Infective endocarditis (IE) caused by Gram-negative bacteria is a rare and insufficiently characterized form of endocarditis. The literature review presents data on the frequency, course, risk factors, diagnosis and treatment of both IE caused by the HACEK microorganisms (Haemophilus spр., Aggregatibacter spp., Cardiobacterium hominis, Eikenella corrodens, Kingella) and other Gram-negative bacteria. Gram-negative bacteria are the cause of 3.6–13.6 % IE cases (HACEK microorganisms in 0.8–3 % of IE cases in adults, non-HACEK in 1.8–3.9 %). Patients with IE caused by the HACEK microorganisms are younger, their disease is not associated with previous in-hospital treatment and is subacute with favorable prognosis (intrahospital mortality is 2–3 %). HACEK microorganisms mostly retain sensitivity to many antibiotics. Risk factors of IE caused by HACEK microorganisms are dental interventions, heart disorders, valve prostheses and other implanted cardiac devices. IE caused by non-HACEK Gram-negative bacteria is more common in elderly with concomitant disorders and usually is acute; intrahospital mortality is 13–36.5 %. Risk factors of IE caused by non-HACEK microorganisms are valve prostheses, electrical pacemakers, venous and central catheters, recent in-hospital treatment, Gram-negative bacteremia, decreased immunity, drug abuse, urinary infection, alcoholism, cirrhosis of the liver, removed spleen, consequences of dog and cat bites, working with the soil. Among Gram-negative non-HACEK bacteria causing IE, 28 % have multi-drug resistance (MDR / XDR) against antibiotics. Therefore, Gram-negative bacteria rarely cause IE but during selection of empiric therapy in patients with IE with corresponding risk factors, probability of Gram-negative causative microorganisms in IE etiology should be taken into account.

The new coronavirus infection (COVID-19) is associated with a wide spectrum of various clinical manifestations including involvement of the musculoskeletal system which can persist for a long time after the infection. Supposedly, pathogenesis of musculoskeletal manifestations of COVID-19 is primarily caused by systemic inflammation accompanied by cytokine hyperexpression (interferon γ, interleukins 1β, 6, 8, 17, tumor necrosis factor α), as well as hypoxia leading to overproduction of inflammatory cytokines, activation of bone reabsorption by osteoclasts and subsequent decrease of mineral bone density and osteonecrosis in some cases. Additionally, some drugs prescribed to patients with COVID-19 (some antiviral drugs and glucocorticoids) should also be taken into account as they can lead to development of musculoskeletal pathology. In the acute period of COVID-19, myalgias are common, but in rare cases myositis with proximal muscular weakness and increased levels of creatine phosphokinase, lactate dehydrogenase can occur. Arthralgias in the acute period of COVID-19 are rarer than myalgias. In the studies of clinical manifestation of COVID-19, frequency of arthralgias and myalgias in the acute period is between 15.5 and 50 %. After COVID-19, frequency of arthralgias and myalgias gradually decreases, however there are cases of long-term joint and muscle pains, as well as post-viral arthritis, development of arthritis in the context of various autoimmune disorders. Myalgias and arthralgias during COVID-19 usually regress spontaneously and in most patients do not require prescription of antipain medications, but in some cases pain management is necessary. Use of non-steroid anti-inflammatory drugs and vitamin D during COVID-19 is a safe and effective method of pain management, including myalgia and arthralgia. Rehabilitation programs play an important role in improvement of functional state and patient recovery after moderate and severe COVID-19.

Heart failure (HF) remains a serious problem in Russian and world health care due to the growing morbidity and mortality from complications of heart failure, despite the development and implementation of programs for the early detection and treatment of heart failure in asymptomatic patients. Currently, a large number of new biological markers have been studied that could serve as a laboratory tool for diagnosing and predicting the course of heart failure, but only brain natriuretic peptides have found application in real clinical practice. Renalase is a recently discovered cytokine that is synthesized by the kidneys and released into the blood. To date, seven subtypes of renalase have been found, each of which plays a different physiological role in the human body. Renalase is usually positioned as a signaling molecule that activates cytoprotective intracellular signals, leading to a decrease in blood pressure and protection of the heart muscle. The concentration of renalase freely circulating in the bloodstream of an adult is approximately 3–5 ng / ml. Currently, the level of renalase is determined by the enzyme immunoassay with a detection range of 3.12 to 200 ng / ml, while the minimum detectable concentration of the marker is less than 1.38 ng / ml. The presence of missense polymorphism of renalase is associated with myocardial dysfunction. Data from animal and human studies have shown that renalase plays a key role in the metabolism of catecholamines and in cardioprotective processes. Studies have shown the contribution of renalase to the occurrence of cardiovascular diseases: ischemic heart disease, arterial hypertension, diabetes mellitus, and aortic stenosis. Moreover, detailed protocols of multicenter prospective studies have demonstrated that functional polymorphism of the renalase gene was associated with myocardial hypertrophy in patients with aortic stenosis, hypertension, metabolic syndrome, unstable angina pectoris and stable forms of coronary artery disease, as well as in patients receiving renal replacement therapy. Based on these data and further studies, renalase has been proposed as a predictive biomarker of ischemia in patients with coronary microvascular dysfunction, as well as a predictor of clinically significant progression of chronic kidney disease in patients with cardiovascular diseases.

