Atrial cardiopathy (AC) and silent atrial fibrillation (AF) are potential causes of embolic cryptogenic stroke (embolic stroke of undetermined source, ESUS) timely diagnosis of which can significantly change the direction of secondary prevention and reduce the risk of repeated brain catastrophe. The article discusses clinical and radiological markers of cardioembolism, the concept of atrial cardiopathy, its electrocardiographic, echocardiographic and serum markers, as well as the possibility of drug prophylaxis of recurrent stroke. The most applicable AC features in daily operation are the ECG data (p-wave terminal force in lead V1 > 5000 μV x ms, supraventricular extrasystoles and advanced interatrial block), 24-hour ECG monitoring (≥ 480 supraventricular extrasystoles per 24-hour, paroxysms of supraventricular tachycardia ≥ 20 complexes), transthoracic (diameter of left atrium > 40 mm, index of diameter of left atrium ≥ 3 cm/m², index of volume of left atrium > 34 ml/m²) and transesophageal echocardiography (spontaneous echo contrast phenomenon, blood flow rate in LA appendage <20 cm/s) and NT-proBNP concentration > 250 pg/ml. An individual, interdisciplinary decision to prescribe an anticoagulant when combined: (1) the presence of structural and functional AC markers, (2) cardioembolic pattern of a cerebral infarction or intracranial artery occlusion by visualization data and (3) high thromboembolic risk and probability of detection of AF on assessment scales (CHA2DS2-VASc, AF-ESUS and C2HEST). The greatest benefit of prescribing anticoagulant therapy can be obtained by patients with recurrent ESUS in whom sufficient secondary prevention and expressed AC, typical cardioembolism imaging pattern and high risk of thromboembolic events have already been achieved.

Introduction. Сhronicbrain ischaemiais associated with the generation of oxygen free radicals resulting in a condition of oxidativestress. Various studies have investigated that antioxidant compounds can neutralize reactive oxygen species and free radicals.
Aim. To evaluate effect of Cytoflavin (INN: inosine + nicotinamide + riboflavin + succinic acid) for the treatment of chronic brain ischemia.
Materialy and methods. In a double-blind, placebo-controlled clinical study 50 patients aged 61 ± 9 years with chronic brain ischemia (vascular cognitive impairment), were randomized into Cytoflavin (n = 32) group or placebo (n = 18) group. The sealed envelopes system was used to randomize patients; 10.0 ml of the compound were infused by drops intravenously for 10-day period. During the course of treatment, therapy with vasoactive, nootropic and psychotropic drugs was excluded. In addition to clinical evaluation were carried outa comprehensive neuropsychological testing of cognitive functions, registration of cognitive induced potentials (IP) P300 and study of cerebral hemoperfusion using single photon emission computed tomography. To assess the intensity of lipid peroxidation we estimated several kinetic parameters of ferrous iron-induced chemiluminescence.
Results. Prevalence of good and excellent results of treatment was registered in patients treated with Cytoflavin comparing with those placebo (56% vs. 22%; р = 0.036). Psychological examination showed more expressed positive dynamics of physic activity rate in treatment with the active preparation comparing with those placebo (972 ± 184 sec vs. 1 251 ± 449 sec; р = 0.005). In the group of patients treated with Cytoflavin IP P300 showed the increase of P300 peak amplitude (before treatment 5.2 ± 1.2 mV, after treatment 7.2 ± 2.1 mV; р = 0.035). The biochemical basis of the therapeutic action of Cytoflavin was its antioxidant activity: Cytoflavin increased the endogenous antioxidant background (before treatment 46.8 ± 16.1 sec, after treatment 62.4 ± 13.6 sec, р = 0.004).
Conclusions. Cytoflavin produces positive effects on the main symptoms in patients with chronic brain ischaemia, increases endogenous antioxidant background and possesses certain neurotropic activity.

