Subjects and methods. The study enrolled 61 inpatients diagnosed with RA (according to the 1987 American College of Rheumatology criteria) who were treated at the V.A. Nasonova Research Institute of Rheumatology; in so doing, high-resolution computed tomography revealed lung changes as a ground glass pattern in 15 patients, reticular striation, traction bronchoectases, and lung tissue changes as honeycomb ones in 25 patients; no lung abnormalities were found in 21 patients. DAS28 was applied to determine the inflammatory activity of RA. The RA patients underwent X-ray studies of the hand, foot, and chest, by using accordingly X-Ray unit and spiral computed tomography scanner (section thickness, 0.65 mm). External respiration function (ERF) indicators were studied with plethysmograph. IgM rheumatoid factor was measured using an immune nephelometer. Serum anti-cyclic citrullinated peptide antibodies were assayed by immunochemiluminescence technique on a Cobas e411 analyzer. The xMAP technology using a BioPlex200 analyzer was employed to determine the serum concentrations of 27 cytokines in 15 patients with subclinical IPI and in 25 with clinical IPI. 

Results and discussion. The major respiratory signs in patients with IPI proved to be cough (24 %), expectoration (20 %), dyspnea (16 %), and crepitation (64 %) on auscultation. Three patients with subclinical IPI were found to have crepitation on auscultation. Respiratory symptoms were absent in the RA patients without IPI. It should be noted that there are a larger number of RA patients with a high smoking index among the RA patients with IPI than among those without IPI (p < 0.05). Investigation of ERF indicators revealed a statistically significantly lower lung diffusing capacity (LDC) in the RA patients with subclinical IPI than in those without IPI (p < 0.05). Other ERF indicators showed no significant deviations of the reference values. LDC and total lung capacity appeared to be statistically significantly lower in the RA patients with clinical IPI than in those without IPI (p < 0.005 and p < 0.05, respectively). The differences in LDC failed to reach the statistical significance in the RA patients with subclinical IPI and in those with clinical IPI. Examination of cytokine concentrations revealed a tendency towards the higher levels of interleukin-7 (IL-7), IL-12, IL-13, IL-15, IL-17, and platelet-derived growth factor BB in the RA patients with subclinical IPI than in those with clinical IPI. At the same time, the differences in the concentration of vascular endothelial growth factor (VEGF) turned out to be statistically significant (p < 0.05). Moreover, the levels of IL-10, interferon-γ, and RANTES proved to be significantly higher in the patients with clinical IPI than in those with subclinical IPI (p < 0.008; p < 0.0003, and p < 0.03, respectively). 

Conclusion. Thus, the problem associated with the early diagnosis and timely adequate treatment of IPI in patients with RA is relevant. The preclinical form of IPI in patients with RA is associated with ground glass radiological and tomographic patterns and lower LDC values. VEGF may lay a claim to the role of a predictor of pulmonary fibrosis in the RA patients with subclinical IPI. 

Objective: to study the specific features of the daily arterial stiffness (AS) profile in men with different phenotypes of chronic obstructive pulmonary disease (COPD) concurrent with hypertension.
Subjects and methods. The investigation enrolled 78 male patients with COPD and hypertension. The patients were divided according to COPD phenotypes into 2 groups: 1) COPD patients with emphysema; 2) those with bronchitis. The exclusion criteria were less than 40 years and more than 80 years of age; diabetes mellitus; coronary heart disease; vascular diseases; an exacerbation of chronic diseases; bronchial and pulmonary diseases of another etiology. The patients underwent 24-hour blood pressure and AS monitoring, external respiratory function testing: spirography with a short-acting β2-agonist test, a six-minute walk test at baseline and after a hemoglobin oxygen saturation test, and a CAT test. Results. The patients of both groups were observed to have a statistically significant increase in (dP/dt)max as compared to those of the control group (p < 0.05; p < 0.01) in both the daytime and nighttime. In these periods, the COPD patients with emphysema had a higher AIx than those with bronchitis (p < 0.001). There was a statistically significantly (p < 0.001) higher AIx in the nighttime than in the daytime in Groups 1 and 2 patients. 

Conclusion. The patients with different COPD phenotypes were noted to have impaired arterial elastic properties, circadian AS changes with predominantly nocturnal impaired vascular stiffness. Relationships were found between 24-hour AS values and clinicoanamnestic findings. 

