


Vol 30, No 5 (2024)
- Year: 2024
- Articles: 10
- URL: https://bakhtiniada.ru/0869-2106/issue/view/18089
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Description:
◆ Human pineal gland
◆ Artificial intelligence: predicting outcomes of ischemic heart disease
◆ Obesity: diagnosis, treatment, prevention
Original Research Articles
The role of transforming growth factor β in COVID-19 lung injury: clinical and diagnostic parallels
Abstract
BACKGROUND: Severe acute respiratory syndrome causes complex immune responses of hyperactivation of immunocompetent cells, including increased degranulation activity of mast cells and release of their secretome products. Mast cell granules may contain a lot of profibrotic enzymes and cytokines (chymase, tryptase, interleukin-4, 10, and 13) as well as growth factors. The entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) into the body and the subsequent strong immune and inflammatory response and dysregulation of coagulation and fibrinolytic pathways cause massive activation of latent (inactive) transforming growth factor β (TGF-β) in the lungs and the latent pool of TGF-β in the blood of patients with coronavirus disease 2019 (COVID-19).
AIM: To evaluate the role of TGF-β in lung involvement in patients with COVID-19 by examining autopsy lung material, determining the quantitative level of TGF-β with further correlation analysis of clinical and laboratory parameters.
MATERIALS AND METHODs: The study included autopsy lung samples from patients who died from severe COVID-19. Autopsies were performed 2 days after the patients died. Autopsy material was collected for histology. Correlation analysis was performed between the number of TGF-β-positive cells and clinical and laboratory parameters.
RESULTS: Extensive representation of TGF-β positive cells was found in autopsy tissues. A negative correlation was found between the number of TGF-β-positive cells and the blood concentration of band neutrophils (r=−0.617; p=0.033); between the number of TGF-β-positive cells and the concentration of C-reactive protein according to blood chemistry (r=–0.491; p=0.013). A positive correlation was found between the number of TGF-β-positive cells and blood platelet concentration (r=0.384; p=0.012); the number of TGF-β-positive cells and erythrocyte sedimentation rate (r=0.409; p=0.025). A positive correlation was also found between the number of TGF-β-positive cells and the presence of a cough in the patient at the beginning of the hospital stay (r=0.367; p=0.046).
CONCLUSION: A correlation was found between the number of TGF-β-positive cells, neutrophil concentration, platelet concentration, erythrocyte sedimentation rate, C-reactive protein concentration, and the presence of cough in patients who died from severe COVID-19. These correlations suggest the negative role of TGF-β and the therapeutic possibilities of regulating its activation. Further studies in a larger number of patients are required.



Genetic factors associated with changes in muscle strength and mass during corticosteroid therapy
Abstract
BACKGROUND: Corticosteroid use is associated with loss of muscle mass and strength, which is associated with an unfavorable prognosis of the underlying disease, as well as an increased risk of cardiovascular disease. Patients with multiple sclerosis (MS) have a higher baseline susceptibility to cardiovascular disease and a higher risk of adverse effects due to corticosteroid use. In clinical practice, different degrees of severity of side effects of corticosteroids are reported. This may be related to the presence of a genetic predisposition, the identification of which should allow a personalized approach to therapy.
AIM: To evaluate the association of polymorphic variants of the glucocorticoid receptor gene NR3C1, the FTO gene, and the melatonin receptor genes MTNR1A, MTNR1B with the development of changes in muscle mass and strength in the context of corticosteroid use in patients with MS.
MATERIALS AND METHODS: The study included 80 patients (mean age 36.3±10.0 years) with MS receiving pulse corticosteroid therapy: 4 (3; 4) g methylprednisolone. Patients were enrolled over the course of one year. To assess the primary endpoint (reduction in muscle mass and strength), muscle strength and mass were monitored before and after therapy using wrist dynamometry, the time-up-and-go test, and bioimpedancemetry. Polymorphic variants of the glucocorticoid receptor gene NR3C1, the FTO gene, and the melatonin receptor genes MTNR1A and MTNR1B were identified by real-time polymerase chain reaction. Intergenic interactions were evaluated using the multifactor dimensionality reduction (MDR) method. R (v. 3.2, R Foundation for Statistical Computing, Austria) was used for statistical analysis.
RESULTS: In women with loss of muscle mass after corticosteroid therapy, there was an increased incidence of depression (p=0.01) for polymorphic variant BclI (rs41423247) of the NR3C1 gene (p=0.005). Reduced dominant arm strength in women was associated with a variant of the BclI gene (rs41423247) (p=0.02), genotypes including BclI (rs41423247) and N363S (rs56149945) (p=0.03). Men with decreased strength in the non-dominant arm were more likely to be smokers (p=0.03). Combinations of genotypes of the NR3C1, FTO, MTNR1B genes were identified with increased and decreased risk of muscle mass loss in women after corticosteroid therapy. Analysis of intergenic interactions showed a strong synergism between the polymorphic variant rs993960 of the FTO gene and rs10830963 of the MTNR1B gene.
CONCLUSION: The presence of polymorphic variants BclI (rs41423247), N363S (rs56149945) of the glucocorticoid receptor gene NR3C1 is associated with loss of muscle strength and mass in women receiving corticosteroid therapy for MS. Combinations of genotypes of the NR3C1, FTO, MTNR1B genes have been identified with an increased risk of muscle mass loss in women after corticosteroid therapy. Modifiable factors associated with loss of muscle mass and strength and cardiovascular risk (depression, smoking) were identified. The data obtained can be used to personalize corticosteroid therapy and prevent cardiovascular and metabolic disorders.



