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Meta-analysis combines the results of several scientific studies to obtain a summary quantitative estimation of effect size in order to compare the results of several studies and to identify patterns among them and possible sources of biases. Since the research teams, patients, research protocol, clinical guidelines and time intervals are often different between original scientific studies all these sources of difference can influence the results of each study, causing statistical heterogeneity. Meta-analyses are the highest level of credibility within evidence-based medicine, as they allow us to take into account the influence of many confounding factors and publication biases on the true effect size. Understanding the possible sources of erroneous conclusions in papers will allow researchers to analyze the results of such studies correctly and properly plan their own experiments. In this article the reader will be introduced to methods for identifying and quantifying hidden heterogeneity, such as subgroup analysis and meta-regression. In addition, the reader will learn how to calculate effect size in studies, estimate publication bias mathematically and graphically, and incorporate this estimate into the overall average effect size estimate in meta-analyses.

Libman–Sachs endocarditis (nonbacterial thrombotic endocarditis, NBTE) may be one of the cardiac manifestations of systemic lupus erythematosus (SLE). It is characterized by the presence of sterile platelet thrombi on previously normal heart valves. The diagnosis of NBTE is difficult as it is often asymptomatic until complications such as systemic emboli or valvular dysfunction occur. Patients with Libman–Sachs endocarditis and SLE are treated with immunosuppressive and anticoagulant therapy and, if it is ineffective, surgical treatment.A clinical case of SLE and Libman–Sachs endocarditis is presented. The clinical manifestations, diagnostic methods and treatment of NBTE in SLE are discussed. The difficulties in differential diagnosis and selection of optimal treatment tactics faced by physicians are highlighted.

The aim of the study was to evaluate the clinical manifestations and survival of patients with giant cell arteritis (GCA).Methods. A retrospective study included 166 patients with newly diagnosed GCA. Clinical, laboratory and instrumental data, three sets of classification criteria were used to confirm the diagnosis: the American College of Rheumatology (ACR) 1990, the revised ACR criteria of 2016 and/or the new ACR and European Alliance of Associations for Rheumatology (EULAR) 2022 criteria. Some of the patients underwent instrumental investigations: temporal artery ultrasound Doppler (n=61), contrast-enhanced computed tomography (CT) (n=5), CT angiography (n=6), magnetic resonance imaging (n=4), magnetic resonance angiography (n=3) and 18F-FDG positron emission tomography/CT (n=47). Overall and recurrence-free survival were analyzed using survival tables, Kaplan – Meier method.Results. The most frequent first manifestations of GCA were headache (81.8%), weakness (64%), fever (63.8%) and symptoms of rheumatic polymyalgia (56.6%). Changes of temporal arteries in color duplex scanning were detected in 44 out of 61 patients. GCs therapy was performed in all patients who agreed to be treated (n=158), methotrexate was used in 49 out of 158 patients, leflunomide – in 9 patients. In 45 (28.5%) out of 158 patients a stable remission was achieved as a result of GCs monotherapy, in 120 (75.9%) patients long-term maintenance therapy with GCs was required to prevent exacerbations, including 71 (44.9%) patients – in combination with methotrexate or other immunosuppressive drugs. The follow-up period of patients with a history of relapses was 21.0 (8.0–54.0) months. Relapses developed in 73 (46.2%) patients. The overall one-year survival rate was 97.1% [95% confidence interval (CI): 94.3; 99.9], and the five-year survival rate of patients was 94.6% [95% CI: 90.2; 99.0]. The one-year relapse-free survival rate was 86.4% [95% CI: 80.5; 92.3], and the five-year relapse-free survival rate was 52.4% [95% CI: 42.0; 62.8]. 12 (7.2%) of 166 patients died. The cause of death was myocardial infarction in two patients, stroke in two patients, and breast cancer in one patient; in the remaining seven cases, the cause of death was not determined.Conclusion. Given the high frequency of disease exacerbation, patients with GCA require long-term follow-up, especially during the first year after diagnosis.

