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

Identification of cortactin molecular forms in human urine and their possible diagnostic value

The protein composition of human urine reflects changes in the biochemical and physiological status of an individual and has an essential diagnostic value. Using precipitation/extraction methods we isolated a protein with Mr ~100 kDa in a human urine. MALDI TOF/TOF mass spectrometry identified this protein as human Src protein kinase substrate cortactin (UniProtKB/Swiss-Prot: Q14247). Screening of urine samples using Western blotting with specific anti-human cortactin antibodies revealed different proteins immunologically related to cortactin in healthy humans and patients with liver cirrhosis and lung cancer diseases. These data suggest that the level of cortacins isoform in urine might serve as a potential marker for testing acute and systemic diseases

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.

Effects of ertugliflozin on kidney composite outcomes, renal function and albuminuria in patients with type 2 diabetes mellitus: an analysis from the randomised VERTIS CV trial

Aims/hypothesis In previous work, we reported the HR for the risk (95% CI) of the secondary kidney composite endpoint (time to first event of doubling of serum creatinine from baseline, renal dialysis/transplant or renal death) with ertugliflozin compared with placebo as 0.81 (0.63, 1.04). The effect of ertugliflozin on exploratory kidney-related outcomes was evaluated using data from the eValuation of ERTugliflozin effIcacy and Safety CardioVascular outcomes (VERTIS CV) trial (NCT01986881). Methods Individuals with type 2 diabetes mellitus and established atherosclerotic CVD were randomised to receive ertugliflozin 5 mg or 15 mg (observations from both doses were pooled), or matching placebo, added on to existing treatment. The kidney composite outcome in VERTIS CV (reported previously) was time to first event of doubling of serum creatinine from baseline, renal dialysis/transplant or renal death. The pre-specified exploratory composite outcome replaced doubling of serum creatinine with sustained 40% decrease from baseline in eGFR. In addition, the impact of ertugliflozin on urinary albumin/creatinine ratio (UACR) and eGFR over time was assessed. Results A total of 8246 individuals were randomised and followed for a mean of 3.5 years. The exploratory kidney composite outcome of sustained 40% reduction from baseline in eGFR, chronic kidney dialysis/transplant or renal death occurred at a lower event rate (events per 1000 person-years) in the ertugliflozin group than with the placebo group (6.0 vs 9.0); the HR (95% CI) was 0.66 (0.50, 0.88). At 60 months, in the ertugliflozin group, placebo-corrected changes from baseline (95% CIs) in UACR and eGFR were −16.2% (−23.9, −7.6) and 2.6 ml min−1 [1.73 m]−2 (1.5, 3.6), respectively. Ertugliflozin was associated with a consistent decrease in UACR and attenuation of eGFR decline across subgroups, with a suggested larger effect observed in the macroalbuminuria and Kidney Disease: Improving Global Outcomes in Chronic Kidney Disease (KDIGO CKD) high/very high-risk subgroups. Conclusions/interpretation Among individuals with type 2 diabetes and atherosclerotic CVD, ertugliflozin reduced the risk for the pre-specified exploratory composite renal endpoint and was associated with preservation of eGFR and reduced UACR. Trial registration ClinicalTrials.gov NCT0198688