Microglia and macrophages in the human pineal gland
Abstract
BACKGROUND: Over the past two decades, inflammatory responses in the central nervous system (CNS) have been shown to play a role in the etiology of most neurological and psychiatric diseases, as well as in the aging process. Microglia and macrophages are the most important immune cells in the CNS. In contrast to the role of microglia and macrophages in various parts of the CNS, the human pineal gland has not been studied.
AIM: To evaluate the morphological characteristics, types and localization of microglial cells in the human pineal gland by immunohistochemistry.
MATERIALS AND METHODS: The study was performed using samples of a pineal gland of the human brain obtained in individuals between the ages of 16 and 61 years (n=7). Immunohistochemistry was performed on pineal gland sections using antibodies against Iba1 and TMEM119, selective markers for microgliocytes. Statistical methods were used to evaluate the frequency of immunostained cells.
RESULTS: The majority of phagocytic cells identified by immunohistochemistry were found to be microglia and not macrophages. Microglia are represented by both inactive and activated forms. Microglia in the human pineal gland are typically localized in connective tissue trabeculae, both near and far from blood vessels. Microgliocytes are also found in the pineal parenchyma in the hormone-synthesizing cells of the pinealocytes. The number of Iba1 and especially TMEM119 immunoreactive cells decreased significantly with age.
CONCLUSION: This study is the first to evaluate microglia and macrophages in the human pineal gland. The prevalence of microglial cells over macrophages was found. The morphological characteristics and localization of the identified microglial cell types suggest their involvement primarily in immune defense and probably also in the regulation of pinealocyte functions. In addition, there are data suggesting the involvement of microglial cells in the development of inflammation in the human pineal gland during aging.



Safety of direct oral anticoagulants in patients with atrial fibrillation aged 80 years and older: clinical risk factors
Abstract
BACKGROUND: Direct oral anticoagulants (DOACs) are associated with bleeding, particularly in the geriatric population. Most studies focus on predicting major bleeding, but clinically relevant non-major bleeding (CRNMB) is equally important in practice.
АIM: To assess the ability of clinical factors to predict the risk of CRNMB with the use of DOACs in patients with atrial fibrillation (AF) aged 80 years and older.
MATERIALS AND METHODS: A total of 367 patients on DOACs with non-valvular AF aged 80 years and older were evaluated; the median age was 84 [82; 88] years. Key characteristics of the groups were analyzed, including gender, age, and body mass index. CHA2DS2-VASc and HAS-BLED scales were used to assess the risk of ischemic stroke and bleeding, respectively. Comorbidities, Charlson Comorbidity Index, and risk factors of chronic non-communicable diseases were considered. In addition, number of medications taken, physical examination data, history of atherosclerosis, and laboratory test results were collected.
RESULTS: In univariate analysis, significant risk factors for the development of CRNMB with all DOACs included higher walking frequency (p=0.022), lower heart rate (p=0.08), and history of gastric and duodenal ulcer [odds ratio 5.34; 95% confidence interval (CI) 2.31–12.0; p <0.001].
In multivariate analysis, a model for predicting CRNMB was developed using age, type of DOAC, liver disease, acute cerebrovascular accident, history of gastric and duodenal ulcer as predictors. The resulting model had a predictive accuracy of 62.6% (95% CI 57.4–67.6), a sensitivity of 66.5% (95% CI 59.4–73.1), and a specificity of 58.2% (95% CI 50.4–65.7).
CONCLUSION: The study identified specific modifiable, potentially modifiable, and non-modifiable risk factors for developing CRNMB in AF patients aged 80 years and over taking DOACs. An electronic system to support medical decision making, risk factor management, and public quality of life can be created using results of the study.