Objective – to evaluate the long-term outcomes of HCV eradication with direct-acting antivirals (DAAs) in patients with hepatitis C-associated cryoglobulinemic vasculitis (HCV-CV)Materials and methods. We retrospectively assessed 48 patients with HCV-CV treated with DAAs. The activity of HCV-CV was assessed by using Birmingham Vasculitis Activity Score version 3 (BVAS v. 3). In patients with HCV-CV the rate of sustained virologic (defined as undetectable HCV-RNA levels 12 weeks after treatment cessation) and immunological (defined as absence of circulating cryoglobulins, rheumatoid factor and normal C4 level) response; and the rate of complete (defined by a BVAS v. 3 score of 0) and partial (defined as BVAS v. 3 score

Meta-analysis is one of the concepts of scientific methodology, and is a frequent but optional component of systematic reviews of empirical research. It joins the results of several scientific studies and tests one or more interrelated scientific hypotheses using quantitative (statistical) methods. This analysis can either use primary data from the original studies or published (secondary) results of studies dealing with the same problem. Meta-analysis is used to obtain an estimate of the magnitude of an unknown effect, and compare the results of different studies, identifying patterns or other relationships in them, as well as possible sources of disagreement. Meta-analyses are the highest level of credibility within evidence-based medicine (EBM), so meta-analysis results are considered as the most reliable source of evidence. Understanding all the procedures of a meta-analysis will allow researchers to analyze the results of such studies correctly, as well as formulate tasks when conducting meta-analyses on their own. In this article the reader will be introduced to key concepts such as weighted effects, heterogeneity, the different types of statistical models used, and how to work with some of the types of plots produced in meta-analyses.

The aim of the study was to assess the incidence of arterial lesions of various localizations in patients with giant cell arteritis (GCA) according to positron emission and computed tomography (PET/CT) with 18F-fluorodeoxyglucose (18F-FDG).Methods. Patients over 50 years of age diagnosed with GCA (with or without polymyalgia rheumatica) were included in a retrospective study. Damage to extracranial arteries was assessed based on the accumulation of 18F-FDG in the walls of large vessels according to PET/CT data.Results. The study included 47 patients, 14 (30%) men and 33 (70%) women, with a median age of 65 [57; 68] years. In 32 (68%) patients, 18F-FDG-PET/CT was performed before the start of therapy with glucocorticosteroids (GCS), in 15 (32%) after the start of treatment. In 40 (91%) patients, signs of damage to extracranial vessels of various localization were revealed, most often in the thoracic and abdominal aorta (72% and 64%, respectively).Conclusions. According to 18F-FDG-PET/CT data, in most patients with GCA, not only the arteries of the head and neck, but also vessels of other localization are involved in the pathological process.

Descriptive statistics provides tools to explore, summarize and illustrate the research data. In this tutorial we discuss two main types of data - qualitative and quantitative variables, and the most common approaches to characterize data distribution numerically and graphically. This article presents two important sets of parameters - measures of the central tendency (mean, median and mode) and variation (standard deviation, quantiles) and suggests the most suitable conditions for their application. We explain the difference between the general population and random samples, that are usually analyzed in studies. The parameters which characterize the sample (for example, measures of the central tendency) are point estimates, that can differ from the respective parameters of the general population. We introduce the concept of confidence interval - the range of values, which likely includes the true value of the parameter for the general population. All concepts and definitions are illustrated with examples, which simulate the research data.

Aim of the work – to compare the frequency of upper respiratory tract (URT) involvement in patients with ANCAassociated vasculitides (AAV), to reveal its main clinical and radiological patterns and to estimate their association with the serological profile (ANCA presence and type).Material and methods. This retrospective study evaluated 369 patients with granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA) and eosinophilic granulomatosis with polyangiitis (EGPA). The enrolled patients were diagnosed with AAV according to the ACR criteria, CHCC classification (2012) and EMA algorithm. Patients with URT manifestations underwent standard ENT assessment and X-ray/CT. Serum ANCA levels were measured by ELISA.Results. URT involvement was diagnosed in 280 (75.9%) patients with AAV. It was significantly more common amongthe patients with GPA (86.4%) and EGPA (85.5%) compared with the MPA group (29.2%) (p

Adequate design is an essential condition for conducting a successful study. This review describes the most common types of research design in medicine. We discuss the differences between different types of observational and interventional studies, their advantages and limitations providing examples for each study design. The concept of bias and its potential sources in different studies are covered. We suggest the most suitable approaches to study design for different research objectives and outline approaches to data presentation. During the last decades, several guidelines for conducting and reporting different types of research were proposed and they are also covered in this manuscript.

