Tactics Of Therapy Research Articles

СОВРЕМЕННЫЕ ПОЗИЦИИ СТАТИНОВ В ПРОФИЛАКТИКЕ СЕРДЕЧНО-СОСУДИСТЫХ СОБЫТИЙ

Progression of the atherosclerotic process with the development of clinical manifestations is associated with an increased level of atherogenic fractions of lipids, primarily low-density lipoprotein cholesterol. The most studied group of lipid lowering drugs, which have proven their effectiveness in reducing cardiovascular morbidity and mortality, and the first choice drugs in the treatment of dyslipidemia are statins. The updated international guidelines for the treatment of dyslipidemia revised approaches to cardiovascular risk stratification and lipid lowering therapy tactics in different patient cohorts.

Therapeutic Drug Monitoring of Antibiotics Is Needed in the Treatment of Sepsis

The article presents the results of a prospective on e-c enter observational clinical study. The level of therapeutic drug monitoring antibiotics was studied in patients with sepsis. The objective: to assess the impact of pharmacokinetics and pharmacodynamics parameters of the main classes of antibacterial drugs using specific indices to improve the effectiveness of ongoing antimicrobial therapy in patients with sepsis asscoaited with the infectious process with pa n-r esistant nosocomial microflora. Subjects and Methods. A total of 8 patients with sepsis meetiing the criteria of Sepsi s-3 were included. Carbapenems, oxazolidinones, and aminoglycosides were used in the treatment. Concentrations of drugs in blood plasma were studied by hig h-p erformance liquid chromatography with mass spectrometry. Analysis of the effectiveness of treatment was performed on the third day of therapy. Results. The T > MIC index reached 40% of the time interval between the two administrations for MIC for Pseudomonas aeruginosa in only two cases for group II carbapenems. In both cases, high peak concentrations of the drug (19.5 and 35.4 m g/L , respectively) were observed, a low static volume of antibiotic distribution (0.06 l/k g and 0,09 l/k g) and reduced total clearance of the drug (7.18 and 4.11 m l/h r) were noted. The peak concentration of amikacin was low (3.35 m g/l ), while the time to achieve it and the level of static volume distribution (356.5 liters) increased. The peak concentration of linezolid was reduced in all observations and amounted to 4.04 and 3.35 m g/l . The time of its achievement was increased (3.27 and 6.6 hours), the ratio of AU C / M IC was low and made 76.8 and 59.2. The resolution of organ dysfunction and reduction of manifestations of infectious intoxication were noted only in three patients on the third day of observation. Conclusion. Static pharmacokineti c/p harmacodynamic criteria may serve as a guideline for antimicrobial therapy. Limitations in changing the tactics of antimicrobial therapy based on the use instruction nevertheless allow optimizing treatment by controlling the volume of distribution of the drug, presence of renal or hepatic insufficiency that, however, does not guarantee treatment success. The volume of therapeutic drug monitoring of antibiotics sufficient for compilation of static pharmakinetic models, does not meet the requirements of modern intensive care.

Expression heterogeneity of ABC-transporter family genes and chemosensitivity genes in gastric tumor, carcinomatosis and lymph node metastases