Despite significant progress in medical technology, many topical issues in neurology remain unresolved; among the latter, acute cerebrovascular accidents (strokes) continue to be one of the most important medical and social problems of the modern world, since their rates of morbidity, mortality and disability are steadily growing. The increase in the incidence of strokes over the past 30 years by 70% reflects the imperfection of modern medical strategies for the primary prevention of stroke and measures for their implementation among the population, which dictates the need to revise the prevailing ideas about the etiology, pathogenetic mechanisms and therapeutic approaches to managing patients with cerebrovascular pathology. The article presents a classification of strokes, a critical analysis of vascular risk factors (in particular, the emergence of new ones, such as acute coronavirus infection COVID-19), fundamental elements of the ischemic cascade, pathomorphological and pathophysiological consequences of ischemic damage to the central nervous system (necrosis and apoptosis of neurons, diaschisis in the penumbra zone), current theoretical (targets of drug exposure) and practical (therapeutic window) aspects of therapy and prevention of acute cerebrovascular accidents are outlined. The place and importance of the use of neuroprotective drugs in the combined therapy of patients with acute and chronic cerebrovascular pathology has been demonstrated. Particular attention is focused on neurometabolic drugs with a multimodal mechanism of action, which not only protect the neuronal cytoskeleton, but also increase the tolerance of brain tissue to hypoxia.

Introduction. The restoration of manipulative activity of the upper limb after an ischemic stroke (IS) requires the development of new technologies aimed at sensorimotor training and retraining. Reduction of spasticity of the upper limb muscles is considered as a necessary component of the program of functional restoration of the hand
Aim. To evaluate the effectiveness and safety of the integrated use of rehabilitation technology with virtual reality and biofeedback “SENSOREHAB simulator glove” (RG) and botulinum neurotoxin type A (BTA) to restore the subject-manipulative function of the hand in comparison with an individual complex of physical therapy in the late recovery period of IS.
Materials and methods. A randomized controlled trial included 76 patients, age 60.8 ± 9.2 years; the duration of the transferred IS was 8.1 ± 1.3 months. The main group (n = 42) received BTA with subsequent use of RP. The control group (n = 34) – individual physical therapy. The primary results were changes in the scores on the Fugl – Meyer scales (FMA–UL), the Action Research Arm Test (ARAT), the test with pegs and nine holes (NHPT). Secondary results: dynamics of MRCS, MAS, MoCA, HADS, Bartel index and quality of life (EuroQol-5D).
Results. Improvement of the motor function of the arm in the main group according to ARAT (an increase of ≥4 points) was noted in 63.8% of cases, on the FMA–UL scale (an increase of ≥7 points in sections A–D) – in 65.5% of patients (p < 0.05), according to the NHPT test – a significant increase in the speed of execution The test was performed in 52.6% of patients. The dynamics of EQ-5D-5 (VAS) at the end of treatment reached 72.3 ± 5.7 in the main group (p = 0.03). In patients of the control group, a statistically significant improvement was noted in terms of pain and EQ-5D-5 (p < 0.05).
Conclusions. A comprehensive program of medical rehabilitation of patients with post-stroke upper limb dysfunction, including the use of BTA and RG, significantly improves the recovery of fine hand movements, functional independence of patients and their quality of life.

Cognitive impairment refers to frequent disorders in the elderly and senile, and their prevalence increases with age significantly. Non-dementia cognitive disorders mean a spectrum of changes in the cognitive sphere that precede the development of dementia over the course of many months and even years. Mild forms of cognitive impairment (MCI) are the most studied type of pre-dementia conditions, which in most cases represent a prodromal stage of disorders progressing over time to a dementia syndrome. Early identification of individuals with MCI is important because timely diagnosis of these disorders is expanding the potential impact of the secondary prevention and therapeutic intervention, which can delay or even prevent the onset of professional and social maladaptation due to development of dementia. The article considers the historical issues of studying these disorders, presents the modern principles of their classification and diagnostic criteria. A clinical observation of a patient with a polyfunctional non-amnestic type MCI syndrome is provided. The features of cognitive disorders typical for chronic cerebrovascular insufficiency, such as mental retardation, impaired activity arrangement, difficulties with generalisation in relative preservation of memory and orientation in combination with emotional and affective disorders are described. The authors discuss issues of treatment of MCI syndrome, which should be comprehensive and include the correction of all vascular risk factors, non-drug (regular physical activity, cognitive training) and pharmacological treatments aimed at improving cognitive performance. The article describes the possibilities of modern neuroprotective and symptomatic therapy of cognitive impairment, showing the role of choline alfoscerate in the treatment of MCI.

