CYTOMEGALOVIRUS AND VIRUS EPSTEIN- BARR INFECTION IN PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS AND ITS DEPENDENCE ON GENDER AND AGE OF PATIENTS

Introduction. Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by various manifestations and clinical course, many aspects of the etiology and pathogenesis of which remain unclear. Recently, the interest of researchers in studying the role of cytomegalovirus (CMV) and Epstein - Barr virus (EBV) has been growing in the occurrence and course of a number of human diseases due to their ability to affect almost all organs and systems of the body, causing the formation of latent, active or chronic infection, which can often cause temporary disability, disability or even death, however, for the patients with SLE, despite the possibility of approaching the difficult problem of diagnosis and treatment of this disease, this issue is given insufficient attention, as evidenced by isolated studies.The aim of the study. Detect cytomegalovirus and Epstein - Barr infection in patients with systemic lupus erythematosus and its dependence on gender and age of patients. Materials and methods of research. The study involved 120 patients (15 men (12.50%) and 105 women (87.50%) aged 18 to 69 years with SLE, who were in the rheumatology department of the Communal Non-Commercial Enterprise of the Lviv Regional Council "Lviv Regional Clinical Hospital" in 2014-2019. To diagnose CMV and EBV infection by enzyme-linked immunosorbent assay, antibodies of IgM and IgG to viruses were detected in blood serum, and viruses were detected by polymerase chain reaction. According to the results of virus detection, formed groups of the patients, namely: patients with active CMV infection, active EBV, active CMV and EBV, without active CMV and EBV. All patients with SLE included in the study were subsequently stratified by age according to the classification of the World Health Organization (2015), according to which the following age limits were determined: young age, middle-aged, elderly, senile. Statistical analysis was performed on a personal computer in MS Excel and Statistica 6.0 using descriptive statistics. The frequency of cases of active CMV and EBV infection was calculated mathematically by the binomial coefficient of I. Newton. Research results and their discussion. We found in the vast majority of patients with SLE (117 patients, 97.50%) increase in the titer of specific antibodies to CMV. Only in 3 patients (2.50%) the titer of antibodies to this virus was within normal limits. Analyzing the frequency of EBV infection in patients with SLE, we recorded an increase in the titer of specific antibodies to the virus in 119 patients (99.17%). Among the examined patients with SLE in all (100.00%) found an increase in the titer of antibodies to CMV and / or EBV, of which 97.50% - infected with CMV and 97.17% - infected with EBV. The active phase of CMV and / or EBV infection was detected in 54.17%, of which 23.33% - active CMV infection, 17.50% - active EBV infection and 12.50% - a combination of active CMV and EBV infection simultaneously, which indicates a high frequency of CMV and EBV infection in patients with SLE and reflects the urgency of the problem of diagnosing herpesvirus infection in them. We found that activeCMV, EBV infections and their combinations are present only in women (64 patients, which is 60.96% of the total number of women with SLE), of which 28 patients (26.67%) there was only active CMV infection, in 21 patients (20.00%) - only active EBV infection and in 15 patients (14.29%) – combination of active CMV and EBV infection. 41 women (39.05%) and all (100.00%) men were not found to have active CMV and EBV infection, which indicates that men at the time of the survey were significantly more likely to have this infection in the integration phase. The most frequently active EBV infection was detected in patients with SLE of young age (17 cases, 24.64%), and in middle-aged patients 3 cases (6.52%) were recorded, which indicates a significant (p <0.05) difference in the frequency of cases of active EBV infection in patients of both groups. Only 1 case (20.00%) of active EBV infection was detected in elderly patients. Conclusions. All patients with systemic lupus erythematosus are infected - 97.50% with cytomegalovirus and 97.17% with Epstein-Barr virus infection, that was confirmed by the increased titer of antibodies to them. Among the mentioned patients 53.33% of them had the active phase of infection (23.33% - cytomegalovirus infection in the replication phase, 17.50% - the Epstein- Barr virus infection in the replication phase and 12.50% - their combination). The prevalence of active viral infection in patients with systemic lupus erythematosus depends on gender (active cytomegalovirus, active Epstein-Barr virus infection and their combination are significantly more common in women) and age - they are probably more common in young patients.  Introduction. Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by various manifestations and clinical course, many aspects of the etiology and pathogenesis of which remain unclear. Recently, the interest of researchers in studying the role of cytomegalovirus (CMV) and Epstein - Barr virus (EBV) has been growing in the occurrence and course of a number of human diseases due to their ability to affect almost all organs and systems of the body, causing the formation of latent, active or chronic infection, which can often cause temporary disability, disability or even death, however, for the patients with SLE, despite the possibility of approaching the difficult problem of diagnosis and treatment of this disease, this issue is given insufficient attention, as evidenced by isolated studies.The aim of the study. Detect cytomegalovirus and Epstein - Barr infection in patients with systemic lupus erythematosus and its dependence on gender and age of patients. Materials and methods of research. The study involved 120 patients (15 men (12.50%) and 105 women (87.50%) aged 18 to 69 years with SLE, who were in the rheumatology department of the Communal Non-Commercial Enterprise of the Lviv Regional Council "Lviv Regional Clinical Hospital" in 2014-2019. To diagnose CMV and EBV infection by enzyme-linked immunosorbent assay, antibodies of IgM and IgG to viruses were detected in blood serum, and viruses were detected by polymerase chain reaction. According to the results of virus detection, formed groups of the patients, namely: patients with active CMV infection, active EBV, active CMV and EBV, without active CMV and EBV. All patients with SLE included in the study were subsequently stratified by age according to the classification of the World Health Organization (2015), according to which the following age limits were determined: young age, middle-aged, elderly, senile. Statistical analysis was performed on a personal computer in MS Excel and Statistica 6.0 using descriptive statistics. The frequency of cases of active CMV and EBV infection was calculated mathematically by the binomial coefficient of I. Newton. Research results and their discussion. We found in the vast majority of patients with SLE (117 patients, 97.50%) increase in the titer of specific antibodies to CMV. Only in 3 patients (2.50%) the titer of antibodies to this virus was within normal limits. Analyzing the frequency of EBV infection in patients with SLE, we recorded an increase in the titer of specific antibodies to the virus in 119 patients (99.17%). Among the examined patients with SLE in all (100.00%) found an increase in the titer of antibodies to CMV and / or EBV, of which 97.50% - infected with CMV and 97.17% - infected with EBV. The active phase of CMV and / or EBV infection was detected in 54.17%, of which 23.33% - active CMV infection, 17.50% - active EBV infection and 12.50% - a combination of active CMV and EBV infection simultaneously, which indicates a high frequency of CMV and EBV infection in patients with SLE and reflects the urgency of the problem of diagnosing herpesvirus infection in them. We found that activeCMV, EBV infections and their combinations are present only in women (64 patients, which is 60.96% of the total number of women with SLE), of which 28 patients (26.67%) there was only active CMV infection, in 21 patients (20.00%) - only active EBV infection and in 15 patients (14.29%) – combination of active CMV and EBV infection. 41 women (39.05%) and all (100.00%) men were not found to have active CMV and EBV infection, which indicates that men at the time of the survey were significantly more likely to have this infection in the integration phase. The most frequently active EBV infection was detected in patients with SLE of young age (17 cases, 24.64%), and in middle-aged patients 3 cases (6.52%) were recorded, which indicates a significant (p <0.05) difference in the frequency of cases of active EBV infection in patients of both groups. Only 1 case (20.00%) of active EBV infection was detected in elderly patients. Conclusions. All patients with systemic lupus erythematosus are infected - 97.50% with cytomegalovirus and 97.17% with Epstein-Barr virus infection, that was confirmed by the increased titer of antibodies to them. Among the mentioned patients 53.33% of them had the active phase of infection (23.33% - cytomegalovirus infection in the replication phase, 17.50% - the Epstein- Barr virus infection in the replication phase and 12.50% - their combination). The prevalence of active viral infection in patients with systemic lupus erythematosus depends on gender (active cytomegalovirus, active Epstein-Barr virus infection and their combination are significantly more common in women) and age - they are probably more common in young patients. &nbsp

