Anti-HBV treatment induces novel reverse transcriptase mutations with reflective effect on HBV S antigen

The identification of novel reverse-transcriptase (RT) drug-resistance mutations is critical in predicting the probability of success to anti-HBV treatment. Furthermore, due to HBV-RT/HBsAg gene-overlap, they can have an impact on HBsAg-detection and quantification

30-day mortality in patients hospitalized with COVID-19 during the first wave of the Italian epidemic: a prospective cohort study

Italy was the first European country hit by the COVID-19 pandemic and has the highest number of recorded COVID-19 deaths in Europe. This prospective cohort study of the correlates of the risk of death in COVID-19 patients was conducted at the Infectious Diseases and Intensive Care units of Luigi Sacco Hospital, Milan, Italy. The clinical characteristics of all the COVID-19 patients hospitalised in the early days of the epidemic (21 February -19 March 2020) were recorded upon admission, and the time-dependent probability of death was evaluated using the Kaplan-Meier method (censored as of 20 April 2020). Cox proportional hazard models were used to assess the factors independently associated with the risk of death. Forty-eight (20.6%) of the 233 patients followed up for a median of 40 days (interquartile range 33-47) died during the follow-up. Most were males (69.1%) and their median age was 61 years (IQR 50-72). The time-dependent probability of death was 19.7% (95% CI 14.6-24.9%) 30 days after hospital admission. Age (adjusted hazard ratio [aHR] 2.08, 95% CI 1.48-2.92 per ten years more) and obesity (aHR 3.04, 95% CI 1.42-6.49) were independently associated with an increased risk of death, which was also associated with critical disease (aHR 8.26, 95% CI 1.41-48.29), C-reactive protein levels (aHR 1.17, 95% CI 1.02-1.35 per 50\u2009mg/L more) and creatinine kinase levels above 185 U/L (aHR 2.58, 95% CI 1.37-4.87) upon admission. Case-fatality rate of patients hospitalized with COVID-19 in the early days of the Italian epidemic was about 20%. Our study adds evidence to the notion that older age, obesity and more advanced illness are factors associated to an increased risk of death among patients hospitalized with COVID-19

Sarilumab in patients admitted to hospital with severe or critical COVID-19: a randomised, double-blind, placebo-controlled, phase 3 trial

Background: Elevated proinflammatory cytokines are associated with greater COVID-19 severity. We aimed to assess safety and efficacy of sarilumab, an interleukin-6 receptor inhibitor, in patients with severe (requiring supplemental oxygen by nasal cannula or face mask) or critical (requiring greater supplemental oxygen, mechanical ventilation, or extracorporeal support) COVID-19. Methods: We did a 60-day, randomised, double-blind, placebo-controlled, multinational phase 3 trial at 45 hospitals in Argentina, Brazil, Canada, Chile, France, Germany, Israel, Italy, Japan, Russia, and Spain. We included adults (≥18 years) admitted to hospital with laboratory-confirmed SARS-CoV-2 infection and pneumonia, who required oxygen supplementation or intensive care. Patients were randomly assigned (2:2:1 with permuted blocks of five) to receive intravenous sarilumab 400 mg, sarilumab 200 mg, or placebo. Patients, care providers, outcome assessors, and investigators remained masked to assigned intervention throughout the course of the study. The primary endpoint was time to clinical improvement of two or more points (seven point scale ranging from 1 [death] to 7 [discharged from hospital]) in the modified intention-to-treat population. The key secondary endpoint was proportion of patients alive at day 29. Safety outcomes included adverse events and laboratory assessments. This study is registered with ClinicalTrials.gov, NCT04327388; EudraCT, 2020-001162-12; and WHO, U1111-1249-6021. Findings: Between March 28 and July 3, 2020, of 431 patients who were screened, 420 patients were randomly assigned and 416 received placebo (n=84 [20%]), sarilumab 200 mg (n=159 [38%]), or sarilumab 400 mg (n=173 [42%]). At day 29, no significant differences were seen in median time to an improvement of two or more points between placebo (12·0 days [95% CI 9·0 to 15·0]) and sarilumab 200 mg (10·0 days [9·0 to 12·0]; hazard ratio [HR] 1·03 [95% CI 0·75 to 1·40]; log-rank p=0·96) or sarilumab 400 mg (10·0 days [9·0 to 13·0]; HR 1·14 [95% CI 0·84 to 1·54]; log-rank p=0·34), or in proportions of patients alive (77 [92%] of 84 patients in the placebo group; 143 [90%] of 159 patients in the sarilumab 200 mg group; difference −1·7 [−9·3 to 5·8]; p=0·63 vs placebo; and 159 [92%] of 173 patients in the sarilumab 400 mg group; difference 0·2 [−6·9 to 7·4]; p=0·85 vs placebo). At day 29, there were numerical, non-significant survival differences between sarilumab 400 mg (88%) and placebo (79%; difference +8·9% [95% CI −7·7 to 25·5]; p=0·25) for patients who had critical disease. No unexpected safety signals were seen. The rates of treatment-emergent adverse events were 65% (55 of 84) in the placebo group, 65% (103 of 159) in the sarilumab 200 mg group, and 70% (121 of 173) in the sarilumab 400 mg group, and of those leading to death 11% (nine of 84) were in the placebo group, 11% (17 of 159) were in the sarilumab 200 mg group, and 10% (18 of 173) were in the sarilumab 400 mg group. Interpretation: This trial did not show efficacy of sarilumab in patients admitted to hospital with COVID-19 and receiving supplemental oxygen. Adequately powered trials of targeted immunomodulatory therapies assessing survival as a primary endpoint are suggested in patients with critical COVID-19. Funding: Sanofi and Regeneron Pharmaceuticals

