Kazan medical journal

BACKGROUND: Patients with cardiovascular diseases are prone to severe acute COVID-19, adverse outcomes, and long post-infection complications.

AIM: This work aimed to study electrocardiographic (ECG) abnormalities in COVID-19 convalescents and their relationship with key cardiometabolic parameters and biochemical markers of inflammation.

METHODS: The analysis included 225 individuals aged 18–84 years (46.7% males; mean age: 50.8 ± 13.2 years). All patients had major and minor ECG abnormalities (Minnesota Code). All patients had standard laboratory tests; we determined their anthropometric parameters and assessed their history. Serum metabolic and inflammatory molecules were determined by the enzyme-linked immunosorbent assay, including interferon alpha, interleukin-1β (IL-1β), IL-6, IL-8, monocyte chemotactic protein-1, insulin, C-peptide, and C-reactive protein detected by the highly sensitive method. Categorical variables are presented as n (%) and continuous variables are presented as Me (25; 75). ROC analysis was performed to determine cutoff points. The relationships were studied using a multivariate logistic regression model. The Mann–Whitney U test was used to compare two independent samples and the Pearson χ² test was used to compare proportions.

RESULTS: ECG abnormalities were detected in 66 (29.3%) COVID-19 convalescents. Minor ECG abnormalities were observed in 51 patients and major abnormalities were observed in 15 patients. COVID-19 convalescents with ECG abnormalities were older (p = 0.020), had common pre-COVID-19 cardiovascular diseases (p = 0.010), including coronary heart disease (p = 0.037), and had common fasting hyperglycemia ≥ 7.0 mmol/L (p = 0.010). These patients had much higher blood IL-6 and monocyte chemotactic protein-1 (p = 0.009 and p = 0.025, respectively) compared to COVID-19 convalescents without ECG abnormalities. IL-6 ≥ 2.6 pg/mL is associated with major and minor ECG abnormalities in COVID-19 convalescents [Exp(B) = 2.180; 95% confidence interval (CI) 1.171–4.058; p = 0.014). Multivariate logistic regression analysis showed that ECG abnormalities in COVID-19 convalescents were associated with male sex [Exp(B) = 1.986; 95% CI 1.069–3.690; p = 0.030] and IL-6 ≥ 2.6 pg/mL [Exp(B) = 2.180; 95% CI 1.171–4.058; p = 0.014].

CONCLUSION: ECG abnormalities in COVID-19 convalescents are associated with male sex and IL-6 ≥ 2.6 pg/mL, regardless of other risk factors.

BACKGROUND: Immune responses differ between chronic rhinosinusitis with and without nasal polyps, which affects the condition of the nasal and paranasal sinus mucosa.

AIM: This work aimed to investigate the characteristics of cytokine regulation in chronic rhinosinusitis with and without nasal polyps.

METHODS: This case–control study included 57 patients with rhinosinusitis (rhinosinusitis with nasal polyps, n = 30; chronic rhinosinusitis without polyps, n = 27) and a control group (n = 43) of apparently healthy individuals. The study was conducted at the Laboratory of Clinical Pathophysiology, Research Institute of Medical Problems of the North. Venous blood and nasal secretions were collected for analysis. Concentrations of IL-2, IFN-γ, TNF-α, IL-6, IL-10, and IL-4 were measured using enzyme-linked immunosorbent assay. Statistical analysis was performed using Statistica 10.0. Data are presented as median and interquartile range (25th–75th percentiles). The groups were compared using the Mann–Whitney U test. Statistical significance was set at p < 0.05.

RESULTS: Significantly higher concentrations of TNF-α, IL-4, and IL-10 were observed in serum (p_1–3 < 0.001) and in nasal secretions (р_1–3 < 0.001) in the rhinosinusitis with nasal polyps group vs. the control group. In patients with chronic rhinosinusitis without polyps, serum levels of IFN-γ, IL-2, TNF-α, and IL-6 were significantly elevated (p_1–4 < 0.001), whereas nasal secretion concentrations of IL-4 and IL-10 were also higher compared with controls (p_1–2 < 0.001). In the rhinosinusitis with nasal polyps group, concentrations of pro-inflammatory cytokines IFN-γ, TNF-α, and IL-6 were significantly lower in both serum (р_1–3 < 0.001) and nasal secretions (р₁ < 0.05; р_2–3 < 0.001) compared with the group without polyps. At the same time, the concentrations of the anti-inflammatory interleukins IL-4 and IL-10 were higher in serum (р_1–2 < 0.001) and in nasal secretions (р_1–2 < 0.001) in patients with rhinosinusitis with nasal polyps.