Aim. In a retrospective study, we evaluated factors associated with the early development of septic shock in patients with severe COVID-19. Materials and methods. We collected medical records of the intensive care unit patients submitted by the local COVID-19 hospitals across Russia to the Federal Center for the Critical Care at the Sechenov First Moscow State Medical University (Sechenov University). Septic shock in crticially ill patients requiring mechanical ventilation was defined as a need in vasopressors to maintain blood pressure. Results. We studied 1078 patients with severe COVID-19 who were admitted to the intensive care units for respiratory support. There were 611 males and 467 females. The mean age was 61.013.7 years. Five hundred twenty five medical records (48.7%) were received from the Moscow hospitals, 159 (14.7%) from the Moscow region, and 394 (36.5%) from the hospitals located in 58 regions of the Russian Federation. In 613 (56.9%) patients, diagnosis of SARS-CoV-2 infection was confirmed by PCR, and in the other cases it was established on the basis of the clinical picture and the results of the chest CT scan. Septic shock developed in 214 (19.9%) of 1078 patients. In the logistic regression model, the risk of septic shock in patients older than 50 years was higher than in patients of a younger age (OR 2.34; 95% CI 1.533.67; p0.0001). In patients with more severe SARS-CoV-2 infection, there was an increase in the prevalence of cardiovascular diseases, including coronary heart disease and atrial fibrillation, type 2 diabetes and malignant tumors. The risk of septic shock in patients with three or more concomitant diseases was higher than in patients without any concomitant chronic diseases (OR 1.76; 95% CI 1.762.70). Conclusion. The risk of septic shock in patients with acute respiratory distress syndrome induced by SARS-CoV-2 is higher in patients older than 50 years with concomitant diseases, although a severe course of the disease is also possible in younger patients without any concomitant disorders.

Neuromyelitis optica ((NMO), Devic's syndrome) is an immune-mediated inflammatory demyelinating disease characterized by transverse myelitis and optic neuritis. Determination of the level of antibodies to aquaporin 4 (NMO-IgG) is presently one of the key methods for the diagnosis and assessment of the activity of ONM, which allows this disease to be differentiated from multiple sclerosis and other demyelinating CNS lesions. ONM can occur not only as an independent disease, but also as a syndrome in different systemic diseases, such as: systemic lupus erythematosus (SLE), antineutrophilic cytoplasmic antibody-associated vasculitides, Sjögren's disease, etc. (up to 50–70%). In such situations, the clinician is always confronted with a question as whether the patient can have two rare autoimmune diseases or develop ONM as a systemic manifestation of rheumatic disease.The paper describes a clinical case of a young female patient with SLE concurrent with a CNS lesion, the manifestations of which corresponded to ONM. The patient had focal changes in the substance of the brain and spinal cord, as evidenced by magnetic resonance imaging, as well as high NMO-IgG titers. The development of ONM worsens SLE prognosis and requires active immunosuppressive therapy. The patient received three plasmapheresis sessions, ultrahigh-dose glucocorticoid and cyclophosphamide therapy, followed by replacement with azathioprine, causing a stable clinical and laboratory disease remission to be achieved.

Fabry disease (FD) is a severe lysosome storage disease caused by congenital deficiency of the enzyme α-galactosidase A and characterized by the risk of renal failure combined with cardiovascular and CNS complications. According to the currently available information, the early start of enzyme replacement therapy (ERT) leads to a significant improvement in patient’s condition.The aim of the study is to assess whether the timely ERT prevents severe FD complications and to calculate the number of prevented cases as depending on the time of ERT start.Materials and methods. The proposed model is based on the published results on patients with FD, receiving agalsidase alpha as ERT (no data for agalsidase beta was found). The expected number of cases with life-threatening complications was calculated for different starting timepoints and durations of the ERT.Results. In patients with FD, continuous ERT during five years reduces the number of serious cardiovascular and renal complications by 25%. An early start of ERT makes it possible to additionally (as compared with a late start) prevent the complications in more than 20% of cases.Conclusion. The early initiation of RPT in patients with FD can significantly reduce the occurrence of severe lifethreatening complications, increase the patients’ survival and improve their quality of life.