Tiotropium versus Salmeterol for the Prevention of Exacerbations of COPD

BACKGROUND Treatment guidelines recommend the use of inhaled long-acting bronchodilators to alleviate symptoms and reduce the risk of exacerbations in patients with moderate-tovery-severe chronic obstructive pulmonary disease (COPD) but do not specify whether a long-acting anticholinergic drug or a β2-agonist is the preferred agent. We investigated whether the anticholinergic drug tiotropium is superior to the β2-agonist salmeterol in preventing exacerbations of COPD. METHODS In a 1-year, randomized, double-blind, double-dummy, parallel-group trial, we compared the effect of treatment with 18 μg of tiotropium once daily with that of 50 μg of salmeterol twice daily on the incidence of moderate or severe exacerbations in patients with moderate-to-very-severe COPD and a history of exacerbations in the preceding year. RESULTS A total of 7376 patients were randomly assigned to and treated with tiotropium (3707 patients) or salmeterol (3669 patients). Tiotropium, as compared with salmeterol, increased the time to the first exacerbation (187 days vs. 145 days), with a 17% reduction in risk (hazard ratio, 0.83; 95% confidence interval [CI], 0.77 to 0.90; P<0.001). Tiotropium also increased the time to the first severe exacerbation (hazard ratio, 0.72; 95% CI, 0.61 to 0.85; P<0.001), reduced the annual number of moderate or severe exacerbations (0.64 vs. 0.72; rate ratio, 0.89; 95% CI, 0.83 to 0.96; P=0.002), and reduced the annual number of severe exacerbations (0.09 vs. 0.13; rate ratio, 0.73; 95% CI, 0.66 to 0.82; P<0.001). Overall, the incidence of serious adverse events and of adverse events leading to the discontinuation of treatment was similar in the two study groups. There were 64 deaths (1.7%) in the tiotropium group and 78 (2.1%) in the salmeterol group. CONCLUSIONS These results show that, in patients with moderate-to-very-severe COPD, tiotropium is more effective than salmeterol in preventing exacerbations. (Funded by Boehringer Ingelheim and Pfizer; ClinicalTrials.gov number, NCT00563381.

The content of some vasoactive humoral-metabolic factors in patients with cirrhosis and their participation in pathogenesis of comorbid syntropical damages of cardiovascular system

Introduction. Liver cirrhosis is an inveterate polyetiological disease that regards to the 6 main reasons of patients’ mortality at the age of 35-60. The management of treatment and prediction for patients with cirrhosis particularly are defined by syntropic polymorbidal damages of other organs and systems among which are circulatory system diseases – cardiomyopathy and arterial hypotension – the most frequent ones. Firts of all, the improvement of diagnostics and treatment of those patients supposes the studying their pathogenesis. For the time being, the most probable pathogenetic chains are endothelial dysfunction, imbalance in renin-angiotensin-aldosterone system, and also overproduction of brain natriuretic peptide. Aim. To examine the content of vasoactive humoral-metabolic factors, i.e. endothelium-dependent (cyclic guanosine monophosphate, endothelin-1), indexes of renin-aldosterone system (renin, aldosterone) and brain natriuretic hormone in blood plasma in patients with cirrhosis and discover their participation in pathogenesis of comorbid syntropical damages of cardiovascular system. Materials and methods. Randomly with the previous stratification due to the presence of cirrhosis there were 603 patients (445 men (73.8 %) and 158 women (26.2 %) at the age of 19-80 (average age 49.2 ± 10.6) who were treated in the Lviv Regional Hepatological Centre, they had the complex clinical-laboratorial and instrumental research of all organs and systems before treatment due to the orders of the Ministry of Healthcare of Ukraine. Using these results we have seperate 490 (81.3 %) cirrhosis patients with extrahepatic damages of cardiovascular system (investigational group which is stratified into 3 subgroups, i.e. those who have only syntropic cardiomyopathy (103 patients) – group A, only syntropic hypotension (89 patients) – group B and others (306 patients)), and also those who don’t have the damages of cardiovascular system (113 patients; 18.7 %) – the comparison group). Randomly, to achieve the aim the part of the patients from every subgroup (30 patients from A-group, 27 – from B-group and 25 from group of comparison) were screened for the content of the vasoactive humoral-metabolic factorsm. There were 17 almost healthy volunteers of the same gender and age in the control group. Results and discussion. The patients of both investigational groups have reasonably higher number of vasoactive humoral-metabolic factors. In particular, patients with cirrhosis and syntopetic cardiomyopathy dominate the effects of endothelin-1, renin and brain natriuretic peptide, and in patients with cirrhosis and syntropic arterial hypotension – cyclic guanosine monophosphate and aldosterone are the main factors. Additionally we recorded the pathological interaction among vasoactive material. Unlike of the results in comparison group, in patients with liver cirrhosis and syntropic cardiomyopathy, the local vasoactive compounds are in such interactions with each other that result in hyperactivity of the renin-angiotensin-aldosterone system and endothelial dysfunction with a significant increase in both vasoconstrictor endothelin-1 and vasodilator NO, and in patients with liver cirrhosis and arterial hypotension – to severe endothelial dysfunction with overproduction of NO. Conclusions. Cyclic guanosine monophosphate, endothelin-1, renin, aldosterone, and brain natriuretic peptide, have a pathological effect on each other and are involved in the pathogenesis of syntropic damages of the circulatory system in patients with liver cirrhosis. In patients with cirrhosis and syntropic cardiomyopathy, heart damage occurs through toxic myocardial damage due to excessive effects of renin, endothelin-1, and brain natriuretic peptide with the onset of systolic and diastolic dysfunction and overload of the heart with blood volume. And in patients with cirrhosis and syntropic arterial hypotension, the damage occurs due to the endothelial dysfunction with excessive cyclic guanosine monophosphate and hyperaldosteronism, which leads to the expansion of peripheral vessels, the depositing of excess blood in the organs and, consequently, the decrease in the effective volume of circulation blood