Group G streptococcus bacteremia in recurrent cellulitis

In recent years, group G Streptococcus has been reported with increasing frequency as the cause of a variety of human infections. Underlying host factors such as immunosuppression, malignancy, diabetes mellitus, and rheumatoid arthritis may be predisposing conditions leading to infection. Toxic involvement and post-streptococcal sequalae, once believed to be exclusive to infections caused by group A Streptococcus, are now known to occur following acute group G Streptococcus and group C Streptococcus infections. We report on a case of group G Streptococcus bacteremia and recurrent cellulitis with toxic involvement. Patient blood cultures were always negative for \u3b2-hemolytic Streptococci in all the recurrences, except during the last one. Antibiotic therapy based on antibiogram quickly resolved the infection. A regimen of intramuscular injection of 1.2 million units of benzathine penicillin every 15 days for one year prevented recurrences of cellulitis

Intestinal lymphangiectasia and reversible high liver stiffness

Primary intestinal lymphangiectasia (PIL) is a protein-losing enteropathy characterized by tortuous and dilated lymph channels of the small bowel. The main symptoms are bilateral lower limb edema, serosal effusions, vitamin D malabsorption resulting in osteoporosis. We reported here a case of long-lasting misdiagnosed PIL with a peculiar liver picture, characterized by very high stiffness value at transient elastography, which decreased with clinical improvement. The complex interplay between lymphatic and hepatic circulatory system was discusse

Hepatic histology of patients with HIV infection and chronic hepatitis C treated with interferon.

AIMS: To evaluate the histological changes seen in liver biopsies after interferon (IFN) treatment in patients with chronic hepatitis C and human immunodeficiency virus (HIV) infection. METHODS: Twenty four intravenous drug users with chronic hepatitis C were investigated histologically before beginning a 12 month course of IFN treatment and 18 months later. Twelve were HIV positive, without opportunistic or other viral infections (group A), and 12 were HIV negative (group B). RESULTS: According to alanine amino-transferase concentrations, four sustained responders and eight non-responders were found in group A; six sustained responders, five relapsers, and one non-responder were found in group B. HCV RNA became negative in one sustained responder of group A and in the six sustained responders of group B. When histological findings of biopsies performed before therapy and 18 months later were compared, no significant changes in the mean value of Knodell's index and subindices were found in group A, whereas in group B Knodell's index, piecemeal necrosis, and focal hepatocellular necrosis decreased significantly. CONCLUSIONS: In chronic hepatitis C, coinfection with HIV showed a tendency towards a lower response to IFN, although this did not reach statistical significance; however, none of the HIV positive patients developed cirrhosis during the follow up and this should be considered in clinical management of such patients

Chronic Hepatitis B in children and adolescents: a longitudinal assessment.

Chronic Hepatitis B in children is a problem alla over the world; paediatrica data are limited. The authors describe clinical, biochemical, virological and imaging data of a cohort of paediatric patients with chronix Hepatitis B infection who attended tha Paediatric Infection Disease Unit of Luigi Sacco Hospital, University of Milan. We followed 13 children and adolescents, all of whom were vertically-infected. Every 6 months patients underwent laboratory assessment and virological examination. seum IgA, IgM, IgG, lipid profile, coagulation assessment, ferritin, alfa-phetoprotein were tested once a year. Lievr ultrasound examination using Esoate Mylab50 and transient elastography usinf Fibroscan was performed once a year. 11 children of of 13 were HBeAg positive; only 1 patient was anti-HBeAg positive. AST and ALT values were elevated in 7/13 and 5/13 respectively. During the follow-up 2 patinets (15%) seroconverted to anti-HBeAg. the mosto common picture at hepatic ultrasoud was grade I steatosis and 2 children showed mild hepatomegaly. the transient elastography evaluation, performed in 7 cases, showed mild increment of liver stiffness values in all cases. The median stiffness was 5.2 KPa. The dicision about when and how star antiviral therapy in children is still a controversial issue; however an early treatment would have tha purpose to reduce viral replication and infectivity, and prevent long-term complications

Progettazione, costruzione ed esercizio di una batteria primaria a flusso zinco-aria equipaggiata con sistema di controllo automatico

La produzione di energia elettrica da fonti rinnovabili potrebbe sostituire quella da combustibili fossili, ma il supporto di sistemi termici \ue8 attualmente inevitabile per la mancanza di dispositivi affidabili della taglia richiesta da applicazioni civili, trasportistiche ed industriali. La ricerca accademica e industriale \ue8 pertanto attivamente impegnata nell\u2019identificazione di nuove strategie di accumulo, specialmente di tipo elettrochimico. Fra le tipologie di batteria in studio, i sistemi Zn-aria sono fra i pi\uf9 promettenti per ragioni di sicurezza, reperibilit\ue0 delle materie prime, costo e sostenibilit\ue0. Questa memoria espone i recenti sviluppi nell\u2019ambito delle celle a combustibile Zn-aria (ZAFC) basati sull\u2019esperienza degli autori nella costruzione ed esercizio di un sistema di 1a generazione ZAFC-G1 (1). Dall\u2019analisi delle criticit\ue0 di ZAFC-G1 \ue8 stato possibile da una parte implementare migliorie cha hanno portato a un aumento della densit\ue0 di potenza di un fattore 2,5, dall\u2019altra si \ue8 riprogettato e realizzato tramite stampa 3D un sistema ottimizzato per alte densit\ue0 di potenza e maggiore durabilit\ue0