Vol 31, No 9 (2024)

Background. The problem of irrational use of antibiotics in children’s hospitals remains relevant. To effectively solve this problem, it is obvious that there is a need to create standards for auditing clinical practice and a unified strategy for monitoring the use of antibiotics both in individual institutions and at the level of regional health authorities. A review of modern pharmaco-epidemiological methods aimed at determining the main criteria of the audit algorithm as a key tool in developing a strategy for monitoring the clinical practice of using antimicrobial drugs was conducted.

Objective. Creation of the audit algorithm for assessing the rationality of the clinical practice of using antibiotics for children’s hospitals.

Methods. A comprehensive assessment of the rationality of antibiotic use in children’s hospitals included an analysis of antibiotic consumption using the WHOAWaRe method based on ATC/DDD analysis for the previous year, as well as an assessment of the clinical practice of using antibiotics based on primary medical documentation by a checklist from the «Toolkit for assessing the quality of inpatient care for children» of the World Health Organization.

Results. The analysis of antibiotic consumption in a specific pediatric hospital, conducted using the WHOAWaRe method and ATC/DDD analysis for the previous year, showed signs of potentially irrational clinical practice in cases where antibiotics from the «Access» category in oral forms are not used, as well as if the share of antibiotics from the «Control» category exceeds the consumption of antibiotics from the «Access» category, or the share of antibiotics from the «Reserve» category is 10% or more. The results of assessing antibiotic consumption in pediatric hospitals using the WHOAWaRe method were fully consistent with the results of the analysis of primary medical documentation using the checklist of the World Health Organization tools.

Conclusion. When implementing a strategy for monitoring antimicrobial consumption in a pediatric hospital at the stage of clinical practice audit, it is advisable to integrate consumption data collected using the WHOAWaRe methodology with the results of a structured analysis of primary medical documentation. This will not only identify trends in the use of antibiotics, but also clarify the factors that contribute to or hinder the maintenance of rational clinical practice.

Atrial fibrillation (AF) is the most common type of tachyarrhythmia among patients with a cardiology profile. AF causes significant changes in the atrial myocardium – remodeling. The concept of atrial remodeling includes changes at several main levels: electrical remodeling, mechanical remodeling, structural remodeling, as well as endocrine and vegetative changes. Modern interventional methods of treating AF demonstrate high efficiency, provide «freedom from arrhythmia» in the long term and improve tolerance of relapses. Long-term persistence of AF reduces the chances of success of catheter treatment methods due to electrical, mechanical and structural remodeling of the atria. Perhaps, upon achieving reverse remodeling of the atria after restoration and maintenance of the rhythm, these chances will increase significantly. This issue currently remains open and requires additional research.

Background. Heart failure (HF) is a significant problem in modern medicine. Loop diuretics are used in 80–90% of patients with HF, representing a long-established basis for symptomatic treatment. However, many complex and unresolved issues for evidence-based medicine regarding diuretic therapy in HF remain. Given the genetic polymorphism of proteins involved in the metabolism and transport of torasemide, a loop diuretic widely used in clinical practice, as well as the importance of optimal dosing of diuretic therapy in patients with HF, it is necessary to personalize treatment and identify factors influencing diuretic therapy.

Objective. Evaluation of the influence of clinical factors and polymorphisms of the CYP2C9*2 (rs1799853, c.430C>T, Arg144Cys), CYP2C9*3 (rs1057910, 1075A>C, Ile359Leu) and SLCO1B1*5 (rs4149056, c.521T>C, Val174Ala) genes on the dosing of torasemide in patients with HF.

Methods. The study included 68 patients hospitalized with HF who received torasemide as diuretic therapy. Therapy adjustment was performed during hospitalization based on clinical, laboratory and instrumental data. Allelic variants of the CYP2C9 and SLCO1B1 genes were determined by real-time PCR.

