Vol 106, No 1 (2025)

BACKGROUND: There is no consensus on the predictors of arrhythmia recurrence following treatment for typical atrial flutter.

AIM: The study aimed to identify the factors associated with arrhythmia recurrence in patients with coronary artery disease and typical atrial flutter after cardioversion.

METHODS: The study included 165 patients who underwent different treatment modalities, including pharmacological cardioversion with amiodarone (61 patients), electrical cardioversion (20 patients), transesophageal atrial pacing (48 patients), and radiofrequency ablation (36 patients). Patients underwent a 5-year follow-up at intervals of 6, 12, 24, 36, 48, and 60 months.

The predictors of arrhythmia recurrence were determined by analyzing correlation coefficients using Pearson’s (r) and Spearman’s (R) tests, depending on data distribution, followed by multiple regression analysis and receiver operating characteristic (ROC) analysis, including area under the curve (AUC) calculation. The statistical analysis assessed the influence of sex, age, height, weight, body mass index, body surface area, smoking status, arrhythmia characteristics, and comorbidities (atrial flutter type, arrhythmia duration, time since last recurrence, history of atrial fibrillation, symptom severity using the EHRA scale, CHA₂DS₂-VASc and HAS-BLED scores, presence of silent myocardial ischemia and ventricular arrhythmias based on 24-hour Holter ECG monitoring, lipid profile, functional class of angina and heart failure, prior percutaneous coronary intervention with stenting, and history of coronary artery bypass grafting). Structural and functional parameters of the atria and left ventricle were assessed using transthoracic echocardiography. Statistical significance was set at p < 0.05.

RESULTS: The success rates in restoring sinus rhythm were as follows: 54.1% with pharmacological cardioversion, 87.5% with transesophageal atrial pacing combined with amiodarone, 95.0% with electrical cardioversion, and 100% with radiofrequency ablation with cryoisolation of the pulmonary vein ostia. Arrhythmia recurrence was identified in 62.42% of patients. Significant predictors of atrial flutter recurrence included obesity grade ≥2 (AUC = 0.655; p = 0.0117), regular-type atrial flutter (AUC = 0.736; p < 0.0001), and a history of coronary angioplasty with stenting (AUC = 0.687; p < 0.0001). Following conservative cardioversion, a history of atrial fibrillation was the primary predictor of atrial fibrillation recurrence. After ablation, recurrence was predicted by age >62 years (AUC = 0.703; p = 0.0211) and left ventricular diastolic diameter >5.3 cm (AUC = 0.703; p = 0.0305). Predictors of atrial flutter-to-fibrillation recurrence included a history of atrial fibrillation (AUC = 0.702; p = 0.0193), left atrial dilation (AUC = 0.714; p = 0.0439), and left ventricular hypertrophy (AUC = 0.703; p = 0.0121).

CONCLUSION: The five-year recurrence of atrial flutter is associated with the severity of underlying cardiovascular pathology, whereas atrial fibrillation recurrence is linked to a history of atrial fibrillation, patient age, and structural remodeling of the left heart chambers.

BACKGROUND: Immune checkpoint inhibitors (ICIs) have become a key component of immunotherapy for malignant neoplasms; however, their use is associated with the risk of cardiovascular toxicity, presenting a significant challenge.

AIM: The study aimed to evaluate the effect of ICI therapy on local vascular stiffness parameters in patients with malignant neoplasms.

