Kazan medical journal

BACKGROUND: Identifying predictors of chronic heart failure is an essential preventive step in patients with pre–heart failure.

AIM: This study aimed to identify predictors of chronic heart failure development in outpatients with hypertension and pre–heart failure.

METHODS: A single-center study included 356 outpatients with hypertension and pre–heart failure. The mean age was 62.65 ± 10.59 years; 128 (36%) participants were men. The patients received drug therapy for hypertension, with treatment adjustment after 1 and 3 months and subsequently annually for 3 years. Later on, outcomes defined as the development of chronic heart failure were evaluated. Multiple binary logistic regression analysis was used to identify predictors of chronic heart failure onset.

RESULTS: Over a 3-year period (2022–2025), chronic heart failure with preserved ejection fraction developed in 8.7% of patients with hypertension and pre–heart failure. Analysis of risk factors showed that patients who developed chronic heart failure were older (66.37 ± 9.55 years; p < 0.001), had a longer duration of hypertension (17.85 ± 10.43 years; p < 0.001), higher body mass index (29.41 ± 4.85 kg/m²; p = 0.002), and a lower glomerular filtration rate (73.23 ± 18.19 mL/min/1.73 m²; p < 0.001). In this group, paroxysmal (p < 0.001) and persistent atrial fibrillation (p < 0.001), as well as type 2 diabetes mellitus (p < 0.001), were observed more frequently. In these patients, more pronounced structural and functional cardiac changes were already present at enrollment into the study, namely, indexed left atrial volume (47.93 ± 14.85 vs 33.68 ± 5.57 mL/m²; p < 0.001), indexed myocardial mass (104.18 ± 29.34 vs 92.55 ± 19.36 g/m²; p = 0.045), maximum pulmonary vein diameter (21.23 ± 2.24 vs 17.34 ± 1.64 mm; p < 0.001), and minimum pulmonary vein diameter (11.09 ± 2.42 vs 7.36 ± 1.53 mm; p < 0.001). The predictors associated with the onset of chronic heart failure after 3 years in patients with hypertension included maximum pulmonary vein diameter, left atrial volume, age, body mass index, and the presence of atrial fibrillation.

CONCLUSION: Within 3 years, chronic heart failure with preserved ejection fraction developed in 8.7% of patients with pre–heart failure. Predictors of its development in patients with hypertension included maximum pulmonary vein diameter, left atrial volume, age, body mass index, and the presence of atrial fibrillation.

BACKGROUND: In patients with gastrointestinal cancers, preoperative malnutrition is associated with decreased plasma serotonin levels and an increased risk of gastrointestinal failure in the postoperative period.

AIM: The work aimed to evaluate the safety and clinical efficacy of serotonin compared with standard prokinetic therapy for the correction of gastrointestinal failure in patients with malnutrition.

METHODS: It was a randomized pilot clinical study including 42 patients aged ≥ 65 years after elective gastrointestinal surgery for cancer. All participants had malnutrition (NRS 2002 ≥ 2) and gastrointestinal failure (LIFE ≥ 2). Patients were randomized as follows: the main group (n = 24) received serotonin at a dose of 20 mg/day intravenously until gastrointestinal failure is resolved; the control group (n = 18) received standard therapy (metoclopramide, 10 mg, and neostigmine methyl sulfate, 0.1 mg, three times daily). Both groups received standardized enteral nutritional support with a semi-elemental formula. Changes in LIFE scores, plasma serotonin and albumin levels, inflammatory markers, hemostasis parameters (piezoelectric thromboelastography), and the incidence of thrombotic complications were assessed. Thromboprophylaxis was performed with enoxaparin sodium, 40 mg/day, administered subcutaneously.