CONCLUSION: Both forms of chronic rhinosinusitis are characterized by increased concentrations of IL-2, IFN-γ, TNF-α, IL-6, IL-10, and IL-4 compared with healthy individuals. Rhinosinusitis with nasal polyps demonstrates a dominant Th2-type immune response at both systemic and local levels, whereas chronic rhinosinusitis without polyps is characterized by mixed immune mechanisms.

BACKGROUND: Cytokines produced by neutrophils may determine their pro- or antitumor activity, thereby contributing either to inhibition or progression of the tumor process.

AIM: This work aimed to evaluate the cytokine-producing function of circulating neutrophils during renal carcinogenesis.

METHODS: Circulating neutrophils were studied in patients with histologically verified early-stage renal cancer (stage I, n = 30) and advanced-stage disease (stage III, n = 30), as well as in conditionally healthy donors (control group, n = 30). Concentrations of monocyte chemoattractant protein-1 (MCP-1) and interleukin-2 (IL-2) (pg/mL) in neutrophil supernatants were determined by enzyme-linked immunosorbent assay. Gene expression of MCP-1 and IL-2 in neutrophils was assessed using quantitative polymerase chain reaction. Data are presented as median (Me) and interquartile range (Q1–Q3). Statistical analysis was performed using Statistica 13 and Jamovi 2.3.28. Differences were assessed using the Mann–Whitney U test (p < 0.05). Correlation analysis was performed using the Spearman coefficient. Event probability was evaluated by odds ratio with 95% confidence intervals. A differential diagnostic model was constructed using binary logistic regression. Sensitivity and specificity were assessed by ROC curve analysis within the regression model. Predictive model performance was evaluated using the area under the ROC curve (AUC).

RESULTS: A significant decrease in MCP-1 levels in neutrophil supernatants after 30 and 60 minutes of incubation was observed at stage III renal cancer compared with stage I, confirmed by an inverse correlation between MCP-1 levels and disease stage (r = −0.456; p = 0.015). At stage I renal cancer, IL-2 levels increased significantly after 30 minutes of incubation compared with controls under both spontaneous (p = 0.007) and induced conditions (p = 0.001). IL-2 gene expression and IL-2 production in neutrophils increased with renal cancer progression (p = 0.01). A direct correlation was observed between IL-2 gene expression in neutrophils and disease stage (r = 0.671; p = 0.001). In univariate logistic regression analysis, IL-2 gene expression in neutrophils demonstrated statistical significance for differentiation between early and advanced renal cancer stages (OR 0.156; 95% CI 0.047–0.525; p = 0.003). The model AUC was 0.932 (sensitivity, 0.938; specificity, 0.750). With renal cancer progression, IL-2 gene expression increased (R² = 0.504; χ² = 38.5; p = 0.001).

CONCLUSION: At the early stage of renal cancer, neutrophils exert their antitumor potential via enhanced MCP-1 secretion. During renal cancer progression, increased IL-2 secretion confers protumor properties on circulating neutrophils.

BACKGROUND: Immunothrombosis, or inflammatory thrombosis, largely determines the course and outcomes of severe infectious and autoimmune diseases. Inflammatory thrombi are rich in neutrophils; however, how inflammatory cells affect the contraction (retraction) of a blood clot, an important process that influences the course and outcomes of hemostatic disorders, remains unknown.

AIM: This study aimed to assess the effect of activated neutrophils and neutrophil extracellular traps on the rate and degree of blood clot retraction mediated by activated platelet contraction.

METHODS: Isolated human neutrophils were activated with phorbol 12-myristate 13-acetate to induce the formation of neutrophil extracellular traps, which were visualized using immunofluorescence (citrullinated histone H3 and DNA) and scanning electron microscopy. Thrombin-induced clots were formed for three sample groups from whole blood (n = 5 for each group) or platelet-rich plasma (n = 4 or n = 5 for each group): (1) without added neutrophils (control), (2) with nonactivated neutrophils, and (3) with activated neutrophils. Clot-retraction kinetics were recorded optically. The final degree of retraction was the difference between the initial and final clot size, expressed as a percentage of the initial value. Statistical analysis was performed using the Student’s t-test, one-way analysis of variance with a Sidak post hoc test, and the Friedman test. The significance level was set at 95%.

