patients) complete for survivors with median follow-up of 16.6 years. At last follow-up there was no TV insufficiency in 16 patients, mild insufficiency in 24 patients, and moderate insufficiency in 1 patient.ConclusionsMore than one-third of patients with a quadricuspid TV require TV surgery. Tricuspidization of the quadricuspid TV appears to be a durable repair option with good long-term outcomes.     

Efficiently stimulated adult microglia cross‐prime naive CD8+ T cells injected in the brain

Microglia are the major myeloid‐immune cells of the brain parenchyma. In a steady state, microglia monitor their environment for pathogens or damaged cells. In response to neural injury or inflammation, microglia become competent APCs able to prime CD4⁺ and CD8⁺ T lymphocytes. We previously demonstrated that neonatal and adult microglia cross‐present exogenous soluble Ags in vitro. However, whether microglia are able to cross‐present Ag to naive CD8⁺ T cells in vivo, within the brain microenvironment, remains undetermined. Here, we have designed an original protocol in order to exclude the involvement in cross‐presentation activity of peripheral migrating APCs and of CNS‐associated APCs. In C57Bl/6 mice, in which the body but not the head has been properly irradiated, we analyzed the ability of resident microglia to stimulate intracerebrally injected CD8⁺ T cells in vivo. This study demonstrates for the first time that adult microglia cross‐present Ag to naive CD8⁺ T cells in vivo and that full microglia activation is required to overcome the inhibitory constrains of the brain and to render microglia able to cross‐prime naive CD8⁺ T cells injected in the brain. These observations offer new insights in brain‐tumor immunotherapy based on the induction of cytotoxic antitumoral T cells.     

MRI assessment of the intra‐carotid route for macrophage delivery after transient cerebral ischemia

The broad aim underlying the present research was to investigate the distribution and homing of bone marrow‐derived macrophages in a rodent model of transient middle cerebral artery occlusion using MRI and ultrasmall superparamagnetic iron oxide (USPIO) to magnetically label bone marrow‐derived macrophages. The specific aim was to assess the intra‐carotid infusion route for bone marrow‐derived macrophage delivery at reperfusion. Fifteen Sprague–Dawley rats sustained 1 h of middle cerebral artery occlusion. USPIO‐labeled bone marrow‐derived macrophages were slowly injected for 5 min immediately after reperfusion in ischemic animals (n = 7), 1 h after the end of surgery in sham animals (n = 5) and very shortly after anesthesia in healthy animals (n = 3). Multiparametric MRI was performed at day 0, just after cell administration, and repeated at day 1. Immunohistological analysis included Prussian blue for iron detection and rat endothelial cell antigen‐1 for endothelium visualization. Intra‐carotid cell delivery brought a large number of cells to the ipsilateral hemisphere of the brain, as seen on both MRI and immunohistology. However, it was associated with high mortality (50%). The study of sham animals demonstrated that intra‐carotid cell delivery could induce ischemic lesions and may thus favor additional brain damage. The present study highlights severe drawbacks to the intra‐carotid delivery of macrophages at the time of reperfusion in this rodent model of transient cerebral ischemia. Multiparametric MRI appears to be a method of choice to monitor longitudinally the effects of cell infusion, allowing the assessment of both cell fate with the help of magnetic labeling and of potential tissue damage. Copyright © 2012 John Wiley & Sons, Ltd.     

CRIPTO overexpression promotes mesenchymal differentiation in prostate carcinoma cells through parallel regulation of AKT and FGFR activities

Members of the EGF-CFC (Cripto, FRL-1, Cryptic) protein family are increasingly recognized as key mediators of cell movement and cell differentiation during vertebrate embryogenesis. The founding member of this protein family, CRIPTO, is overexpressed in various human carcinomas. Yet, the biological role of CRIPTO in this setting remains unclear. Here, we find CRIPTO expression as especially high in a subgroup of primary prostate carcinomas with poorer outcome, wherein resides cancer cell clones with mesenchymal traits. Experimental studies in PCa models showed that one notable function of CRIPTO expression in prostate carcinoma cells may be to augment PI3K/AKT and FGFR1 signaling, which promotes epithelial-mesenchymal transition and sustains a mesenchymal state. In the observed signaling events, FGFR1 appears to function parallel to AKT, and the two pathways act cooperatively to enhance migratory, invasive and transformation properties specifically in the CRIPTO overexpressing cells. Collectively, these findings suggest a novel molecular network, involving CRIPTO, AKT, and FGFR signaling, in favor of the emergence of mesenchymal-like cancer cells during the development of aggressive prostate tumors.     

Autoimmune neutropenia in children: analysis of 116 cases

To cite this article: Audrain M, Martin J, Fromont P, Prié N, Thomas C, Muller J‐Y. Autoimmune neutropenia in children: analysis of 116 cases. Pediatr Allergy Immunol 2011; 22 : 494–496. Diagnosis of autoimmune neutropenia (AIN) in infants is important, because it allows the exclusion of more severe forms of neutropenia that have an increased risk for leukemia. AIN is characterized by chronic neutropenia, which spontaneously resolves within several months to a few years, and mild infections. Diagnosis is confirmed by the presence of antibodies directed against neutrophil antigens. The human neutrophil antigen (HNA) system is a polymorphic system, which includes five antigen groups with different polymorphisms. In AIN, antibodies are mostly directed against HNA‐1 (or against a specific allele of HNA‐1) and HNA‐4. Here, we present a series of 116 infants with AIN. We observed that anti‐neutrophil antibodies were present in 60% cases; directed against HNA‐1a in 73% of cases. In addition, we showed there was a bias in the HNA allele distribution in these infants because the frequency of the HNA‐1a allele was greater in comparison with controls.