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

Visual Signs of Chronic Diffuse Liver Diseases: the Stigma of Skin, its Appendages and Mucous Membranes

Introduction. The condition of the skin has always been a reflection of the state of the internal organs, in particular, organs of the gastrointestinal system, liver. Most skin symptoms are not specific to the hepatobiliary system, and therefore can be observed in other diseases. However, often the presence of skin stigma and patient complaints can be very helpful in verifying the diagnosis. According to the results of research in the world, palmar erythema occurs in 23.0%, telangiectasias (vascular “spiders”) – in 33.0%, and the triad of symptoms – palmar erythema, telangiectasias and white nails – in 21.0% of the patients with the liver cirrhosis. Despite all the importance, the topic is not sufficiently covered in the medical literature. Aim. Comprehensively describe stigmata of the skin, its appendages and mucous membranes in patients with chronic digguse liver diseases (CDLD). Materials and methods. The results of complex clinical-laboratory and instrumental examination of 2 007 patients with CDLD that were treated during the period of 2005-2013 in the Lviv Regional Hepatologic Center, which was created on the basis of the Department of Internal Medicine N 1 of the Danylo Halytsky Lviv National Medical University and the Gastroenterological Department of the Lviv Regional Clinical Hospital are presented. Among these patients there were 1 508 men (75.1%) and 499 women (24.9%) at the age of 47.9 ± 0.2 years. Before the start of treatment in a hospital, they were examined (according to the order of the Ministry of Health of Ukraine N 271 dated 13.06.05 “On Approval of Protocols of the Providing of Medical Care on the Specialty “Gastroenterology”), on the basis of the results of which the clinical diagnoses were set. Results. Skin changes are often the first predictors of CDLD. For example, a combination of pigmentation, jaundice and xanotomy confirms the diagnosis of primary liver biliary cirrhosis. In the vast majority of patients with chronic liver diseases there are pathogenetically syntropical co- and polistigmata of the skin, which are of great diagnostic value. They allow an experienced doctor to suspect or to set the diagnosis before the special comprehensive examination and to determine the tactics of treatment. The most widespread disorders found in the cirrhotic patients were dyschromia, in particular, jaundice, spider nevi, palmar erythema, «cardinal» tongue, «paper-money» skin, «caput medusae», «lacquer» nails. Conclusions. Chronic diffuse liver diseases are mainly accompanied by the pathogenic syntropic skin, its appendages and mucous membranes lesions, which are of important diagnostic value and help the experienced physician suspect or set the diagnose before a special comprehensive examination, choose the treatment tactics before the getting the results of this examination

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

Modified Сomplex Treatment of the Cirhotic Patients with the Hepatopulmonary Syndrome of the Different Severity Degrees: Pathogenetic Reasoning and Efficiency