Hereditary connective tissue disorders (HCTDs) are a genetically and clinically diverse group of diseases, which encompasses common congenital disorders of fibrous connective tissue structures. Out of the whole variety of the clinical manifestations of NCTDs, only differentiated monogenic syndromes with the agreed guidelines for their diagnosis have been long the focus of the medical community’s attention. Many unclassified forms of the pathology (dysplasia phenotypes) have been disregarded while assessing a person’s prognosis and defining treatment policy. With no clear definition of NCTDs or their approved diagnostic algorithm, it is difficult to study their real prevalence in the population, to compare literature data, and to constructively discuss various scientific and practical aspects of this disease. Efforts to systematize individual clinical types of NCTD and to formulate their diagnostic criteria are set forth in the All-Russian Research Society Expert Committee national guidelines approved in 2009 and revised in 2012. The paper gives current views on the nomenclature of NCTDs, considers diagnostic criteria for both classified monogenic syndromes (Marfan's syndrome, Ehlers–Danlos' syndrome, MASS phenotype, primary mitral valve prolapse, joint hypermobility syndrome) and unclassified dysplasia phenotypes (MASS-like phenotype, marfanoid appearance, Ehlers–Danlos-like phenotype, benign joint hypermobility syndrome, unclassified phenotype). The above abnormalities are presented as a continuous list drawn up in the decreasing order of the degree of their clinical manifestations and prognostic value (the phenotypic continuum described by M.J. Glesby and R.E. Pyentz): from monogenic syndromes through dysplasia phenotypes to an unclassified phenotype. Emphasis is laid on the clinical NCTD identification difficulties associated with the lack of specificity of external and visceral markers of connective tissue asthenia and with the certain conventionality of NCTD diagnostic criteria. Debatable problems in the diagnosis and interpretation of the clinical significance of individual NCTDs are represented. 

The communication between the median and ulnar nerves on the forearm, known as the Martin–Gruber anastomosis, is widespread in the general population. Despite the fact that this connection is described by anatomists in XVIII century, its importance has only recently been appreciated because of the widespread of the electrophysiological techniques in clinical practies. However, in the Russian literature aspects of its practical value described so far is not enough. This article deals with the prevalence of the anastomosis, its anatomical and electrophysiological classification, options innervation of muscles of the hand, is carried out through him, described electrophysiological methods and criteria for its diagnosis, including the collision technique, in healthy subjects and patients with lesions of the median and ulnar nerves, given its practical value. Such a course of nerve fibers through this anastomosis can have a significant impact on the clinical manifestations in patients with lesions of the median and ulnar nerves, as well as the results of an electrophysiological study. Martin–Gruber anastomosis provides variability innervation muscles of the hand, which can make it difficult topic diagnostic damage to the median and ulnar nerves, in addition, because of the connection between the nerves of the clinical presentation may not reflect the extent of their defeat: the hand muscles function can be preserved with full nerve damage or, conversely, significantly disrupted with minimal nerve lesions. Moreover, different electrophysiological findings on patients with pathology of the median or ulnar nerves in the conditions of functioning anastomosis may also complicate the interpretation of the clinical data. Thus, knowledge of the anatomy and physiology of the Martin–Gruber communication as necessary for the electrophysiologist for correct interpretation of the finding and the clinician to accurately diagnose the pathology of the median and ulnar nerves and correct choice of treatment. 

Objective: to study the clinical efficacy, immunogenicity, and safety of a 23-valent pneumococcal vaccine in patients with rheumatoid arthritis (RA).
Subjects and methods. The investigation enrolled 70 patients (55 women and 15 men) aged 23–70 years, including 40 patients with RA and 30 people without systemic inflammatory rheumatic diseases (a control group) who had a recent history of 2 and more cases of lower respiratory tract infections (bronchitis, pneumonia). When included, all the patients received anti-inflammatory therapy with methotrexate (MT) (n = 24), leflunomide (LEF) (n = 6), or MT + tumor necrosis factor-α (TNF-α) inhibitors (n = 10). A single 0.5-ml dose of the 23-valent pneumococcal vaccine Pneumo-23 (Sanofi Pasteur) was administered subcutaneously or intramuscularly during continuous MT or LEF therapy for the underlying disease or 3–4 weeks before the use of a TNF-α inhibitor. During control visits (1 and 3 months and 1 year after administration of the vaccine), the patients underwent physical examination and routine clinical and laboratory studies. 

Results. No clinical and radiological symptoms of pneumonia were recorded in any case during a 12-month follow-up. The RA and control groups showed a more than 2-fold increase in anti-pneumococcal antibody levels 1 year after vaccination. The vaccine was well tolerated by 50 patients. Sixteen patients were observed to have pain, cutaneous swelling and hyperemia and 4 had subfebrility. There were neither episodes of RA exacerbation nor new autoimmune disorders during the follow-up. 