The issue of cerebral vascular pathology is one of the most important social problems in the modern world, and Russia is no exception. Cerebrovascular diseases are distinguished by high prevalence, mortality and disability rates. They are of great importance from a health perspective of not only each individual, but total nation. Acute or chronic disorders of cerebral circulation naturally results from atherosclerosis of the major arteries of the head, hypertensive disease, and other cardiovascular diseases. These factors cause pathology of large and small cerebral vessels, which leads to chronic cerebral ischemia and (or) acute cerebrovascular accident with damage to various brain structures. Cognitive impairment is probably the most common presentation of cerebrovascular insufficiency. The severity of cognitive impairment can vary significantly depending on the stage of the condition and the severity of the underlying vascular disease - from mild cognitive impairment to dementia. Vascular cognitive impairment can be caused by several mechanisms. Small vessel ischemic disease is one of the pathological conditions that cause the development of cognitive impairment and dementia. Other presentations of cerebrovascular disorders can include multi-infarction, hypoperfusion, hemorrhagic, hereditary and mixed dementia. Current strategies for the management of patients with vascular cognitive impairment and dementia include symptomatic treatment, risk factor management, and non-pharmacological approaches aimed at preventing their progression.

Doctors of various specialties face orofacial and facial pain in their practice: dentists, maxillofacial surgeons, neurologists, neurosurgeons, otorhinolaryngologists, therapists, general practitioners, traumatologists, ophthalmologists, psychotherapists, physiotherapists, aesthetic medicine doctors, anesthesiologists, plastic surgeons and other specialists. The novel coronavirus infection (COVID-19) pandemic, spread by the SARS-CoV-2 virus, has become a challenge for all medical specialties and health care systems around the world. The respiratory system is the dominant target of SARS-CoV-2. The oral mucosa is also highly susceptible to SARS-CoV-2 infection, due to the wide distribution of angiotensin-converting enzyme type II receptors in the oral cavity. We searched the literature for the period from the beginning of the pandemic until August 22, 2022, on the study of the association of orofacial pain with a new coronavirus infection COVID-19 in the electronic search engines PubMed and Scopus. Analysis of the found sources indicates an increase in the frequency of various types of orofacial pain associated with 1) violation of dentoalveolar and related structures during the COVID-19 pandemic; 2) temporomandibular disorders; 3) with damage or disease of the cranial nerves; and 4) like manifestations of primary headache. This growth is due both directly to the infection caused by SARS-CoV-2, its complications, and to a complex of biopsychosocial factors directly related to the pandemic. In the second part of the article, as part of the review, the possibility of using nimesulide for the treatment of orofacial and facial pain during the COVID-19 pandemic is discussed. The choice of nimesulide is supported by 1) the likely coadjuvant effect of nimesulide in the treatment of COVID-19; 2) positive experience with the use of nimesulide in the treatment of facial and orofacial pain in the period preceding the COVID-19 pandemic; 3) the safety of using nimesulide in comorbid patients, who are the main risk group for the development and severe course of COVID-19.

Introduction. Understanding the clinical and psychological characteristics of migraine patients is essential for developing effective multidisciplinary treatment that includes psychological methods. The personality characteristics of migraine patients continue to be studied and discussed. The study of individual-psychological characteristics of personality in patients with migraine of different frequency is topical.
Aim. To assess clinical and psychological characteristics in patients with varying frequency of migraine.
Materials and Methods. Sixty migraine patients, mean age 32.92 ± 6.23 years, were included in the study. Depending on the frequency of migraine, all study participants were allocated to 1 of 3 groups: Group 1 – patients with rare episodic migraine; Group 2 – patients with frequent episodic migraine; Group 3 – patients with chronic migraine. All patients were interviewed and tested.
Results and discussion. There were no significant differences between the groups in terms of the mean values of neuroticism, psychoticism, extraversion or introversion. Most patients in each group were moderately neurotic and all others were highly neurotic; most patients were ambivalent, i.e., shared both introvert and extrovert personality traits, with the rest being either pure extrovert or pure introvert. None of the patients were psychotic (prone to inappropriate emotional reactions). In each group, patients with a normal temperament type and melancholic spectrum temperaments predominated.
Conclusion. Depressive and anxiety disorders are more common in chronic and frequent episodic migraine than in rare episodic migraine. Neuroticism, psychoticism and extraversion/introversion were found regardless of the frequency of migraine attacks.