Results. The distribution of CYP2C9 gene genotypes in the study population was as follows: 52 (76.5%) patients had the CYP2C9*1/*1 genotype, 9 (13.2%) – CYP2C9*1/*2, 6 (8.8%) – CYP2C9*1/*3, 1 (1.5%) – CYP2C9*2/*2, and the distribution of SLCO1B1*5: 46 (67.6%) – TT, 16 (23.5%) – TC and 6 (8.8%) – CC. The frequency of alleles and genotypes of CYP2C9*2 (χ2=0.82; p=0.66), CYP2C9*3 (χ2=0.14; p=0.93) and SLCO1B1*5 (χ2=5.35; p=0.07) corresponded to the Hardy–Weinberg equation; 30 (44.1%) patients did not require dose adjustment of torasemide, 14 (20.6%) patients required dose increase, 6 (8.8%) patients required dose decrease, 5 (7.4%) patients required loop diuretic therapy discontinued, and 13 (19.1%) patients were replaced with furosemide. Comparison of diuretic therapy depending on CYP2C9 (p=0.879) and SLCO1B1 (p=0.297) genotypes revealed no statistically significant differences. The need to replace torasemide with furosemide was statistically significantly higher in patients with more severe manifestations of HF (p=0.002), renal failure (p=0.020) and polypharmacy (p=0.001). Progression of the HF stage increases the chances of increasing the dose of torasemide or replacing it with furosemide by 4.94 times (95% CI 1.92–12.69); an increase in serum creatinine by 1 μmol/l increases the chances of increasing the dose of torasemide or replacing it with furosemide by 1.02 times (95% CI 1.01–1.04).

Conclusion. Polymorphisms of the CYP2C9*2, CYP2C9*3 and SLCO1B1*5 genes did not demonstrate a statistically significant association with the features of torasemide dosing in patients with HF in the current study. The stage of HF and the serum creatinine level had a direct relationship with the probability of increasing the dose of torasemide or replacing it with furosemide.

Acute sinusitis (AS) is an inflammatory disease of the paranasal sinuses, accompanied by nasal congestion, difficulty in nasal breathing, mucopurulent discharge from the nose and the appearance of pain in the projection of the sinuses. The main cause of this pathology is impaired drainage due to blockage of the sinus ostia with edematous mucous membrane. The main etiological role in the development of AS belongs to respiratory viruses and only 0.5-2.0% to bacterial microbiota. In the pathogenesis of the disease, in addition to swelling of the mucous membrane of the nasal cavity and sinuses, a violation of the mucociliary clearance is of great importance, in particular a change in the composition of mucus and ciliary dysfunction, which results in the appearance of thick, viscous and difficult to separate pathological secretions. This circumstance negatively affects the course of inflammation, since it activates the adhesive properties of transient microorganisms and prolongs their presence on the mucous membrane of the upper respiratory tract and contributes to a long-term recurrent course of sinusitis and even its transition to a chronic form. In this regard, one of the most important areas of treatment for all forms of AS is mucoregulatory therapy, which is achieved through a variety of pharmacological properties of carbocysteine, such as improving the rheological properties of mucus, its qualitative and quantitative composition, regeneration of epithelial cells, and regulation of the number of goblet cells. The effects provided allow to recommend the use of carbocysteine in the complex therapy of acute sinusitis.

Background. Acute sinusitis (AS) is one of the most common diseases that determines a high incidence of visits to otolaryngologists. Empirical diagnostics of sinusitis does not allow to judge with sufficient reliability the presence or absence of this disease in a patient with acute respiratory infection. This circumstance determines the high frequency of erroneous diagnoses of AS in general medical practice, irrational antibiotic therapy. The article analyzes literature data on the diagnosis of AS and the potentials for the use of topical antimicrobial therapy of this disease. The data sources include MEDLINE, EMBAS, PubMed with subsequent systematization of the material according to the degree of its compliance with the information request.