DIAGNOSTIC VALUE OF SYSTEMIC LUPUS ERYTHEMATOSUS CLASSIFICATION CRITERIA (AMERICAN COLLEGE OF RHEUMATOLOGY, 1997)

The criteria for the classification of systemic lupus erythematosus were proposed in 1971 by the American College of Rheumatology. They have been clarified since then, but need to be revised.Objective. To determine the diagnostic value of the criteria for the classification of systemic lupus erythematosus proposed by the American College of Rheumatology.Materials and methods. 370 patients (331 women (89.46%) and 39 men (10.54%), average age 41.24 ± 0.63 years) with SLE and 234 patients (150 women (64.10%) and 84 men (35.90%), average age 48.82 ± 0.85 years) with other rheumatic diseases (rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis) were randomly enrolled into the study. The patients had undergone comprehensive clinical-laboratory and instrumental examinations in 2010–2018 before they received treatment. The analysis was conducted in MS Excel and SPSS by constructing contingency tables and calculating indicators of diagnostic value.Results. We identified the following criteria as those that can with statistical significance predict the presence of systemic lupus erythematosus: butterfly rash, photosensitivity, serositis (pleuritis, pericarditis), neurologic disorders (seizures, psychosis), thrombocytopenia, renal disorders (proteinuria, cylindruria), anti-dsDNA and antinuclear antibodies.The criteria for the classification of systemic lupus erythematosus were proposed in 1971 by the American College of Rheumatology. They have been clarified since then, but need to be revised.Objective. To determine the diagnostic value of the criteria for the classification of systemic lupus erythematosus proposed by the American College of Rheumatology.Materials and methods. 370 patients (331 women (89.46%) and 39 men (10.54%), average age 41.24 ± 0.63 years) with SLE and 234 patients (150 women (64.10%) and 84 men (35.90%), average age 48.82 ± 0.85 years) with other rheumatic diseases (rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis) were randomly enrolled into the study. The patients had undergone comprehensive clinical-laboratory and instrumental examinations in 2010–2018 before they received treatment. The analysis was conducted in MS Excel and SPSS by constructing contingency tables and calculating indicators of diagnostic value.Results. We identified the following criteria as those that can with statistical significance predict the presence of systemic lupus erythematosus: butterfly rash, photosensitivity, serositis (pleuritis, pericarditis), neurologic disorders (seizures, psychosis), thrombocytopenia, renal disorders (proteinuria, cylindruria), anti-dsDNA and antinuclear antibodies

COMPLAINTS OF THE PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS AND ACTIVE CYTOMEGALOVIRUS AND EPSTEIN-BARR VIRUS INFECTION; THEIR DIAGNOSTIC VALUE