RESULTS: Baseline characteristics of the groups did not differ significantly. Serotonin levels were decreased in both groups (50.37 ng/mL in the control group; 51.6 ng/mL in the main group; p = 0.782). During serotonin administration, its concentration was maintained within the reference range, whereas in the control group it continued to decrease by day 2. By day 5, the severity of gastrointestinal failure according to the LIFE scale was significantly lower in the main group (0.3 vs 2.6 points; p = 0.045), which was accompanied by earlier recovery of peristalsis and bowel movements. A strong negative correlation was found between serotonin levels and the severity of gastrointestinal failure (r_s = −0.69; p = 0.012). In patients receiving serotonin, hypoalbuminemia was corrected more rapidly (p = 0.0057); albumin levels also negatively correlated with the severity of gastrointestinal failure (r_s = −0.71; p = 0.010). Inflammatory markers and hemostasis parameters did not differ between the groups. Thrombotic events were not observed in either group.

CONCLUSION: In patients with gastrointestinal cancers and preoperative malnutrition, serotonin as part of complex therapy for gastrointestinal failure was associated with faster resolution and correction of hypoalbuminemia without signs of increased inflammatory response or an increased risk of thrombotic events.

BACKGROUND: Early and accurate assessment of inflammatory and renal tubular biomarkers is clinically relevant to diagnose and evaluate progression of type 2 cardiorenal syndrome; however, their combined diagnostic value remains insufficiently studied.

AIM: This study aimed to evaluate the diagnostic value of inflammatory and renal tubular biomarkers in patients with type 2 cardiorenal syndrome.

METHODS: The study was conducted at the 1st Clinical Medical Center in Baku in 2020–2024 and included 200 patients with type 2 cardiorenal syndrome and 51 apparently healthy individuals. Patients were stratified by functional class of chronic heart failure based on the New York Heart Association classification and the stage of chronic kidney disease: group 1 (n = 74) with functional class I–II and stage I–II, respectively; group 2 (n = 9) with functional class I–II and stage III–IV, respectively; group 3 (n = 73) with functional class III–IV and stage I–II, respectively; group 4 (n = 44) with functional class III–IV and stage III–IV, respectively. The levels of cystatin C, lipocalin, liver-type fatty acid–binding protein, kidney injury molecule 1 (KIM-1) in blood and urine, interleukin-6, interleukin-18, and tumor necrosis factor-alpha were determined. Diagnostic accuracy was assessed using receiver operating characteristic (ROC) analysis, and correlations were evaluated using the Spearman correlation method.

RESULTS: In all groups, a pronounced increase in the studied markers compared with the control group was observed (p <  0.001), with progressive elevation in line with disease severity. The levels of cystatin C, lipocalin, liver-type fatty acid–binding protein, and KIM-1 increased 2.9-, 2.1-, 3.1-, and 2.3/2.0-fold, respectively, in group 1 (p <  0.001); 4.2-, 2.9-, 5.6-, and 5.1/2.7-fold in group 2 (p <  0.001); 3.4-, 2.4-, 4.2-, and 2.6/2.3-fold in group 3 (p <  0.001); and 6.4-, 3.4-, 7.2-, and 5.8/3.4-fold in group 4 (p <  0.001). The levels of interleukin-6, interleukin-18, and tumor necrosis factor-alpha also increased: 3.9- and 2.8-fold and by 89.0%, respectively, in group 1; 5.2-, 2.9-, and 2.5-fold in group 2; 4.4-, 4.0-, and 2.1-fold in group 3; and 6.4-, 5.2-, and 3.1-fold in group 4 (p <  0.001). Marker concentrations correlated with the stage of chronic kidney disease (ρ = 0.676–0.861; p <  0.001) and the functional class of chronic heart failure (ρ = 0.301–0.514; p <  0.001), whereas lipocalin and KIM-1 correlated with interleukin-6 and interleukin-18 levels (ρ = 0.894–0.920; p <  0.001). The highest diagnostic value was identified for liver-type fatty acid–binding protein (AUC: 0.819; 95% CI: 0.761–0.876; p <  0.001), lipocalin (AUC: 0.768; 95% CI: 0.702–0.834; p <  0.001), and KIM-1 (AUC: 0.745; 95% CI: 0.678–0.813; p <  0.001).