The outbreak of the novel coronavirus infection pandemic has spread all over the world millions of people have been recovered from it that makes necessary the research of their health status after the acute infection phase. The accumulated data about previous coronavirus epidemics showed their prolonged impacton the nervous system with the manifestation of mental and neurological symptoms. Specialists from different countries from the beginning of the pandemic have revealed typical symptoms in patients recovered from coronavirus infection with negative tests still complained on residual respiratory, gastroenterological and psychoneurological symptoms that manifested with asthenic, cognitive, dissomnic and affective disorders, anosmia and changes in taste preferences. No correlation between infection severity and symptoms set in the reconvalescence period has been found. Different countries have been used different terms to describe it like prolonged, long, chronic covid.The leading medical centers have made their impact in this problem analysis During the two recent years a big international research base, including the data from electronic medical histories has been accumulated concerning COVID 19 reconvalescents health status. WHO has presented the postcovid 19 syndrome work definition, in its structure psychoneurological symptoms such as asthenia, anxietydepressive and cognitive disorders, insomnia play an important role. The healthcare provision for the patients with postcovid syndrome remains the issue needed further elaboration , the most promising treatment plan seems the combination of pharmacotherapy with psychosocial interventions. Tofizopam as a drug with anxiolytic, secondary precognitive and aniastenic effects can be recommended for the postocovid syndrome psychoneurological symptoms.

Stress is an integral part of every person’s daily personal and work life, and one of the important factors affecting health and longevity. Excessive or prolonged stress, exceeding natural regulatory capabilities and adaptive resources of the body, leads to changes in homeostasis and a wide range of problems, including metabolic syndrome, obesity, mental disorders, cardiovascular disease, etc. Given that stress in this context acts as a risk factor for these conditions, and they can be combined in a patient, it can be seen as the basis for the development of polymorbidity. Polymorbidity, the combination of two or more diseases in a patient, is currently regarded as one of the most serious problems of modern medicine, requiring from the doctor in-depth knowledge in various interdisciplinary areas. Polymorbidity is associated with more frequent use of medical care, lower quality of life, and a higher risk of premature mortality. In this regard, understanding the pathophysiology of stress and knowing how to correct it early is an urgent medical challenge that needs to be solved. The present work gives a brief overview of the organization and (patho-)physiology of the human stress system, discusses the role of stress in the development of polymorbidity, in particular its cardiometabolic phenotype, using the example of the relationship between acute and chronic psychological stress and the development of cardiovascular disease, describes ways of stress management in the early stages, including the use of the combined drug phenobarbital and ethylbromizovalerianate with a multimodal spectrum of action.

Introduction. The relevance of the study is determined by the increase of atypical forms of depression, which is especially characteristic of outpatient affective disorders. In this case, the frequency of occurrence of individual atypical depressive symptoms requires clarification.
Aim. To determinate the prevalence of atypical symptoms in patients with depressive disorder.
Materials and methods. Patients (87 subjects) with depressive disorder, aged 18–70, who gave inform consent. The selection criterion was the result of psychometric research using The Hospital Anxiety and Depression Scale (HADS): the study included patients who scored more than 7 points. Patients with severe organic insufficiency and neurological diseases, alcohol and substance abuse were excluded. The study used clinical psychometric and statistical methods. The main examination tool is stimulus material in the form of a table with a list of atypical depressive symptoms.
Results. Based on the psychometric assessment, patients were divided into two groups: patients with subclinical depression included 19 patients, patients with clinically severe depression included 68 patients. Among patients with subclinical depression, increased anxiety (89.5%), mood reactivity (84.2%), hypersonium (78.9%), hyperphagia (73.7%) and somatized symptoms (73.7%) were most often recorded. Among patients with clinically pronounced depression, increased anxiety (91.2%), somatized symptoms (80.9%), hypersonium (79.4%) and inverted daily rhythm (72.1%) were most common.
Conclusion. The data obtained confirm the high prevalence of symptoms of atypical depression among patients with depressive spectrum disorders. The frequent occurrence of anxious and somatized symptoms in the structure of depression, as well as hypersomnia, was demonstrated. It seems relevant to further study the prevalence of separate symptoms of atypical depression.