RESULTS: Phorbol 12-myristate 13-acetate induced the activation of neutrophils and formation of neutrophil extracellular traps, which merged into the fibrin structure. When added to whole blood or platelet-rich plasma, activated neutrophils significantly (p < 0.05) increased the final degree of clot retraction (50% ± 5% in blood and 86% ± 3% in platelet-rich plasma) compared with nonactivated neutrophils (45% ± 3% and 80% ± 1%, respectively). The kinetic parameters of retraction demonstrated accelerated contraction in the presence of activated neutrophils (greater mean velocity in platelet-rich plasma: 0.070%/s ± 0.003%/s vs. 0.065%/s ± 0.001%/s; p = 0.03). The stimulatory effect of activated neutrophils on clot retraction disappeared following neutrophil extracellular trap degradation with deoxyribonuclease I, in whole blood (degree of retraction 44% ± 5% vs. 54% ± 2%; p = 0.02) and platelet-rich plasma (82% ± 3% vs. 87% ± 2%; p = 0.03), indicating a key role of neutrophil extracellular traps within clots.

CONCLUSION: Activated neutrophils accelerate and enhance blood clot retraction. This effect is mediated by the formation of neutrophil extracellular traps that merge into the fibrin network.

This review commemorates Irina Zimakova, Doctor of Medical Sciences, professor, who dedicated her life to the development, implementation, and extensive clinical study of a fundamentally new, original Russian drug product — temgicoluril — best known under its first trade name, Mebikar^®. The paper reviews publications on the use of the drug product for various medical conditions and substantiates its possible use as a tranquilizer with adaptogenic, nootropic, antidepressant, antioxidant, and hypolipidemic effects without pronounced side effects and behavioral toxicity and with a positive performance effect. The review includes 50 papers in Russian and English published between 1978 and 2025 and found in Cochrane Library, PubMed, and Google Scholar databases and open sources using scientific search engines and databases, including Google Scholar (Google Academy), CyberLeninka, Mediasphere, and eLibrary.Ru. Most studies were conducted in the Russian Federation, the Republic of Belarus, and Ukraine. The studies showed that temgicoluril had an anti-anxiety effect in various medical conditions, improved blood supply and reduced hypoxia in the heart muscle, had an anti-anginal effect, increased the brain-derived neurotrophic factor in the blood serum in traumatic brain injuries, and reduced hyperactivity and impulsiveness in attention deficit hyperactivity disorder without significant changes in attention and psychomotor ability. In addition, temgicoluril has been shown to have hypolipidemic and nootropic effects. Well-controlled clinical studies involving large patient samples are required to verify previous findings, to study more fully its efficacy and safety, and to understand better its pharmacological profile.

Ocular diseases can substantially reduce patients’ quality of life due to disturbed vision. For some hereditary and acquired eye conditions, only conservative and supportive therapies are available, which do not address the underlying cause. Gene therapy is a promising approach that has shown encouraging results in some clinical trials; however, it requires further research due to the limited evidence and potential long-term risks. By targeting specific regions of defective genes, this therapy may help slow or even reverse disease progression. Adeno-associated viruses, which have shown high efficacy and a favorable safety profile, are of particular interest as delivery vectors. To date, only one gene therapy drug has been approved by the US Food and Drug Administration for inherited retinal dystrophy caused by pathogenic variants of the RPE65 gene. Preclinical and clinical trials of gene therapy for ocular diseases are contributing to the development of this branch of medicine and the search for new approaches to diseases with no potential of restoring the functions of damaged tissues and organs. This review investigates the concept of gene therapy and its use for ocular diseases and presents the latest scientific evidence and their potential effect on visual function. The work is focused on the analysis of clinical trials, safety, efficacy, and prospects of personalized therapy based on the molecular and genetic characteristics of patients. In addition, it highlights the available barriers to the clinical use of gene therapy and the main areas for further research.