Objective. To compare the frequency, clinical features and outcomes of renal involvement in ANCA-associated vasculitides (AAV) in patients with antibodies against proteinase-3 (pr3-ANCA) and myeloperoxidase (MPO-ANCA). Materials and methods. In our retrospective study we enrolled 264 patients, 94 males and 170 females, median age 53 [36; 62] years. Among them 157 were pr3-ANCA positive and 107 were MPO-ANCA positive. AAV was diagnosed according to ACR criteria and Chapel Hill consensus conference definition (2012). Median follow up was 44 [18; 93] months. We assessed baseline BVAS and VDI by the end of the follow up. Serum creatinine (sCr), estimated glomerular filtration rate (eGFR), hematuria and daily proteinuria were estimated. Diagnosis and stage of chronic kidney disease (CKD) and acute kidney injury (AKI) were established according to KDIGO guidelines (2012) and Scientific Society of Russian Nephrologists (2016). Results. Renal involvement was present in 181 (68.6%) patients, and its frequency was similar in pr3-ANCA and MPO-ANCA subgroups. Patients with MPO-ANCA developed rapidly progressive glomerulonephritis and hypertension significantly more often than patients with pr3-ANCA: 50.7% vs 35.6% (p=0.049) and 46.1% vs 29.8% (p=0.029) respectively. At disease onset, median sCr was significantly higher and eGFR was significantly lower in patients with MPO-ANCA (p

Aim. To estimate the frequency of lesions in the organ of vision in granulomatosis with polyangiitis (GPA) (Wegener’s) and to determine their relationship to systemic diseases. Subjects and methods. The retrospective study enrolled 218 patients followed up at the E.M. Tareyev Clinic of Nephrology, Internal and Occupational Diseases, with a diagnosis of GPA. The frequency and association of ophthalmic manifestations with systemic involvement were statistically analyzed using PASW Statistics 18. Results. The organ of vision was impaired in 48.1% of the patients with GPA. The most common manifestations were orbital space-occupying lesion (22.9%), conjunctivitis/episcleritis (14.7%), dacryocystitis (6.0%), and scleritis (4.6%). Orbital space-occupying lesions occurred more frequently in the local type of the disease (p=0.0003), and, on the contrary, the involvement of the conjunctiva and eyeball was seen in patients with the systemic types of GPA (p=0.02). Conclusion. The findings may suggest that the orbital lesion is an independent manifestation of GPA, which develops more commonly in its local type. Conjunctivitis/episcleritis is, on the contrary, more frequently seen in the active phase of the disease and generally in the involvement of other organs and systems.

Aim. To determine clinical significance of urinary biomarkers of proteolysis/fibrinolysis and fibroangiogenesis in essential hypertension (EH). Material and methods. Examination of the kidneys was made in 71 patients with EH degree 1-3. Renal function was assessed by 24-h albuminuria, calculated glomerular filtration rate (GFR) by Cockroft-Golt. Early signs of renal damage were microalbuminuria - MAU (diurnal albuminuria 30-300 mg/day), reduction of GFR ( < 90 ml/min/1.73 m2). EH patients with hypercreatininemia and GFR under 60 ml/min/1.73m2 corresponding to stage III of chronic kidney disease were not included in the study. An additional nephropathy marker was an elevated index of resistance of interlobular renal arteries (RI > 0.65) as shown by dopplerometry. ELISA examined urinary biomarkers of intercellular and cell-matrix interactions in the kidney in EH patients and healthy controls (n = 12). Results. MAU was detected in 54 (76%) of 71 EH patients, elevated RI > 0.65 - in 37 (52%) patients. Urinary biomarkers of proteolysis/fibrinolysis and fibroangiogenesis were higher in EH patients then in the controls. Urinary excretion of PAI-1, TGF-beta1, VEGF and collagen of type IV in EH patients with MAU was significantly higher than in patients with normoalbuminuria. A strong direct correlation between MAU and the rest above urinary biomarkers was found as well as between urinary excretion of collagen IV and RI. An inverse negative relationship was seen between RI and GFR. Conclusion. Renal impairment in EH patients is a progressive disorder. Each stage of this process has its own clinicodiagnostic markers. Urinary biomarkers of proteolysis/fibrinolysis and fibroangiogenesis in the kidney are informative for monitoring of early HNP.