Introduction. Metastatic tumors (particularly gastric cancer) have been found to be characterized by heterogeneity between the primary tumor and metastases. This type of heterogeneity comes to the fore when treating primary-metastatic forms of tumor and is an important reason for the low effectiveness of their treatment. In this regard, comparative analysis of ABC-transporter gene expression and chemosensitivity genes will allow to characterize to a certain extent the resistance and sensitivity of primary tumor, carcinomatosis and metastases to therapy and provide the basis for personalized treatment approach.Aim. To evaluate expression heterogeneity of ABC-transporter genes and chemosensitivity genes in gastric tumor, carcinomatosis and lymph node metastases.Materials and methods. Overall 41 patients with disseminated gastric cancer stage IV with carcinomatosis of peritoneum were included in the investigation. All patients underwent surgery according to Roux palliative gastrectomy. After surgery patients underwent chemotherapy depending on indications. RNA was isolated using RNeasy Plus mini kit (Qiagen, Germany). The expression level of ABC transporter genes (ABCB1, ABCC1, ABCC2, ABCC5, ABCG1, ABCG2) and chemosensitivity genes (BRCA1, RRM1, ERCC1, TOP1, TOP2α, TUBβ3, TYMS, GSTP1) was assessed by reverse transcription polymerase chain reaction (RT-PCR) in primary tumor, carcinomatosis and lymph node metastases.Results. The expression levels of the genes under study were shown to vary widely. For ABC transporter genes, ABCG1 (3.1 ± 1.1; max 32.0), ABCG2 (7.9 ± 2.3; max 54.1), ABCG2 (9.6 ± 3.8; max 101.0) were the most expressed genes in gastric tumor tissue, carcinomatosis and lymph node metastasis, respectively. Hyperexpression among chemosensitivity genes at all three sites was characteristic only of TOP2α (17.2 ± 6.0; max. 161.9; 10.8 ± 4.1; max. 105.1; 35.3 ± 0.8; max. 439.6, respectively). We found that TOP2α and BRCA1 gene expression levels were higher in lymph node metastasis compared with gastric tumor tissue and carcinomatosis (at p = 0.005 and p = 0.001). Whereas ABCC1 gene expression was statistically significantly higher in carcinomatosis (p = 0.03).Conclusion. Thus, a high level of expression heterogeneity is observed in gastric cancer, which affects the expression patterns of various genes in different localizations. The expression profile can be used to determine the level of heterogeneity and approach to personalized therapy tactics.

Heart failure with preserved left ventricular ejection fraction amidst diabetes mellitus: from general mechanisms to possible therapy tactics

The review discusses the relationship between chronic heart failure and diabetes mellitus type 2, metabolic phenotypes of patients w ith chronic heart failure with preserved left ventricular ejection fraction (HFpEF), features of the pathophysiological interaction between diabetes mellitus and HFpEF. Chronic inflammatory condition, metabolic disorders and comorbidities are the pathophysiological basis of HFpEF. The review discusses the concept of diabetic cardiomyopathy, its molecular mechanism and current possibilities of treating this pathology, considering the impact on the prognosis.

Combination of ibrutinib and venetoclax followed by Chimeric Antigen Receptor T-cell therapy in the first line of treatment in an elderly patient with mantle cell lymphoma with hyperleukocytosis and mutation in the TP53 gene

Introduction. The tactics of therapy for elderly comorbid patients with mantle cell lymphoma with unfavorable prognosis factors (complex karyotype, 17p13 deletion, mutations in the TP53 gene) have not been developed. The use of intensive chemotherapy regimens and transplantation of allogeneic hematopoietic stem cells (allo-HSCT) is impossible due to severe comorbidity in elderly patients. A rational approach is the use of a combination of ibrutinib and venetoclax. As an alternative to allo-HSCT, a new option for elderly patients with poor prognostic factors is Chimeric Antigen Receptor T-cell therapy (CAR-T) cell therapy.Aim — to present the experience of using ibrutinib and venetoclax with CAR-T-cell therapy in the first line of treatment in an elderly patient with MCL with a mutation in the TP53 gene and hyperleukocytosis.Main findings. Patient M., 68 years old. The examination revealed hyperleukocytosis 978 × 109/L, anemia (55 g/L), thrombocytopenia (30 × 109/L), and splenomegaly 250 × 180 mm. According to the results of laboratory studies, the diagnosis of lymphoma from mantle cells with a complex karyotype, deletion 17p13, 13q14 and mutation p.R248W in exon 7 of the TP53 gene (VAF = 26 %) was verified. For cytoreductive purposes, two sessions of leukocytapheresis and prephase with cyclophosphamide (200 mg/m2) and dexamethasone (10 mg/m2) were performed. From day 3, therapy with ibrutinib 420 mg/day and venetoclax 100 mg/day was started. After 2 days, the leukocytes were 0.7 × 109/L, and the size of the spleen decreased, as a result of which the development of tumor lysis syndrome was noted. As a result of intensive therapy, the patient’s condition stabilized, which allowed him to resume treatment. After 7 days, the number of leukocytes was 2.5 × 109/L, neutrophils — 70 %, platelets — 90 × 109/L, hemoglobin — 95 g/L. According to immunophenotyping, the population of B-lymphocytes was 4 %. According to NGS data, the allelic load of the mutation in the TP53 gene is 0.8 %. The patient underwent anti-CD19 CAR-T-cell therapy and achieved complete remission. Three months after therapy, MRD remains-negative remission and the persistence of CAR-T cells is determined.

