Early prone positioning does not improve the outcome of patients with mild pneumonia due to SARS-CoV-2: results from an open-label randomised controlled trial - the EPCoT study.

Background: Prone positioning is routinely used among patients with COVID-19 requiring mechanical ventilation. However, its utility among spontaneously breathing patients is still debated. Methods: In an open-label randomised controlled trial, we enrolled patients hospitalised with mild COVID-19 pneumonia, whose arterial oxygen tension to inspiratory oxygen fraction ratio (PaO2/FIO2) was >200 mmHg and who did not require mechanical ventilation or continuous positive airway pressure at hospital admission. Patients were randomised 1:1 to prone positioning on top of standard of care (intervention group) versus standard of care only (controls). The primary composite outcome included death, mechanical ventilation, continuous positive airway pressure and PaO2/FIO2 <200 mmHg; secondary outcomes were oxygen weaning and hospital discharge. Results: A total of 61 subjects were enrolled, 29 adjudicated to prone positioning and 32 to the control group. By day 28, 24 out of 61 patients (39.3%) met the primary outcome: 16 because of a PaO2/FIO2 ratio <200 mmHg, five because of the need for continuous positive airway pressure and three because of the need for mechanical ventilation. Three patients died. Using an intention-to-treat approach, 15 out of 29 patients in the prone positioning group versus nine out of 32 controls met the primary outcome, corresponding to a significantly higher risk of progression among those randomised to prone positioning (HR 2.38, 95% CI 1.04-5.43; p=0.040). Using an as-treated approach, which included in the intervention group only patients who maintained prone positioning for ≥3 h·day-1, no significant differences were found between the two groups (HR 1.77, 95% CI 0.79-3.94; p=0.165). Also, we did not find any statistically significant difference in terms of time to oxygen weaning or hospital discharge between study arms in any of the analyses conducted. Conclusions: We observed no clinical benefit from prone positioning among spontaneously breathing patients with COVID-19 pneumonia requiring conventional oxygen therapy.

Behavioural survey and street-based HIV and HCV rapid testing programme among transgender sex workers.

BACKGROUND: Transgender women sex workers (TGW-SW) are disproportionally affected by HIV and have reduced access to testing. Moreover, information regarding their behaviours and health needs is scarce. METHODS: A behavioural survey and a targeted testing programme in prostitution sites were conducted in Milan and Monza areas. The non-profit organisation 'ALA Milano Onlus' and 'San Gerardo' Hospital (Monza) implemented a mobile HIV testing unit involving a TGW peer educator, four physicians, a counsellor, a psychologist and a cultural mediator. All TGW-SW were offered anonymous HIV and hepatitis C virus (HCV) oral testing and asked to fill a questionnaire on sexual habits, drug abuse, and knowledge and attitudes towards HIV and STDs. RESULTS: Between May and July 2017, 130 TGW-SW, predominantly migrants, were contacted during 15 street visits; among them, 78 (60%) were interviewed. HIV and HCV testing were accepted by 53 (42%) and 67 (52%) TGW-SW, respectively. Twenty-five (19.8%) subjects who reported already established HIV infection were not retested. Seven patients received a new diagnosis of HIV, while nobody tested positive for HCV. Overall, HIV prevalence was 13.2% (25% including those with already known HIV infection). Recent arrival in Italy and young age were associated with risk of undiagnosed HIV infection. Inconsistent condom use was commonly reported during commercial sex (27%) and with non-commercial partners (64%). Alcohol and cocaine abuse were common problems which facilitated risky behaviours. CONCLUSIONS: Oral rapid HIV and HCV testing for TGW-SW in outreach settings were feasible and acceptable and led to a considerable number of new diagnoses. Interventions tailored to TGW-SW, focused on HIV prevention, testing and engagement in care, are fundamental.

Antibiotic stewardship and empirical antibiotic treatment: How can they get along?

The aim of this review is to focus on the recent knowledge on antibiotic stewardship and empiric antibiotic treatment in cirrhotic patients. The application of antimicrobial stewardship (AMS) rules appears to be the most appropriate strategy to globally manage cirrhotic patients with infectious complications: indeed they represent a unique way to provide both early diagnosis and appropriate therapy in order to avoid not only antibiotic over-prescription but, more importantly, selection and spread of antimicrobial resistance. Moreover, cirrhotic patients must be considered "frail" and susceptible to healthcare associated infections: applying AMS policies would assure a cost reduction and thus contribute to the improvement of public health strategies.

Emerging biological agents for hepatitis C.

INTRODUCTION: New direct-acting antiviral agents have changed the landscape of treatment of chronic HCV infection. Despite current treatments are well tolerated with a high rate of sustained virological response (SVR), some medical needs remain. Nowadays there are a large number of approved medications for the treatment of HCV infection; nevertheless, new studies are conducted to find new agents and new combinations. AREAS COVERED: A literature research of new antiviral compounds indicated for the treatment of HCV infection was achieved by an online search of medication undergoing development on Pubmed and clinicalTrials.gov clinical trials registry. We considered phase I/II studies and some randomized Phase III trials. EXPERT OPINION: More knowledge about impact of HCV eradication on disease progression and more confidence regarding drug-drug interaction are needed. Furthermore, each treatment should be individualized targeting the patients needs with the aim not only to obtain viral suppression but also to stop progression of liver disease and HCV related conditions, and to improve patient health status.

Beyond the gut bacterial microbiota: The gut virome.

The gastrointestinal tract is colonized with a highly different population of bacterial, viral, ad fungal species; viruses are reported to be dominant. The composition of gut virome is closely related to dietary habits and surrounding environment. Host and their intestinal microbes live in a dynamic equilibrium and viruses stimulate a low degree of immune responses without causing symptoms (host tolerance). However, intestinal phages could lead to a rupture of eubiosis and may contribute to the shift from health to disease in humans and animals. Viral nucleic acids and other products of lysis of bacteria serve as pathogen-associated molecular patterns (PAMPs) and could trigger specific inflammatory modulations. At the same time, phages could elicit innate antiviral immune responses. Toll-like receptors (TLRs) operated as innate antiviral immune sensors and their activation triggers signaling cascades that lead to inflammatory response. J. Med. Virol. 88:1467-1472, 2016. © 2016 Wiley Periodicals, Inc.

Understanding the Mechanisms of Fibrogenesis in HIV/HCV-Coinfected Patients: Implications for Clinical Practice.

HIV/HCV coinfection is associated with accelerated progressive liver disease. Understanding the pathogenesis of liver fibrosis remains crucial to improving the global management of this patient population. This review will mainly focus on the mechanisms involved in the faster progression of liver fibrosis seen in HIV/HCV coinfection, which is caused by a multiplicity of complex factors including virus features, the immune system, interactions between viruses and the immune response, the direct effects of HIV on hepatocytes, fibrinogenetic/inflammatory mediators, microbial translocation, and metabolic abnormalities. The direct role of viruses as well as chronic inflammation, deterioration of immune status, and the harmful effect of antiretroviral agents may all concur to produce dyslipidemia and insulin resistance. Metabolic abnormalities play an important role in the genesis of hepatic steatosis, which is closely linked to liver fibrosis progression. There is also a link between immunologic and metabolic abnormalities: increased expression of leptin and reduced expression of adiponectin seems to be associated with advanced hepatic injury. New antifibrotic strategies are outlined. Ultimately, sustained virological response to hepatitis C therapy is associated with liver fibrosis regression in patients with HIV/HCV coinfection.