Actuality. The infection with cytomegalovirus (CMV) and Epstein-Barr virus (EBV) in the patients with systemic lupus erythematosus (SLE) is of particular interest to researchers. SLE is a chronic autoimmune disease of unknown etiology that is characterized by multisystemic lesions and is potentially life-threatening [1, 2, 3]. The severity of the problem is caused by the fact that active viral infection can change the manifestations of SLE, but these changes are not always specific, so primary care physicians have no reason to suspect active virus infection at the first stage of examination of SLE patients and prescribe expensive direct virological tests accordingly. It has not been definitively established yet which complaints are the most meaningful regarding the presence of active viral infection in patients with SLE.The purpose of the research was to study complaints in SLE patients with active cytomegalovirus and Epstein-Barr virus infection and determine their diagnostic value. Materials and methods. We randomly enrolled 120 SLE patients – 15 men (12.50%) and 105 women (87.50%) aged 18 to 69 years. All patients received treatment at the Rheumatology Department of Lviv Regional Clinical Hospital in 2014-2019. The diagnosis of SLE was established based on the diagnostic criteria of the American College of Rheumatologists (ACR, 1997). In addition, IgM and IgG antibodies to serum viruses were detected for the diagnosis of CMV and EBV infection. To confirm the presence of active viral infection, viruses were detected in media (CMV - urine, blood; EBV - oral mucosa, blood) by polymerase chain reaction, resulting in 28 patients with SLE (23.33%) detected active CMV infection, in 21 patients with SLE (17.50%) - active EBV infection and in 15 patients with SLE (12.5%) - a combination of active CMV and EBV infection. To achieve the purpose of the study, we identified three steps: the first step was to analyze complaints in patients with SLE with active CMV infection and determine their diagnostic value, the second - in the analysis of complaints in patients with SLE with active EBV infection and clarify their diagnostic values and the third - in the analysis of complaints in patients with SLE with a combination of active CMV and EBV infection and clarification of their diagnostic value. We identified three steps: the first step was to analyze complaints in patients with SLE with active CMV infection and determine their diagnostic value, the second - in the analysis of complaints in patients with SLE with active EBV infection and clarify their diagnostic values and the third - in the analysis of complaints in patients with SLE with a combination of active CMV and EBV infection and clarification of their diagnostic value.Statistical analysis was performed by calculating the chances of establishing the phase of CMV and EBV infection in patients with SLE, using a separate feature - a marker that can be detected during the initial examination of the patient. The probable probability of active infection was determined using indicators of sensitivity, specificity and accuracy [4]. The actual material was processed on a personal computer in MS Excel and SPSS on the basis of conjugation tables with calculation of diagnostic value indicators. The association between active infection and a particular patient complaint was considered to be confirmed when the coefficient of association exceeded 0.5 (or 0.3 for the coefficient of contingency). Research results. It was found that in patients with SLE the presence of active cytomegalovirus infection among the main complaints significantly more often indicate the presence of myalgias (coefficient of association 0.79) or fever (0.51), or chills of the extremities (0.51), or arthralgia (coefficient of contingent 0.31). The presence of active virus Epstein - Barr infections are significantly more often evidenced by the presence of myalgias (coefficient of contingent 0.31) or sleep disorders (coefficient of association 0.84), or mood swings (0.74), or fever (0.61), or the appearance of new rashes (0.53). On the presence of a combination of active cytomegalovirus and virus Epstein - Barr infections significantly more often indicate complaints of sleep disturbances (coefficient of association 0.97) or mood swings (0.83), or a feeling of dryness in the eyes (0.51), or fever (0.50). Conclusions. The presence of active cytomegalovirus infection in patients with systemic lupus erythematosus among the main complaints often indicates the presence of myalgias or fever, or chills of the extremities, or arthralgia, the presence of active virus Epstein - Barr infection - myalgia or sleep disturbances, or mood swings, or fever, or the appearance of new rashes, the presence of their combination - sleep disturbances or mood swings, or a feeling of dryness in the eyes, or fever, which can be used in the diagnostic algorithm. The established patterns of complaints allow us to reasonably suspect in patients with systemic lupus erythematosus the presence of active cytomegalovirus and Epstein-Barr virus infection, the final verification of which requires the use of direct serological