The effectiveness of vortioxetine in patients with depression in real clinical practice

The opinion article is devoted to the analysis of a large-scale 24-week multinational observational prospective cohort study «The effectiveness of vortioxetine in depression in real clinical practice» (BELIEVE). The study demonstrated the achievement of functional recovery of patients with depressive disorder when using vortioxetine, good efficacy and tolerability of the drug for the treatment of depression in a large and heterogeneous patient population representative of everyday psychiatric practice. A significant improvement in depressive and cognitive symptoms, productivity and quality of life of patients was achieved, while the greatest effect was observed when using vortioxetine as the first line of therapy. The results of the study confirmed the data of numerous RCTs devoted to the use of vortioxetine in the treatment of depressive disorder, and they can be used when choosing tactics of antidepressant therapy in conditions of routine psychiatric.

ALDH3A2, ODF2, QSOX2, and MicroRNA-503-5p Expression to Forecast Recurrence in TMPRSS2-ERG-Positive Prostate Cancer.

Following radical surgery, patients may suffer a relapse. It is important to identify such patients so that therapy tactics can be modified appropriately. Existing stratification schemes do not display the probability of recurrence with enough precision since locally advanced prostate cancer (PCa) is classified as high-risk but is not ranked in greater detail. Between 40 and 50% of PCa cases belong to the TMPRSS2-ERG subtype that is a sufficiently homogeneous group for high-precision prognostic marker search to be possible. This study includes two independent cohorts and is based on high throughput sequencing and qPCR data. As a result, we have been able to suggest a perspective-trained model involving a deep neural network based on both qPCR data for mRNA and miRNA and clinicopathological criteria that can be used for recurrence risk forecasts in patients with TMPRSS2-ERG-positive, locally advanced PCa (the model uses ALDH3A2 + ODF2 + QSOX2 + hsa-miR-503-5p + ISUP + pT, with an AUC = 0.944). In addition to the prognostic model’s use of identified differentially expressed genes and miRNAs, miRNA–target pairs were found that correlate with the prognosis and can be presented as an interactome network.

Glutathione Component of Antioxidant Status in Menopausal Women with Insomnia.

The study involved 138 women aged 45-60 years in perimenopause (n=55) and postmenopause (n=83) with insomnia (main groups) and without it (control). The levels of reduced (GSH) and oxidized (GSSG) glutathione and glutathione peroxidase activity were determined in erythrocytes; activities of glutathione S-transferase and glutathione reductase were measured in blood serum. The differences with the control groups were found only in perimenopause: higher glutathione reductase activity and reduced GSSG level and GSH/GSSG ratio in women with insomnia (p<0.05). The results of the comparative analysis between the main groups showed lower glutathione reductase activity, increased GSSG level, and a decrease the GSH/GSSG ratio in the postmenopausal period compared with the perimenopause (p<0.05). These results can be used in choosing the tactics for complex therapy of insomnia in menopausal women to correct free radical homeostasis and prevention of oxidative stress.