Gestational weight gain may affect the health of a woman and her child in the short and long term. Both inadequate and excessive weight gain are associated with several adverse pregnancy and delivery outcomes for the mother and fetus. However, optimal ranges of weight gain during pregnancy remain unclear and insufficiently studied for all categories of pregestational body mass index. This review aimed to examine the relationship between ranges of gestational weight gain and the risk of adverse maternal and fetal outcomes. It also aimed to assess the specific features of gestational weight gain based on pregestational body mass index and which strategies can optimize it. The source search was conducted in eLibrary.Ru, PubMed, Medline, Crossref, and Google Scholar databases from 2009 to 2025 using the following keywords: “гестационная прибавка веса” (gestational weight gain), “осложнения беременности” (pregnancy complications), “ожирение” (obesity), “гестационный сахарный диабет” (gestational diabetes mellitus), and “макросомия” (macrosomia). Preference was given to data from randomized controlled trials, systematic reviews, and meta-analyses. Pregestational body mass index is a crucial predictor of favorable pregnancy outcomes. Therefore, it should be considered the primary target for preventing pregnancy and delivery complications associated with excessive body weight and obesity. Inadequate and excessive gestational weight gain are linked to an increased risk of adverse pregnancy and delivery outcomes for the mother (e.g., gestational hypertension, gestational diabetes mellitus, preterm birth, complicated labor, and increased risk of cesarean section) and fetus (e.g., growth disorders, prematurity, and birth trauma). Currently, no unified protocol exists for managing patients with weight changes during preconception care and pregnancy. This is further complicated by regional factors (e.g., place of residence, dietary traditions, and cultural differences) and individual factors (e.g., influence of the immediate social environment, constitutional characteristics, and childhood and adolescent conditions). Population-level studies examining the causes and consequences of variations in gestational weight gain should be continued as they are critical for decreasing maternal and perinatal morbidity and mortality.

BACKGROUND: Over the last decade, studies have reported that primary colorectal anastomosis can be used to manage purulent inflammatory complications of diverticular disease. However, the indications for this intervention remain debatable.

AIM: To review early experiences with primary anastomosis for diverticular abscesses.

METHODS: The treatment outcomes of 58 patients with diverticular abscesses were studied. The evaluated abscesses were located in pericolic (32 [55.2%] patients), pelvic (19 [32.7%]), and distant sites (7 [12.1%]). Treatment included drug therapy, minimally invasive interventions, and combined surgical interventions. Treatment outcomes in 26 patients who underwent bowel resection with primary anastomosis and 11 patients who underwent Hartmann’s procedure were compared. Significant differences were assessed using Fisher’s exact test and Student’s t-test for independent samples using the GraphPad QuickCalcs online calculator based on standard statistical analysis algorithms.

RESULTS: Primary anastomosis was performed in 12 patients (37.5%) with pericolic abscesses, 11 patients (57.9%) with pelvic abscesses, and 3 patients (42.9%) with distant abscesses. The surgical option was selected based on the abscess’ location and extent and the patient’s condition, age, and comorbidities. In patients with primary diverticular abscesses who underwent urgent surgeries, anastomosis was conducted in 10 of 21 (47.6%) patients, and in all 16 patients with recurrent abscesses. Young and middle-aged individuals (55.5 ± 9.42 years) predominated in the primary anastomosis group, while elderly and senile individuals (71.6 ± 8.94 years) predominated in the stoma group. Bowel resection, although more technically complex than Hartmann’s procedure, showed no significant increase in complications (p = 0.119) and resulted in less severe outcomes.

CONCLUSION: Primary anastomosis for diverticular abscesses is a surgical option for young and middle-aged individuals without comorbidities and generalized inflammation.

This publication is the Russian translation of the Plain Language Summary (PLS) of the Cochrane Systematic Review: Meza N, Bracchiglione J, Escobar Liquitay CM, Madrid E, Varela LB, Guo Y, Urrútia G, Er S, Tiller S, Shokraee K, Alvarez Busco F, Solà I, Ocara Vargas M, Novik AV, Poloni D, Franco JVA. Liraglutide for adults living with obesity. Cochrane Database of Systematic Reviews. 2025, Issue 10. Art. No.: CD016017. DOI: 10.1002/14651858.CD016017.