tests.Actuality. The infection with cytomegalovirus (CMV) and Epstein-Barr virus (EBV) in the patients with systemic lupus erythematosus (SLE) is of particular interest to researchers. SLE is a chronic autoimmune disease of unknown etiology that is characterized by multisystemic lesions and is potentially life-threatening [1, 2, 3]. The severity of the problem is caused by the fact that active viral infection can change the manifestations of SLE, but these changes are not always specific, so primary care physicians have no reason to suspect active virus infection at the first stage of examination of SLE patients and prescribe expensive direct virological tests accordingly. It has not been definitively established yet which complaints are the most meaningful regarding the presence of active viral infection in patients with SLE.The purpose of the research was to study complaints in SLE patients with active cytomegalovirus and Epstein-Barr virus infection and determine their diagnostic value. Materials and methods. We randomly enrolled 120 SLE patients – 15 men (12.50%) and 105 women (87.50%) aged 18 to 69 years. All patients received treatment at the Rheumatology Department of Lviv Regional Clinical Hospital in 2014-2019. The diagnosis of SLE was established based on the diagnostic criteria of the American College of Rheumatologists (ACR, 1997). In addition, IgM and IgG antibodies to serum viruses were detected for the diagnosis of CMV and EBV infection. To confirm the presence of active viral infection, viruses were detected in media (CMV - urine, blood; EBV - oral mucosa, blood) by polymerase chain reaction, resulting in 28 patients with SLE (23.33%) detected active CMV infection, in 21 patients with SLE (17.50%) - active EBV infection and in 15 patients with SLE (12.5%) - a combination of active CMV and EBV infection. To achieve the purpose of the study, we identified three steps: the first step was to analyze complaints in patients with SLE with active CMV infection and determine their diagnostic value, the second - in the analysis of complaints in patients with SLE with active EBV infection and clarify their diagnostic values and the third - in the analysis of complaints in patients with SLE with a combination of active CMV and EBV infection and clarification of their diagnostic value. We identified three steps: the first step was to analyze complaints in patients with SLE with active CMV infection and determine their diagnostic value, the second - in the analysis of complaints in patients with SLE with active EBV infection and clarify their diagnostic values and the third - in the analysis of complaints in patients with SLE with a combination of active CMV and EBV infection and clarification of their diagnostic value.Statistical analysis was performed by calculating the chances of establishing the phase of CMV and EBV infection in patients with SLE, using a separate feature - a marker that can be detected during the initial examination of the patient. The probable probability of active infection was determined using indicators of sensitivity, specificity and accuracy [4]. The actual material was processed on a personal computer in MS Excel and SPSS on the basis of conjugation tables with calculation of diagnostic value indicators. The association between active infection and a particular patient complaint was considered to be confirmed when the coefficient of association exceeded 0.5 (or 0.3 for the coefficient of contingency). Research results. It was found that in patients with SLE the presence of active cytomegalovirus infection among the main complaints significantly more often indicate the presence of myalgias (coefficient of association 0.79) or fever (0.51), or chills of the extremities (0.51), or arthralgia (coefficient of contingent 0.31). The presence of active virus Epstein - Barr infections are significantly more often evidenced by the presence of myalgias (coefficient of contingent 0.31) or sleep disorders (coefficient of association 0.84), or mood swings (0.74), or fever (0.61), or the appearance of new rashes (0.53). On the presence of a combination of active cytomegalovirus and virus Epstein - Barr infections significantly more often indicate complaints of sleep disturbances (coefficient of association 0.97) or mood swings (0.83), or a feeling of dryness in the eyes (0.51), or fever (0.50). Conclusions. The presence of active cytomegalovirus infection in patients with systemic lupus erythematosus among the main complaints often indicates the presence of myalgias or fever, or chills of the extremities, or arthralgia, the presence of active virus Epstein - Barr infection - myalgia or sleep disturbances, or mood swings, or fever, or the appearance of new rashes, the presence of their combination - sleep disturbances or mood swings, or a feeling of dryness in the eyes, or fever, which can be used in the diagnostic algorithm. The established patterns of complaints allow us to reasonably suspect in patients with systemic lupus erythematosus the presence of active cytomegalovirus and Epstein-Barr virus infection, the final verification of which requires the use of direct serological tests