RETRACTED: Non-coding RNA in SARS-CoV-2: Progress toward therapeutic significance

The recently developed pathogenic virus, SARS-CoV-2, was found in the Hubei Province, China. Giving rise to a broad spectrum of symptoms, SARS-CoV-2 rapidly spread across the globe, causing multi-systemic and dangerous complications, with death in extreme cases. Thereby, the number of research cases increases every day on preventing infection and treating its resulting damage. Accumulating evidence suggests noncoding RNAs (ncRNAs) are necessary for modifying virus infection and antiviral immune reaction, along with biological processes regulating SARS-CoV-2 and subsequent disease states. Therefore, understanding these mechanisms might provide a further understanding of the pathogenesis and feasible therapy alternatives against SARS-CoV2. Consequently, the molecular biology of SARS-CoV-2, ncRNA's role in its infection, and various RNA therapy tactics against the virus have been presented in this review section.

Major features of the 2021 WHO Classification of Tumors of the Central Nervous System: clinician’s view

Advances in the understanding of the molecular biology of central nervous system (CNS) tumors have prompted a new WHO classification of brain and spinal cord tumors in 2021 and integration it in routine clinical practice. Nowadays accurate diagnosis verification consists not only of the histological tumor type, but also includes its molecular-genetic characteristics. Differences in the genetic features of a tumor, even within the same histological type, will determine differences in the prognosis of the disease, and in the tactics of anticancer therapy. The introduced changes necessitate a comprehensive diagnosis of CNS tumors, thereby placing the responsibility for formulating the final diagnosis not only on pathologists. New approaches to classification make it possible to personalize anticancer treatment, as well as including new methods of targeted and immunotherapy, which today seems to be a key aspect of improving the survival of this category of patients.

Clinical features and tactics of therapy of comorbid dermatoses

Case of possible comorbidity in dermatological practice is presented in the article. Skin infections are known to be common in patients with chronic eczema and may be bacterial, fungal or viral in nature. The surface layer of the epidermis is damaged with eczema. This moment is usually hereditary and leads to a violation of the protective and barrier functions of the skin. There are violations of the lipid mantle of the skin, transepidermal loss of water, a shift in the pH of the skin to the alkaline side. These changes increase the probability of developing not only a skin infection, but also increased sensitization to an infectious agent. In clinical practice, infectious dermatitis is rarely combined with other allergic skin diseases, more often developing against the background of metabolic and vascular disorders, however, such clinical combinations are possible. The article describes a case of chronic eczema and infectious dermatitis. This comorbid pathology is of particular practical interest to clinicians, as it requires a more detailed approach to diagnostics and treatment. Along with systemic therapy in external treatment, combined topical glucocorticosteroids are the drugs of choice.

ИНФЕКЦИИ НИЖНИХ МОЧЕВЫХ ПУТЕЙ (ЦИСТИТ, БАКТЕРИУРИЯ) В АМБУЛАТОРНОЙ ПРАКТИКЕ: ИЗМЕНЕНИЕ СТРАТЕГИИ И ТАКТИКИ ЭМПИРИЧЕСКОЙ АНТИМИКРОБНОЙ ТЕРАПИИ (НОВЫЕ КЛИНИЧЕСКИЕ РЕКОМЕНДАЦИИ)