Insomnia is a public health problem and one of the most common complaints in medical practice. Sleep disturbances may manifest as difficulty falling asleep (sleep-onset insomnia), maintaining sleep continuity (waking in the middle of the night and difficulty going back to sleep) or waking too early in the morning long before the desired time (early morning insomnia). Insomnia can significantly affect daytime functioning, leading to waking up in the morning tired, reduced productivity, a tendency to make mistakes and have accidents, inability to concentrate, frequent daytime sleep and a poor quality of life. The etiology and pathophysiology of insomnia include genetic, environmental, behavioural and physiological factors. Although insomnia can affect any gender and age group, women and the elderly are more vulnerable and are more likely to develop insomnia. A detailed sleep history is key to assessing insomnia. Clinicians must be able to recognise sleep disturbances and rule out other sleep-related disorders. The aim of treating insomnia is to improve sleep and alleviate the distress or dysfunction caused by this disorder. Psychological therapy methods, drug therapy, or combinations of these methods can be used to treat insomnia. Some behavioural interventions are feasible in primary care, but lack of training in these methods limits their
use. Various natural and over-the-counter drugs, such as melatonin-based drugs, are used as sleeping pills. Melatonin has been evaluated as a sleeping pill in different doses, demonstrating a small but significant effect on sleep latency.

Sleep disorders and back pain are often found in the practice of various doctors specialties. Often these two conditions are comorbid. Sleep disorders can be both acute and chronic. To verify the state of insomnia, diagnostic criteria (MKRS-3) are proposed. Sleep disorder therapy is a complex task and includesnon-drug approaches (sleep hygiene, psychotherapeutic techniques, etc.) with more lasting effect. Drug therapy is considered as additional method of treatment using several groups of drugs. Doxylamine H1-receptor antagonists, is one of the well-known and promising drugs. The article describes two clinical cases of patients with back pain and concomitant sleep disorders. To relieve pain in both cases, standard therapy was prescribed, including NSAIDs, a muscle relaxants, B vitamins, and physiotherapy exercises. In order to normalize night sleep, the Doxylamine was additionally in a standard dosage. However, the second patient developed morning sleepiness while taking the standard dose, which required a dose reduction. Taking Doxylamine at a lower dosage effectively stopped sleep disorders and did not cause the development of drowsiness and lethargy.

Introduction. Scientific discussions about ways to improve the effectiveness and safety of osteoarthritis (OA) therapy do not stop. The article discusses the most controversial issues of the problem and presents the results of a study on the use of sodium hyaluronate in gonarthrosis.
Aim. To compare the clinical efficacy, tolerability and safety of the use of synovial fluid substitute of domestic manufacture and symptomatic slow-acting drugs (SYSADOA) in patients with gonarthrosis.
Study design. Prospective, comparative, randomized, single center study. The duration of the study was 12 months.
Materials and methods. The study included 180 patients with gonarthrosis, randomized into three groups. Study group: 50 patients treated with Ripart® sodium hyaluronate solution intra-articularly. Comparison group: 30 patients treated with SYSADOA, intraarticular. Control group: 100 patients treated with SYSADOA intramuscularly.
Results. The most rapid and pronounced decrease in the VAS index was obtained during sodium hyaluronate therapy: by 31% at the 1st week, by 48% by the end of the 2nd week, with a maximum decrease by 49.1% by the 3rd month (p < 0.001). After 12 months, a lower level of the VAS index was observed: 32% lower than before the start of therapy (t = 47.23; p < 0.001). Comparable results were observed in this group in terms of the dynamics of the AUSCAN/WOMAC index. The effectiveness of therapy in the comparison and control groups was lower (p < 0.05). In addition, the use of sodium hyaluronate provided a significant reduction in the need for taking NSAIDs: 20 patients completely stopped taking NSAIDs (40%), 25 (50%) – they began to take NSAIDs less often or reduced the dose of drugs by 2 times, after 12 months they continued taking NSAIDs only 20% of patients in this group (p < 0.05).
Сonclusions. Thus, Ripart® demonstrated high efficiency in reducing pain, contributed to a significant reduction in the need for NSAIDs in patients with gonarthrosis, and has a good safety profile.