Conclusion. Differential diagnostics of acute bacterial and acute viral sinusitis is one of the most important factors determining the treatment of such patients, in particular the decision on the use of antibacterial drugs with proven efficacy against etiologically significant pathogens and regional patterns of their resistance to antibiotics. The use of topical antibacterial drugs in these cases allows to increase the local concentration of drugs in the inflammation site, minimizing side effects. The domestic drug hydroxymethylquinoxaline dioxide has certain advantages in these situations, the use of which in standard treatment regimens for acute tonsillopharyngitis and acute bacterial sinusitis is of great importance in terms of controlling the infectious process and prognosis of the disease.

Background. Osteoarthritis (OA) accounts for 70–80% of all rheumatic pathologies, and degenerative-dystrophic changes account for 48–52%, ranking first in the number of days of disability.

Description of the clinical case. The article describes the clinical case of successful treatment of patient B., 56 years old, suffering from osteoarthritis of the joints of the hands of the 2nd stage according to Kellgren-Lawrence in combination with osteoarthritis of the intervertebral joints of the lumbosacral spine, with a tablet form of a combination of glucosamine hydrochloride 500 mg and sodium chondroitin sulfate 500 mg) according to the standard scheme: 1 tablet 2 times a day – 3 weeks, then 1 tablet per day – 2 months

Analysis of the patient’s objective data before and after treatment. During the treatment, clinical indicators that reflected the state of motor function, inflammation and pain syndrome in the joints of the hands and spine were studied. The values of the following functional indices and pain scales were assessed: the VAS scale (visual analogue pain scale), the Numeric Rating Scale (NRS-) for determining the intensity of acute pain, the Australian-Canadian functional index AUSCAN used to assess the severity of pain, stiffness in the hands and the state of joint function, as well as laboratory parameters (ESR, RF, CRP, fibrinogen) in dynamics.

Conclusion. High efficiency of a combination of glucosamine hydrochloride 500 mg and sodium chondroitin sulfate 500 mg was noted in a patient with osteoarthritis of the joints of the hands and osteoarthritis of the intervertebral joints of the lumbosacral spine. Good tolerability when taking this drug and long-term maintenance of the effect of treatment were also noted.

The article discusses the features of thrombolytic therapy with alteplase in the treatment of ischemic stroke (IS) and acute coronary syndrome (ACS). Acute IS and ST-segment elevation myocardial infarction (STEMI) have a number of common features, but important differences in pathophysiology, diagnostics, and clinical features require an individual approach to each disease, with rapid treatment playing a decisive role in the prognosis of patients. According to the latest international and Russian guidelines and data from randomized clinical trials, approaches to various types of reperfusion therapy in IS and STEMI are analyzed. The objective of this review was to provide an understanding of the common and distinct pathophysiology underlying modern reperfusion strategies in IS and STEMI and to describe new ways to improve their clinical efficacy.

Reducing the «door-to-needle» time for revascularization procedures is crucial in providing effective care to patients with acute stroke. Since the «time-to-brain» concept requires rapid diagnostics, multimodal brain imaging is rarely used, and emergency computed tomography (CT) can only exclude the presence of hemorrhage. As a result, according to various meta-analyses, the incidence of stroke imitation in acute vascular departments can reach 25%. At the same time, the incidence of thrombolytic therapy in patients with a «stroke mimics» can reach 17%. Peripheral vestibular dysfunction, toxic/metabolic encephalopathy, seizures, functional disorder, transient global amnesia, migraine, neuropathies, space-occupying lesions, acute confusion are usually hidden under the «mimics of stroke». Clinical neurological examination plays a decisive role in the differential diagnosis of acute stroke and other «disease mimics». The absence or small number of vascular risk factors, younger age, and careful analysis of subtle clinical signs should alert the physician to a possible ischemic stroke-chameleon.