Cornea verticillata is the typical sign of ocular involvement in Fabry disease and manifests by the whorl-like, linear opacities in the inferior part of the cornea. Aim. To study the frequency of cornea verticillata in patients with Fabry disease and it’s relation to the severity of the disease and the types of mutation in the GLA gene. Materials and methods. We studied 69 adult (over 18 years) patients with a classic form of Fabry disease that was confirmed by enzymatic and molecular genetic studies. There were 39 males and 30 females. The median age was 39 years [30.0; 50.0]. The severity of Fabry disease was assessed using the Mainz Severity Score Index (MSSI) with a maximum value of 76 points. Depending on the MSSI score, patients were classified into mild (40) clinical categories. Results and discussion. At least one classic symptom of Fabry disease was present in 88.4% of patients. The majority of patients had the missense mutations of the GLA gene. Cornea verticillata was found in 65.2% of patients and occurred with a similar frequency in males (56.4%) and females (76.7%; p=0.07). Cornea verticillata was the single classic symptom of Fabry disease in only 4.9% of cases, while the rest of the patients presented with angiokeratoma, neuropathic pain and/or hypohidrosis. The frequency of classic symptoms of Fabry disease, as well as renal disease (with the exception of terminal chronic renal failure), brain and heart damage was similar in patients with and without cornea verticillata. Median MSSI scores were also similar in patienths with and without cornea verticillata (20.0 and 18.5 points, respectively; p=0.92). Similar results were obtained in males (26.5 and 30.0 points, p=0.97) and females (16.0 and 16.0 points, p=0.45). The frequency of cornea verticillata did not differ in patients with different types of mutations in the GLA gene. Conclusion. Cornea verticillata occured in 65% of adult patients with Fabry disease, was usually accompanied by the other classic symptoms of the disease, and was not associated with the severity of the disease.

Goodpasture’s disease (anti-GBM disease) is a rare small vessels vasculitis characterized by the presence of autoantibodies directed against the glomerular basement membrane (GBM) and alveolar basement membrane. Common feature of anti-GBM disease is a combination of rapidly progressive glomerulonephritis and alveolar hemorrhage (pulmonary-renal syndrome). We present a case of atypical disease course in a young male patient who developed alveolar hemorrhage without renal failure. The only symptom of renal involvement was isolated hematuria. Plasmapheresis combined with immunosuppression (cyclophosphamide and corticosteroids) was effective. We present a review of state-of-art data on the pathogenesis and disease course of anti-GBM disease.

Aim. To evaluate clinical features and outcomes of renal involvement in patients with microscopic polyangiitis (MPA). Materials and methods: We enrolled 99 patients with MPA, diagnosed in accordance with the algorithm of the European Medicines Evaluation Agency (EMEA) and the Chapel Hill consensus conference definition (2012). Serum creatinine (sCr), estimated glomerular filtration rate (eGFR), hematuria and proteinuria were estimated. Frequency of rapidly progressive renal failure (a twofold increase in the sCr level in ≤3 months) was regarded as the clinical equivalent of rapidly progressive glomerulonephritis (RPGN). Results and discussion. Renal involvement was present in 92 (92.9%) patients. RPGN developed in 51 (55,4%) patients. The most common features of kidney involvement were hematuria and subnephrotic proteinuria. Arterial hypertension was revealed in 32 (34.7%) patients and was associated with RPGN (p

AIM: To assess the risk of severe adverse events (AEs) within 6 months after treatment with biological agents in patients with rheumatic diseases (RD)/MATERIAL AND METHODS: The 6-month open-label trial included 107 patients with rheumatoid arthritis, antineutrophil cytoplasmic antibody-associated vasculitides, systemic lupus erythematosus, and other RDs who received genetically engineered biological agents (GEBAs), primarily rituximab (n=66) and infliximab (n=31)/RESULTS: The majority of patients were noted to have improvements, including complete and partial remission in 62 (57.9%) and 42 (39.3%), respectively. There were mild or moderate AEs in 22 (20.6%) of the 107 patients, severe AEs in 6 (5.6%): grade IV neutropenia in 2 patients (after the use of rituximab), severe infusion reactions in 2 (after the administration of infliximab and rituximab), and systemic infections in 2 (fatal nocardial sepsis after rituximab treatment and unspecified sepsis after infliximab treatment)/CONCLUSION: The rate of serious AEs, mainly infusion AEs and infections during treatment with infliximab, rituximab, and other GEBAs proved to be relatively low in patients with different RDs. At the same time, the use of biological agents could lower RD activity in the presence of severe visceral injuries refractory to conventional immunosuppressive therapy.