Our review presents data on the role of renalase in heart failure. Further study of the structure and function of renalase, as well as future clinical studies, will allow determining the diagnostic, prognostic and, possibly, therapeutic significance of this biological marker in HF and other cardiovascular diseases.

Pain syndrome in the shoulder occurs in every 5th adult and is the 2nd most frequent reason for seeking primary medical care among all musculoskeletal disorders. Group of local causes of pain syndrome in the shoulder area. The starting point for differential search is patient’s age. For persons younger than 40, the most common causes are joint instability (dislocations / subluxations), as well as mild damage of the rotator cuff muscles due to injury. Patients older than 40 have an increased risk of severe chronic disorders of the above-mentioned muscles, adhesive capsulitis, and osteoarthritis of the shoulder joint. Treatment of shoulder joint and soft tissue pathology is nosological in nature and has to be justified by pathogenesis. Chondroreparants are a new class of pharmaceuticals based on hyaluronic acid modified by low molecular weight compounds using solid-phase stabilization. During physical stabilization (mechanosynthesis) of hyaluronic acid, chemical crosslinkers are not used, which leads to high tolerability and safety. Modified hyaluronic acid in Hyalrepair formulas has a number of structural features leading to its slower biodegradation in the tissues. Chondroreparant Hyalrepair-10 consists of hyaluronic acid, ascorbyl phosphate, zinc, cysteine, and glutathione; Hyalrepair- 2 consists of hyaluronic acid, ascorbyl phosphate, L-proline, L-lysine, and glycine. Use of intra-joint and periarticular injection of hyaluronic acid can be an effective approach in combination pathogenesis-directed therapy of the shoulder and soft tissues.

Currently, one of the key methods of treating a patient with ST-elevation myocardial infarction is to restore blood flow to the infarct-related artery as quickly, completely and steadily as possible. However, in some cases, it is not possible to achieve adequate myocardial reperfusion, despite the restoration of coronary blood flow. This phenomenon was named no-reflow. Due to the lack of a unified approach to the diagnosis of no-reflow, its occurrence varies widely – from 2 to 44 %. Failure to achieve adequate myocardial perfusion leads to a higher mortality rate – from 7.4 to 30.3 %, as well as to more aggressive remodeling of the myocardium. For a long time, distal embolization in percutaneous coronary intervention was considered one of the leading mechanisms. However, the routine use of protective devices did not show a pronounced effect on the outcome and prognosis, although it is justified in certain clinical situations. Ischemic injury directly plays a significant role due to overload of cardiomyocytes with calcium, cellular edema, necrosis and apoptosis, which is significantly aggravated by myocardial reperfusion and forms obstruction at the level of the microcirculatory bed. More data is being accumulated about immune-mediated injury through activation of cellular immunity, intense inflammation and thrombosis in situ. Despite the success in the animal experiment, the clinical use of certain groups of drugs showed an ambiguous results. According to the latest recommendations European Society of Cardiology / European Association for Cardio-Thoracic Surgery (ESC / EACTS) 2018, GPIIb / IIIa platelet receptor inhibitors are recommended in the case of no-reflow. Besides this, according to the literature nicorandil and sodium nitroprusside, as well as IL-1β antagonists, seem to be promising. As a non-drug therapy, selective intracoronary hypothermia also has shown its effectiveness and safety in a pilot study. To date, it is clear that the no-reflow phenomenon is a manifestation of a complex cascade of reactions, including ischemic, reperfusion and immune-related injury, as well as distal embolization. Considering its significant contribution to the frequency of adverse outcomes and late complications, it seems necessary to introduce unified approaches to the diagnosis, prevention and treatment of no-reflow, which requires high-quality clinical studies.