Risk factors for decreased bone mineral density in patients with Hodgkin’s lymphoma
Abstract
BACKGROUND: Osteoporosis is a disease characterized by a decrease in bone mineral density that leads to low-energy fractures. Hodgkin’s lymphoma, which occurs mainly in young people (16–35 years), may be one of the causes of impaired bone remodeling. Given the high prevalence of osteoporosis in young patients with Hodgkin’s lymphoma, it is important to identify early predictors of the development of osteoporosis.
AIM: To evaluate risk factors for decreased bone mineral density in patients with Hodgkin’s lymphoma receiving pathogenetic therapy.
MATERIALS AND METHOD: The study included 63 patients with Hodgkin’s lymphoma and 30 healthy volunteers who served as controls. All participants completed a questionnaire to identify common and specific risk factors for osteoporosis. Common risk factors included sex, age, body mass index, history of fractures in the patient and immediate family, use of hormone replacement therapy, proton pump inhibitors, corticosteroids, comorbidities, amenorrhea in women, level of physical activity, and calcium intake. Specific risk factors for osteoporosis included polychemotherapy as a pathogenetic therapy for Hodgkin’s lymphoma.
RESULTS: The study identified four main risk factors for the development of osteopenia/osteoporosis in young patients with Hodgkin lymphoma following pathogenetic therapy such as use of proton pump inhibitors, corticosteroids, chemotherapy-induced amenorrhea in women, and low physical activity.
CONCLUSION: Methods for predicting and preventing osteoporosis have not yet been developed for young patients, as this disease is considered to be associated with old age. However, some groups of young patients are at high risk for disruption of bone microarchitecture with low-energy fractures, significantly reducing quality of life. All these factors make early detection of osteoporosis predictors important.



Reviews
Artificial intelligence systems for predicting chronic ischemic heart disease outcomes in cardiac surgery patients based on presence of anemia: a literature review
Abstract
BACKGROUND: In Russia, the number of people undergoing heart surgery exceeds 600 thousand annually. These include anemia in 30–70% of patients with a 4-fold increased risk of one-year death, a 5-fold increased risk of stent thrombosis, a 1.3-fold increased risk of recurrent acute coronary events, and a 2-fold increased risk of bleeding. However, among the prognostic systems developed using artificial intelligence (AI) technologies, few take the presence of anemia into account. Existing digital platforms are not designed to support clinical decision making.
AIM: The review aimed to evaluate existing AI platforms for predicting the course of ischemic heart disease (IHD) and systems that take into account the presence of anemia.
MATERIALS AND METHOD: The PubMed and Russian Science Citation Index databases from 2000 to January 2024 were analyzed. Using Keywords of “artificial intelligence”, “anemia”, “coronary heart disease”, “hemoglobin”, and “cardiac surgery”, 906 articles were found, of which 38 met the inclusion criteria for analysis.
RESULTS: In some countries, AI platforms have been created to predict the course of IHD. This review analyzes published data on the development and use of AI-based digital products for the management of patients with IHD, including those that take into account key hemodynamic parameters.
CONCLUSION: Analysis of existing developments revealed a focus on solving prognostic problems. However, in our opinion, the range of parameters analyzed is not wide enough. For example, anemia, which plays a key role in modifying the risk of adverse outcomes in IHD, has not been considered as a factor.



