Broad neutralization of wild-type dengue virus isolates following immunization in monkeys with a tetravalent dengue vaccine based on chimeric yellow fever 17D/dengue viruses

The objective of the study was to evaluate if the antibodies elicited after immunization with a tetravalent dengue vaccine, based on chimeric yellow fever 17D/dengue viruses, can neutralize a large range of dengue viruses (DENV). A panel of 82 DENVs was developed from viruses collected primarily during the last decade in 30 countries and included the four serotypes and the majority of existing genotypes. Viruses were isolated and minimally amplified before evaluation against a tetravalent polyclonal serum generated during vaccine preclinical evaluation in monkey, a model in which protection efficacy of this vaccine has been previously demonstrated (Guirakhoo et al., 2004). Neutralization was observed across all the DENV serotypes, genotypes, geographical origins and isolation years. These data indicate that antibodies elicited after immunization with this dengue vaccine candidate should widely protect against infection with contemporary DENV lineages circulating in endemic countries.     

Symptoms of sleep apnea syndrome: high prevalence and underdiagnosis in the French population

ObjectiveTo determine the prevalence of symptoms evocative of obstructive sleep apnea (SE-OSA) and the magnitude of obstructive sleep apnea (OSA) underdiagnosis.MethodsWe used data from a cross-sectional survey conducted in 2008 in a representative sample of the French general population. Data were collected through interviews and self-administrated questionnaires and were complete for 12,203 adults (?16 years old). SE-OSA was defined by snoring almost every night plus witnessed apneas or excessive daytime sleepiness (Epworth sleepiness scale score > 10).ResultsThe prevalence of SE-OSA was 4.9% (95% CI: 4.5–5.3), and that of self-reported OSA diagnosis was 2.4% (2.1–2.7). The prevalence of SE-OSA was 8% among people with hypertension and 11% among obese people. A previous sleep monitoring session was reported by 2.7% (2.4–3.0) of the participants and by 15.1% of people with SE-OSA. This latter proportion increased with age (24% in people with SE-OSA aged 60 years or over) and was higher in obese people (26%) and in those with chronic diseases (27% among people with hypertension).ConclusionThe prevalence of SE-OSA is high in France and OSA remains underdiagnosed, even in people with obesity or hypertension. Further efforts are needed to improve the diagnosis of OSA.     

Long-term outcome in acquired aplastic anemia treated with an intensified dose schedule of horse antilymphocyte globulin in combination with androgens

Aplastic anemia (AA) is a rare hematopoietic stem cell disease, which can be treated with horse antilymphocyte globulin (ALG) for patients not eligible for bone marrow transplantation. ALG gives about 60% overall survival rate (OS) after 5 years, a 30% of persistent complete remission and a 20% early death rate related to failure. ALG has been incriminated in the emergence of 10 to 20% therapy-related AML/MDS (t-AML/MDS) with the usual doses. Questions remain whether higher doses of ALG could improve the response and OS rates and whether the combination with androgens is able to protect patients from t-AML/MDS. We have carried out a single institutional retrospective study of 87 AA treated with higher doses of ALG, twice the usual posology (140 mg/kg instead of 75 mg/kg), combined to androgens. The overall response rate was 77% and the OS rate at 5 years was 78%. Androgens in combination with ALG improved response and OS rates. At diagnosis, 6% of AA had an abnormal karyotype using conventional cytogenetic not related to any time-to-event. Two patients displayed a cytogenetic conversion related to the occurrence of secondary malignancies. The incidence of t-AML/MDS was 2.3% with an estimated 10-year cumulative incidence of 3.1. Our results show that higher doses of ALG combined to androgens are feasible and give results close to those recently describe with the immunosuppressive treatments including ALG associated to cyclosporine, with a low SMD/AML incidence rate.     

Congenital hyperinsulinism

Congenital hyperinsulinism (CHI or HI) is a condition leading to recurrent hypoglycemia due to an inappropriate insulin secretion by the pancreatic islet β cells. HI has two main characteristics: a high glucose requirement to correct hypoglycemia and a responsiveness of hypoglycemia to exogenous glucagon. HI is usually isolated but may be rarely part of a genetic syndrome (e.g. Beckwith-Wiedemann syndrome, Sotos syndrome etc.). The severity of HI is evaluated by the glucose administration rate required to maintain normal glycemia and the responsiveness to medical treatment. Neonatal onset HI is usually severe while late onset and syndromic HI are generally responsive to a medical treatment. Glycemia must be maintained within normal ranges to avoid brain damages, initially with glucose administration and glucagon infusion then, once the diagnosis is set, with specific HI treatment. Oral diazoxide is a first line treatment. In case of unresponsiveness to this treatment, somatostatin analogues and calcium antagonists may be added, and further investigations are required for the putative histological diagnosis: pancreatic ₁₈F-fluoro-l-DOPA PET-CT and molecular analysis. Indeed, focal forms consist of a focal adenomatous hyperplasia of islet cells, and will be cured after a partial pancreatectomy. Diffuse HI involves all the pancreatic β cells of the whole pancreas. Diffuse HI resistant to medical treatment (octreotide, diazoxide, calcium antagonists and continuous feeding) may require subtotal pancreatectomy which post-operative outcome is unpredictable. The genetics of focal islet-cells hyperplasia associates a paternally inherited mutation of the ABCC8 or the KCNJ11 genes, with a loss of the maternal allele specifically in the hyperplasic islet cells. The genetics of diffuse isolated HI is heterogeneous and may be recessively inherited (ABCC8 and KCNJ11) or dominantly inherited (ABCC8, KCNJ11, GCK, GLUD1, SLC16A1, HNF4A and HADH). Syndromic HI are always diffuse form and the genetics depend on the syndrome. Except for HI due to potassium channel defect (ABCC8 and KCNJ11), most of these HI are sensitive to diazoxide. The main points sum up the management of HI: i) prevention of brain damages by normalizing glycemia and ii) screening for focal HI as they may be definitively cured after a limited pancreatectomy.