Abstract. Introduction. When treating urinary tract infections, especially lower urinary tract cystitis and asymptomatic bacteriuria, quite a few factors have to be considered, such as first episode of cystitis or recurrence, presence of pregnancy or lactation, suspected pathogen and its sensitivity/resistance to antimicrobial agents in the region, recent antibiotic treatment and many others. One such factor that determines disease outcome is the rational choice of empirical antimicrobial therapy. The results of domestic and foreign epidemiological studies indicate a global increase in resistance of uropathogens to antibiotics, which has influenced the change of modern strategy and tactics of antimicrobial therapy. Aim. To review current data on the results of epidemiological and clinical studies and substantiate clinical recommendations for rational empirical therapy of uncomplicated lower urinary tract infections. Material and methods. The original epidemiological and clinical studies in the foreign and domestic literature and clinical guidelines on the topic for the last 5 years were searched. Results and its discussion. Data from epidemiological studies of community-acquired urinary tract infections in the Russian Federation show decreasing sensitivity and increasing resistance among outpatient strains of uropathogenic E. coli and Klebsiella pneumoniae to antibiotics commonly used in outpatient practice: fluoroquinolones, betalactams (including protected ones), cephalosporins, trimethoprim/sulfamethoxazole. which was a prerequisite for limiting the use of many antibiotics widely used in the treatment of urinary tract infections in the last decade. The findings were the basis for changes in the strategy and tactics of empirical antimicrobial therapy, in particular to the exclusion of quinolones/fluoroquinolones and restriction of betalactams from the treatment of uncomplicated cystitis. This review presents indications for a rational choice of empirical antimicrobial therapy for acute and recurrent cystitis and asymptomatic bacteriuria: recommended regimens, doses and duration of therapy. Conclusion. The decision to prescribe antibiotic therapy for lower urinary tract infections should be made after ineffectiveness and non-antimicrobial prophylaxis, and the choice of antibiotic should be based on its environmental safety and prevention of global antimicrobial resistance buildup.

Recent trends in the application of nanoparticles in cancer therapy: The involvement of oxidative stress.

In the biomedical area, the interdisciplinary field of nanotechnology has the potential to bring numerous unique applications, including better tactics for cancer detection, diagnosis, and therapy. Nanoparticles (NPs) have been the topic of many research and material applications throughout the last decade. Unlike small-molecule medications, NPs are defined by distinct physicochemical characteristics, such as a large surface-to-volume ratio, which allows them to permeate live cells with relative ease. The versatility of NPs as both therapeutics and diagnostics makes them ideal for a broad spectrum of illnesses, from infectious diseases to cancer. A significant amount of data has been participated in the current scientific publications, emphasizing the concept that NPs often produce reactive oxygen species (ROS) to a larger degree than micro-sized particles. It is important to note that oxidative stress governs a wide range of cell signaling cascades, many of which are responsible for cancer cell cytotoxicity. Here, we aimed to provide insight into the signaling pathways triggered by oxidative stress in cancer cells in response to several types of nanomaterials, such as metallic and polymeric NPs and quantum dots. We discuss recent advances in developing integrated anticancer medicines based on NPs targeted to destroy malignant cells by increasing their ROS setpoint.

PB1953: ASSESSMENT OF THE EFFICACY OF BORTEZOMIB-CONTAINING THERAPY REGIMENS DEPENDING ON MAGE-C1 GENE EXPRESSION IN MULTIPLE MYELOMA PATIENTS.