CONCLUSION: Inflammatory and renal tubular biomarkers have high diagnostic value and are consistent with the progression of cardiorenal dysfunction in type 2 cardiorenal syndrome.

BACKGROUND: In autoimmune thyroiditis, hormone replacement therapy generally does not inhibit the activity of autoreactive T lymphocytes destroying the thyroid gland and promoting the antithyroid antibody response at the early stages of the disease.

AIM: This work aimed to find an approach aimed at suppressing the autoimmune reaction in autoimmune thyroiditis.

METHODS: Experimental autoimmune thyroiditis (EAT) was induced by double (at day 1 and day 14) thyroglobulin immunization of 15 weeks old C57BL/6 mice using complete and incomplete Freund’s adjuvant. Experimental animals were given a 0.05% NaI solution during feeding. The mice were divided into three groups; group 1 included intact mice (n = 5), group 2 included mice with induced EAT (n = 7), and group 3 included mice with induced EAT and subsequently administered sirolimus (n = 7). CD4⁺, CD8⁺, double-positive and double-negative T lymphocytes, and CD4⁺CD25⁺FoxP3⁺ T cell levels were determined using flow cytometry. Follicle destruction was measured by hematoxylin and eosin staining and the apoptosis was measured by staining with active caspase-3 antibodies. Thyroid antibodies were determined using enzyme-linked immunosorbent assay. Statistical processing was performed using one-way ANOVA and Student’s t-test (p <  0.05); data were presented as mean ± standard deviation (SD). Distribution normality was tested using the Shapiro–Wilk and Bartlett tests.

RESULTS: In the EAT group, the mTOR protein inhibitor (sirolimus) prevented thymus involution, increased the number of thymic regulatory T cells, and suppressed the secretion of IFN-γ and IL-17A cytokines. The inhibitor reduced lymphoid infiltration (D₄₅₀ = 0.25) compared to mice with EAT (D₄₅₀ = 2.4) and cellular apoptosis (D₄₅₀ = 0.005 vs 0.0125 in the EAT group). This, in turn, resulted in lower levels of thyroid peroxidase autoantibodies (D₄₅₀ = 3.0 compared to 19 in the experimental group). Therefore, sirolimus suppresses the autoimmune reaction by activating regulatory T immunity.

CONCLUSION: Sirolimus helps reduce the autoimmune aggression, improve the thyroid gland structure, and mitigate the severity of the disease.

Restoring damaged tissues and organs, particularly in cases of acute radiation injury, remains one of the major challenges in regenerative medicine. Acute radiation syndrome caused by high-dose ionizing radiation exposure is associated with profound suppression of hematopoiesis and damage to the bone marrow stroma. Multipotent mesenchymal stromal cells are regarded as a promising therapeutic tool because of their differentiation potential, immunomodulatory properties, secretion of trophic factors, and ability to support the hematopoietic niche. However, their clinical efficacy is limited by low survival under conditions of oxidative stress and inflammation. Mechanisms that increase the resistance of multipotent mesenchymal stromal cells to damaging factors and enhance their regenerative potential remain insufficiently studied.

This work reviews current data on the role of autophagy—an evolutionarily conserved process of intracellular renewal—as a potential approach to increasing the functional activity of multipotent mesenchymal stromal cells.

Pharmacologic strategies for autophagy modulation are discussed, including mTOR-dependent (sirolimus) and mTOR-independent (lithium, trehalose) approaches, as well as their effects on the survival, migration, and secretory activity of multipotent mesenchymal stromal cells. Particular attention is given to cell preconditioning as a strategy to enhance therapeutic efficacy in radiation injury.