Aging is a natural biological process that affects all levels of life organization. Understanding the mechanisms of aging is of great importance for developing effective strategies for the prevention and treatment of the phenomenon of premature aging in cosmetology, dermatology and aesthetic medicine. Cellular aging – senescence, is considered one of the central links in the aging process. Research in this area can lead to the development of new methods for locally slowing down the aging process, treating the phenomenon of premature aging and increasing the effectiveness of the procedures. One of the promising areas in the framework of injection cosmetology is biorevitalization – an invasive procedure aimed at restoring and optimizing the quality characteristics of the skin, in particular the intercellular matrix. This work is devoted to the description of a new direction of biorevitalization based on a multimarker approach within the framework of molecular cosmetology – senotherapeutic biorevitalization or senobirevitalization. The effect of this group of drugs is achieved by intradermal administration of a gel containing hyaluronic acid with additional senotherapeutic components. These components contribute to the partial or complete blockade of pathways associated with the expression of the senescence associated secretory phenotype (SASP) without cell death. The article also examines in detail the regulation and functional role of SASP, the mechanism of action of senotherapeutic drugs, their advantages and prospects for the development of this direction.

Background. Skin itching is a dominant symptom in most dermatoses. It has a negative impact on the general condition of the patient, his working capacity, social communication, which significantly reduces the quality of life and requires active therapy.

Objective. Evaluation of the antipruritic and anti-inflammatory effects of the Fleming’s ointment in various itchy dermatoses.

Methods. An open comparative study involving 30 patients with atopic dermatitis, eczema and skin itching of other etiologies was conducted. For rashes accompanied by itching, it was recommended to apply Fleming’s ointment 2–3 times a day together with basic skin care products. The intensity of skin itching, the time of onset of the antipruritic effect against the background of the study drug, its duration, the anti-inflammatory effect of the drug, as well as its safety were assessed in patients.

Results. The use of Fleming’s ointment in patients with itchy dermatoses made it possible to reduce the intensity of skin itching in most patients (26 people) on the 3rd day of treatment. The anti-inflammatory effect of the drug was noted in most patients (in 24 people) on the 10th day of the study. By the end of the study, according to the doctor’s assessment, 26 patients showed significant improvement from the therapy. No side effects were detected in any patient.

Conclusion. The results of the study allow to recommend Fleming’s ointment as an effective and safe remedy for the treatment of skin itching in dermatoses.

Fungal infections are an important public health problem due to their high prevalence worldwide (20–25% of the population is infected); dermatophytes of the Microsporum, Trichophyton, Epidermophyton, and Candida genera are the most common pathogens. The nature and frequency of detection of this pathology is influenced by the climate in a particular region and the socio-economic status of the population. Dermatomycetes lead to damage to nails, skin of the feet and hands, scalp, smooth skin and folds. Infection is possible through contact with a sick person or animal, or with the patient’s personal belongings. Risk factors include damage to the integrity of the skin, increased sweating or dry skin, changes in skin pH, and poor hygiene. However, the main reason for contamination with dermatomycetes is the presence of chronic diseases of the endocrine, cardiovascular, circulatory systems, metabolic and oncological diseases. Long-term use of systemic and local glucocorticosteroid drugs (GCS), cytostatics, irrational antibacterial therapy; the presence of the human immunodeficiency virus, smoking, and heavy physical labor contribute to the chronicity of fungal infection, poor response to antifungal therapy, and can cause a recurrent course. Also in practice, there are often cases of modification of the clinical picture of dermatophytosis as a result of the influence of the above factors and incorrect therapy. The article discusses the clinical case of a patient with late diagnosis of mycosis of smooth facial skin, developing against the background of diabetes mellitus and long-term use of local combined corticosteroids. Possible causes, differential diagnosis with other dermatoses and methods for diagnosing the “transformed” variant of microsporia (Tinea incognito) are also outlined. Successful diagnosis and effective treatment with local and systemic terbinafine led to the patient’s recovery and avoided the development of complications. Terbinafine has shown high efficacy, safety, local availability, and ease of use, which increases the likelihood of treatment compliance and patient’s and physician adherence to treatment.

Irritable bowel syndrome (IBS) is a chronic functional bowel disease in which abdominal pain is associated with defecation, changes in the frequency and nature of stool [1, 2].