METHODS: This prospective study included 47 patients (27 men and 20 women) with a mean age of 59.5 ± 7.38 years, all of whom had been diagnosed with malignant neoplasms. The specific diagnoses included lung cancer (n = 30), melanoma (n = 6), urothelial carcinoma (n = 5), head and neck tumors (n = 5), and esophageal cancer (n = 1). The patients received therapy with ICIs, including nivolumab (n = 9), pembrolizumab (n = 23), and atezolizumab (n = 15). The control group included 20 individuals (10 men and 10 women) without malignant neoplasms, acute conditions, decompensated chronic non-communicable diseases, or acute or chronic infectious diseases. These individuals underwent evaluation as part of a preventive medical examination and screening. The control group was comparable to the study group in terms of age (59.3±6.52 years), sex distribution, and the prevalence of cardiovascular comorbidities. Ultrasound examination of the brachiocephalic arteries, calculation of local vascular stiffness parameters, and measurement of the ankle-brachial index were performed dynamically (before the initiation of anticancer drug therapy and three months after treatment initiation). The statistical analysis included descriptive statistics, Student’s t-test, the Mann–Whitney test, Fisher’s exact test, and Pearson’s chi-square (χ²) test. A significance level of p = 0.05 was used for all analyses.

RESULTS: An analysis of the structural and functional parameters of the vascular wall in patients undergoing ICI therapy demonstrated the progression of atherosclerotic changes in the carotid arteries. During anticancer therapy, an increase in common carotid artery stenosis was observed (p = 0.05) compared with the control group, along with a trend toward an increased number of visualized atherosclerotic plaques (p = 0.06). A tendency toward a decline in vascular wall distensibility (p = 0.07) was associated with an increase in Peterson’s modulus of elasticity (p = 0.05), Young’s modulus (p = 0.04), stiffness index (p = 0.09), and pulse wave velocity (p = 0.01). A significant decline in the ankle-brachial values index was identified (p = 0.001).

CONCLUSION: ICI therapy is associated with a greater severity of atherosclerotic lesions in the carotid arteries, increased local vascular stiffness, and a decrease in the ankle-brachial index.

BACKGROUND: The risk of developing immune tolerance to autoantigens in autoimmune thyroiditis is largely associated with mutations in the CTLA-4 gene, whose product negatively regulates T-cell activity.

AIM: The study aimed to investigate the +49A/G (rs231775) polymorphism of the CTLA-4 gene in patients with autoimmune thyroiditis within a sample of the Azerbaijani population and assess the impact of allele and genotype frequencies on anti-thyroperoxidase and anti-thyroglobulin antibodies.

METHODS: A study was conducted from 2021 to 2023 and included 170 patients with autoimmune thyroiditis (study group) and 65 individuals without thyroid pathology or other autoimmune diseases (control group). The sex and age of the groups were comparable. Autoimmune thyroiditis was diagnosed on the basis of medical history, assessment of thyroid status, thyroid ultrasound, and the presence of organ-specific antibodies. The results of routine thyroid function tests in the control group were within the normal range. Genotyping of the +49A/G (rs231775) polymorphism was performed by polymerase chain reaction followed by restriction fragment length polymorphism analysis using PspEI endonuclease. Quantitative variables were presented as the median (Me) and interquartile range (IQR; 25th percentile, 75th percentile). Hardy–Weinberg equilibrium for genotype frequencies was assessed using the χ² test.

RESULTS: The study revealed a statistically significant increase in the frequency of the G allele (48%) compared with the control group (33.8%; p = 0.039, χ² = 4.27, odds ratio [OR] = 1.865, 95% confidence interval [CI]: 1.028–3.382) and a decrease in the frequency of the A allele (51.2%) relative to the control group (66.1%; p = 0.0389, χ² = 4.27, OR = 0.536, 95% CI: 0.296–0.973). Anti-thyroglobulin antibody titers exceeding 100 IU/mL were detected in 22.4% of patients with the GG genotype (p = 0.005, χ² = 7.86, OR = 0.237, 95% CI: 0.088–0.635) and 55.6% of patients carrying the G allele (p = 0.0012, χ² = 10.43, OR = 0.360, 95% CI: 0.192–0.674). Anti-thyroperoxidase antibody levels ≥100 IU/mL were found in 22.7% of individuals with the GG genotype (p = 0.030) and 50.0% of those carrying the G allele (p = 0.048).

CONCLUSION: Elevated anti-thyroperoxidase and anti-thyroglobulin antibody titers were identified in individuals carrying the G allele and the homozygous GG genotype of the +49A/G polymorphism of the CTLA-4 gene in the Azerbaijani population.