Available evidence supports the use of targeted autophagy activation as a key component in the development of standardized next-generation cell-based products capable of not only supporting but also actively restoring hematopoiesis after acute radiation exposure.

The autonomic nervous system is a critical regulator of cardiovascular function, and its imbalance contributes substantially to cardiovascular diseases and their complications.

This work aimed to analyze studies addressing the impact of the autonomic nervous system on the course and prognosis of chronic heart failure, including in patients with comorbidities.

The review included 47 papers published between 2000 and 2025 in PubMed and eLIBRARY.RU journals that investigated the role of the autonomic nervous system in chronic heart failure. The article discusses the origins of heart rate variability assessment and diagnostic tools for evaluating autonomic nervous system function in various cardiovascular diseases. The review describes the pathogenetic mechanisms underlying changes in autonomic status and the key parameters used to assess it, predominantly based on noninvasive time- and frequency-domain heart rate variability analysis for a more accurate evaluation of adaptation level, stress reactivity, and the degree of autonomic imbalance.

Data on age- and sex-related differences in heart rate variability in patients with chronic heart failure are presented, including those with comorbidities such as chronic kidney disease, chronic obstructive pulmonary disease, and diabetes mellitus.

Evidence is provided to support the prognostic value of heart rate variability parameters that influence disease course and cardiovascular risk in patients with chronic heart failure. Investigating the pathogenetic mechanisms underlying autonomic dysfunction in patients with cardiovascular diseases is relevant for developing new therapeutic approaches to restore autonomic nervous system balance.

Time- and frequency-domain heart rate variability analysis is an accessible and convenient noninvasive method that can be used in a wide patient population to provide valuable information for personalized therapeutic strategies.

This work outlines the clinical manifestations and main diagnostic approaches in carpal tunnel syndrome, as well as the rationale for selecting the diagnostic workup required to establish the diagnosis and determine treatment strategy. The work is based on information available in university and institutional libraries, as well as electronic scientific databases.

This work aimed to review diagnostic methods for carpal tunnel syndrome described in international publications and to identify the most effective and priority diagnostic approaches for this condition.

According to the analyzed sources, most authors identify a basic diagnostic workup that is required to confirm the final diagnosis and determine further management strategy for this tunnel neuropathy. This includes a comprehensive neurologic examination with provocation tests and electroneuromyography, as well as imaging modalities such as ultrasonography, computed tomography, and magnetic resonance imaging.

Carpal tunnel syndrome remains one of the most common tunnel neuropathies, particularly among individuals who do a lot of computer work, such as information technology professionals who use a mouse and keyboard for long periods of time. This has contributed to an increase in occupational disorders associated with chronic compression of the median nerve within the carpal tunnel.

Carpal tunnel syndrome has been a major concern for many years due to its latent and gradual onset. Early clinical manifestations may be mild or nonspecific, making timely diagnosis difficult.

The diagnosis of carpal tunnel syndrome does not follow a strictly defined algorithm, and additional diagnostic tests are selected on a case-by-case basis depending on the clinical presentation identified during the assessment of complaints and medical history, as well as during the neurologic examination. All diagnostic methods may be used; however, their simultaneous application is not required. In the presence of a typical clinical presentation, the diagnosis may be established without the use of high-tech diagnostic modalities.

BACKGROUND: At present, there is a lack of detailed information on the activities of organizations engaged in drug compounding, the state of their infrastructure, and the demand for services related to drug compounding for state and municipal needs.

AIM: This work aimed to systematize indicators characterizing the activities of organizations engaged in drug compounding and to determine future directions for the development of drug compounding in the Volga Federal District.

METHODS: A sociological study of medical and pharmacy organizations licensed for pharmaceutical activity with authorization to compound medicinal products was conducted using remote questionnaire-based surveys. Data from the Unified Register of Licenses; data from the Unified Register of Licenses for Activities Related to the Circulation of Narcotic Drugs, Psychotropic Substances, and Their Precursors; results of the socioeconomic assessment conducted by the Federal State Statistics Service; and data from the Unified Information System for Procurement were used. The work applied a survey method in the form of remote questionnaires as well as desk research methods.