Background. Angiotensin-converting enzyme inhibitors (ACE inhibitors), in particular enalapril, have retained a leading role in the treatment of arterial hypertension (AH) over the past decades, but at the same time have a side effect in the form of cough, which is one of the main reasons for a significant decrease in the quality of life of patients and subsequent drug withdrawal. An important clinical task is to create an algorithm for predicting the risk of cough development for personalizing enalapril therapy.

Objective. Creation of an algorithm for predicting the risk of cough development while taking enalapril for personalizing ACE inhibitor therapy in hypertensive patients.

Methods. To create an algorithm for predicting the risk of cough development while taking enalapril, multivariate modeling was performed using the logistic regression method.

Results. During the multivariate logistic regression analysis, genetic factors were selected in the form of rs2306283 SLCO1B1, rs495828 ABO, rs8176746 ABO gene polymorphisms, as well as data on the presence of allergic diseases and manifestations in close relatives, which together formed a model for predicting the risk of cough development while taking enalapril in hypertensive patients.

Conclusion. The presented model demonstrates high prognostic significance, has sufficient information content (R2=0.31) and allows to predict the development of cough while taking enalapril with an accuracy of 76.5%.

Background. Chemotherapeutic drugs have a wide range of side effects, in particular, a characteristic side effect of doxorubicin is the occurrence of cardiotoxicity, including asymptomatic. In our study, we determined the relationship between polymorphisms of genes encoding proteins involved in doxorubicin metabolism, minimum steady-state concentration of doxorubicin, and troponin I levels, a laboratory marker of myocardial damage, in patients with breast cancer (BC).

Objective. Determination of the effect of CYP3A5, CYP2D6, CYP2C19, and ABCB1 gene polymorphisms on minimum steady-state concentration of doxorubicin and troponin I levels in BC patients.

Methods. The study included 69 patients with a confirmed diagnosis of BC, hospitalized for the third or fourth course of chemotherapy in the AC regimen (doxorubicin and cyclophosphamide). Blood was collected to determine the minimum steady-state concentration of doxorubicin, troponin I levels, and to perform genotyping.

Results. The median plasma doxorubicin concentration was 132.4 ng/ml (95% CI: 126.118–144.029). An increase in troponin I levels above the reference value was observed in 11 patients, while in 10 of them the doxorubicin concentration was higher than the median value (OR=5.76, 95% CI: 1.36–24.4; p=0.018]. To determine the statistically significant relationship between the concentration of doxorubicin and the level of troponin I, the AUC was calculated (0.757, 95% CI: 0.639–0.852). A statistically higher concentration of doxorubicin was observed in carriers of the 1236TT, 3435TT and 2677TT genotypes.

Conclusion. Carriage of the 1236TT, 3435TT and 267TT genotypes may be associated with an increased risk of developing acute anthracycline cardiotoxicity and an increase in the troponin I level due to the effect on the plasma concentration doxorubicin.

Acute circulatory disorder in the mesenteric vessels is a pathology with high mortality rates, reaching 95%. One of the reasons is that during the diagnostic window corresponding to intestinal ischemia lasting up to 12 hours, most district hospitals in emergency surgery settings conduct routine tests that are not highly specific to this pathology and force the doctor to adopt a wait-and-see approach. A new laboratory indicator is intestinal protein binding fatty acids (I-FABP). When the integrity of the enterocyte membrane is compromised, it enters the venous system from the intracellular space. Thus, with the development of acute mesenteric ischemia and, as a consequence, damage to enterocytes, the I-FABP level in urine and blood tests increases significantly. The sensitivity and specificity of the marker, according to various authors, range from 80 and 85% to 90 and 89%, respectively. Laboratory determination of blood serum I-FABP level in patients with suspected acute mesenteric ischemia will reduce the diagnostic time, select the optimal treatment tactics, improve treatment results and, accordingly, reduce mortality from this pathology.