Single-dose (4.5 mg/m2 ) gemtuzumab ozogamicin in combination with fludarabine, cytarabine and anthracycline as reinduction therapy in relapsed or refractory paediatric acute myeloid leukaemia.

Despite major therapeutic improvements, children with relapsed/refractory Acute Myeloid Leukaemia still have poor outcomes and overall survival does not exceed 40%. New treatments are required to improve their outcome; Gemtuzumab ozogamicin (GO), an anti-CD33 immunoconjugate antibody, is a potent cytotoxic agent whose efficacy has been demonstrated mainly in adults. The main objective of this retrospective multicentre study was to assess the outcome of children treated, between February 2008 and August 2019, with GO at a single 4.5 mg/m2 dose, in combination with Fludarabine, Cytarabine and antssshracyclines, in context of a first relapse (n = 26) or refractory disease (n = 3). The remission rate was 83% (24/29 children) and 20 children (69%) were allografted. With a median follow-up of 1.2 years (range: 0.1-8), the overall survival was 49% (CI95% = 33; 72). Most common adverse event was febrile neutropenia with microbiological identification in 55% of cases. Veno-occlusive disease occurred in 6 patients (21%), of which 5 subvened after bone marrow transplantation, and resolved within 2-32 days (median 10.5 days). Administration of GO in combination with FLA-anthracyclines chemotherapy appears to be a good reinduction regimen for relapsed or refractory AML with a good safety profile. These results warrant larger prospective study.

Specific autoantigens in experimental autoimmunity-associated atherosclerosis.

Higher cardiovascular morbidity in patients with a wide range of autoimmune diseases highlights the importance of autoimmunity in promoting atherosclerosis. Our purpose was to investigate the mechanisms of accelerated atherosclerosis and identified vascular autoantigens targeted by autoimmunity. We created a mouse model of autoimmunity-associated atherosclerosis by transplanting bone marrow from FcγRIIB knockout (FcRIIB(-/-)) mice into LDL receptor knockout mice. We characterized the cellular and molecular mechanisms of atherogenesis and identified specific aortic autoantigens using serologic proteomic studies. En face lesion area analysis showed more aggressive atherosclerosis in autoimmune mice compared with control mice (0.64 ± 0.12 vs 0.32 ± 0.05 mm(2); P < 0.05, respectively). At the cellular level, FcRIIB(-/-) macrophages showed significant reduction (46-72%) in phagocytic capabilities. Proteomic analysis revealed circulating autoantibodies in autoimmune mice that targeted 25 atherosclerotic lesion proteins, including essential components of adhesion complex, cytoskeleton, and extracellular matrix, and proteins involved in critical functions and pathways. Microscopic examination of atherosclerotic plaques revealed essential colocalization of autoantibodies with endothelial cells, their adherence to basement membranes, the internal elastica lamina, and necrotic cores. The new vascular autoimmunosome may be a useful target for diagnostic and immunotherapeutic interventions in autoimmunity-associated diseases that have accelerated atherosclerosis.-Merched, A. J., Daret, D., Li, L., Franzl, N., Sauvage-Merched, M. Specific autoantigens in experimental autoimmunity-associated atherosclerosis.

Newborn Life Support course: does it make me more confident when resuscitating a newborn?

AIM: To describe the effectiveness of the Newborn Life Support (NLS) course in terms of attendees' knowledge, perceived self-efficacy, and clinical applicability. METHODS: We conducted an electronic survey of NLS course attendees (NLS + group). A control group (NLS-) was recruited via our regional perinatal network. The survey data were analyzed anonymously. Multiple linear regression analysis examined the following: NLS course, job tenure, maternity level, and profession. RESULTS: The survey completion rate was 62% (200/323) for the NLS + group. Among participants, 84% had participated in neonatal resuscitation since their course. The scores for positive perceived experience for neonatal resuscitation (fluency, security, and quality of care delivered) were higher in the NLS + group than the NLS- group (p<.006). After adjustment, the independent factors associated with a higher positive perceived experience were the NLS course, work in tertiary level maternity ward, and job tenure >5 years. The multiple-choice questions (MCQs) score (n = 10) was 8.2 ± 1.3 (NLS+) vs. 6.7 ± 1.5 (NLS-) (p<.0001). NLS course, medical degree, and work in a tertiary level maternity ward were independently associated with higher knowledge scores. CONCLUSIONS: The NLS course was associated with a positive perceived experience regarding neonatal resuscitation.Key notesNeonatal resuscitation training programs, like the Newborn Life Support (NLS), have been developed to improve the management and outcomes of newborns with poor adaptation at birth.The NLS course was associated with better knowledge of, and a positive perceived experience (fluency, safety, and quality of care delivered) regarding, neonatal resuscitation.Participation to the NLS course seems to strengthen the perceived self-efficacy in healthcare professionals, which is critical to performing neonatal resuscitation.