RESULTS: The findings indicate a more than 1.5-fold increase in demand for drug compounding services in the public healthcare sector of the Volga Federal District from 2021 to 2024, reaching 487.16 million rubles. Procurement of drug compounding services for medical use funded by regional budgets was carried out in 8 of the 14 constituent entities of the Volga Federal District, with an annual increase in demand of 40.2%. It was established that at least 127 organizations engaged in drug compounding (by registered addresses of pharmaceutical activity) operate within the district, accounting for 18.6% of the total number in the Russian Federation. Authorization to compound medicinal products from the list of narcotic drugs and psychotropic substances is held by pharmacy organizations operating in 9 of the 14 analyzed constituent entities of the Russian Federation, indicating limited accessibility of personalized pharmacotherapy. In 2023, a total of 6320 medicinal products were compounded, representing approximately 14.0% of the total compounding volume in the Russian Federation. Compounding was performed using at least 128 pharmaceutical substances. During compounding, at least 147 international nonproprietary names of registered medicinal products were used.

CONCLUSION: The study identified the main qualitative and quantitative characteristics of organizations engaged in drug compounding in the Volga Federal District and determined the demand within public procurement of services related to drug compounding in the district.

BACKGROUND: Necrotizing soft tissue infection represents a massive soft tissue lesion accompanied by sepsis.

AIM: This work aimed to identify predictors of adverse outcome in patients with necrotizing soft tissue infection treated in the intensive care unit.

METHODS: Among 89 patients with sepsis of various etiologies treated in the intensive care unit, 12 patients (6 men and 6 women) with necrotizing soft tissue infection were selected. The patients were divided into two groups according to clinical outcome: group 1 (n = 8) consisted of discharged patients; group 2 (n = 4) included patients with fatal outcome. The obtained data were subjected to statistical analysis. The significance of intergroup differences was assessed using nonparametric statistical methods (Mann–Whitney U test and Pearson’s χ² test). Differences were considered statistically significant at p = 0.05–0.01.

RESULTS: All patients included in the study demonstrated clinical and laboratory signs of sepsis (septic shock). Group 1 demonstrated a significant reduction in inflammatory markers by day 3 of intensive care during intensive therapy including extracorporeal detoxification techniques: C-reactive protein decreased from 296.5 (Me 282.7–361.7) to 66.5 (Me 62.7–105.5) mg/L (p = 0.011), and procalcitonin decreased from 14.66 (Me 1.94–33.20) to 2.81 (Me 0.89–6.03) ng/mL (p = 0.027), along with regression of organ dysfunction. Group 2 showed no positive clinical trends: vasopressor support remained necessary, and levels of inflammatory markers (procalcitonin and C-reactive protein) exceeded baseline values. By day 3 of intensive care, no significant changes in C-reactive protein or procalcitonin levels were detected (p = 0.179). Limb amputations were performed in four patients: in one patient in group 1 and in three patients in group 2.

CONCLUSION: Predictors of adverse outcome in necrotizing soft tissue infection include limb amputation due to persistent inflammatory process, sustained requirement for vasopressor support, and absence of positive trends in procalcitonin and C-reactive protein levels.

This publication is the Russian translation of the Plain Language Summary (PLS) of the Cochrane Systematic Review: Garegnani L, Oltra G, Burgos MA, Ivaldi D, Varela LB, Díaz Menai S, Puga-Tejada M, Escobar Liquitay CM, Franco JVA. Proton pump inhibitors for the prevention of non-steroidal anti-inflammatory drug-induced ulcers and dyspepsia. Cochrane Database of Systematic Reviews. 2025, Issue 5. Art. No.: CD014585. DOI: 10.1002/14651858.CD014585.pub2.