Evaluation of the effect of sofosbuvir and daclatasvir in hospitalized COVID-19 patients: a randomized double-blind clinical trial (DISCOVER).

BACKGROUND: The combination of sofosbuvir and daclatasvir has shown preliminary efficacy for hospitalized patients with COVID-19 in four open-label studies with small sample sizes. This larger trial aimed to assess if the addition of sofosbuvir/daclatasvir to standard care improved clinical outcomes in hospitalized patients with COVID-19. METHODS: This was a placebo-controlled, double-blind, randomized clinical trial in adults hospitalized with COVID-19 at 19 hospitals in Iran. Patients were randomized to oral sofosbuvir/daclatasvir 400/60 mg once-daily or placebo in addition to standard of care. Patients were included if they had positive PCR or diagnostic chest CT, O2 saturation <95% and compatible symptoms. The primary outcome was hospital discharge within 10 days of randomization. Secondary outcomes included mortality and time to clinical events. The trial is registered on the Iran Registry of Clinical Trials under IRCT20200624047908N1. RESULTS: Between July and October 2020, 1083 patients were randomized to either the sofosbuvir/daclatasvir arm (n = 541) or the placebo arm (n = 542). No significant difference was observed in the primary outcome of hospital discharge within 10 days, which was achieved by 415/541 (77%) in the sofosbuvir/daclatasvir arm and 411/542 (76%) in the placebo arm [risk ratio (RR) 1.01, 95% CI 0.95-1.08, P = 0.734]. In-hospital mortality was 60/541 (11%) in the sofosbuvir/daclatasvir arm versus 55/542 (10%) in the placebo arm (RR 1.09, 95% CI 0.77-1.54, P = 0.615). No differences were observed in time to hospital discharge or time to in-hospital mortality. CONCLUSIONS: We observed no significant effect of sofosbuvir/daclatasvir versus placebo on hospital discharge or survival in hospitalized COVID-19 patients.

Comparison of two therapeutic approaches for the management of ventilator-associated pneumonia due to multidrug-resistant Acinetobacter: a randomized clinical trial study.

Management of ventilator-associated pneumonia (VAP) is a puzzling issue for infectious disease specialist. The present clinical trial study was aimed to comparing the effects of injectable colistin plus nebulized colistin and injectable colistin plus nebulized tobramycin on management of patients with VAP due to multidrug-resistant Acinetobacter. VAP patients were randomly divided into two groups (n = 30/each): Group 1 - patients that received intravenous (IV) meropenem, injectable colistin plus nebulized colistin, as a routine treatment, and Group 2 - patients that received IV meropenem, injectable colistin plus nebulized tobramycin. A total of 14 days of therapeutic intervention are required for every case. Follow-up for subjects was performed at five time-points: days 1, 3, 5, 7, and 14 after intervention. Also, a mean of creatinine levels of patients was determined in five times. In the present study, the clinical pulmonary infection score (CPIS) was determined on the basis of points assigned for various clinically manifestations of VAP. Based on our statistical analysis, there was no significant difference between CPIS and creatinine level in both Groups 1 and 2 (p > .05). CPIS and other clinical investigation appeared effectiveness of the treatment with injected colistin plus nebulized tobramycin; on the other hand, the results of present clinical trial showed that aforementioned therapeutic approach can be used as an alternative treatment for the management of infection in VAP patients.

Report of a Hydatid Cyst Case with Biceps Brachii Involvement.

Muscular hydatid cyst is a rare condition mainly secondary to the cysts from other organs. We hereby present an uncommon case of primary hydatid cyst found in the right biceps brachii muscle of a 36-year-old male. Magnetic resonance revealed no Echinococcus involvement in any other part of his body. Chest X-ray was normal, and no trace of cyst was found in the lung. In areas where echinococcosis is endemic, any tumor or mass in any part of the patient's body should be evaluated and examined for Echinococcus infestation. This paper is the second case report article on echinococcal biceps brachii infestation existing to this date.

microRNAs: Key players in virus-associated hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is known as one of the major health problems worldwide. Pathological analysis indicated that a variety of risk factors including genetical (i.e., alteration of tumor suppressors and oncogenes) and environmental factors (i.e., viruses) are involved in beginning and development of HCC. The understanding of these risk factors could guide scientists and clinicians to design effective therapeutic options in HCC treatment. Various viruses such as hepatitis B virus (HBV) and hepatitis C virus (HCV) via targeting several cellular and molecular pathways involved in HCC pathogenesis. Among various cellular and molecular targets, microRNAs (miRNAs) have appeared as key players in HCC progression. miRNAs are short noncoding RNAs which could play important roles as oncogenes or tumor suppressors in several malignancies such as HCC. Deregulation of many miRNAs (i.e., miR-222, miR-25, miR-92a, miR-1, let-7f, and miR-21) could be associated with different stages of HCC. Besides miRNAs, exosomes are other particles which are involved in HCC pathogenesis via targeting different cargos, such as DNAs, RNAs, miRNAs, and proteins. In this review, we summarize the current knowledge of the role of miRNAs and exosomes as important players in HCC pathogenesis. Moreover, we highlighted HCV- and HBV-related miRNAs which led to HCC progression.