Conclusion. The findings suggest that 23-valent pneumococcal vaccine shows a good clinical efficacy, adequate immunogenicity, and good tolerability in the patients with RA. 

Objective: to describe a clinical case of evolving acute eosinophilic myocarditis simulating coronary heart disease.
Subjects and methods. Patient B. aged 62 years was admitted to Intensive Care Unit Fifteen, N.I. Pirogov First Moscow City Clinical Hospital, by being transferred from Thailand with a referral diagnosis of acute myocardial infarction made on November 1, 2012, with complaints of pressing and aching heart pains. At a Phuket hospital, his electrocardiogram recorded atrial fibrillation; indirect cardiac massage, electric pulse therapy, and mechanical ventilation were performed. After being admitted to the N.I. Pirogov First Moscow City Clinical Hospital, the patient underwent examination: estimation of laboratory indicators over time, electrocardiography (ECG), echocardiography, Holter ECG monitoring, and myocardial scintigraphy.
Results. The patient had a history of an allergic reaction as urticaria to the ingestion of fish products. His examination showed practically all diagnostic criteria for allergic myocarditis: hypereosinophilia (the admission level of eosinophils was 9% with their further normalization); the characteristic clinical presentation of myocarditis (pressing retrosternal pain); elevated levels of cardiac specific enzymes (creatinine phosphokinase-MB, lactate dehydrogenase, troponin T); ECG changes – myocardial hypokinesis in the acute period, followed by its pattern normalization. of the pattern. Myocardial scintigraphy (by taking into account the fact that the patient had had a new allergic reaction episode, the investigators decided not to perform coronary angiography) revealed decreased radiopharmaceutical accumulation in the lower left ventricular wall in the right coronary arterial bed; perfusion remained in the other myocardial walls.
Conclusion. This clinical case reflects the specific features of the course of and difficulties in the diagnosis of acute allergic myocarditis that, in most cases, has no specific clinical manifestations and may mimic different diseases. 

Acute stroke manifesting as focal neurological deficit is a leading cause of death and disability. Of interest is the problem of asymptomatic cerebral infarctions (AСI), in which there is focal medullary involvement unaccompanied by the development of focal symptoms. The role of AСI as a marker for the progression of vascular dementia and for the further development of symptomatic stroke has not been adequately explored. There are current instrumental (neuroimaging) criteria for diagnosing AСI. An update on the risk factors of AСI and their association with the further course of cerebrovascular involvement is analyzed. The results of a number of prospective studies conducted in the countries of Asia and Europe to investigate risk factors for AСI and their prognostic value are considered in detail. There is a relationship between hypertension, blood pressure instability, type 2 diabetes mellitus, some other factors, and a significantly increased risk for AСI. Based on the results of analyzing the data available in the literature, the authors demonstrate the association of prior AСI with the higher rates of progressive vascular cognitive impairments. A correlation is shown between prior AСI and an increased risk for further development of ischemic stroke accompanied by its clinical symptoms, which leads to disability. 

It is suggested that it is advisable to implement measures for secondary cardiovascular disease prevention, including the administration of antiaggregatory and antihypertensive agents, in patients with AСI. 

Vitamin metabolic disorders can cause diverse dysfunctions of both the peripheral and central nervous systems. There is conclusive evidence that cyanocobalamin (vitamin B12) and folic acid deficiencies may lead to diminished cognitive functions even to the extent of developing dementia. Cognitive impairments may be accompanied by involvement of other regions of the central nervous system, the corticospinal tract in particular, less frequently by brainstem and cerebellar disorders. Changes in nervous system functions in the presence of cyanocobalamin deficiency may predominate in the clinical picture, ahead of the occurrence of hematological changes. The paper considers the possible mechanisms for involvement of brain neurons in deficiency of cyanocobalamin and in that of folic acid in particular in patients with hyperhomocysteinemia. The low serum concentration of folic acid or cyanocobalamin in the elderly raises the risk of developing Alzheimer’s disease in future (by almost twice) and vascular dementia. The authors give the results of randomized clinical trials evaluating the efficacy of the vitamins used in patients with cognitive impairments. Thus, there are data that the use of cyanocobalamin in patients with lacunar infarcts and moderate cognitive impairments may give rise to their complete recovery and reduce the risk of depressive disorders. Intramuscular cyanocobalamin used in a daily dose of 1000 μg for 5 days, then 1000 μg once monthly is demonstrated to be efficacious. This therapy may be effective in patients with different types of dementia and cognitive diminution, primarily in those with these conditions and its serum concentration of less 150 pmol/l. Among the side effects while taking folic acid, there may be higher incidence rates of convulsive attacks. A number of trials have shown the efficacy of cyanocobalamin, pyridoxine, and folic acid in preventing acute cerebral ischemic episodes; however, not all the investigations could confirm this relationship. This may be related to patients’ age, therapy duration, blood inflammatory marker concentrations, and other factors.