The article presents a review of the basic data on the efficacy and safety of the drug tofacitinib, the place of the drug in the treatment of rheumatoid arthritis (RA) patients according to current international and Russian recommendations. Data on the mechanism of action of Janus kinase inhibitors, the spectrum of cytokines inhibited by tofacitinib is presented. The results of major randomised controlled trials demonstrating high clinical efficacy in patients who have not responded to methotrexate (MT) and other synthetic classical anti-rheumatic drugs (SCARDs), genetically engineered biologic drugs, are presented, with equal efficacy of tofacitinib when given as monotherapy or in combination with MT or other SCARDs, with adalimumab. The safety of tofacitinib with long-term treatment (up to 9.5 years) is analysed. The cardiovascular tolerability of tofacitinib is presented separately, considering the proposals discussed at the last EULAR 2022 Congress. The low incidence of serious cardiovascular adverse events, including venous thrombosis and thromboembolism over the long-term follow-up period, and the risk of these adverse events, which was no higher than on the selective Janus kinase inhibitor baricitinib, are presented. Changes in laboratory parameters (haemoglobin, neutrophil count, aminotransferase concentration) during tofacitinib administration are described. Domestic data on the use of tofacitinib in the treatment of RA patients is demonstrated. An association was shown between early clinical response to tofacitinib (5 mg twice daily) and a reduction in RA activity after 3 and 6 months in RA patients. Tofacitinib in real clinical practice showed early development of effect (by week 12) in the group of patients who did not respond to MT and in 60% of cases to genetically engineered biologic drugs, with respect to indicators of inflammatory activity of RA and functional status of patients. Domestic authors have noted the high safety of tofacitinib. A domestic generic version of the original drug tofacitinib has been reported to be registered for the same indications: RA, psoriatic arthritis, plaque psoriasis, ulcerative colitis.

The article discusses the prevalence of osteoarthritis of the joints of the hands. The modern aspects of pathogenesis and the leading role of inflammation in it are highlighted. The article assesses the risk factors for osteoarthritis of the joints of the hands. According to recent studies, one of the important factors that increase the risk of developing osteoarthritis of the joints of the hands are gender (in premenopausal women, due to a decrease in estrogen levels, a higher risk of developing osteoarthritis of the joints of the hands is determined compared to men of the same age) and obesity as one of the causes of systemic inflammation. The article draws attention to studies studying a wide range of serum biomarkers with diagnostic and prognostic value, as well as the role of synovitis imaging as a factor contributing to the progression of the disease. The article also discusses the latest recommendations of the leading professional communities of EULAR and ARC on the treatment of patients with osteoarthritis of the joints of the hands. According to modern principles, the treatment of patients should include a combination of pharmacological and non-pharmacological methods and is aimed not only at reducing pain and improving the functional state of the joints, the quality of life of patients, but also at preventing / slowing the progression of the disease. Attention is also drawn to the main provisions on the rational use of NSAIDs by leading Russian associations and communities, which focus on possible adverse reactions of NSAIDs. The article pays great attention to the use of chondroitin sulfate as a substance recommended for the treatment of osteoarthritis of the joints of the hands by leading international communities. The authors present the results of a number of studies proving the safety and effectiveness of the use of chondroitin sulfate in osteoarthritis of the joints of the hands.