Introduction. Engaging of the different organs and systems into the pathological process, including the organs of the respiratory system, interpretated as syntropic co­ and polymorbid lesions, including the most common ­ hepatopulmonary syndrome (HPS), in many cases determines the severity of the general condition of the cirrhotic patients, leads to a significant reduction of their life quality, disability, has a decisive prognostic value at all the stages of the treatment and is the leading cause of the death of the hepatological patients. Taking into the account the poor prognosis and high mortality (41.0 %) of the patients with the HPS, it is required the constant monitoring and paying the special attention of the physicians to such patients and also prescribing the adequate pathogenesis­based drugs to optimize the treatment. The aim of our study was to modify the treatment of the cirrhotic patients with the hepatopulmonary syndrome of different severity degrees on the base of clarifying the characteristics of their pathogenesis and to evaluate its effectiveness. Materials and methods. Into the study in randomized manner with the preliminary stratification by the presence of the HPS were involved 93 patients [26 women (28.0 %) and 67 men (72.0 %); aged 27 to 67 years, who were treated in Lviv Regional Hepatological Center during 2012­2015. To elucidate the pathogenesis of the HPS for appointing the most effective pathogenetically reasonable treatment, we have determined the content of some vasoactive humoral and metabolic factors, namely the endothelium­dependent (cyclic guanosine monophosphate (cGMP), endothelin­1 (E­1)), tumor necrotizing factor α (TNF α) and the indices of the renin­aldosterone system (renin, aldosterone) in the blood plasma of the patients by ELISA. Also there were examined the gas composition of the venous blood and the acid­base balance (ABB) state. To determine the effect of the mediators of the autonomic nervous system (ANS) on the vascular tone, we have assessed its state by the registration of the heart rate variability (HRV). After the treatment clinically and laboratory indices and life quality of the patients of the experimental group (EG) who were treated by the modified by us technique and of the control group (CG), where the patients received the standard treatment were evaluated. Results. During the study of some pathogenetic mechanisms of the HPS it was found the inverse correlative connection between the values of carbon dioxide partial pressure, bicarbonate, standard bicarbonate, bases excess in the blood and in the extracellular fluid and the severity of the HPS, which was manifested by the progressive metabolic acidosis that required the medical correction. With the growth of the severity of the respiratory lesions the levels of cGMP, E­1, TNF α, renin and aldosterone in the blood plasma of the cirrhotic patients were significantly (p < 0.05) increased, which made theim to be the criteria to justify the appointment of the pathogenetic treatment. During the diagnosis of the ANS state in the cirrhotic patients with the syntropic respiratory lesions using HRV registration we proved the overwhelming influence of the sympathetic part over the parasympathetic in the patients with the I degree HPS with the directly proportional increase of the neurohormonal effects according to its severity. The modified by us method of the treatment of the patients considering the investigated pathogenic mechanisms of the liver cirrhosis and the HPS, its severity, as well as the conventional one, gave the positive result, but by its quality parameters the conventional medical complex significantly yielded comparing to the modified by us algorithm. Statistical analysis of the questionnaires MOS SF­36 before and after the treatment indicated a significant (p < 0.05) improvement of the physical activity, vitality, mental and general health, reducing of the pain and the role of the emotional stress in disability, resulting into the improvement of the physical and mental status of the patients treated by the modified by us technique and shows its effectiveness. Conclusions. Investigations of the indices of ABB (carbon dioxide partial pressure, levels of bicarbonate, standard bicarbonate, bases excess in the blood and in the extracellular fluid) the endothelium­dependent (cGMP, E­1), TNF α and the indices of the renin­aldosterone system (renin, aldosterone), the state of the ANS and their dependence on the severity of the HPS substantiated the advisability of including into the medical complex of the patients with the I degree HPS in addition to the detoxification, diuretic and hepatoprotective treatment the electrolyte combined isotonic solution (sodium, potassium, magnesium, calcium chloride, acetate, malate) ­ 500.0 ml intravenously once a day, pentoxifylline ­ 1 tablet (100.0 mg) twice daily, spironolactone ­ 1 tablet (25.0 mg) twice daily, carvedilol ­ 1 tablet (3,125 mg) once a day; with the II degree HPS ­ 4.0% sodium bicarbonate ­ 100.0 ml intravenously once a day, sol. Pentoxifyllini 0.05% ­ 100.0 ml intravenously once daily, valsartan ­ 1 tablet (40.0 mg) once daily, spironolactone ­ 1 caps. (50.0 mg) twice a day; with the III degree HPS ­ 4.2% sodium bicarbonate ­ 100.0 ml intravenously once a day, sol. Pentoxifyllini 0.05% ­ 200.0 ml intravenously once a day with the transition to oral use – 1 tablet (100.0 mg) of pentoxifylline twice daily, enalapril ­ 1 tablet (5.0 mg) once daily, spironolactone ­ 1 caps. (100.0 mg) twice a day. Using the modified pathogenetic reasonable treatment in the cirrhotic patients taking into account the severity of the HPS allowed us to increase its efficiency by 13.7 % and to improve the physical activity, vitality, mental and general health, reduce pain and the role of the emotional problems in disability, leading to the improvement of physical and mental status of the patients