BACKGROUND: The evident rise in the number of patients with liver failure underscores the need for new therapeutic agents that meet modern efficacy standards for treating this condition.

AIM: The study aimed to evaluate the survival rate of animals treated with a lyophilic composition in an experimental model of acute toxic liver injury.

METHODS: The study was conducted in vivo using Wistar rats (n = 135). Acute toxic liver injury was modeled in male rats weighing 200–250 g via subcutaneous administration of carbon tetrachloride (CCl₄) at a dose of 0.5 mg per 100 g of animal weight. The animals were divided into groups according to the administered substance. Group 1 was injected subcutaneously with 0.5 mL of physiological saline (n = 30). Group 2 was injected subcutaneously with 0.5 mL of isolated hepatocyte growth factor (HGF; n = 30). Group 3 was administered with 0.5 mL of HGF antibodies into the tail vein (n = 15). Group 4 was injected subcutaneously with 0.5 mL of lyophilic composition 12 hours after CCl₄ administration (n = 30). Group 5 was injected subcutaneously with 0.5 mL of lyophilic composition immediately after CCl₄ administration (n = 15). Group 6 was injected subcutaneously with 0.5 mL of a lyophilizate of isolated hepatocytes (n = 15). The study lasted six days. Kaplan–Meier survival curves were used to evaluate survival rates, and statistical significance of intergroup differences was evaluated using the stratified log-rank test. Statistical analysis was performed using Statistica 10.0 software. Differences were considered significant at p < 0.05.

RESULTS: The administration of the lyophilic composition enriched with HGF significantly increased animal survival compared with the control group. A comparison of mortality rates between the experimental and control groups revealed the following levels of significance: group 2 vs. control, p < 0.0001 (exogenous HGF administration); group 4 vs. control, p < 0.0001 (lyophilic composition administered 12 hours after CCl₄); group 5 vs. control, p = 0.4103 (lyophilic composition administered immediately after CCl₄); group 6 vs. control, p = 0.3263 (injection of isolated hepatocytes). The lower survival rate in group 6 was attributed to the insufficient HGF content in the isolated hepatocyte environment.

CONCLUSION: The lyophilic composition containing HGF as an active ingredient improves survival in rats with experimentally induced acute toxic liver injury.

BACKGROUND: Infections in surgical practice remain one of the most pressing challenges in modern medicine.

AIM: The study aimed to evaluate the effectiveness of high-intensity pulsed broadband irradiation for infected wounds in an experimental setting using cytological monitoring.

METHODS: The experiment was conducted on 90 male Wistar rats using a model of infected skin wounds created with a mixed culture of Staphylococcus aureus, Pseudomonas aeruginosa, Klebsiella pneumoniae, and Candida albicans. All animals were randomly divided into three groups of 30 animals each. In group 1, the wounds and the surrounding area were treated with high-intensity pulsed broadband irradiation using an experimental device with a pulsed xenon lamp operating in a pulsed-periodic mode at a frequency of 5 Hz and an average ultraviolet C (UV-C) emission power of 200–280 nm. Group 2 used conventional UV irradiation with a mercury bactericidal lamp emitting in the UV-C spectrum of 180–275 nm. Both groups received irradiation for 10 days, followed by only local wound treatment. In group 3, the wounds were treated with antiseptic only. Cytological examination of wound scrapings was performed. Cytological samples were evaluated qualitatively by cytogram type and quantitatively by counting cellular elements. Non-parametric statistical methods were applied, including the Shapiro–Wilk and Friedman tests with calculation of the concordance correlation coefficient, Wilcoxon signed rank test with Bonferroni correction, and Pearson’s chi-square (χ²) test.