Background: The treatment of multiple myeloma (MM) has undergone significant changes over the past decade due to the emergence of new therapeutic agents and the development of personalized approaches. The search for factors to predict the course of the disease remains relevant. MAGE-C1 gene expression is considered as a possible marker of refractoriness to bortezomib-containing therapy regimens. Aims: Determine MAGE-C1 gene expression by real-time polymerase chain reaction (RT-PCR). Evaluate the effectiveness of bortezomib-containing regimens in MM patients depending on MAGE-C1 gene expression. Methods: The prospective study from February 2019 to November 2021 included 81 MM patients (37 men, 44 women), aged 35 to 82 years (Me 59). The level of MAGE-C1 gene expression by RT-PCR in bone marrow samples, enriched with CD138+ cells, was determined in all patients. The diagnosis of MM was made according to the IMWG (2014). The ISS stage was determined as I in 24 (20%) patients, II in 21 (67%), III in 36 (13%). Plasma cell content ranged according to myelogram from 1 to 89% (Me 26%), paraprotein secretion was 0.1 to 85 g/L, Bens-Jones protein in urine (from trace values to 12.54 g/day) was determined in 54 patients. Bone plasmacytomas were documented in 42 patients, myeloma nephropathy in 19 cases, high risk cytogenetic in 25. Induction of remission was carried out by three-component regimens including bortezomib, 30 patients required two or more lines of therapy with lenalidomide or daratumumab. The number of courses was 4 to 10 (median 7). The anti-tumor response after 2-6 courses of therapy with bortezomib-containing regimens was evaluated in 68 patients according to the IMWG (2016). Anti-tumor ≥partial response (PR) was achieved in 52, refractory to bortezomib MM was found in 16 patients. As a control, similar bone marrow cells of 7 healthy donors were investigated. Results: The maximum value of MAGE-C1 gene expression in donors was 0.06 (2ΔCt). The MAGE-C1 gene expression value >0.06 (2ΔCt) in patients was accepted as increased. The group with normal MAGE-C1 gene expression (0.003 to 0.05, 2ΔCt) consisted of 25 patients and the group with increased expression (0.07 to 14.12, 2ΔCt) consisted of 56 patients. The probability of achieving ≥PR in patients with normal MAGE-C1 gene expression was 87.8% and in patients with increased expression- 72.8%. The median time to achieve ≥PR in patients with an expression value ≤0.06 (2ΔCt) was 1.77 months, and in patients with an expression >0.06 (2ΔCt) was 3.06 months, p=0.03 (Fig. 1). In addition, we were able to determine that the expression values of the studied gene were significantly lower in patients with ≥PR compared to patients who were refractory to bortezomib: median 0,15 vs 0.27 (2ΔCt), p=0.05. Image:Summary/Conclusion: In a single-factor analysis, we were able to determine that patients with normal MAGE-C1 gene expression were significantly more likely to achieve an overall response (≥PR) compared to patients whose MAGE-C1 gene expression was increased. Achievement of ≥PR on bortezomib-containing therapy regimens was documented twice as fast in patients with normal expression of the investigated gene. Further study of the MAGE-C1 gene may allow to determine the tactics of induction therapy already at the diagnostic stage.

Efficacy and safety of ultra-low dose inhaled melphalan in the treatment of hospitalized patients with COVID-19

Background. One of the most important components of COVID-19 therapy is the suppression of the hyperergic immune response. There is an urgent need of creating the optimal tactics of efficient and safe anti-inflammatory therapy. A new method of treatment of COVID-19 with inhalation of ultra-low (non-cytotoxic) doses of the alkylating drug melphalan is proposed, based on previous experimental, preclinical, and clinical data on its use in severe bronchial asthma.The aim. To evaluate the efficacy and safety of inhalation of ultra-low doses of melphalan in hospitalized patients with COVID-19-associated lung damage.Materials and methods. A prospective, open, controlled, blind for the central expert study was conducted. Sixty adult patients were included, 30 patients were consecutively admitted to the hospital and received nebulized inhalations of 0.1 mg of melphalan for 7 days. Thirty patients of the control group were selected by an independent expert retrospectively using the computer algorithm for selecting «close» patients based on the «case-control» principle. The primary endpoints were the dynamics on the WHO Clinical Improvement Scale and the dynamics of dyspnea according to the modified Borg scale, secondary – assessment of adverse events, dynamics of indicators of clinical, biochemical blood tests, lungs computed tomography data from the beginning of inhalations in the melphalan group and from the corresponding day in the control group.Results. Inhalations of melphalan led to a significant improvement in the clinical condition of patients according to the WHO scale, decrease in the intensity of dyspnea on day 7 of treatment and by the time of discharge, a significant anti-inflammatory effect. Adverse events and dynamics of laboratory parameters did not differ from the control group.Conclusion. The method of treatment of COVID-19 by inhalation of ultra-low doses of the alkylating drug melphalan is safe and leads to a significant clinical improvement of hospitalized patients with COVID-19-associated lung damage.

