Importance of Demographic and Clinical Features in Evaluating the Severity of COVID-19 in Hospitalized Patients: A Serbian Retrospective Study in the First Pandemic Year.

The aim of this study is to determine the demographic and initial clinical characteristics of patients with COVID-19 and their importance in evaluating the severity of the disease. A retrospective study included patients suffering from COVID-19 who were hospitalized at The Department of Infectious Disease of the Clinical Hospital Center Pristina-Gracanica from the beginning of the pandemic until the end of 2020. We compared the symptoms of the disease, radiographic findings of pneumonia, laboratory parameters, duration of symptoms before admission, the difference in the need for certain therapies, and the presence of comorbidities between non-severe and severe groups of patients. Patients with a severe disease were statistically significantly older. Hypertension was significantly associated with severe clinical conditions. Radiographic findings of bilateral pneumonia on admission were much more frequent among the severe group, and these patients' need for oxygen support was significantly higher. Lower neutrophil and higher lymphocyte counts were statistically significant in the non-severe group. Biochemical parameters at admission also showed statistical significance between the examined groups. Based on our research, we can conclude that a complete overview of the patient, including demographic and laboratory parameters as perhaps the most significant attributes, can help doctors in the timely clinical assessment of patients and, thus, in the timely application of adequate therapeutic protocols in the treatment of COVID-19.

In silico approach for the development of novel antiviral compounds based on SARS-COV-2 protease inhibition.

The COVID-19 pandemic emerged in 2019, bringing with it the need for greater stores of effective antiviral drugs. This paper deals with the conformation-independent, QSAR model, developed by employing the Monte Carlo optimization method, as well as molecular graphs and the SMILES notation-based descriptors for the purpose of modeling the SARS-CoV-3CLpro enzyme inhibition. The main purpose was developing a reproducible model involving easy interpretation, utilized for a quick prediction of the inhibitory activity of SAR-CoV-3CLpro. The following statistical parameters were present in the best-developed QSAR model: (training set) R 2 = 0.9314, Q 2 = 0.9271; (test set) R 2 = 0.9243, Q 2 = 0.8986. Molecular fragments, defined as SMILES notation descriptors, that have a positive and negative impact on 3CLpro inhibition were identified on the basis of the results obtained for structural indicators, and were applied to the computer-aided design of five new compounds with (4-methoxyphenyl)[2-(methylsulfanyl)-6,7-dihydro-1H-[1,4]dioxino[2,3-f]benzimidazol-1-yl]methanone as a template molecule. Molecular docking studies were used to examine the potential inhibition effect of designed molecules on SARS-CoV-3CLpro enzyme inhibition and obtained results have high correlation with the QSAR modeling results. In addition, the interactions between the designed molecules and amino acids from the 3CLpro active site were determined, and the energies they yield were calculated. Supplementary Information: The online version contains supplementary material available at 10.1007/s11696-022-02170-8.

Two different melatonin treatment regimens prevent an increase in kidney injury marker-1 induced by carbon tetrachloride in rat kidneys.

Acute kidney injury is a frequent disorder that can be mimicked by the application of different nephrotoxic agents, including carbon tetrachloride (CCl4), where kidney injury marker-1 (KIM-1) has been recognized as a highly specific marker. Melatonin is one of the most powerful natural antioxidants and has numerous beneficial properties. We evaluated the nephroprotective potential of 2 melatonin treatment regimens (pre- and post-intoxication) in a CCl4-induced acute kidney injury model based on the standard serum parameters, kidney tissue antioxidative capacity, KIM-1 levels, and kidney tissue morphological changes. The two treatment regimens were found to preserve kidney function, as judged from the evaluated standard serum parameters. Only when administered after the intoxication, melatonin preserved total kidney antioxidant capacity; pre-treatment melatonin only preserved reduced glutathione levels. An increase in tissue KIM-1 level was found to be prevented by both treatment regimens, which correlated with the morphological changes seen in the kidney tissues of animals treated with melatonin and CCl4. The findings of our study are in agreement with the known actions of melatonin in relieving kidney tissue oxidative burden, but also contribute to the understanding of its action by preventing an increase in KIM-1.

Hyperlactatemia and the Outcome of Type 2 Diabetic Patients Suffering Acute Myocardial Infarction.

Background. Increased lactate production is frequent in unregulated/complicated diabetes mellitus. Methods. Three groups, each consisting of 40 patients (type 2 diabetics with myocardial infarction, DM+AMI, nondiabetics suffering myocardial infarction, MI, and diabetics with no apparent cardiovascular pathology, DM group), were tested for pH, serum bicarbonate and electrolytes, blood lactate, and CK-MB. Results. Blood lactate levels were markedly higher in AMI+DM compared to MI group (4.54 ± 1.44 versus 3.19 ± 1.005 mmol/L, p < 0.05); they correlated with the incidence of heart failure (ρ = 0.66), cardiac rhythm disorders (ρ = 0.54), oxygen saturation (ρ = 0.72), CK-MB levels (ρ = 0.62), and poor short-term outcome. Lactic acidosis in DM+AMI group was not always related to lethal outcome. Discussion. The lactate cutoff value associated with grave prognosis depends on the specific disease. While some authors proposed cutoff values ranging from 0.76 to 4 mmol/L, others argued that only occurrence of lactic acidosis may be truly predictive of lethal outcome. Conclusion. Both defective glucose metabolism and low tissue oxygenation may contribute to the lactate production in diabetic patients with acute myocardial infarction; high lactate levels indicate increased risk for poor outcome in this population comparing to nondiabetic patients. The rise in blood lactate concentration in diabetics with AMI was associated with increased incidence of heart failure, severe arrhythmias, cardiogenic shock, and high mortality rate.