RESULTS: Before treatment, cytological profile corresponded to the degenerative/necrotic or inflammatory degenerative types, with no significant differences between the groups. On day 7, 12 (40%) animals in group 1 exhibited regenerative-type cytograms, whereas 18 (60%) animals demonstrated inflammatory-regenerative-type cytograms. The distribution of animals in group 1 by cytogram type was significantly different from other groups (p < 0.0001; χ² = 31.2; p < 0.0001; χ² = 42.0). By day 14, regenerative-type cytograms were observed in the majority of animals in groups 1 and 2 (90% and 63.3%, respectively), whereas in group 3, most animals (66.7%) maintained the inflammatory-regenerative cytogram type (p < 0.0001; χ² = 49.56; p < 0.0001; χ² = 31.6 compared with groups 1 and 2).

CONCLUSION: The use of broadband pulsed high-intensity irradiation for treating infected wounds, as compared with traditional UV irradiation and local drug therapy, enables earlier suppression of inflammation and accelerates reparative processes.

BACKGROUND: Molecular genetic studies in the treatment of rectal cancer focus on identifying specific genetic mutations and associated alterations.

AIM: The study aimed to investigate the relationship between KRAS and BRAF gene mutations and tumor response to preoperative chemoradiotherapy in patients with rectal cancer.

METHODS: A total of 65 patients with locally advanced rectal cancer were enrolled in the study, including 31 women and 34 men with a mean age of 54 ± 6.9 years. All patients underwent a course of prolonged neoadjuvant chemoradiotherapy. The patients were categorized into three clinical groups based on tumor regression. Group 1 included 16 (24.6%) patients with minimal response (TRG 0–1), group 2 included 34 (52.3%) patients with partial tumor regression (TRG 2–3), and group 3 comprised 15 (23.1%) patients with complete pathomorphological response (TRG 4). Pearson’s χ² test was employed for statistical analysis using IBM SPSS Statistics 20 software, and cross-tabulations were generated.

RESULTS: A mutation in the KRAS gene was identified in 17 (26.2%) patients. The distribution of patients with this mutation among the clinical groups was as follows: six (37.5%) patients in group 1, eight (23.5%) patients in group 2, and three (20%) patients in group 3. A BRAF mutation was identified in nine (13.9%) patients, including seven (43.8%) and two (13.5%) patients in groups 1 and 3, respectively, whereas no BRAF mutations were found in group 2.

CONCLUSION: The study of the frequency of KRAS and BRAF gene mutations in patients with rectal cancer in various clinical groups showed that the group with low sensitivity to neoadjuvant therapy exhibited a higher frequency of BRAF mutations (χ² (2) = 16.688; p = 0.001; w = 0.52). This may suggest a potential association between this mutation and radioresistance in rectal cancer patients.

This review focuses on the use of the antidiabetic drug metformin as one of the most studied geroprotective candidates with a well-established safety profile. The primary theories of aging and the development of age-related diseases, such as type 2 diabetes mellitus (T2DM) and Alzheimer disease, as well as the relationship between T2DM and the development of cognitive impairment, are reviewed. Metformin is hypothesized to improve cognitive function, mitigate the severity of anxiety, and reduce the risk of developing Alzheimer disease. In addition, metformin is able to decelerate the aging process and increase longevity in experiments in mice and rats. Despite being among the most frequently prescribed medications globally, with the ability to cross the blood-brain barrier and distribute to all brain regions, the precise mechanisms underlying its effects on the brain remain unclear. Studies show that metformin is able to activate 5'-adenosine monophosphate-activated protein kinase, reduce the levels of advanced glycation endproducts, and restore mitochondrial function. Moreover, metformin enhances autophagy and exerts a neuroprotective effect on neural stem cells. The findings of numerous studies indicate that metformin has antioxidant and anti-inflammatory properties.

BACKGROUND: The development of new and more precise methods for determining the boundary between necrotic and viable tissue is essential for accurately determining the level of amputation.

AIM: The study aimed to evaluate the first results of ultraviolet photoluminescence spectroscopy in determining the level of the proposed amputation of the lower limb.