Cardiovascular Outcomes with Ertugliflozin in Type 2 Diabetes

BACKGROUND The cardiovascular effects of ertugliflozin, an inhibitor of sodium–glucose cotransporter 2, have not been established. METHODS In a multicenter, double-blind trial, we randomly assigned patients with type 2 diabetes and atherosclerotic cardiovascular disease to receive 5 mg or 15 mg of ertugliflozin or placebo once daily. With the data from the two ertugliflozin dose groups pooled for analysis, the primary objective was to show the noninferiority of ertugliflozin to placebo with respect to the primary outcome, major adverse cardiovascular events (a composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke). The noninferiority margin was 1.3 (upper boundary of a 95.6% confidence interval for the hazard ratio [ertugliflozin vs. placebo] for major adverse cardiovascular events). The first key secondary outcome was a composite of death from cardiovascular causes or hospitalization for heart failure. RESULTS A total of 8246 patients underwent randomization and were followed for a mean of 3.5 years. Among 8238 patients who received at least one dose of ertugliflozin or placebo, a major adverse cardiovascular event occurred in 653 of 5493 patients (11.9%) in the ertugliflozin group and in 327 of 2745 patients (11.9%) in the placebo group (hazard ratio, 0.97; 95.6% confidence interval [CI], 0.85 to 1.11; P<0.001 for noninferiority). Death from cardiovascular causes or hospitalization for heart failure occurred in 444 of 5499 patients (8.1%) in the ertugliflozin group and in 250 of 2747 patients (9.1%) in the placebo group (hazard ratio, 0.88; 95.8% CI, 0.75 to 1.03; P=0.11 for superiority). The hazard ratio for death from cardiovascular causes was 0.92 (95.8% CI, 0.77 to 1.11), and the hazard ratio for death from renal causes, renal replacement therapy, or doubling of the serum creatinine level was 0.81 (95.8% CI, 0.63 to 1.04). Amputations were performed in 54 patients (2.0%) who received the 5-mg dose of ertugliflozin and in 57 patients (2.1%) who received the 15-mg dose, as compared with 45 patients (1.6%) who received placebo. CONCLUSIONS Among patients with type 2 diabetes and atherosclerotic cardiovascular disease, ertugliflozin was noninferior to placebo with respect to major adverse cardiovascular events. (Funded by Merck Sharp & Dohme and Pfizer; VERTIS CV ClinicalTrials.gov number, NCT01986881.)

Extended Thromboprophylaxis with Betrixaban in Acutely Ill Medical Patients

Background Patients with acute medical illnesses are at prolonged risk for venous thrombosis. However, the appropriate duration of thromboprophylaxis remains unknown. Methods Patients who were hospitalized for acute medical illnesses were randomly assigned to receive subcutaneous enoxaparin (at a dose of 40 mg once daily) for 10±4 days plus oral betrixaban placebo for 35 to 42 days or subcutaneous enoxaparin placebo for 10±4 days plus oral betrixaban (at a dose of 80 mg once daily) for 35 to 42 days. We performed sequential analyses in three prespecified, progressively inclusive cohorts: patients with an elevated d-dimer level (cohort 1), patients with an elevated d-dimer level or an age of at least 75 years (cohort 2), and all the enrolled patients (overall population cohort). The statistical analysis plan specified that if the between-group difference in any analysis in this sequence was not significant, the other analyses would be considered exploratory. The primary efficacy outcome was a composite of asymptomatic proximal deep-vein thrombosis and symptomatic venous thromboembolism. The principal safety outcome was major bleeding. Results A total of 7513 patients underwent randomization. In cohort 1, the primary efficacy outcome occurred in 6.9% of patients receiving betrixaban and 8.5% receiving enoxaparin (relative risk in the betrixaban group, 0.81; 95% confidence interval [CI], 0.65 to 1.00; P=0.054). The rates were 5.6% and 7.1%, respectively (relative risk, 0.80; 95% CI, 0.66 to 0.98; P=0.03) in cohort 2 and 5.3% and 7.0% (relative risk, 0.76; 95% CI, 0.63 to 0.92; P=0.006) in the overall population. (The last two analyses were considered to be exploratory owing to the result in cohort 1.) In the overall population, major bleeding occurred in 0.7% of the betrixaban group and 0.6% of the enoxaparin group (relative risk, 1.19; 95% CI, 0.67 to 2.12; P=0.55). Conclusions Among acutely ill medical patients with an elevated d-dimer level, there was no significant difference between extended-duration betrixaban and a standard regimen of enoxaparin in the prespecified primary efficacy outcome. However, prespecified exploratory analyses provided evidence suggesting a benefit for betrixaban in the two larger cohorts. (Funded by Portola Pharmaceuticals; APEX ClinicalTrials.gov number, NCT01583218. opens in new tab.

