VINYL: Variant prIoritizatioN bY survivaL analysis

Motivation: Clinical applications of genome re\uadsequencing technologies typically generate large amounts of data that need to be carefully annotated and interpreted to identify genetic variants associated with pathological conditions. In this context, accurate and reproducible methods for the functional annotation and prioritization of genetic variants are of fundamental importance, especially when large volumes of data \uad like those produced by modern sequencing technologies \uad are involved. Results: In this paper, we present VINYL, a highly accurate and fully automated system for the functional annotation and prioritization of genetic variants in large scale clinical studies. Extensive analyses of both real and simulated datasets suggest that VINYL show higher accuracy and sensitivity when compared to equivalent state of the art methods, allowing the rapid and systematic identification of potentially pathogenic variants in different experimental settings

Subcutaneous REGEN-COV Antibody Combination to Prevent Covid-19

BACKGROUND REGEN-COV (previously known as REGN-COV2), a combination of the monoclonal antibodies casirivimab and imdevimab, has been shown to markedly reduce the risk of hospitalization or death among high-risk persons with coronavirus disease 2019 (Covid-19). Whether subcutaneous REGEN-COV prevents severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and subsequent Covid-19 in persons at high risk for infection because of household exposure to a person with SARS-CoV-2 infection is unknown. METHODS We randomly assigned, in a 1:1 ratio, participants (=12 years of age) who were enrolled within 96 hours after a household contact received a diagnosis of SARSCoV- 2 infection to receive a total dose of 1200 mg of REGEN-COV or matching placebo administered by means of subcutaneous injection. At the time of randomization, participants were stratified according to the results of the local diagnostic assay for SARS-CoV-2 and according to age. The primary efficacy end point was the development of symptomatic SARS-CoV-2 infection through day 28 in participants who did not have SARS-CoV-2 infection (as measured by reverse-transcriptase- quantitative polymerase-chain-reaction assay) or previous immunity (seronegativity). RESULTS Symptomatic SARS-CoV-2 infection developed in 11 of 753 participants in the REGEN-COV group (1.5%) and in 59 of 752 participants in the placebo group (7.8%) (relative risk reduction [1 minus the relative risk], 81.4%; P104 copies per milliliter) was shorter (0.4 weeks and 1.3 weeks, respectively). No dose-limiting toxic effects of REGEN-COV were noted. CONCLUSIONS Subcutaneous REGEN-COV prevented symptomatic Covid-19 and asymptomatic SARS-CoV-2 infection in previously uninfected household contacts of infected persons. Among the participants who became infected, REGEN-COV reduced the duration of symptomatic disease and the duration of a high viral load

Il panorama internazionale dell’epidemia : il rischio di AIDS nel Viaggiatore Internazionale

Vengono descritte le caratteristiche epidemiologiche della infezione da HIV in ambito internazionale, nazionale e regional

High prevalence of peripheral neuropathy in hepatitis C virus infected patients with symptomatic and asymptomatic cryoglobulinaemia

BACKGROUND: Fifty per cent of patients with chronic hepatitis C, show detectable cryoglobulinaemia, even though most of them do not show cryoglobulinaemia related symptoms. Peripheral neuropathy is present in most of the patients with symptomatic cryoglobulinaemia, where it may be the first clinical manifestation. The prevalence of peripheral neuropathy in patients with hepatitis C and cryoglobulinaemia is unknown. AIMS: To assess the prevalence of peripheral neuropathy in HCV infected patients with symptomatic or asymptomatic detectable cryoglobulinaemia. PATIENTS AND METHODS: Eighty-nine patients with HCV infection and detectable cryoglobulinaemia underwent electrophysiological studies. RESULTS: Electrophysiological evidence of peripheral neuropathy was found in 37% and was significantly associated with: the presence of cryoglobulinaemia syndrome, older age, higher rheumatoid factor reactivity and immunoglobulin M levels and reduced complement C4 activity. However, electrophysiological evidence of peripheral neuropathy was unrelated to cryocrit levels and type of cryoglobulinaemia and was found in 23/68 patients without any symptoms of cryoglobulinaemia other than pain and paresthesia. CONCLUSIONS: These findings suggest that peripheral neuropathy is frequent in patients with hepatitis C and detectable cryoglobulins. Neuropathy was found to be present in 1/3 of patients without other cryoglobulinaemia-related symptoms, thus a direct or indirect role of HCV, independent of cryoglobulinaemia, in the pathogenesis of nerve damage cannot be ruled out