Coronavirus disease 19 (Covid-19): A comparative study of pattern of liver injury in adult patients in different waves of Covid-19 infection.

BACKGROUND AND STUDY AIMS: Liver dysfunction is a common manifestation of the COVID-19 infection. We aimed to study transaminase abnormalities through different waves of COVID-19 and their relations to disease severity or mortality. PATIENTS AND METHODS: A retrospective study included 521 Egyptian patients diagnosed with COVID-19. Data was retrieved from the medical records of patients who were admitted from April 2020 to October 2021 in Kasr Al-Ainy Hospitals, Cairo University, with categorization according to disease severity in correspondence to the four waves. RESULTS: The median age was lower in the first wave compared to other waves, with male predominance across all waves. The most commonly encountered comorbidity overall was hypertension, followed by diabetes mellitus. White blood cells, ferritin, and interleukin-6 showed the highest median values in the second wave, with significantly higher median C-reactive protein on day 1 in the first wave. Forty percent of the patients showed elevated hepatic transaminases on admission in four waves, with no statistically significant difference between waves. On day 5, around half of the patients had elevated transaminases, with no significant difference between waves. Most CT findings were of moderate severity. Clinical severity was higher in the second wave. It was observed that the higher the disease severity, the greater the proportion of patients with elevated hepatic transaminases. The mortality rate was markedly high in cases who had elevated ALT or AST on day 5. The association between elevated enzymes on admission and mortality was seen in the first wave only, with a fatality rate of 22.5% in cases with increased baseline ALT and AST versus 5% in those with normal baseline enzymes. CONCLUSION: There was no significant difference in transaminases between the four waves. Elevated transaminases were positively associated with increased mortality and severity, reflecting their prognostic value.

A Systematic Review of Novel Therapies of Pulmonary Arterial Hypertension.

BACKGROUND: Pulmonary arterial hypertension (PAH) is a progressive, cureless disease, characterized by increased pulmonary vascular resistance and remodeling, with subsequent ventricular dilatation and failure. New therapeutic targets are being investigated for their potential roles in improving PAH patients' symptoms and reversing pulmonary vascular pathology. METHOD: We aimed to address the available knowledge from the published randomized controlled trials (RCTs) regarding the role of Rho-kinase (ROCK) inhibitors, bone morphogenetic protein 2 (BMP2) inhibitors, estrogen inhibitors, and AMP-activated protein kinase (AMPK) activators on the PAH evaluation parameters. This systematic review (SR) was registered in the International Prospective Register of Systematic Reviews (PROSPERO) database (CDR42022340658) and followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. RESULTS: Overall, 5092 records were screened from different database and registries; 8 RCTs that met our inclusion criteria were included. The marked difference in the study designs and the variability of the selected outcome measurement tools among the studies made performing a meta-analysis impossible. However, the main findings of this SR relate to the powerful potential of the AMPK activator and the imminent antidiabetic drug metformin, and the BMP2 inhibitor sotatercept as promising PAH-modifying therapies. There is a need for long-term studies to evaluate the effect of the ROCK inhibitor fasudil and the estrogen aromatase inhibitor anastrozole in PAH patients. The role of tacrolimus in PAH is questionable. The discrepancy in the hemodynamic and clinical parameters necessitates defining cut values to predict improvement. The differences in the PAH etiologies render the judgment of the therapeutic potential of the tested drugs challenging. CONCLUSION: Metformin and sotatercept appear as promising therapeutic drugs for PAH. CLINICAL TRIALS REGISTRATION: This work was registered in PROSPERO (CDR42022340658).

Effect of Oral Methyl Prednisolone on Different Radiological Patterns of Hypersensitivity Pneumonitis.

BACKGROUND: Hypersensitivity pneumonitis (HP) is an immune-mediated disorder that causes inflammation of interstitial lung, bronchioles, and alveoli. Although corticosteroids have been used as first line treatment for HP for many years, it does not provide satisfactory results in all patients. The aim of this study is to compare the effect of oral methylprednisolone on different radiological patterns of HP to identify the most adequate candidates for corticosteroids. PATIENTS AND METHODS: Fifty-three patients with confirmed diagnosis of HP were divided into two groups according to their radiological patterns based on high resolution computed tomography (HRCT) findings. The first group included 21 patients with fibrotic HP (fHP), the second group included 32 patients without fibrosis; non-fibrotic HP patients (nfHP). The second group is divided into 3 subgroups: mosaic, attenuation, centrilobular nodules and finally, ground-glass opacities. All patients were administered methylprednisolone by dose 0.5mg/kg/day for eight consecutive weeks. HRCT was performed at the beginning of the study. Spirometry, six-minute walk and oximetry were performed periodically to assess the patients' progress. RESULTS: Upon finalizing the treatment process, a significant improvement was noticed in FEV1 (p < 0.001), FVC (p <0.001), six-minute walk test (p =0.001) and oximetry (p <0.05) in nfHP compared to the fHP patients. However, there was a significant improvement in (p <0.01), FVC (p <0.01), oximetry (p <0.01) and six-minute walk test (p <0.01) in fibrotic patients after receiving the treatment. There was no significant difference in the response of FEV1 (p =0.82), FVC (p =0.15), six-minute walk test (p =0.36) and oximetry (p =0.27) among the subgroups of nfHP patients. CONCLUSION: It was accordingly concluded that corticosteroid treatment is more effective in treatment of nfHP than fHP patients but still has effect on fibrotic patients. There is no significant difference in the response to corticosteroids among nfHP patients' subgroups.

Role of microRNA-21 and microRNA-155 as biomarkers for bronchial asthma.

MicroRNA (miRNA)-21 and miRNA-155 are important regulators of gene expression of different immunological molecules. This study aimed to investigate the role of miRNA-21 and miRNA-155 as biomarkers in asthma by comparing their serum expression levels in asthmatic patients to those in healthy controls and correlating their levels with serum IL-4. The expression levels of miRNA-21 and miRNA-155 were evaluated by quantitative RT-PCR. Serum levels of IL-4 were determined using ELISA. Asthmatic patients showed significantly higher serum miRNA-21 and miRNA-155 expression levels compared to controls. A statistically significant positive correlation between the expression levels of miRNA-21 and IL-4 serum levels in asthmatic patients was detected. Nonetheless, no correlation was detected between miRNA-155 expression and each of IL-4 and miRNA-21. A receiver operating characteristic curve analysis showed that at a cut-off value of 1.37, the sensitivity of miRNA-21 as an asthma biomarker was 100% and the specificity was 95%. At a cut-off value of 1.96, the sensitivity of miRNA-155 as an asthma biomarker was 100% and the specificity was 100%. It can be concluded that miRNA-21 and miRNA-155 are potential non-invasive biomarkers in the diagnosis of eosinophilic asthma and its response to therapy.