Herpesviruses in Patients With Systemic Lupus Erythematosus (Literature Review and Clinical Cases Description)

Introduction. Systemic lupus erythematosus is one of the autoimmune diseases prevailing in women of reproductive age and is, quite often, the cause of their disability. In recent years, the attention of researchers has been focused on clarifying the role of herpesviruses in origin, pathogenesis, the ability to influence the clinical and laboratory signs, course and prognosis of the disease. The aim of our study was to make an overview of the modern literature on the role of herpesviruses in patients with systemic lupus erythematosus and describe two clinical cases from our own practice. Materials and methods. The content analysis, method of the system and comparative analysis, the bibliosemantic method of study of the actual scientific researchers concerning the role of herpesviruses in the patients with systemic lupus erythematosus were used. Results. The analysis of the modern literature shows the important role of herpesviruses in the initiation, pathogenetic mechanisms, exacerbation and the course of systemic lupus erythematosus. The herpesviruses that are pathogenic to humans are the herpes simplex virus type 1 and type 2, the chicken pox virus, cytomegalovirus, the herpesvirus type 6, the herpesvirus type 7, M. I. Epstein-I. Barr virus and herpesvirus type 8. Viral infections cause the significant immunological disorders that contribute to the occurrence of various, often nonspecific clinical signs, which in turn are of the complex diagnostic problems for the clinicians, since they can be considered as symptoms of exacerbation of systemic lupus erythematosus or clinical manifestations of infections. Herpesviruses infections in such patients in many cases cause the deterioration of the course of the disease, lead to the increase of the frequency of the disease exacerbation and the increase of the doses of the immunosuppressive drugs. Additional laboratory and instrumental investigations of the presence of herpesviruses in patients with systemic lupus erythematosus are not often used in practice, and the prescribing of the immunosuppressive treatment often worsens the prognosis of such patients. For the examination of the patients with systemic lupus erythematosus with suspected infections and fever, it is necessary to detect not only the general bacterial infections (usually urinary and respiratory tract infections) but also the opportunistic viral infections, especially in those receiving immunosuppressive treatment; to carry out a survey of persons suspected of having systemic lupus erythematosus, to detect, in the first place, the most common viral infections described in the patients with the presence of the disease or in the persons with confirmed systemic lupus erythematosus, which are manifested by a fever without any clear indication of its exacerbation; to conduct a complex clinical and laboratory, and, if necessary, an instrumental examination in order to exclude the infection. The appropriate use of antiviral drugs, interferons and immunoglobulins are recommended for the complex treatment of patients with systemic lupus erythematosus with herpesviruses. In both our clinical cases, we have not previously detected viral infections that negatively affected the course of the disease, and our optimization of the complex treatment with the inclusion of antiviral drugs has had a positive effect. Conclusions. An overview of the modern literature and clinical presentations from our own practice suggest that herpesviruses, in particular, cytomegalovirus and the M. E. Epstein-I. Barr virus may be as risk factors for the systemic lupus erythematosus, its causes, triggers, one of the pathogenetic mechanisms, especially in those who are genetically predisposed. The similarity of clinical manifestations of polysyndromic disease, with a lesion of various organs in a patient with systemic lupus erythematosus, and herpesviruses infections significantly complicates the determination whether there is only an infection that is primary or chronic in the phase of exacerbation and clinically similar to systemic lupus erythematosus, or clinical symptoms in the patients with already diagnosed systemic lupus erythematosus are caused by the acute infection, exacerbation of chronic infection, or exacerbation of the systemic lupus erythematosus, which requires us to deepen our knowledge about the role of herpesviruses in patients with systemic lupus erythematosus, especially in the occurrence of comorbidities, isolating from them syntropic lesions of internal organs

TORCH-Infection and Its Possible Role in Syntropic Liver Damage in Patients with Systemic Lupus Erythematosus (literature review and clinical case description)

