Acetaminophen (APAP) is the main cause of acute liver failure in the West. Specific efficacious therapies for acute liver failure (ALF) are limited and time-dependent. The mechanisms that drive irreversible acute liver failure remain poorly characterized. Here we report that the recently discovered platelet receptor CLEC-2 (C-type lectin-like receptor) perpetuates and worsens liver damage after toxic liver injury. Our data demonstrate that blocking platelet CLEC-2 signalling enhances liver recovery from acute toxic liver injuries (APAP and carbon tetrachloride) by increasing tumour necrosis factor-α (TNF-α) production which then enhances reparative hepatic neutrophil recruitment. We provide data from humans and mice demonstrating that platelet CLEC-2 influences the hepatic sterile inflammatory response and that this can be manipulated for therapeutic benefit in acute liver injury. Since CLEC-2 mediated platelet activation is independent of major haemostatic pathways, blocking this pathway represents a coagulopathy-sparing, specific and novel therapy in acute liver failure.

Background: Pandemic of COVID-19 has engulfed Nepal as well. In this paper, we studied the demographic, clinical, laboratory findings as well as the treatment modalities, prognostic factors and outcome of patients admitted with COVID-19.Methods: This was an observational cross-sectional study that included all patients admitted to the General Medicine Department of College of Medical Sciences, Bharatpur, during the first wave of COVID-19 from April 2020 to February 2021 after obtaining the ethical clearance. Data analysis was done using statistical packages for social sciences version 16.Results: A total of 119 patients with mean age of 61.5 years were admitted. They had a mean duration of onset of symptoms of 7.1 days. Commonest symptoms were fever (70.6%), cough (67.2%) and dyspnea (64.7%). Severe COVID-19 at admission with a median CT severity score of 15 was found in 49.7% of them. Total 83.2% patients required ICU care and 10.9% required mechanical ventilation. ARDS and secondary infection occurred in 17.6% each. Median length of hospital stay was 6 days. In total, 56.3% recovered 27.7% left against medical advice and 16.0% expired. Severity of COVID at admission, CT severity score at presentation and D-dimer at admission were found to be significantly associated with mortality (P<0.05).Neither of the age, duration of illness, CRP at admission nor the use of remdesivir or convalescent plasma had significant relation with the mortality (P>0.05).Conclusions: Severity of illness at presentation, CT severity score and D-dimer level at admission are significantly associated with mortality of the patients admitted with COVID-19.Keywords: COVID-19; prognosis; SARS-CoV-2

Introduction: We aim to compare Rapid Antigen Test and HRCT chest with Reverse Transcriptase-Polymerase chain reaction (RT-PCR) for diagnosis of COVID-19. Methods: This was a cross-sectional analytical study that included patients tested with RT-PCR and at least one of Rapid Antigen test or HRCT chest, conducted at College of Medical Sciences, Bharatpur, from June 2020 to Feb 2021 after obtaining the ethical clearance. Data analysis was done using statistical packages for social sciences version 16. Results:  315 of 755(41.7%) patients had positive RT-PCR and 18.4% of 733 patients had positive antigen test. Of 600 patients, 106(14.0%) were found to have CO-RADS 1,152(20.1%) had CO-RADS 2, 77(10.2%) had CO-RADS 3, 18(2.4%) had CO-RADS 4 and 247(32.7%) had CO-RADS 5 score on HRCT. Rapid Antigen Test was found to have 43.6% sensitivity, 98.6% specificity, 95.6% Positive predictive value (PPV) and 72.1% negative predictive value (NPV).CO-RADS scoring system was able to distinguish between RT-PCR positive and RT-PCR negative results with an average Area under curve 0.787. CO-RADS 5 had a sensitivity of 71.6%, specificity of 85.1%, PPV of 80.6% and NPV of 77.6% for a positive RT-PCR result. A combination of CO-RADS 1 in HRCT chest and Negative Antigen test can predict PCR negative result with 23.6% sensitivity, 97.3% specificity, 90.5% PPV and 54.0% NPV. Conclusions: Rapid Antigen Test is a better tool for confirmation rather than screening of COVID-19. HRCT chest with higher CO-RADS can be useful to diagnose COVID-19  in suspected patients, even if RT-PCR is negative.