Guidelines of the Association of Anesthesiologists-Intensivists, the Interregional Non-Governmental Organization Alliance of Clinical Chemotherapists and Microbiologists, the Interregional Association for Clinical Microbiology and Antimicrobial Chemotherapy (IACMAC), and NGO Russian Sepsis Forum "Diagnostics and antimicrobial therapy of the infections caused by multiresistant microorganisms" (update 2022)

Strains of microorganisms characterized by resistance to antimicrobial drugs used in medical organizations continue to spread In most regions of the world including Russia. It is clear that it affects both the effectiveness of antimicrobial therapy and tactics and strategy of its use not only in adults patients but also in children. The pandemic of coronavirus infection, in addition, highlighted the growing problems in treatment of invasive mycoses, the dose adjustment of antibiotics during sorption and dialysis therapy methods. These circumstances made it necessary to make adjustments to Guidelines on Diagnostics and Antimicrobial Therapy of Infections Caused by Multiresistant Strains of Microorganisms, which were prepared by a group of leading Russian experts in 2020 [1]. The submitted version of the recommendations was approved on 25.03.2022 at a joint meeting of the working group with representatives of public organizations: Association of Anesthesiologists-Intensivists, the Interregional Non-Governmental Organization Alliance of Clinical Chemotherapists and Microbiologists, the Interregional Association for Clinical Microbiology and Antimicrobial Chemotherapy (IACMAC), and NGO Russian Sepsis Forum. These recommendations reflect an interdisciplinary consensus opinion on approaches to the diagnosis and antimicrobial therapy of infections caused by multiresistant microorganisms. They are based on data from publications obtained from randomized trials as well as based on international clinical guidelines with a high degree of evidence.It is rational to use the Guidelines for determining the tactics of empirical and etiotropic therapy of the most severe infections.

Superoxide Dismutase Activity in Male and Female Patients of Different Age with Moderate COVID-19.

The study involved 271 patients (132 men and 139 women) with moderate COVID-19. Superoxide dismutase (SOD) activity in erythrocytes was measured spectrophotometrically. In total group of patients (divided into age groups of 18-35, 36-45, 46-60, and 61-90 years), higher SOD activity was found in the 18-35 age group in comparison with the groups 46-60 years (p<0.01) and 61-90 years (p<0.05). Then, the groups were additionally divided by sex. In men, no differences in enzyme activity were found between the age groups. In women of early reproductive age, SOD activity was higher than in groups 36-45, 46-60, and 61-90 years. The sex differences consisted in higher SOD activity in women aged 18-35 years in comparison with men of this age. These data should be taken into account when choosing the tactics of therapy for patients with moderate COVID-19 course.

Is psoriasis therapy an art based on experience?

Psoriasis is a chronic immune-associated skin disease of a multifactorial nature with phenotypic diversity in the general population, as well as a large number of comorbid diseases in patients. The generalized pustular psoriasis, historically was considered one of the variants of the course of psoriasis. Today some authors classify it as a genetically different condition combined with a plaque psoriasis. The selected tactics of psoriasis therapy can become a trigger for the manifestation of a pustular form. Despite the availability of modern data on the immunopathogenesis of the disease, there are no standardized methods of treatment that can take into account the individual characteristics of patients, which is doubly important in pediatric practice, since the arsenal of drugs approved for use is limited. We demonstrate the clinical case of a patient with progressive plaque psoriasis, earlier getting systemic and topical corticosteroids for a long time. This therapy did not allowed to take the course of the disease under control, even more it caused appearance of complications. Our clinical example from practice allows us to focus on the problem of complications of classical therapy for psoriasis and the intricacies of prescribing both topical and systemic drugs. Systemic therapy requires the development of algorithms based on objective diagnostic criteria and the results of studies on the effectiveness and safety of modern drugs in pediatric practice.