Introduction. One of the topical issues of clinical medicine is the effective providing of help to patients with syntropic and polymorbid lesions, among which special attention is paid to patients with diffuse connective tissue diseases (DCTD), primarily with systemic lupus erythematosus (SLE) and syntropic involvement of the liver into the pathological process. In this sense, the role of TORCH infection deserves the special attention, as there is a fragmentary information that some representatives of this group may also have an effect on the DCTD, in particular, the SLE, and liver diseases, which gives the basis to assume the possibility of their participation in the pathogenesis of syntropic co- and polymorbid lesions of organs and systems. Aim. Analysis of scientific literature and a description of a clinical case to highlight the role of TORCH infection in the syntropic lesions of the liver in patients with SLE. Materials and methods. The results of scientific works are analyzed, an example of a clinical case concerning the possible participation of TORCH infection in syntropic affection of the liver of the patients with SLE is given. Results. Summarizing a retrospective analysis of the sources of scientific data, we can say that the majority of the representatives of TORCH-complex may be related to the diffuse connective tissue diseases, in particular SLE, and also to liver diseases. This gives grounds for suggesting the possibility of their participation in the pathogenesis of syntropic co- and polymorbid damages of the organs and organ systems. Methods of laboratory diagnosis occupy a central place in the detection of TORCH infection altogether, and their application requires the appropriate tactics. Today, the defining tests of microbiological diagnosis of TORCH infections are the ELISA and the polymerase chain reaction (PCR) method. Today, in world practice, there are no unified recommendations not only for diagnostic schemes, but also for the treatment of liver lesions in patients with SLE infected with TORCH infection, and doctors of all specialties have some difficulties in assisting such patients. The success of treating of TORCH infections in patients with liver damage can be achieved only if it is comprehensive, individualized for each patient and as safe as possible method. The clinical case describes the importance of diagnosing the TORCH-infection in SLE patients with syntropic liver damage. Conclusions. The information received on TORCH infection in patients with SLE and syntropic liver diseases does not allow to determine definitively whether it is the cause of one of the trigger mechanisms, whether it participates in the pathogenesis of comorbid lesions, if so, in what form, or it is an intercurrent infection. So, the information mentioned above indicates the relevance of the problem, that requires a comprehensive solution through the development of an adequate diagnostic and treatment algorithm for patients with SLE considering the possible presence of the TORCH infection and the involvement of liver into the pathological process

Comorbidity: a Modern View on the Problem; Classification (first notice)

Introduction. Researches of the famous scientists proved, that comorbid diseases often worsen the course of the underlying disease and/or lead to its chronicity, cause disability and premature death of the working population, often make inefficient diagnosis and treatment, increase the costs of the health system to provide medical care. According to the research of WHO experts, people under 40 usually have 2-4 diseases, under 60 – there is a “bouquet” of 5-7 diseases, after 70 – 8-10 or more diseases. So-called “polymorbidity” increases from 10.0 % in patients aged 80 years old. Materials and research methods. The work analyzes the literature sources, which deal with the study of comorbid diseases and sufficiently thoroughly reflect the current views of the scientists on the issue. Results of the investigation and their discussion. There are many synonyms of the term “comorbidity”, among them, often are used the following: “polymorbity”, “multimorbidity”, “multifactorial diseases”, “polypathy”, “multicausal diagnosis”, “dual diagnosis”, “pluripathology” etc., which complicates the understanding of the problem and minimizes the ability to use scientific achievements in clinical practice. In Ukrainian literature the authors often use the term “bicausal diagnosis” to describe comorbidity when there are two underlying diseases, to describe polymorbidity – “multicausal diagnosis” (three or more pathological conditions in one individual). In English scientific literature the authors often use the terms “comorbid diseases”, “comorbid conditions”. In general, the sources of information, used by the researchers to study the problem of polypathies, were and are medical histories, hospital records of the patients and other medical records of family doctors, of insurance companies, archives of the pensions for the elderly. Comorbidity itself can be interpreted as a random combination of the diseases, different by its’ etiology and pathogenesis such as nosological syntropy, ie natural occurrence of the regular determined diseases combinations in one patient. The main causes of comorbidity are: affected organs anatomical proximity, common pathogenesis, causal connections, combination of the diseases or iatrogenic causes. Among the factors, that influence the occurrence of comorbidity in humans, is a chronic infection, inflammation, involutive and systemic metabolic changes, iatrogenic factors, social status, environment and genetic predisposition, and the main way of the development of comorbid disorders is causal. The appearing of a particular disease leads to functional first, and later – to organic lesions and further – to an increase of nosologies quantity. Despite the large number of studies, proposed definitions and synonyms, standardized terminology and conventional classification of comorbidity, that would greatly help in the study of its problems, until now is missing. Conclusions. Despite many unsolved patterns of comorbidity and lack of the unified terminology, the search for the new variants of combinations of these diseases continues. After all, they can simply be not yet classified syndromal diseases, or vice versa – to be completely incompatible for the appearance and coexistence in one body. This is the key to solve more and more problems for the diagnosis and treatment of the diseases in the field of the practical medicine

