People with type 1 diabetes have an increased risk of developing microvascular complications, which have a negative impact on the quality of life and reduce life expectancy. Numerous studies in animals with experimental diabetes show that c-peptide supplementation exerts beneficial effects on diabetes-induced damage in peripheral nerves and kidneys. There is substantial evidence that c-peptide counteracts the detrimental changes caused by hyperglycemia at the cellular level, such as decreased activation of endothelial nitric oxide synthase and sodium potassium ATPase, and increase in formation of pro-inflammatory molecules mediated by nuclear factor kappa-light-chain-enhancer of activated B cells: cytokines, chemokines, cell adhesion molecules, vascular endothelial growth factor, and transforming growth factor beta. However, despite positive results from cell and animal studies, no successful c-peptide replacement therapies have been developed so far. Therefore, it is important to improve our understanding of the impact of c-peptide on the pathophysiology of microvascular complications to develop novel c-peptide-based treatments. This article aims to review current knowledge on the impact of c-peptide on diabetic neuro- and nephropathy and to evaluate its potential therapeutic role.

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Aim: Methotrexate (MTX) administered at the dose 10-15 mg/m 2 is recommended as the first-line therapy in most juvenile idiopathic arthritis (JIA) subtypes. The diseasemodifying effect of methotrexate is associated with release of adenosine and mediated via binding to adenosine receptor A2A (ADORA2A) and 3 (ADORA3). The aim of our study was to determine the association between single nucleotide polymorphisms in ADORA2A (rs2236624, rs2298383) and ADORA3 (rs3393) receptor genes on the disease activity and presence of MTX therapy side effects in patients with JIA. Methods: One hundred children with JIA of all subtypes treated with MTX were recruited to the study. Demographic and clinical parameters were collected at the baseline of MTX therapy and on a control visit 4-6 months after starting MTX. Single nucleotide polymorphism genotyping was performed using genomic DNA isolated from peripheral blood samples. Results: The polymorphic variant of ADORA2A rs2236624 was associated with ~3.5 times higher odds of gastrointestinal side effects occurrence (odds ratio: 3.59, 95% CI: 1.15-11.22, P = 0.0282). Children with the ADORA3 rs3393 polymorphic variants (CT/CC) after 6 months of MTX treatment had significantly lower number of joints with active arthritis (median: 0.00 vs 1.00, P = 0.0400) and value of C-reactive protein (0.60 vs 2.40, P = 0.0242) in comparison to TT variant. Conclusion: Although future studies are needed to verify our findings, polymorphisms in ADORA2A and ADORA3 genes may become the determinants of MTX treatment efficacy and gastrointestinal toxicity in children with JIA.

Prophylaxis, diagnostics and correction of nutritional status disturbances is considered as one of the main treatment methods of patients with COVID-19 infection-directed to resolve systemic inflammatory response and correction of metabolic response to a viral infection. Systemic Inflammatory Reaction (SIR) manisfestation as a result of viral infection leads to pronounced metabolic processes disturbances. The main metabolic manifestations of SIR is reflected as hypermetabolic-hypercatabolic syndrome with complex disturbances of protein, lipids and carbohydrates metabolism, increased consumption of carbohydrate-lipid reserves and breakdown of tissue proteins. Thus, adequate correction of metabolic disorders and a wholesome nutritional support, taking into account the clinical picture, severity of the disease, ongoing respiratory and intensive care therapy is an integral component in treating patients with COVID-19 infection which determines the efficiency of its treatment and reduction in mortality. Given the relevance of the problem, the authors decided that it was important to increase the COVID-19 treatment efficacy by producing guidelines based on the most fundamental provisions of the modern approach to nutritional support in critical patients with community acquired pneumonia, acute respiratory failure, ARDS, sepsis, multiple organ failure.

Background: Aortic stenosis (AS) is the most common acquired valvular disease. There are two methods of interventional treatment: surgical aortic valve replacement (SAVR) and transcatheter aortic valve implantation (TAVI). The choice between SAVR and TAVI depends on the assessment of individual perioperative risk and long-term treatment outcomes. It is essential to identify factors that may influence the outcomes of the treatment to minimize their negative effects. Aims:The study aimed to identify the most important risk factor which affects treatment outcomes in patients with AS undergoing SAVR/TAVI. Methods:This study reviewed retrospectively patients with AS who underwent SAVR or TAVI. The primary outcomes included incidences of major adverse cardiovascular events (MACE) defined as cardiovascular death, stroke, and hospitalization for cardiovascular issues assessed over a one-year follow-up period. An occurrence of postprocedural AKI (acute kidney injury) was identified as an independent predictor of MACE. Results:The study included 78 patients, with the same number of subjects in each group (SAVR/TAVI [n = 39]). Twenty-nine patients developed AKI. It was similar in both groups (SAVR [n = 15]; TAVR [n = 14]). In the SAVR group, 13 (33%) patients developed at least one MACE compared to 5 (13%) patients in the TAVI group. AKI and the type of procedure (SAVR) were shown to be significantly and independently associated with the development of MACE (P = 0.01 and P = 0.03, respectively) as shown in the Cox multivariable regression model. Conclusions:Our study demonstrated that AKI is the strongest predictor of major adverse cardiovascular events after using both methods of aortic valve replacement (SAVR/TAVI).