Blood pressure monitoring using telemedicine technologies in patients with chronic heart failure
Abstract
Continuous monitoring of cardiovascular patients is one of the most important tasks in modern cardiology. Monitoring chronic heart failure (CHF) patients is critical because of instability, high prevalence and life-threatening nature of this disease. Currently, active search and development of optimal devices and programs for medical telemonitoring continues.
This review presents the results of Russian and foreign studies on the use of invasive and non-invasive technologies for monitoring blood pressure (BP) levels and demonstrates their clinical significance. Innovative cuffed and cuffless BP monitoring devices are evaluated. The effectiveness of hypertension and CHF management using remote monitoring is compared with standard practice. The relationship between the risk of hospitalization for CHF and the monitoring is demonstrated. The paper presents data on the cost-effectiveness of using telemedicine technologies such as BP monitoring for CHF management.



Modern approaches to the diagnosis, treatment and prevention of obesity
Abstract
Approximately 2 billion people worldwide are overweight, including about 20% of adults and a quarter of a billion children. In Russia and Europe, about 60% of the population is diagnosed with obesity. According to global data, obesity is the fifth leading risk factor for premature death. The World Health Organization predicts that the number of people with morbid obesity will nearly double in the near future. Obesity increases the risk of cardiovascular, endocrine, and digestive diseases, obstructive sleep apnea, osteoarthritis, etc. Socio-demographic, behavioral and genetic factors are common causes of obesity. The diagnosis of obesity is made through the integrated use of parameters such as body mass index, waist circumference, fasting triglyceride levels, and others. Radiographic and ultrasound methods are being actively implemented. Today in Russia the choice of drugs for the treatment of obesity is very limited. Orlistat, sibutramine, liraglutide are approved for this indication. In addition, gastric electrostimulation and various surgical methods of treatment are effectively used. A targeted and comprehensive approach to improving the healthcare system for people with overweight and obesity should be a key factor in achieving the national goal of improving people’s health and well-being. Escalation of prevention efforts at all levels will help significantly reduce the spread of this disease and prevent its development around the world.



Case reports
A case report of congenital cystic adenomatous malformation of the lung type II in a two-month-old infant associated with complications
Abstract
BACKGROUND: Cystic adenomatous malformation of the lung (CAML), or congenital airway malformation, is a relatively rare birth defect. This condition is difficult to diagnose both in the antenatal and postnatal periods. The relevance of the problem of diagnosing CAML is demonstrated by the clinical case identified in the postnatal period.
CLINICAL CASE DESCRIPTION: This article discusses a case report of CAML in a child. From the age of two months, the disease manifested as monthly episodes of respiratory infections complicated by bronchitis, bronchial obstruction syndrome, and a single case of community-acquired bilateral polysegmental pneumonia, which led to the initiation of multicomponent conservative pharmacotherapy prior to surgery.
CONCLUSION: This case report illustrates the importance of early diagnosis of CAML. Considering that in most cases this is the patient’s first visit to a pediatrician, there is no doubt that primary care pediatricians need to be aware of this condition in order to refer the patient to a specialist as soon as possible for proper diagnosis and treatment.



Reconstructive and plastic treatment of extensive laryngotracheostomy following mine blast injury
Abstract
BACKGROUND: The nature of combat operations in modern military conflicts is leading to an increase in the number of casualties due to mine blast trauma. Combat wounds to the neck are often associated with damage to the larynx and trachea, resulting in scarring airway stenosis. Surgery is the primary treatment for chronic scarring stenosis of the larynx and trachea. However, despite the large number of surgical techniques, not all of them are effective. Anatomic features of the larynx and trachea, difficulties in maintaining the formed airway lumen in most cases lead to postoperative restenosis of the larynx and trachea, which significantly reduces the effectiveness of surgical treatment and complicate the rehabilitation of the patient.
CLINICAL CASE DESCRIPTION: This article presents the experience of treating an extensive laryngotracheal defect resulting from a mine blast injury. A patient with an extensive defect of the anterior wall of the larynx and trachea was admitted to the Department of Reconstructive Surgery of Cavitary Organs of the Neck of L.I. Sverzhevsky Research Clinical Institute of Otolaryngology. After clinical evaluation, laryngotracheoplasty was performed with alloimplant material, followed by stenting of the lumen of the larynx and trachea with a specially developed silicone stent.
CONCLUSION: The use of the most advanced medical technologies allowed to achieve a positive clinical outcome, to reduce the number of stages of surgical treatment, to prevent restenosis of the lumen of the larynx and trachea, to restore breathing through the natural ways of breathing, the physiological process of swallowing and the voice of the patient.


