SARS-CoV-2 is causing an increasing number of deaths worldwide because no effective treatment is currently available. Remdesivir has shown in vitro activity against coronaviruses and is a possible antiviral treatment for SARS-CoV-2 infection.This prospective (compassionate), open-label study of remdesivir, which was conducted at Luigi Sacco Hospital, Milan, Italy, between February 23 and March 20, 2020, involved patients with SARS-CoV-2 pneumonia aged ≥18 years undergoing mechanical ventilation or with an oxygen saturation level of ≤94 % in air or a National Early Warning Score 2 of ≥4. The primary outcome was the change in clinical status based on a 7category ordinal scale (1 = not hospitalised, resuming normal daily activities; 7 = deceased).The 35 patients enrolled from February 23 to March 20, 2020, included 18 in intensive care unit (ICU), and 17 in our infectious diseases ward (IDW). The 10-day course of remdesivir was completed by 22 patients (63 %) and discontinued by 13, of whom eight (22.8 %) discontinued because of adverse events. The median follow-up was 39 days . At day 28, 14 (82.3 %) patients from IDW were discharged, two were still hospitalized and one died (5.9 %), whereas in ICU 6 (33.3 %) were discharged, 8 (44.4 %) patients died, three (16.7 %) were still mechanically ventilated and one (5.6 %) was improved but still hospitalized. Hypertransaminasemia and acute kidney injury were the most frequent severe adverse events observed (42.8 % and 22.8 % of the cases, respectively).Our data suggest that remdesivir can benefit patients with SARS-CoV-2 pneumonia hospitalised outside ICU where clinical outcome was better and adverse events are less frequently observed. Ongoing randomised controlled trials will clarify its real efficacy and safety, who to treat, and when.
Several strategies have been developed for the control of DNA translocation in nanopores and nanochannels. However, the possibility to reduce the molecule speed is still challenging for applications in the field of single molecule analysis, such as ultra-rapid sequencing. This paper demonstrates the possibility to alter the DNA translocation process through an elastomeric nanochannel device by dynamically changing its cross section. More in detail, nanochannel deformation is induced by a macroscopic mechanical compression of the polymeric device. This nanochannel squeezing allows slowing down the DNA molecule passage inside it. This simple and low cost method is based on the exploitation of the elastomeric nature of the device, can be coupled with different sensing techniques, is applicable in many research fields, such as DNA detection and manipulation, and is promising for further development in sequencing technology.
We present the development and the electrical characterization of a polymeric nanochannel device. Standard microfabrication coupled to Focused Ion Beam (FIB) nanofabrication is used to fabricate a silicon master, which can be then replicated in a polymeric material by soft lithography. Such an elastomeric nanochannel device is used to study DNA translocation events during electrophoresis experiments. Our results demonstrate that an easy and low cost fabrication technique allows creation of a low noise device for single molecule analysis.
ObjectivesTo identify predictive factors for moderate/severe liver fibrosis and to analyse fibrosis progression in paired liver biopsies from HIV-positive patients with chronic hepatitis C virus (HCV) infection.
MethodsHIV/HCV coinfected patients followed at the 2nd Department of Infectious Diseases of L. Sacco Hospital in Milan, Italy, with at least one liver biopsy specimen were retrospectively evaluated.
ResultsA total of 110 patients were enrolled in the study. In a univariate analysis, predictive factors of Ishak-Knodell stage ! 3 were a history of alcohol abuse [odds ratio (OR) 3.6, P 5 0.004], alanine aminotransferase level 4100 IU/L at biopsy (OR 2.4, P 5 0.05), necro-inflammatory grade ! 9 (OR 37.14, Po0.0001) and CD4 count o350 cells/mL at nadir (OR 5.3, P 5 0.05). In a multivariate analysis, age 435 years (OR 3.19, P 5 0.04) and alcohol abuse (OR 4.36, P 5 0.002) remained independently associated with Ishak-Knodell stage. Paired liver biopsies were available in 36 patients; 18 showed an increase of at least one stage in the subsequent liver biopsy. Either in a univariate or in a multivariate analysis, a decrease of CD4 cell count of more than 10% between two biopsies (OR 6.85, P 5 0.002) was significantly associated with liver fibrosis progression.
ConclusionOur findings highlight the relevance of encouraging a withdrawal of alcohol consumption in people with chronic HCV infection and of carrying out close follow-up of patients, especially if they are more than 35 years old. It is therefore mandatory to evaluate HIV/HCV coinfected patients for anti-HCV treatment and to increase CD4 cell count through antiretroviral therapy in order to reduce the risk of fibrosis progression and to slow the evolution of liver disease.
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