Retrospective French nationwide survey of childhood aggressive vascular anomalies of bone, 1988-2009

<p>Abstract</p> <p>Objective</p> <p>To document the epidemiological, clinical, histological and radiological characteristics of aggressive vascular abnormalities of bone in children.</p> <p>Study design</p> <p>Correspondents of the French Society of Childhood Malignancies were asked to notify all cases of aggressive vascular abnormalities of bone diagnosed between January 1988 and September 2009.</p> <p>Results</p> <p>21 cases were identified; 62% of the patients were boys. No familial cases were observed, and the disease appeared to be sporadic. Mean age at diagnosis was 8.0 years [0.8-16.9 years]. Median follow-up was 3 years [0.3-17 years]. The main presenting signs were bone fracture (n = 4) and respiratory distress (n = 7), but more indolent onset was observed in 8 cases. Lung involvement, with lymphangiectasies and pleural effusion, was the most frequent form of extraosseous involvement (10/21). Bisphosphonates, alpha interferon and radiotherapy were used as potentially curative treatments. High-dose radiotherapy appeared to be effective on pleural effusion but caused major late sequelae, whereas antiangiogenic drugs like alpha interferon and zoledrenate have had a limited impact on the course of pulmonary complications. The impact of bisphosphonates and alpha interferon on bone lesions was also difficult to assess, owing to insufficient follow-up in most cases, but it was occasionally positive. Six deaths were observed and the overall 10-year mortality rate was about 30%. The prognosis depended mainly on pulmonary and spinal complications.</p> <p>Conclusion</p> <p>Aggressive vascular abnormalities of bone are extremely rare in childhood but are lifethreatening. The impact of anti-angiogenic drugs on pulmonary complications seems to be limited, but they may improve bone lesions.</p

Absence of association between Plasmodium falciparum small sub-unit ribosomal RNA gene mutations and in vitro decreased susceptibility to doxycycline

BACKGROUND: Doxycycline is an antibiotic used in combination with quinine or artesunate for malaria treatment or alone for malaria chemoprophylaxis. Recently, one prophylactic failure has been reported, and several studies have highlighted in vitro doxycycline decreased susceptibility in Plasmodium falciparum isolates from different areas. The genetic markers that contribute to detecting and monitoring the susceptibility of P. falciparum to doxycycline, the pfmdt and pftetQ genes, have recently been identified. However, these markers are not sufficient to explain in vitro decreased susceptibility of P. falciparum to doxycycline. In this paper, the association between polymorphism of the small sub-unit ribosomal RNA apicoplastic gene pfssrRNA (PFC10_API0057) and in vitro susceptibilities of P. falciparum isolates to doxycycline were investigated. METHODS: Doxycycline IC50 determinations using the hypoxanthine uptake inhibition assay were performed on 178 African and Thai P. falciparum isolates. The polymorphism of pfssrRNA was investigated in these samples by standard PCR followed by sequencing. RESULTS: No point mutations were found in pfssrRNA in the Thai or African isolates, regardless of the determined IC50 values. CONCLUSIONS: The pfssrRNA gene is not associated with in vitro decreased susceptibility of P. falciparum to doxycycline. Identifying new in vitro molecular markers associated with reduced susceptibility is needed, to survey the emergence of doxycycline resistance

Distinct Genetic Loci Control Plasma HIV-RNA and Cellular HIV-DNA Levels in HIV-1 Infection: The ANRS Genome Wide Association 01 Study

Previous studies of the HIV-1 disease have shown that HLA and Chemokine receptor genetic variants influence disease progression and early viral load. We performed a Genome Wide Association study in a cohort of 605 HIV-1-infected seroconverters for detection of novel genetic factors that influence plasma HIV-RNA and cellular HIV-DNA levels. Most of the SNPs strongly associated with HIV-RNA levels were localised in the 6p21 major histocompatibility complex (MHC) region and were in the vicinity of class I and III genes. Moreover, protective alleles for four disease-associated SNPs in the MHC locus (rs2395029, rs13199524, rs12198173 and rs3093662) were strikingly over-represented among forty-five Long Term HIV controllers. Furthermore, we show that the HIV-DNA levels (reflecting the HIV reservoir) are associated with the same four SNPs, but also with two additional SNPs on chromosome 17 (rs6503919; intergenic region flanked by the DDX40 and YPEL2 genes) and chromosome 8 (rs2575735; within the Syndecan 2 gene). Our data provide evidence that the MHC controls both HIV replication and HIV reservoir. They also indicate that two additional genomic loci may influence the HIV reservoir

COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study

Background: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results: ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P &lt; 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men

Distribution of total DNA and cccDNA in serum and PBMCs may reflect the HBV immune status in HBsAg+ and HBsAg− patients coinfected or not with HIV or HCV

International audienceBackgroundThe potential reservoir role of serum and peripheral blood mononuclear cells (PBMCs) for total HBV DNA (tDNA) and cccDNA still remains unknown.Material and methodsWe analyzed tDNA and cccDNA with a single sensitive and validated standardized real-time PCR method in serum and PBMCs in two populations of chronic HBV infection coinfected or not with HCV and/or HIV viruses: a retrospective cohort of 130 HBsAg-negative (HBsAg−) patients with “anti-HBc alone” or anti-HBc and anti-HBs antibodies (Ab) and a cohort of 70 HBsAg-positive patients, 16 of them being prospectively followed under treatment.ResultsAmong HBsAg− patients, HBV DNA was detected in serum or PBMCs in about half of the cases with various distributions of tDNA and cccDNA: in HIV-negative patients with an “antiHBc alone” profile, tDNA was mostly detected in PBMCs suggesting a possible active role of PBMCs; although cccDNA was not detected in PBMCs in HIV-positive patients, tDNA and cccDNA were mostly observed in serum, suggesting a specific pattern of more “persistent” than “occult” infection in this population. Patients with anti-HBc and anti-HBs Ab harbored tDNA in serum or in PBMCs, regardless of their HIV or HCV status, raising the question of a viral reactivation risk during immunosupression in these patients. Among HBsAg+ patients, tDNA was detected in serum and PBMCs of 88.5% of the cases and cccDNA in 22%. Levels of tDNA in both compartments were highly correlated during treatment, suggesting a passive reservoir role for PBMCs.ConclusionThe respective distribution of tDNA and cccDNA in serum and PBMCs may reflect the different immune statuses of the host in HBsAg+ and HBsAg− patients. The frequency of HBV DNA in PBMCs from AgHBs− patients suggests a viral reactivation risk during immunodepression in those patients.</p

Changing of hepatitis C virus genotype patterns in France at the beginning of the third millenium: The GEMHEP GenoCII Study

International audienceThis cross-sectional study aimed to investigate, during a short period between 2000 and 2001, in a large population of patients with chronic hepatitis C, the epidemiological characteristics of hepatitis C virus (HCV) genotypes in France. Data from 26 referral centres, corresponding to 1769 patients with chronic hepatitis C were collected consecutively during a 6-month period. HCV genotyping in the 5'-non-coding region (NCR) was performed in each center using the line probe assay (LiPA, in 63% of cases), sequencing (25%) or primer-specific polymerase chain reaction (PCR) (12%). HCV genotypes 1a, 1b, 2, 3, 4, 5, non-subtyped 1 and mixed infection were found in 18, 27, 9, 21, 9, 3, 11 and 1% of our population, respectively. HCV genotype distribution was associated with gender, age, source and duration of infection, alanine aminotransferase (ALT) levels, cirrhosis, alcohol consumption, hepatitis B virus (HBV) and human immunodeficiency virus (HIV) coinfection. In multivariate analysis, only the source of infection was the independent factor significantly associated with genotype (P = 0.0001). In conclusion, this study shows a changing pattern of HCV genotypes in France, with i.v. drug abuse as the major risk factor, an increase of genotype 4, and to a lesser extent 1a and 5, and a decrease of genotypes 1b and 2. The modification of the HCV genotype pattern in France in the next 10 years may require new therapeutic strategies, and further survey studies