Characteristics of the Autonomic Nervous System State in Patients with Systemic Lupus Erythematosus with the Different Activity Degree According to the Indices of Heart Rate Variability

Introduction. Vegetative disorders are a term that unites varieties of origin and manifestations of the violation of vegetative functions of the organism, which are caused by the disorders of their neurogenic regulation. Regarding the pathogenesis of the autonomic nervous system (NS) dysfunction in the presence of systemic lupus erythematosus (SLE), there are several hypotheses: the occurrence of vasculitis with the involvement of vessels of the nerves, or secondary amyloidosis; the influence of immunological factors, in particular, circulating antibodies to the structures of the NS were detected. However, none of them has a definitive confirmation. The aim of the study was to describe the autonomic NS state in the patients with SLE with the different activity degree of the disease according to the heart rate variability indices. Materials and methods. 83 patients were examined. Among them, 65 women (78.3%) and 18 men (21.7%) aged 18 to 74 years (mean age 44.2 years), who were diagnosed with SLE according to the criteria of the American College of Rheumatologists (1982, 1997). Patients are divided into three groups according to the randomized principle with pre-stratification on the activity of the pathological process of the underlying disease – SLE at the time of the heart rate variability (HRV) conducting: the first group – with the first degree of activity, the second group – with second degree of activity, the third group – with the third degree of activity. There were also 40 practically healthy persons (27 women (67.5%) and 13 men (32.5%)) aged 19-70 years old (mean age 41.8 ± 4.2 years), of which the control group was formed. Recording of the HRV was performed for 5 minutes in the lying position (state to the physical activity) and for 6 minutes in standing position (after physical activity, orthostatic test). Results. The value of the heart rate allows to characterize the balance between the tone of the sympathetic and parasympathetic parts of the autonomic NS, since the change in the heart rate is a universal reaction of the organism to various stimuli of the internal or external environment. The state of the autonomic NS in patients with SLE with varying degrees of activity is characterized by a decrease in the total activity of vegetative effects on the heart rhythm due to the reduction of sympathetic and parasympathetic effects, as well as the humoral component. Conclusions. Based on the reduced total spectral power in patients with SLE, an unbalance of the autonomic NS is observed due to the predominance of the sympathetic NS, especially expressed in the sample before the physical activity

Peculiarities of Calcium-Phosphorus Metabolism and Bone State in Patients with Liver Cirrhosis: Diagnosis and Principles of Differential Treatment (Literature Rewiev and Clinical Case Description)

Introduction. The disorders of calcium-phosphorus metabolism and bone tissue state, which are the main cause of spontaneous fractures and motor activity disorders in patients with liver cirrhosis, they require deeper understanding of etiology and pathogenesis, the use of laboratory-instrumental methods of diagnosis, taking into account risk factors and prescribing of the effective treatment to improve the quality of life. Conducting the additional studies will give impetus to the search for new methods of treatment of not only individual nosolenias, but also co- and polymorbid diseases and will help to reduce the effect of radiation from the use of medications. Aim. To make the literature review devoted to the peculiarities of calcium-phosphorus metabolism and the state of bones in patients with liver cirrhosis, methods of diagnostics and the principles of differentiated treatment, to describe the clinical case. Materials and Methods. The content analysis, the method of system and comparative analysis, the bibliosemantic method of studying the actual scientific studies of the peculiarities of calcium-phosphorus metabolism and the state of bones in patients with liver cirrhosis, methods of diagnostics and the principles of differentiated treatment are described. Results. The review of the literature shows the importance and urgency of the problem of studying calcium-phosphorus metabolism and the state of bone tissue in patients with cirrhosis of the liver. Mechanisms leading to pathological changes in bone tissue in such patients has been insufficiently studied. Nevertheless, there are number of common factors affecting bone metabolism: malformation of calcium and vitamin D, vitamin K deficiency, hormonal disregulation, cytokine release, insulin-like growth factor 1 (IFR-1) deficiency, etc. All efforts in the treatment are aimed at minimizing the loss of bone mass, preventing the fractures and kneading bone pain. First of all, it’s important to persuade the patient to stop smoking and drink alcohol, exercise regularly, and maintain a balanced diet with high levels of calcium and vitamin D. In the described clinical case, the patient with cirrhosis of the liver is diagnosed with osteoporosis confirmed by ultrasound densitometry and examination of calcium-phosphorus metabolism and bone tissue state by measuring the content of total calcium, ionized calcium, phosphorus, vitamin D, parathyroid hormone and markers of bone metabolism (b- crossLaps, P1NP, osteocalcin). Conclusions. The study of the state of calcium-phosphorus metabolism and the state of bone tissue in patients with liver cirrhosis requires the use of safe and informative diadynamic methods that will be used at any stage of the disease and will help in choosing the therapeutic tactics