The paper considers the problems of comorbidities in patients with rheumatoid arthritis (RA). Two or more RA-related conditions were diagnosed according to the results of the QUEST-RA program implemented in 34 countries. Osteoarthritis along with hypertension, hyperlipidemia, and osteoporosis was detected among the most commonly diseases. Owing to expanded diagnostic capabilities, the recognition and treatment of the comorbidities have recently received much attention, as embodied in the draft Association of Rheumatologists of Russia Guidelines for RA management (2014; Part 1). The concept and major characteristics of secondary osteoarthritis in RA are analyzed. It is precisely the inflammatory process and underlying disease-related risk factors, including treatment, that have impact on the development of secondary osteoarthritis and patients’ quality of life as a whole. All this allows an inference about the mechanisms closely intertwined with the underlying disease for the development of secondary osteoarthritis, which initiates cartilage damage and further remodeling. Primary and secondary osteoarthritis was comparatively analyzed. Particular emphasis is placed on current cartilage biomarkers, their diagnostic value and role in monitoring the efficiency of treatment in clinical trials. The paper provides a comparative analysis of detectable serum and urine biomarkers according to the results of the complex analysis made by the National Institutes of Health. Particular attention is given to cartilage oligomeric matrix protein (COMP). Foreign authors’ investigations suggest that there is a relationship between serum COMP levels and disease severity and joint X-ray changes. There is evidence for the efficacy of hyaluronic acid used in the treatment of secondary osteoarthritis in patients with RA. 

Myocardial infarction and ischemic stroke remain to be of the greatest medical and social importance because of their high prevalence, disability, and mortality rates. Intractable thrombotic occlusion of the respective artery leads to the formation of an ischemic lesion focus in the tissue of the heart or brain. Emergency reperfusion serves to decrease a necrotic focus, makes its formation reversible, and reduces patient death rates. The paper considers main reperfusion therapy lines: medical (with thrombolytic drugs) and mechanical (with primary interventions) one and their combination in treating patients with acute myocardial and cerebral ischemia. Each reperfusion procedure is discussed in view of its advantages, disadvantages, available guidelines, and possibilities of real clinical practice. Tenecteplase is assessed in terms of its efficacy, safety, and capacities for bolus administration, which allows its use at any hospital and at the pre-hospital stage. Prehospital thrombolysis permits reperfusion therapy to bring much closer to the patient and therefore aids in reducing time to reperfusion and in salvaging as much the myocardial volume as possible. The rapidest recovery of myocardial and cerebral perfusion results in a decreased necrotic area and both improved immediate and late prognosis. The results of randomized clinical trials studying the possibilities of the medical and mechanical methods to restore blood flow are analyzed in the context of evidence-based medicine. The reason why despite the available contraindications, limited efficiency, and the risk of hemorrhagic complications, thrombolytic therapy remains the method of choice for prehospital reperfusion, an alternative to primary percutaneous coronary intervention (PCI) if it cannot be carried out in patients with myocardial infarction at the stated time, and the only treatment ischemic stroke treatment that has proven its efficiency and safety in clinical trials is under discussion. The benefits of a novel pharmacoinvasive approach to treating patients with acute coronary syndrome, as well as possible promises for its use to manage patients with ischemic stroke are depicted. The main results of a large STREAM trial, showing that early prehospital thrombolysis in conjunction with tenecteplase administration and subsequent PCI enables effective myocardial reperfusion in patients with ECG ST-segment elevation acute coronary syndrome within 3 hours after the occurrence of the first symptoms of the disease and in the absence of a chance of doing primary PCI within one hour after the first medical contact, are given and discussed. Reperfusion therapy for ischemic stroke now implies the preference of systemic thrombolytic therapy with recombinant tissue plasminogen activator. The established inadequate efficiency and safety of this technique lend impetus to a search for new approaches and novel fibrinolytic agents. Tenecteplase is a probable alternative to alteplase in treating patients with ischemic stroke.