Thrombotic Conditions in Patients with COVID-19: Dynamics of D-Dimer and Tactics of Anticoagulant Therapy

In patients with COVID-19, histological examination of the pulmonary vessels shows serious disorders (local thrombosis and microangiopathy), significantly different to those in the control group composed of patients with influenza. Some studies have shown that coronavirus enters cells by binding angiotensin-converting enzyme 2 which is found mainly on the alveolar epithelium and endothelium. The increase in D-dimer levels is typical for patients with COVID-19. Although many inflammatory processes can affect D-dimer levels, an increase in D-dimer during COVID-19 is more likely to indicate thrombosis. The aim. To analyze the patients who have suffered from COVID-19 and to determine possible risk factors for the development of thrombotic complications and define the surgical or medical therapy tactics. Material and methods. The study was conducted from October 2020 to April 2021 in Ukraine (Zaporizhzhia, Uzhhorod, Kherson and Kyiv). We analyzed 121 patients aged 46.9± 15.3 years, 64 (52.8%) men and 57 (47.1%) women. All the patients had positive PCR test for COVID-19. The changes in D-dimer were analyzed. Results. Forty-one (33.9%) patients had thrombotic complications. Pulmonary embolism (PE) was diagnosed in 14 patients, deep vein thrombosis (DVT) in 17, acute stroke in 2 and peripheral artery thrombosis in 8 cases. An increase in D-dimer level was observed in most patients and was not associated with clinical manifestations of thrombosis. At a D-dimer level of 11,000-10,564 ng/ml the patients had clinical symptoms of thrombotic condition which was confirmed by computed tomography or ultrasound examination. At an increase over 725-7000 ng/ml, there were no clinical signs of thrombosis. We performed standard medical therapy in patients with PE and DVT. In case of arterial thrombosis open surgery was performed in 4 patients and direct catheter thrombolysis in 1 case. Conclusion. In our opinion, anticoagulants should be prescribed for patients with a D-dimer level of more than 700 ng/ml. Full anticoagulation is prescribed for severe forms of COVID-19 or confirmed thrombosis. We didn’t find any correlation between the development of thrombotic complications in patients with COVID-19 and comorbidities, body mass index and other factors. Medical therapy was successful in all cases of PE and DVT, anticoagulants were prescribed for 1 year. Femoral artery thrombectomy was successfully performed in 4 patients. After direct catheter thrombolysis we got peripheral pulse. In all cases of arterial thrombosis, we prescribed anticoagulants for 2 months after discharge and acetylsalicylic acid for a long time.

Assessment of the severity of patients with widespread peritonitis based on the new classification

Aim. To study the efficiency of a new classification of the widespread peritonitis in the estimation of patients’ state severity.Material and methods. 160 patients with widespread peritonitis aged 16 to 76 were examined; 104 (65%) were men and 56 (35%) were women. The patients were divided into 3 groups: 1 - endogenous intoxication (n=95), 2 - abdominal sepsis (n=46), and 3 - septic shock (n=19). The results of treatment were evaluated according to the incidence of postoperative complications, terms of hospitalization, mortality rate.Results and discussion. When analyzing the results of clinical studies, it was found that according to the stages of endogenous intoxication, abdominal sepsis and septic shock, the indicators were as follows: APACHE II 13.8±0.5 - 16.1±0.4 - 18.5±0.5; MIP 22 - 25 - 25; SOFA 3.3±0.2 - 3.7±0.1 - 4.2±0.1; presepsin (pg/mL) 355.6±8.6 - 783.4±24.0 - 1587.7±70.5; tumor necrosis factor-α (pg/mL) 105.5±1.9 - 853.3±17.6 - 24.5±6.8 p/o complications (%) 13.6±3.6 - 35.1±6.1 - 41.9±7.1; hospital stay (days) 19.2±0.8 - 25.9±2.2 - 13.8±1.9; 12 patients died in the stage of septic shock. There were statistically significant differences between the groups (p&lt;0,01).Conclusion. The improved classification stratifies patients with diffuse peritonitis according to severity into the following groups: endogenous intoxication, abdominal sepsis, septic shock. It allows determining in time the necessary volume of intensive therapy and surgical tactics.