METHODS: This prospective, open-label, and non-randomized study included 20 patients with critical lower limb ischemia and suspected toe gangrene who underwent percutaneous transluminal balloon angioplasty. The patients were divided into two groups. Group 1 (n = 10) included patients who did not require major limb amputation during follow-up, whereas group 2 (n = 10) included patients who underwent above-knee amputation during follow-up. The groups were comparable in age (62.5 [53.25; 74.5] years in group 1; 65.5 [60.5; 76] years in group 2; p = 0.352). All patients underwent clinical monitoring and serial photoluminescence measurements of the affected limb using a device composed of a laser radiation source (diode laser) as the excitation signal and a mini-spectrometer for signal detection. Measurements were performed during hospitalization and at re-admission. The luminescence amplitude was correlated with the clinical manifestations of critical limb ischemia during inpatient treatment and at follow-up hospitalization. A one-month post-discharge telephone follow-up was conducted to monitor patient status. In cases of recurrent critical ischemia and gangrene progression, patients were re-hospitalized for above-knee re-amputation. The results are presented as mean values, standard deviations, or medians with the 25th and 75th percentiles.

RESULTS: Following vascular reconstruction of the affected limb, a statistically significant decrease in luminescence amplitude was observed at 400 and 420 nm (nicotinamide adenine dinucleotide peak) and 450 nm (negative hemoglobin peak) in group 1 compared with preoperative levels in the critical ischemia zone (98.5 [52.9; 508.6] × 10⁵ photons before surgery; 81.5 [42.9; 117.4] × 10⁵ photons after surgery; p = 0.001]). No significant amplitude changes were observed in group 2 before and after surgery (p = 0.245). In the gangrene zone, all amplitude values at 400–600 nm exhibited minimal intensity values. Near the visible boundary between necrotic and healthy tissue, a sharp increase in photoluminescence amplitude was detected, with a difference of 81.2 (42.9; 120.4) × 10⁵ photons at 450 nm.

CONCLUSION: Laser-induced ultraviolet photoluminescence spectroscopy may serve as a potential method for determining the precise level of amputation in cases of dry gangrene of the lower limb.

Disorders of sex development (DSD) are increasingly discussed in modern medicine. Advances in diagnostic methods have led to an increased identification of individuals with these conditions. This study presents a rare case of a patient with DSD and describes the treatment strategy. A male infant, aged 11 months, was admitted to the urology department for inpatient treatment with a diagnosis of 46XY DSD accompanied by suspected urogenital sinus and vaginal aplasia. According to the medical history, the child’s sex at birth could not be determined with certainty. Externally, the genitalia resembled female structures with incomplete feminization. Karyotyping confirmed a 46XY result. Physical examination in the pediatric hospital revealed that the external genitalia did not correspond to the karyotype. Bilateral, painless, and mobile gonad-like masses were palpated in the inguinal region. The urethral opening was located under a hypertrophied clitoris between hypoplastic labia minora. The labia majora exhibited transverse folds resembling a scrotum, and the vaginal introitus was absent. Whole-exome sequencing identified two mutations in the LHCGR gene. Diagnostic laparoscopy confirmed the absence of Müllerian and Wolffian duct remnants. A multidisciplinary medical council recommended that the parents raise the child as a female, and bilateral orchiectomy was performed. A feminizing genitoplasty is planned. This clinical case illustrates the management of a patient with DSD, emphasizing the key factors influencing treatment decisions. The availability of genetic testing in patients with DSD enables precise identification of the underlying cause, allowing for early adaptive surgical intervention, before the age of gender self-identification. Further analysis of these mutations and their clinical manifestations will contribute to improving the management of patients in this population.

This publication is the Russian translation of the Plain Language Summary (PLS) of the Cochrane Systematic Review: Esezobor CI, Bhatt GC, Effa EE, Hodson EM. Fenoldopam for preventing and treating acute kidney injury. Cochrane Database of Systematic Reviews. 2024. Issue 11. Art. No.: CD012905. DOI: 10.1002/14651858.CD012905.pub2.