Introduction. Joint hypermobility is a common polyetiological condition that can be accompanied by pain in the joints and lead to the early onset of osteoarthritis. The study of the comorbidity of JH and somatic pathology, in connective tissue dysplasia, is fragmentary and relevant for optimizing the classification and criteria for early diagnosis of this condition.
Aim. Analysis of the frequency of phenotypic signs of uCTD in individuals with JH.
Materials and methods. A cross-sectional study of 35 men (21.77 ± 0.60 years) and 226 women (21.42 ± 0.18 years) was carried out. 2 groups were formed – with the presence of HMS (n = 156) and the control group (n = 105). JH was determined according to the Beighton scale, phenotypic signs of uCTD – according to the modified table by T. Kadurina.
Results. Statistically significant differences were found in the frequency of occurrence of phenotypic signs of CTD in individuals with hypermobility – a decrease in BMI < 18 kg/m² (p = 0.0001), skin hyperelasticity (p = 0.0001), ptosis of internal organs (p = 0.038), dolichostenomyelia (p = 0.010), hyperkyphosis/hyperlordosis (p = 0.003), joint crunch (p = 0.009), GERD (p = 0.021) and arterial hypotension (p = 0.0001). Mild myopia was more common in the control group (p = 0.020), and severe myopia was more common in the JH group (p = 0.003). Keloid scars were more common in the group with severe JH (p = 0.021).
Conclusions. In patients with joint hypermobility, phenotypic manifestations of connective tissue dysplasia were revealed, most often involving the musculoskeletal system (dolichostenomelia, crunching in the joints, curvature of the spine) and skin (hyperelasticity, keloid scars).

Zoledronic acid is a third-generation amino-containing BF that has been used to treat patients with osteoporosis for more than 15 years. Over the years, numerous experimental and clinical studies have proven the high efficacy of the drug in osteoporosis, both in women of various age groups, and in men, with primary and secondary osteoporosis, in patients with varying degrees of bone loss and risk of fractures. Intravenous infusions of zoledronic acid have been shown to result in a rapid gain of bone mass, a significant reduction in the risk of low-energy fractures of the vertebrae (spine), proximal femoral and nonvertebral fractures on the whole. However, in recent years, the use of the drug has significantly decreased, which is associated both with the lack of awareness of primary care physicians about the possibilities of this drug, and the fear of such complications of its use as atypical fractures and osteonecrosis of the jaw bones. The presented review aims to increase the knowledge of physicians regarding the mechanism of action of zoledronic acid, the regimens for prescribing the drug in various forms of osteoporosis and fractures against its background. The given clinical example shows the ability of zoledronic acid (osteostatics) to increase the mass of not only cancellous, but also the cortical bone of the proximal femur, which increases the role of zoledronic acid in the prevention of recurrent fractures. On top of that, the prolonged effect of the drug allows, when the desired therapeutic effect is achieved, to reduce the frequency of prescribing according to the ‘drug holiday’ principal, decreasing economic expenditures and medical and social burden.

Intravenous thrombolysis (IT) with recombinant tissue plasminogen activator has remained the main method of reperfusion therapy in ischaemic stroke for a quarter of a century. The main trends in the use of IT in recent years are the expansion of the therapeutic window using additional methods of neuroimaging, reducing the number of contraindications and introduction into clinical practice of bolus forms of drugs. Providing IT to the largest number of patients should be considered a major challenge for the primary vascular department. This article presents 10 clinical rules for extending IT in stroke while ensuring its efficacy and safety: 1) conduct IT in suspected stroke; 2) conduct IT in patients over 80 (and even 90) years of age; 3) conduct IT in minor but disabling stroke; 4) conduct IT in minor vertebrobasilar stroke and central acute vestibular syndrome; 5) perform IT in cases of large artery occlusion; 6) perform IT in suspected lacunar stroke and chronic neuroimaging changes (lacunas, white matter hyperintensity, atrophy); 7) reduce door-to-needle time, use thrombolytics with bolus administration; 8) use neuroimaging options (CT perfusion, MR perfusion, MR DWI/FLAIR) to expand the therapeutic window; 9) ensure the safety of IT; 10) be prepared for complications. Increasing the frequency of IT should not be seen as a goal, but intensifying the use of this method of treatment is associated with the improvement of all areas of the diagnostic and treatment process in the clinic and the improvement of stroke outcomes.